1536106348

ENDOCRINOLOGY RESEARCH AND CLINICAL DEVELOPMENTS
CASE DISCUSSIONS
IN ENDOCRINOLOGY
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ENDOCRINOLOGY RESEARCH AND
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ENDOCRINOLOGY RESEARCH AND CLINICAL DEVELOPMENTS
CASE DISCUSSIONS
IN ENDOCRINOLOGY
MUSTAFA ŞAHIN
DEMET ÇORAPÇIOĞLU
NILGÜN BAŞKAL
ALI RIZA UYSAL
A. VEDIA TONYUKUK GEDIK
MURAT FAIK ERDOĞAN
SEVIM GÜLLÜ
AND
RIFAT EMRAL
EDITORS
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CONTENTS
Preface ix
Chapter 1 Micropapillary Thyroid Cancer in Patients with
Graves’ Ophtalmopathy 1
Mustafa Şahin and Rifat Emral
Chapter 2 Neuroendocrine Tumor of the Thyroid and Pancreas 7
Asena Canpolat and Mustafa Şahin
Chapter 3 A Case of MEN Presenting with ZES 11
Asena Canpolat, Mustafa Şahin, Sevim Güllü and
Murat Faik Erdoğan
Chapter 4 Adrenal Incidentaloma with Subclinical Cushing
Syndrome: How to Treat? Whom to Treat? 17
Chapter 5 A Relapsing Conn’s Syndrome 21
Chapter 6 Co-Existence of Type 1 DM and Sarcoidosis 25
Chapter 7 A 44-Year-Old Woman Presented with Multiple
Hormone Secreting Adrenal Cortical Adenoma 31
Çağlar Keskin and Mustafa Şahin
vi Contents
Chapter 8 A Case of Insulinoma Presented with

Postprandial Hypoglycemia 35
Asena Canpolat, Mustafa Şahin,
Murat Faik Erdoğan and Ali Rıza Uysal
Chapter 9 Metastatic Papillary Thyroid Carcinoma -
Cribriform Morular Variant 39
Berna İmge Aydoğan, Mustafa Şahin and
Sevim Güllü
Chapter 10 Idiopathic Prolactinoma 47
Şule Canlar and Asena Canpolat
Chapter 11 Malignant Pheochromocytoma with
Papillary Thyroid Carcinoma 53
Özgür Demir and Mustafa Şahin
Chapter 12 Recurrent Papillary Thyroid Cancer after Primary
Surgical Resection Requiring Re-Operations and
Radioiodine Therapy 59
Şule Canlar, Mustafa Şahin and
Murat Faik Erdoğan
Chapter 13 Two Sporadic Medullary Thyroid Cancer Cases 65
Şule Canlar, Mustafa Şahin, Sevim Güllü,
Murat Faik Erdoğan and Demet Çorapcioglu
Chapter 14 Composite Pheochromocytoma 69
Berna İmge Aydoğan, Mustafa Şahin and
Rifat Emral
Chapter 15 Cervico-Mediastinal Mass Mimicking Giant
Thyroid Nodule 75
Asena Canpolat, Şule Canlar, Mustafa Şahin and
Sevim Güllü
Chapter 16 Fahr’s Disease with Dystonia: A Case Report 81
Berna İmge Aydoğan, Uğur Ünlütürk, Ferda Demir,
Mustafa Şahin and Ali Rıza Uysal
Chapter 17 Adrenal Insufficiency Case Presenting with
Hypercalcemia and Hypotension 87
Şule Canlar, Rifat Emral and Mustafa Şahin
Contents vii
Chapter 18 Hypercalcemia Due to Diabetic Ketoacidosis 91

Şule Canlar, Mustafa Şahin and Demet Çorapcioglu
Chapter 19 Sulfasalazine-Related False Positive Urinary
Normetanephrine Result 95
Berna İmge Aydoğan, Pinar Kubilay, Ali Riza Uysal
and Sevim Güllü
Chapter 20 A 55-Year-Old Woman with Hemangiopericytoma-
Associated Hypoglycemia 99
Chapter 21 A 58-Year-Old Woman with Ankylosing Spondylitis
who developed Papillary Thyroid Cancer 103
Chapter 22 A 35-Year-Old Woman with Left Non-Functional
Adrenal Adenoma after Right Adrenalectomy
for Pheochromocytoma 107
Chapter 23 A 22-Year-Old Woman with Type 1 Congenital
Generalized Lipoatrophy 111
Chapter 24 A 38-Year-Old Woman with Hurthle Cell Carcinoma
and Recurrent Lymph Node Metastases 115
Çağlar Keskin, Mustafa Şahin and Seher Demirel
Chapter 25 A 56-Year-Old Woman with an Elevated
Parathormone Level after the Surgery for
Secondary Hyperparathyroidism 119
Editor Contact Information 123
Index 125
PREFACE
Endocrine and metabolic diseases involve very common diseases like

diabetes, obesity, polycystic ovary syndrome, hypertension and thyroid
disorders. Endocrine diseases especially adrenal, pituitary, thyroid, gonadal,
and metabolic-related diseases require clinical experience, expertise and
collaboration with other departments, and different opinions and discussion are
so important for evaluating endocrine diseases. Expertise can only be gained
by different case evaluations. Endocrinologists and internal medicine
specialists should increase their capacity of creative thinking about their
patients for more accurate patient care. They are also so common in the
population. This book is a compilation of work that may be beneficial for
endocrinology and internal medicine residents, surgeons, and medical
students. The purpose of this book is to cover up-to-date practical endocrine
case management, daily practice and manage difficult cases in endocrinology.
The authors would be happy if readers would send comments, feedback and
suggestions so they can correct their mistakes and can arrange a second book
with new cases according to their suggesitons.
Special thanks are given to the consultants in the Endocrinology
Department and other departments in Ankara University for sharing their
clinical expertise with the authors. Many thanks are also given to Nadya S.
Gotsiridze-Columbus, Carra Feagaiga, Stella Rosa and Nova Science
Publishers for their extraordinary organizational help.
Mustafa Şahin MD
In: Case Discussions in Endocrinology ISBN: 978-1-53610-634-3
Editors: Mustafa Şahin et al. © 2017 Nova Science Publishers, Inc.
Chapter 1
MICROPAPILLARY THYROID CANCER IN

PATIENTS WITH GRAVES’ OPHTALMOPATHY
Mustafa Şahin and Rifat Emral

Endocrinology and Metabolic Diseases Department,
Ankara University School of Medicine, Ankara, Turkey
Compliant: Dry Mouth at Night, Nocturia

History: In 2008, during the investigation of his complaints (redness of his
eyes, periorbital edema and palpitation) hyperthyroidism was diagnosed. We
have learnt that patient had been treated with antithyroid therapy and for
ophtalmopathy with glucocorticoids for a period of 6 months.
While the ocular findings were relieved, hyperglycemia and dyslipidemia
emerged after the use of glucocorticoids. Gliclazide and atorvastatin therapy
was started, the patient consulted to us for the first time in April 2009, his
body mass index (BMI) was 33.75 kg/m2 and blood pressure (BP) was 145/95
mmHg. In his eyes, chemosis, caruncle hypertrophy, mild periorbital edema
and conjunctival injection had observed and also he was found to have
strabismus.
According to his laboratory results: the fasting plasma glucose (FPG) :
105 mg / dl and postprandial glucose: 284 mg / dl, creatinine: 0.7 mg / dl,
calcium: 7.1 mg / dl, phosphorus: 2.5 mg / dl, Total Cholesterol: 221 mg / dl,
HDL 33 mg / dl, LDL: 185 mg / dl, triglycerides: 107 mg / dl, SGPT: 199 U /
L, AST: 101 U / L, ALP: 83 U / L, HbA1c: 11.1%, free T3 : 3.68 pmol / L,
2 Mustafa Şahin and Rifat Emral
TSH: 0.08 mIU / ml, complete blood count WBC: 10200/mm3, Platelets:
270000/mm3, Hb 16.7 g / dl.
In thyroid sonography thyroid volume was 29.6 ml in right lobe there was
nodule with diameters 6x8x6 mm, in left lobe there were two nodules with
diameters 7x13x9 mm and 11x22x19 mm. Thyroid scintigraphy revealed in
hyperactivity and I-131 uptake at fourth hour was significantly high. Fine
needle aspiration biopsy (FNAB) from hypoactive nodules result revealed as
lymphocytic thyroiditis. For his diabetes management, novomix insulin 30/70
was started (Total dose was 26 Unit /day). He was diagnosed as toxic diffuse
nodular goiter. At that time, his results were found as FPG: 113 mg/dl, free
T4: 17,9 pmol/L, TSH: 0,148 mIU/L, Anti-TPO: 35,66 IU/ml, Anti-Tg: 14,26
IU/ml.
Because he has also ophtalmopathy with diagnosis of toxic diffuse nodular
goiter we preferred surgery as initial therapy. In May 2009 bilateral total
thyroidectomy had been done.
Histopathology result: Papillary microcarcinoma 2mm long diameter in
isthmus, there is tumor capsule without infiltration; thyroid paranchyme has
nodular goiter with benign pathology.
Continued observation, remnant ablation dose of radioactive iodine,
therapeutic dose of radioactive iodine three possible appropriate manegement
options at his time.
At this stage according to his diagnosis as low risk well differentiated
thyroid microcarcinoma no extra therapy was considered. Also, orbitopathy
may progress after radioactive iodine treatment particularly in smokers.
At that stage how much TSH suppression is required? TSH is lower than ‹
0.1 mU/L, TSH in between 0.1-0.5 mU/L or TSH between 0.3-2 mU/L? We
prefer TSH between the (0.1–0.5 mU/L) in patients at low risk of having
recurrence at that time.
In June 2010 when he came to control he was using Novo Mix 30/70
morning 18 unit, evening 10 unit, Coversyl 5 mg, Euthyrox 100 mcg,
Calcimax-D3. There was significant improvement in his eyes (mild GO, CAS
score 1)
FPG: 99 mg/dl, PPG: 103 mg/dl, Creatinine: 0,9 mg/dl, Sodium: 145
mEq/L, K: 4,3 mEq/L, Calcium: 9,5 mg/dl, P: 2,7 mg/dl, Total Cholesterol :
250 mg/dl, HDL: 49 mg/dl, LDL: 173 mg/dl, trygiceride: 140 mg/dl, SGPT:
107 U/L, SGOT: 61 U/L, GGT: 64 U/L, ALP: 77 U/L, HbA1c: %6.5, TSH:
6,5 mIU/ml, Anti-Tg: < 0,9 IU/ml, h-Tg: 2,43 ng/ml.
Micropapillary Thyroid Cancer in Patients with Graves’ Ophtalmopathy 3
According to these results, the patient's insulin dose was recommended as

in the morning 16 unit, in the evening 10 unit. He was told to keep the blood
pressure medication; Lescol XL 80 mg was added to the treatment.
For this thyroglobulin level some authors may consider recurrence. Fixed
thyroglobulin cut-off may sometimes be problematic. Our patient did not
receive RAI treatment so our patient may have 1-2 gram of remnant caused by
non-compliance of thyroxine therapy. After appropriate TSH suppression it is
better to evaluate the thyroglobulin level for persistence. Because of the high
TSH, L-T4 dose was increased to 150 mcg / day.
In the November 2009 control his results were: FPG: 106 mg/dl, PPG: 98
mg/dl, HbA1c: %5.6, Calcium: 9,7 mg/dl, P: 2,9 mg/dl, LDL-cholesterol: 121
mg/dl, TSH: 1,28 mIU/L, Anti-Tg: < 0,9 IU/ml, h-Tg: 0,96 ng/ml. Hertel
ophtalmometer at 110 mm range, the right eye was measured 24 mm, left eye
was measured 23 mm. Neck sonography 0,24 ml residuel tissue (right and left
totally).
May 2010 control blood pressure was 130/90 mmHg, BMI was 33.12
kg/m2. Bilateral proptosis especially in the right eye was observed. Periorbital
edema was seen. In new hertel measurement at 105 mm range right eye was 27
mm, left eye was 25 mm. Neck sonography no residual tissue was detected his
results were: FPG: 102 mg/dl, PPG: 133 mg/dl, creatinine 0.9 Na: 139
mEq/L,K: 4,3 mEq/L, Calcium: 9,2 mg/dl, P: 3,1 mg/dl, T.cholesterol: 162
mg/dl, HDL: 41 mg/dl, LDL: 93 mg/dl, Trygliceride: 139 mg/dl, SGPT: 22
U/L, SGOT: 16 U/L, ALP: 97 U/L, GGT: 23 U/L, HbA1c: %6.1, TSH: 2,54
mIU/ml, Anti-Tg: <0,9 IU/ml, hTg: 1,09 ng/ml. For more suppression for
better eye control, LT-4 dose was increased to 175 mcg/day.
03/2012 Physical Examination: Height: 179 cm Weight: 125 kg, BMI =
39.06 kg/m2, BP 120/70 mmHg, thyroidectomy scar, no palpable residual
thyroid tissue. Fine tremor is negative. There is Strabismus; chemosis and mild
hypertrophy of the caruncle. periorbital edema are present. Dupuytren's
contracture is present in the left hand. Existing bilateral gynecomastia was
involutional. His waist circumference was 136 cm.
FPG: 117 mg/dl, PPG: 131 mg/dl, creatinine: 0,94 mg/dl, Na: 139 mEq/L,
K: 4,6 mEq/L,calcium: 9,1 mg/dl, P: 3,3 mg/dl, T. Cholesterol: 199 mg/dl,
HDL: 37 mg/dl, LDL: 127 mg/dl, Trygliceride: 173 mg/dl, SGPT: 22 U/L,
SGOT: 17 U/L, GGT: 18 U/L, ALP: 69 U/L, HbA1c: %6.6, Microalbuminuria
(spot): 22 mg/L, free T4: 11,22 pmol/L, TSH: 8,39 mIU/ml, Anti-Tg: <0,9
IU/ml, hTg: 2,4 ng/ml. Leukocyte: 11600/mm3, Trombocyte: 298000/mm3,
Hb: 16 gr/dl.
Tiroid USG: Total thyroidectomy. No enlarged cervical

lymphadenopathy.
No residual tissue, whereas h-tg was high >1 ng/ml. Euthyrox 200
mcg/day is recommended. Because of stable eye findings control was planned
6 months later 02.09.2013: Palpable mass in right neck, dry mouth, nocturia,
edema of the legs.
PE: Height: 179 cm, weight: 128 kg, BMI: 40 kg/m2, BP: 140/80 mmHg,
in right cervical region 5; 3cm LAP was detected. Left eye predominant
proptosis; waist circumference: 139 cm
Neck Ultrasound
 In right cervical 3 cm LAP was detected. Left eye predominant

proptosis
 No residual tissue
 Right cervical region (Level 2) 13x25x19mm
 Right (Level 3) 5x15mm LAP
Aspiration biopsy under ultrasonography guidance of the probable LN

metastasis and cytological exam as well as determining the tg concentration in
saline washout of the aspiration needles.
Tg wash-out results: Region II: 5.7 ng / ml, Region III: 4.8 ng / mL,
Serum Tg: 1.82 ng / mL.
FNA: Non Diagnostic
According to these wash-out results according to serum thyroglobulin

level could not be accepted as positive.
These are therapeutic dilemmas that are not addressed in current
guidelines. Although incidence and aggressiveness of cancer in Graves’
patients has been debated. The overall incidence of thyroid cancer and
aggressiveness increased according to our study [1]. High TSH receptor
antibodies may affect the tumor progression.
Micropapillary Thyroid Cancer in Patients with Graves’ Ophtalmopathy 5
Decision: Re-biopsy.
Tg wash-out results: Region II: 3.31 ng / ml.
Re-bx was benign, close follow up with neck sonography was decided.
Concomitant papillary thyroid carcinoma may complicate the

management, TSH suppression may aggravate the ophtalmopathy. In low risk
thyroid cancer patients, slightly below the lower limit of normal TSH (0.1–0.5
mU/L) is enough for TSH suppression according to recent data [2]. Also
radioactive iodine may also aggrevate the orbitopathy. If we decide to give
RAI which method we must prefer LT4 withdrawal or thyrogen stimulated?
For mild Graves ophtalmopathy glucocorticoid therapy may also be required.
The acute exacerbation is usually transient and preventable with prophylactic
corticosteroids [3]. It will be more problematic if there would high risk thyroid
cancer with graves orbitopathy.
REFERENCES
[1] Sahin, M., Guvener, N. D., Ozer, F., Sengul, A., Ertugrul, D., Tutuncu,
B. N., “Thyroid Cancer in Hyperthyroidism: Incidence Rates and Value
of Ultrasound-Guided Fine-Needle Aspiration Biopsy in This Patient
Group”, J. Endocrinol. Invest., 28(9):815-818 (2005).
[2] Haugen B. R.1, Alexander E. K.2, Bible K. C.3, Doherty G. M.4, Mandel
S. J.5, Nikiforov Y. E.6, Pacini F.7, Randolph G. W.8, Sawka A. M.9,
Schlumberger M.10, Schuff K. G.11, Sherman S. I.12, Sosa J. A.13,
Steward D. L.14, Tuttle R. M.15, Wartofsky L.16. 2015 American Thyroid
Association Management Guidelines for Adult Patients with Thyroid
Nodules and Differentiated Thyroid Cancer: The American Thyroid
Association Guidelines Task Force on Thyroid Nodules and
Differentiated Thyroid Cancer. Thyroid. 2016 Jan; 26(1):1-133. doi:
10.1089/thy.2015.0020.
[3] Mansberg R.1. Thyroid remnant radioiodine ablation in a case of
concurrent thyroid carcinoma, Graves' disease, and thyroid
ophthalmopathy. Clin. Nucl. Med. 2007 Jul;32(7):513-5.
Chapter 2
NEUROENDOCRINE TUMOR OF
THE THYROID AND PANCREAS

A 47-year-old man with a 4-year history of non-toxic multinodular goiter

consulted to our hospital because of the suspicious results of his thyroid fine
needle aspiration cytology which was performed at another hospital and
reported as clear cell renal carcinoma. He had no associated symptoms such as
dysphagia, dyspnea, or dysphonia or family history of both thyroid and
genitourinary malignancies.
He was a non-smoker and was not on any medications. There was hard
fixed palpable nodule in thyroid gland found on the physical examination. The
rest of his detailed physical examination was normal. A neck ultrasound
examination showed an enlarged thyroid gland and several nodules in the
thyroid gland: 15x9 mm in the right lobe and 5 mm in the left. No suspicious
central or lateral neck lymph nodes were found.
Subsequently fine needle aspiration cytology (FNA) was taken from the
right thyroid mass, which revealed clear cell histology. Findings were reported
to be compatible with metastatic renal cell carcinoma or clear cell follicular
neoplasia or intrathyroidal parathyroid lesion. The repeated FNA resulted
same as the previous reported cytology results.
An abdominal ultrasonography was ordered to rule out possible renal
tumor; and nothing was found remarkable.
8 Asena Canpolat and Mustafa Şahin
Figure 1. CT scan of neck and abdomen.
The patient also suffered from epigastric pain and postprandial fullness.
Upper endoscopy was performed and erosive antral gastritis was observed.
The histological examination revealed well-differentiated neuroendocrine
tumor with strong and diffuse immunoexpression of neuroendocrine markers
such as chromogranin A (CGA) and synaptophysin. The evaluation of the
entire gastrointestinal tract did not reveal any pathology.
Chromogranin A level was found to be high 326 (27-94). The result of
octreotide scintigrapy pointed to the presence of somatostatin reseptor positive
cells at physiological accumulation localisations. A galium 68 pet-ct scan was
done thereafter and a focal accumulation of galium 68 was observed at the
head of pancreas. PTH level was normal. Calcitonin level was normal.
Patient underwent bilateral total thyroidectomy. Pathological evaluation
revealed neuroendocrine tumor that strongly express of chromogranin A and
Neuroendocrine Tumor of the Thyroid and Pancreas 9
synaptophysin, but has not calcitonin expression with 1.5 cm in diameter.

Previously NET metastasis to thyroid as initial presentation has been reported
[1]. As previously reported thyroid metastasis may be initial presentation of
renal cell carcinomas [2]. Both tumors may metastasis to thyroid and fine
needle aspiration may not differentiate each other. Also neuroendocrine
tumors may be present together. Differential diagnosis is important for
subsequent follow-up.
REFERENCES
[1] Sivrikoz E1, Ozbey NC, Kaya B, Erbil Y, Kaya S, Yilmazbayhan D,
Firat P, Kapran Y. Neuroendocrine tumors presenting with thyroid gland
metastasis: a case series. J Med Case Rep. 2012 Feb 27;6:73.
[2] Ramírez-Plaza CP1, Domínguez-López ME2, Blanco-Reina F3. Thyroid
metastasis as initial presentation of clear cell renal carcinoma. Int J Surg
Case Rep. 2015;10:101-3.
Chapter 3
A CASE OF MEN PRESENTING WITH ZES

Sevim Güllü and Murat Faik Erdoğan
Multiple endocrine neoplasia type 1 (MEN1) is an inherited disorder

comprising primary hyperparathyroidism, duedenopancreatic neuroendocrine
tumors and pituitary tumors especially prolactinomas [1].
Manifestations of MEN1 include carcinoids, facial angiofibromas,
collagenomas and lipomas. Adrenal cortical adenomas, hyperplasia are also
common. Pheocromocytoma has also been reported [2, 3]. We represent a case
of MEN 1 with surrenal incidentaloma.
A 31 year-old man was admitted to the hospital because of vomitting and
epigastric pain. It was learned that he had had hematochezia for more than
three months. An upper gastrointestinal endoscopy had been performed which
releaved active gastritis and multiple bleeding duedenal ulcers.
On examination, the blood pressure was 110/60 mm Hg and pulse was
115/dk. He looked pale and anxious.
Initial laboratory data revealed the following hemoglobin 11,5 g/dl,
sodium, 135 mEq/L; potassium, 3.9 mEq/L; chloride, 108 mEq/L, blood urea
nitrogen, 18 mg/dL; creatinine, 0,9 mg/dL; and fasting glucose, 84 mg/dL.
Other significant laboratory values included the following: calcium, 14.5
mg/dL; phosphate, 2.0 mg/dL; total protein, 6.8 g/dL; albumin, 3,8 g/dL,
magnesium, 1.7 mEq/L and the alkaline phosphatase level is 396 IU/L.
Urinalysis findings were normal.
12 Asena Canpolat, Mustafa Şahin, Sevim Güllü et al.
After his hemodynamic parameters were restored and active bleeding

ulcers were sclerosed; special endocrine laboratory tests were done including
parathormone: 184 pg/ml (12-88), 25-OH vitamin D 19, Gastrin 459 (28-185)
pg/ml. Anterior hypophysis hormones were all in normal ranges including
prolactin levels. His glucose level, C-peptide and fasting insulin were also
within normal ranges.
His calcium levels fell to 10,4 mg/dl after initiating force diuresis.
His neck ultrasonography revealed a hypoechoic mass localized on the left
side of the thyroid which might be compatible with parathyroid adenoma. He
had multiple nephrocalcinosis on left kidney and osteoporosis at femur neck
with a Z-score of -2,6.
His hypophysis MRI did not reveal an adenoma and surrenal CT showed
adrenocortical hyperplasia bilaterally and left adrenocortical adenoma which
was found to be non-functional by biochemical analysis.
A pancreas MRI was performed which reported a mass with 23x17 mm
diameter at tail and corpus of pancreas (Figure 1). Endosonographic evaluation
confirmed the mass.
He was diagnosed as MEN 1 and his family members were called for
evaluation. Autosomal dominant inheritance pattern was observed in this
family in which a mother and 3 sons were affected.
Hypergastrinemia in the absence of increased acid production is not due to
gastrinoma. It is important to stop H2 blockers, proton pump inhibitors at least
one week before gastrin measurement. High index of suspicion is necessary
for diagnosis. Early surgical intervention is recommended to prevent
malignant progression.
First he underwent a parathyroid surgery and then a distal pancreatectomy
was performed. Pathology revealed parathyroid adenoma and multiple
endocrine tumor grade 2 with no lymphovascular invasion respectively. The
tissue was positive for gastrin on immunohistochemical staining.
He has been still following with diagnosis of MEN 1, secondary diabetes
mellitus due to distal pancreatectomy and non-functional adrenocortical mass
for four years time.
A Case of MEN Presenting with ZES 13
Figure 1. (Continued).
14 Asena Canpolat, Mustafa Şahin, Sevim Güllü et al.
Figure 1. MRI imaging of pancreatic neuroendocrine tumor in corpus and tail of the
pancreas.
This case is interesting because of localization of gastrinoma and bening

course of the tumor. It is very well known that gastrin secreting tumors which
represent about 54% of neuroendocrine tumors in MEN1 are located mostly
(90%) in duedenum. Most of them are malignant and about 50% of MEN 1
patient s’ gastrinomas having metastazied before diagnosis [1].
His mother and siblings have prolactinoma but our patient up to now has
not got prolactinoma. MEN-1 tumors may not follow the same order in the
sibling, sex is important; prolactinoma are more seen in women and
hyperparathyroidism in men.
Adenomectomy in first diagnosis may not be enough therapy for his
parathyroid situation close follow up is necessary because of parathyroid
hyperplasia. Recurrence risk is high for this patient. And then 3.5
parathyroidectomy may be more helpful. Close follow up is necessary
In hypercalcemia there may be multiple ulcer and increased gastrin levels
and it is important to distinguish it from ZES. Level of gastrin levels and
history may be helpful. Chromogranin A levels also may help for differential
diagnosis. After high chromogranin A and endosonography revealed 2 cm
mass. Dinamic CT and Distal pancreatectomy-was planned.
A Case of MEN Presenting with ZES 15
REFERENCES
[1] Brandi ML, Gagel RF, Angeli A et al. Guidelines for diagnosis and
therapy of MEN type 1 and type 2. The Journal of clinical
endocrinology and metabolism 2001;86:5658-71.
[2] Langer P, Cupisti K, Bartsch DK et al. Adrenal involvement in multiple
endocrine neoplasia type 1. World journal of surgery 2002;26:891-6.
[3] Waldmann J, Bartsch DK, Kann PH, Fendrich V, Rothmund M, Langer
P. Adrenal involvement in multiple endocrine neoplasia type 1: results
of 7 years prospective screening. Langenbeck’s archives of surgery /
Deutsche Gesellschaft fur Chirurgie 2007;392:437-43.
Chapter 4
ADRENAL INCIDENTALOMA
WITH SUBCLINICAL CUSHING SYNDROME:
HOW TO TREAT? WHOM TO TREAT?

The incidence of adrenal incidentaloma is 8.7% reported in autopsy series.

Approximately 80% of patients with incidentalomas had a nonfunctioning
adenoma, 5%-10% had subclinical Cushing syndrome (SCS), 5% had a
pheochromocytoma, 1% had an aldosteronoma, <5% had an adrenocortical
carcinoma (ACC), and 2.5% had a metastatic lesion; the remaining were
ganglioneuromas, myelolipomas, or benign cyst. The surgical treatment for
SCS is still controversial [1].
Surgical resection should be decided for patients with abnormal glucose
tolerance, dyslipidemia, osteoporosis and uncontrolled hypertension. Here, we
presented a 58-year-old woman who was found to have a left adrenal tumor
associated with subtle cortisol hypersecretion.
A 56 -year-old woman was found to have a left adrenal tumor with 14x17
millimeters in diameter incidentally by the abdominal ultrasonography which
was ordered for evaluation of renal artery stenosis for her worsening
hypertension. Therefore, she was admitted to our Metabolism and
Endocrinology outpatient clinic.
She had a history of hyperlipidemia and hypertension. She has poorly
controlled hypertension (treated with combination of Angiotension Converting
inhibitor plus thiazide diuretic and calcium channel bloker) and

hyperlipidemia (statin therapy). She was 156 cm tall, 82 kg weight, and had
33,6 kg/m2 body mass index. Physical examination was unremarkable on
admission except her obesity and high blood pressure. She had no features of
typical physical stigmas of hypercortisolism like facial plethora, dorsocervical
fat pad on her neck (buffalo hump) or striae.
CT scan of the adrenal glands showed a 30x13 mm well encapsulated left
adrenal mass together with a clearly normal right adrenal gland.
She was evaluated for functionality of the adrenal adenoma for
pheocromacytoma, conn, cushing syndrome and hyperandrogenism. Her
biochemical evaluation were in normal ranges except for cushing syndrome.
Diurnal variation of ACTH and cortisol was normal. Early morning
cortisol was 10,76 µg/dl (6,7-22,6), early morning ACTH was 1,61 pg/mL
(normal range for the lab 7,2-63) and DHEA-S was 6 µg/dl (7-188). After 1-
mg overnight dexamethasone suppression test, morning cortisol value 2,91
µg/dl indicated additional work up. Urinary-free cortisol was 159,3 µg/day
(normal range19,5-115). A 2-day low-dose dexamethasone suppression test
was performed and cortisol level was found to be 2,1 which was not
suppressed. Her bone mineral density parameters were compatible with
osteopenia.
She was diagnosed as subclinical cushing syndrome (SCS) and decided to
be followed. After 6 months later a CT scan and biochemical evaluation was
repeated. CT was reported same as the previous scan and cortisol metabolism
tests were again compatible with SCS. Follow-up was recommended in our
clinical council instead of surgery. After 6 month her biochemical evaluation
revealed hypercalcemia (Ca = 10.6 mg/dl) with high PTH level (144 pg/mL
(12-88)) and low phosphor level. Her 25 hidroxy vitamin D3 level was 28,2
µg/L. Primary hyperparathyroidism was diagnosed after high urinary calcium
and low phosphor levels. Parathyroid adenoma was diagnosed after open
parathyroid surgery. According to our opinion, calcium levels should be
checked in adrenal patients who may candidate for surgery because after
surgery significant hypercalcemia may be seen. Multiple endocrine neoplasia
should be ruled out in hyperparathyroidism diagnosis in addition do adrenal
cushing syndrome. Patients with adrenal cushing syndrome should be
followed-up even after adrenal surgery.
As far as we know, no prospective data are available to make a choice
between medical and surgical therapies for SCS patients. However, surgical
resection should be reserved for patients with worsening hypertension,
abnormal glucose tolerance, dyslipidemia, or osteoporosis [1]. Recommended
Adrenal Incidentaloma with Subclinical Cushing Syndrome 19
surgery for patients with SCS is minimally invasive adrenalectomy with

laparoscopy [2].
Figure 1. Adrenal adenoma on the left side of the patient.

REFERENCES
[1] Zeiger MA, Thompson GB, Duh QY et al. The American Association of
Clinical Endocrinologists and American Association of Endocrine
Surgeons medical guidelines for the management of adrenal
incidentalomas. Endocrine practice: official journal of the American
College of Endocrinology and the American Association of Clinical
Endocrinologists 2009; 15 Suppl 1:1-20.
[2] Starker LF1, Kunstman JW1, Carling T2. Subclinical Cushing
syndrome: a review. Surg. Clin. North Am. 2014 Jun; 94(3):657-68.
Chapter 5
A RELAPSING CONN’S SYNDROME

Ankara University, School of Medicine, Ankara, Turkey
A 50-year-old white male with hypertension was admitted to our hospital

with frequent urination four years ago. He was noted to have persistent
hypokalemia in the 2.7–3.3 meq/L range over more than a year in his past
medical history. He smoked one pack of cigarettes per day and did not drink
alcohol. His family history was insignificant. His physical findings were
unremarkable; except his blood pressure was high which was measured as
140/ 90 mmHg. Biochemical analysis showed severe hypokalemia (2.1 meq/L;
normal range, 3.6 to 4.5 mmol/L). ECG was suggestive of sine wave pattern,
corresponding with the changes of hypokalemia. As the patient had
hypokalemia with metabolic alkalosis and with history of hypertension,
hyperaldosteronism was suspected. The morning supine plasma aldosterone
concentration (PAC) was elevated at 34 ng/dL (supine normal range: 2.9-16.1)
and the simultaneous plasma renin activity (PRA) was low at 0.1 ng/mL/h
(supine normal range: 0.2-2.8). Abdominal computed tomography (CT)
showed a low-density left adrenal mass measuring 10x10 cm in diameter.
Adrenal venous sampling revealed right laterilization of aldosteron levels.
Primary Hyperaldosteronism (PA) was suspected and the patient was referred
to surgery for laparoscopic right adrenalectomy. Pathologic examination
revealed a benign adrenocortical adenoma. But material was composed of
small pieces. After surgery, he had no complaint and did not need any
medication for hypertension or hypokalemia.
After a year he was admitted again with the same complaints and he had
been found to have hypertension and hypokalemia (2,6 Meq/L) that were
consistent with his past medical history one year ago. Radiological and
pathological re-evaluation is required [1]. His laboratory was again consistent
with aldesteronism and his abdominal CT showed a left adrenal mass with
11x8 mm and a right mass with 12x11 mm in diameter (Figure 1). He went
under open surgery for right adrenolecomy again and pathologic examination
of the specimen was reported as mainly granulamatous inflammation tissue.
After his second surgery; hypertension and hypokalemia persisted. His
abdominal CT did not reveal significant difference. Patient did not want AV
sampling and third operation and third operation postponed after medical
therapy follow up.
Potassium and anti-hypertensive treatment (Anjiotension Converting
Enzyme Inhibitor- valsartan; beta blocker – nebivolol and mineralocorticoid
receptor antagonist –sprinalactone) were initiated. After initiation of therapy,
he has been found normotensive and normokalemic. After sprinalactone side
effects (gynecomastia, breast tenderness, and reduced libido) eplerenone has
been started. Primary hyperaldosteronism results from bilateral adrenal
hyperplasia in two thirds of the patients meanwhile it results from adenoma in
one thirds of the patients. Adrenolectomy is the choice of treatment once Conn
syndrome diagnosis is established while bilateral hyperplasia is managed with
mineralocorticoid antagonists [1].
Conn syndrome is known as a bening disease in majority of cases but
malign transformation has also been observed. Tumor size above 4 cm and
high ratios of aldosteron/ renin are claimed to be associated with malign conn
syndrome and tumor recurrences [2]. Recurrent hyperaldosteronism may also
be related to inadequate surgery especially when pathology is composed of
small pieces. This case was presented firstly as a Conn syndrome but during
his follow-up the bilateral adrenal disease is observed. In these situations
adrenal venous sampling may be important for selection site of surgery [3].
For most benign adrenal lesions laparoscopic adrenalectomy is accepted as the
gold standard with experienced surgeons [4, 5]). As in this case, the follow-up
is important in these patients, especially if pathology revealed small pieces
after the surgery [1, 4, 5]. Adrenal scintigraphy with iodo-cholesterol may
assist localize the cause of recurrent the hyperaldosteronism. Scintigraphy may
discriminate fibrotic tissue from functional tissue.
A Relapsing Conn’s Syndrome 23
Figure 1. Computed tomography (CT) scanning for adrenal imaging.

REFERENCES
[1] Recurrent hyperaldosteronism after adrenalectomy: an indication for
careful radiologic and histologic re-evaluation. Gundara JS, Gill AJ,
Glover A, Benson K, Clifton-Bligh R, Roxburgh S, Sywak M. ANZ J
Surg. 2013 Oct 28. doi: 10.1111/ans.12433.
[2] Aronova A, Iii TJ, Zarnegar R. Management of hypertension in primary
aldosteronism. World journal of cardiology 2014;6:227-33.
[3] Agha A, Hornung M, Iesalnieks I et al. Predictors of malignancy in
primary aldosteronism. Langenbeck's archives of surgery / Deutsche
Gesellschaft fur Chirurgie 2014;399:93-8.
[4] An expert consensus statement on use of adrenal vein sampling for the
subtyping of primary aldosteronism. Rossi GP, Auchus RJ, Brown M,
Lenders JW, Naruse M, Plouin PF, Satoh F, Young WF Jr.
Hypertension. 2014 Jan; 63(1):151-60.
[5] Shada AL1, Stokes JB, Turrentine FE, Simpson VB, Padia SH, Carey
RM, Hanks JB, Smith PW. Adrenalectomy for adrenal-mediated
hypertension: National Surgical Quality Improvement Program analysis
of an institutional experience. Am Surg. 2014 Nov; 80(11):1152-8.
[6] Harvey AM. Hyperaldosteronism: diagnosis, lateralization, and
treatment. Surg Clin North Am. 2014 Jun; 94(3):643-56.
Chapter 6
CO-EXISTENCE OF TYPE 1 DM
AND SARCOIDOSIS

A 49 year old woman was admitted to the hospital because of polyuria and
polydipsia. The patient had a history of type 1 diabetes mellitus that had begun
when she was 33 years old; she was not known to have retinopathy,
nephropathy and neuropathy. She did not drink alcohol and had ceased
smoking 10 cigarettes daily 15 years ago.
Her customary medications were basal insulin at bed-time and rapidly
acting insulin three times a day preprandially. There was a family history of
hypertension and hyperlipidemia. Her laboratory tests were normal except for
hypercalcemia, hypophosphatemia and mild anemia. Her all other laboratory
parameters were in normal reference ranges including parathormone level,
vitamin D status and alkaline phosphatase.
The patient was evaluated for possible causes of hypercalcemia and during
this diagnostic work-up; multiple myeloma, primary hyperparathyroidism and
malignancies with bone metastasis were assessed.
Parathormone (11,3pg/mL) and TSH level (1,33 mIU/L) were in
normal limits. Sedimentation rate were 57 mm/hour. A routine chest
radiograph was obtained. A PA view of the chest demonstrated bilateral
hilar lymphadenopathy. The CT scan had confirmed bilateral hilar
lymphadenopathy and multiple millimetric nodular densities localized
bilaterally. Bronchoscopy was performed with biopsy from the carina and
bronchoalveoler lavage fluid was obtained from right middle lobe, which
revealed noncaseating granulomas consistent with pulmonary sarcoidosisosis.
ARB was repetitively negative. Bone survey was normal and both urinary and
serum electrophoresis were normal. Vitamin D3 level were 36,2μg/l, 1,25
(OH) vitamin D3 level was 15 pg/ml (20-80). Tumor markers were in normal.
Her Angiotensin Converting Enzyme (ACE) level was found to be high (92)
which was also compatible with the diagnosis of sarcoidosis. Prednisolone
treatment improved symptoms of sarcoidosis and normalised serum calcium
levels.
The most common causes of hypecalcemia are malignancy (45%) and
hyperparathyroidism (45%). The differential diagnosis includes endocrine
disorders, medications, granulomatous disease such as sarcoidosis and other
miscellaneous disorders [1, 2]. It is important to exclude lymphoma, lung
cancer, ankilosan spondylitis, and ketotic hypercalcemia. In a patient who was
known as having an autoimmune disease like type 1 DM urges a clinician to
another auto-immune disease or endocrinopathy but it can be possible that
different diseases can be seen together. The occurrence with sarcoidosis and
auto-immune diseases is a well-known entity.
Figure 1. Chest radiograph revealing bilateral hilar masses.

Co-Existence of Type 1 DM and Sarcoidosis 27
Figure 2. Chest radiograph revealing bilateral reticulonodülar opacity.
Figure 3. Thorax CT images showing miliar opacities and middle mediastinal lymph
node involvement.
Figure 4. Bone scintigraphy showing bone involvement of axial bones (sternum and
pelvis).
Five to ten percent of sarcoidosis patients may have hypercalcemia [3].

Hypercalcemia thought to due to high concentrations of 1,25-
dihydroxyvitamin D3 [3]. But in our patient 1.25-dihydroxyvitamin D3 was
low. But also granulomas may also produce parathyroid hormone related-
protein (PTHrp) and may cause humoral hypercalcemia [4]. Steroid therapy
may be used for hypercalcemia and sarcoidosis.
Co-Existence of Type 1 DM and Sarcoidosis 29
REFERENCES
[1] Inzucchi SE. Management of hypercalcemia. Diagnostic workup,
therapeutic options for hyperparathyroidism and other common causes.
Postgraduate medicine 2004;115:27-36.
[2] Inzucchi SE. Understanding hypercalcemia. Its metabolic basis, signs,
and symptoms. Postgraduate medicine 2004;115:69-70, 73-6.
[3] Porter N, Beynon HL, Randeva HS. Endocrine and reproductive
manifestations of sarcoidosis. QJM. 2003 Aug; 96(8):553-61.
[4] Raalte DH1, Goorden SM2, Kemper EA3, Brosens LA4, Ten Kate RW1.
Sarcoidosis-related hypercalcaemia due to production of parathyroid
hormone-related peptide. BMJ Case Rep. 2015 Jul 9;2015.
Chapter 7
A 44-YEAR-OLD WOMAN
PRESENTED WITH MULTIPLE HORMONE
SECRETING ADRENAL CORTICAL ADENOMA

A 44- year-old women presented with uncontrolled hypertension despite

of multiple antihypertensive drug treatments especially in the last three months
have remained irregular blood pressure and hypokalemia. Physical
examination revealed no pathological findings except second degree diastolic
murmur in aortic area. The average systolic blood pressure was 170 mm Hg
and diastolic blood pressure was 105 mm Hg in ambulatory blood pressure
monitoring. Laboratory tests showed severe hypokalemia (K:2.4mEq/L),
elevated urinary catecholamines (normetanephrine:1267 normal range 88-444
μg/d), elevated basal cortisol level and supressed ACTH level. Cortisol levels
was not supressed by low dose and high dose dexametazone supression test
4.91 µg/dl 6.35 µg/dl respectively. Upright position aldosterone/renin ratio
value was consistent with hyperaldosteronism (aldosterone:388 ng/dl; A/R
ratio>20 ). Thyroid function tests, DHEA-S and total testosterone levels were
within normal range. Adrenal tomography revealed an adenoma 50 mm
diamater in right adrenal gland. Intravenous potassium replacements were
started then they were continued with oral potassium therapy. In past medical
history, three years ago she admitted to our hospital with chest pain, exertional
dyspnea and orthopnea. Myocardial perfusion scan revealed ischemia in
32 Çağlar Keskin and Mustafa Şahin
anteroapical and anterior wall. Coronary anjiography showed non-critical

stenosis in right coronary artery and renal artery angiography that performed
in same session was normal. Otherwise she had chronic hepatitis B since 1990
and for eleven years she had used interpherone (IFN) treatment. She did not
use any treatment for hepatitis in the last two years. Consequently the patient
underwent a right adrenalectomy for multiple hormone secreting adenoma
after appropriate preparation. Pathological examination was consistent with
benign cortex adenoma and did not show nuclear polymorphism, mitotic
activity or any other findings suggested adrenocortical cancer also with benign
medullary component. After the surgery patient’s adrenal functions (all three
hormone groups) were totally normal and do not have any complaints.
Figure 1. Adrenal adenoma on the right side of the patient.
DISCUSSION
Adrenal cortical adenoma is a benign tumor arising from the adrenal
cortex [1]. Incidence is reported to be 8.7% in autopsy and 4% in radiology
series [2]. Most benign adrenal tumors are non-functioning and do not need
immediate treatment, but some may become functioning and require treatment
including medications or surgery. About 10 % of incidentalomas are
defined as subclinical Cushing’s syndrome (SCS), approximately 4% are
pheochromocytomas, 1% of them are aldosteronomas. Coexisting multiple
hormone secreting benign adenomas are very rare in clinical practice. Both
medulla and cortical tumors may occur in the same adrenal gland. Our case is
unique and interesting in terms of all three layers of the adrenal gland to be
affected [3, 4]. Both medulla and cortical tumors may occur in the same
adrenal gland [5]. Complete adrenal function tests should be made in adrenal
A 44-Year-Old Woman Presented with Multiple Hormone … 33
tumors. We could not able to make ACTH staining in immunohistochemistry

medullary component of tumor. Peptides such as ACTH secreted from
medullary part may cause cortical adenoma development. Severe hypokalemia
and hypertension may be related to both cushing and aldosteronoma.
Pheochromocytoma should be ruled out to decrease intraoperative risk before
adrenal adenoma operations.
REFERENCES
[1] Terzolo, M., et al., Management of adrenal incidentaloma. Best Pract
Res Clin Endocrinol Metab, 2009. 23(2): p. 233-43.
[2] Bovio, S., et al., Prevalence of adrenal incidentaloma in a contemporary
computerized tomography series. J Endocrinol Invest, 2006. 29(4): p.
298-302.
[3] Mantero F, Terzolo M, Arnaldi G, Osella G, Masini AM, Ali A,
Giovagnetti M, et al. A survey on adrenal incidentaloma in Italy. Study
Group on Adrenal Tumors of the ItalianSociety of Endocrinology. J
Clin Endocrinol Metab 2000;85: 637–44.
[4] Cawood, T.J., et al., Recommended evaluation of adrenal
incidentalomas is costly, has high false-positive rates and confers a risk
of fatal cancer that is similar to the risk of the adrenal lesion becoming
malignant; time for a rethink? Eur J Endocrinol, 2009. 161(4): p. 513-
27.
[5] Nieman, L.K., Approach to the patient with an adrenal incidentaloma. J
Clin Endocrinol Metab, 2010. 95(9): p. 4106-13.
[6] Sakamoto N, Tojo K, Saito T, Fujimoto K, Isaka T, Tajima N, Ikeda K,
Yamada H, Furuta N, Sasano H Coexistence of aldosterone-producing
adrenocortical adenoma and pheochromocytoma in an ipsilateral adrenal
gland. Endocr J. 2009;56(2):213-9.
Chapter 8
A CASE OF INSULINOMA PRESENTED WITH

POSTPRANDIAL HYPOGLYCEMIA

Murat Faik Erdoğanand Ali Rıza Uysal
A 63-year-old morbid obese woman has a 3-year history of episodic

confusion especially early in the morning after breakfast but her neurologic
evaluation and CT scan of head were normal.
Confusion, sweating, palpitations and weakness occurred in the morning
after breakfast. She had gained 20 kilograms in a year and she admitted to eat
more frequent and much more than before. Her blood glucose level had been
measured 33 mg/dL when she was symptomatic with a personal glucometer of
her sister.
She denied taking any prescription medications and alcohol. Her sister had
type 2 diabetes mellitus. On physical examination, she was found to be a
overweight woman with a body mass index of 28,4 kg/m 2 who appears to be
healthy. Her examination findings were normal, as were her initial laboratory
results.
An overnight fasting blood sugar level combined with a simultaneous
plasma insulin, and C peptide was ordered for suspicion of an insulinoma. The
tests were found in normal reference ranges and non-diagnostic; a 72-hour fast
test was done with blood glucose, insulin levels and c peptide. The test was
36 Asena Canpolat, Mustafa Şahin, Murat Faik Erdoğan et al.
considered positive for insulinoma when she was symptomatic and her plasma
insulin/glucose ratios were more than 0.3 (Table 1).
Table 1. Insulin –glucose-c peptide levels
Insulin Glucose c-peptide

116 45 18,2
65 36 15
29,8 43 9,1
9,3 26 6,4
The serum calcium and prolactin levels were checked and found to be
normal and complete history and physical examination was performed to look
for evidence of the other potentially associated conditions especially for
Multiple Endocrine Neoplasia (MEN-1).
Once the biochemical diagnosis of insulinoma had been established, a
pancreas dinamic CT was ordered which revealed a 21 mm hypervascular
mass which could be interpreted as islet cell tumor localized in head of
pancreas. Liver images was suitable with chirotic process. Splenomegaly was
reported. Esophagial varices were also detected.
An endoscopic ultrasonography was performed and a hypoechoic mas
localized in head of pancreas was approved. She was offered surgical removal
but she did not accept the procedure because surgery was reported to be in
high risk category by anestesiology department. Alcohol injection to tumor
was made once. But few months later so acute general recommendations for
hypoglycemia was told and diazoxide was initiated. At follow-up 2 x 100 mg
diazoxide was given with no hypoglycemia. But prerenal azotemia observed
and dose was decreased to 100 mg/day. After hydration and azotemia
resolved, diazoxide dose was increased again.
She has been followed for more than 3 years time under this
circumstances and she is still well under this treatment.
Hypoglycemia in insulinoma may occur in the postprandial state, but
generally there is also fasting hypoglycemia in these patients.
Eighty percent of sporadic nonfamilial insulinomas are solitary and benign
and 6% are single and malignant. The standard approach in patients with a
suspected insulinoma is a 72-hour fasting test [1].
Surgical removal performed by an experienced surgeon is main goal but
for those who are not cured by surgery, long-acting somatostatin analogs,
diazoxide, verapamil, propranolol can be used successfully in some cases [2].
A Case with Insulinoma Presenting with Postprandial Hypoglycemia 37
She had Child B criptogenic chirosis with ascites. He is more prone to

hypoglycemia and surgery will be more risky because of chirosis. Normally,
surgery should be chosen first but, laparoscopic surgery may increase
intrabdominal pressure, ascites also morbid obesity may complicate the
procedure. She also had high anesthesia risk because of comorbid conditions.
Also cirrhosis is associated with hyperinsulinemia due to decreased
clearance of insulin. In these cases, C-peptide levels may be important for
diagnosing insulinoma.
REFERENCES
[1] Field JB. Hypoglycemia. Definition, clinical presentations,
classification, and laboratory tests. Endocrinology and metabolism
clinics of North America 1989;18:27-43.
[2] Okamoto M, Kishimoto M, Takahashi Y et al. A case of malignant
insulinoma: successful control of glycemic fluctuation by replacing
octreotide injections with octreotide LAR injections. Endocrine journal
2013;60:951-7.
Chapter 9
METASTATİC PAPİLLARY THYROİD

CARCİNOMA - CRİBRİFORM
MORULAR VARİANT
Berna İmge Aydoğan, Mustafa Şahin and Sevim Güllü

INTRODUCTION
A-61 years old male patient was referred to our clinic with hoarseness and
a large mass located in the anterior neck. He was investigated in another clinic
with thyroid malignancy suspicion. Thyroid fine needle aspiration biopsy
specimens which were obtained from the nodule located in the left lobe were
evaluated in our cytology department and papillary thyroid carcinoma was
confirmed.
Neck Computed tomography (CT) scan imaging showed multiple nodules
with calcifications in left lobe of thyroid gland and metastatic lymph nodes
with 44 mm diameter in left supraclavicular and cervical area. Thorax CT
revealed multiple nodules with 1 cm diameter in both lungs and these nodules
were interpreted suspicious for metastases. Trachea and esophagus are
deviated to the right.
Total thyroidectomy, central and left neck lymph node dissection was
performed. Histopathologically multifocal papillary thyroid carcinoma was
documented. The tumor located in the left lobe was a cribriform-morular
variant of papillary thyroid carcinoma with 8 cm diameter. Surgical margins
40 Berna İmge Aydoğan, Mustafa Şahin and Sevim Güllü
were positive and invasion to extrathyroidal soft tissue invasion was found. In
right lobe of gland, multiple tumor foci with 5 mm greatest diameter were
found. There were five metastatic central lymph nodes and 12 metastatic left
lateral lymph nodes were demonstrated.
Postoperative TSH level was 15 µıu/ml, thyroglobulin was >475 ng/ml
and anti-thyroglobulin was lower than 0.9 IU/ml.
Thyroid scintigraphy was performed and no residuel thyroid tissue was
shown.
Subsequently radioiodine ablation treatment was given at 150 mci dose.
Postablative whole body scan showed focal uptake in both thyroid lobe and
also in lungs.
Whole body scan using 99mTc - MDP radioisotope showed physiological
distribution of radiotracer throughout the skeletal system and in lateral of right
scapula. This uptake was reported to be suspicious for bone metastases.
A control Thorax CT revealed lymphadenopathies greater than 3 cm
located in anterior mediastinum, paratracheal, subcarinal regions and multiple
metastatic nodules in both lungs (Figure 1). Serum thyroglobulin level was
greater than 1000 ng/ml under TSH suppression therapy.
Figure 1a. Lung X-Ray: Trachea shifted to right

Metastatic Papillary Thyroid Carcinoma - Cribriform Morular Variant 41
Figure 1b. Continued.

Figure 1b. Neck CT: left calcification mass; 4 cm metastatic.

Figure 1c. Thorax CT revealed lymphadenopathies greater than 3 cm located in

anterior mediastinum, paratracheal, subcarinal regions and multiple metastatic nodules
in both lungs.
Figure 1d. Posttherapy Scan.

We recommend patient to have surgery for mediastinal lesions with thorax

surgeon (left thoracotomy) and right neck revision. After then then RAI with
higher dose was planned. Huge local lesions reduce the effectiveness of the
radioactive iodine treatment for metastasis. We tought that, if right
thoracotomy will be done lung lesion may be removed even bronchial/vascular
invasion may cause incomplete removal. Following surgical debulking,
radioiodine therapy may be more effective. Patient refused surgery and 250
mci radioiodine ablation treatment was given. Postablative whole body scan
was not performed because of patient’s refusal.
DISCUSSION
Cribriform-morular variant (CMV) is a rare subtype of papillary thyroid
carcinoma (PTC) [1].
Accumulation of the β-catenin due to mutation in this gene may have role
in the devolopment of this cribriform morular variant PTC [1].
PTC-CMV may be FAP associated and sporadic. CMV-PTC may be
associated with familial adenomatous polyposis (FAP). Multifocality of
thyroid tumor generally present with FAP. Recognition of this variant must
alert the clinician to perform colonoscopy. In our case the patient did not agree
additional diagnostic procedures so colonoscopy was not performed. These
tumors may be first clue of underlying FAP syndrome [2].
PTC-CMV reported to have very good prognosis [2]. Bilateral total
thyroidectomy is recommended because of the likelihood of multifocality but
central lymph node dissection generally is not recommended [2]. But as in our
case we believe that some of these tumors may be very aggressive and
recommended treatment advices may not be enough. Also these tumors are
very rare, we are not sure that these tumors have generally good prognosis.
REFERENCES
[1] Boonyaarunnate, T., Olson, M. T., Bishop, J. A., Yang, G. C., Ali, S. Z.
Cribriform morular variant of papillary thyroid carcinoma: clinical and
cytomorphological features on fine-needle aspiration. Acta Cytol. 2013;
57(2):127-33.
[2] Singh Malika Chowdhry and Sacks Wendy. Clinical Thyroidology. April
2014, 26(4): 111-113.
Chapter 10
IDIOPATHIC PROLACTINOMA
Şule Canlar and Asena Canpolat

A 32 year-old woman presented with galactorrhea and menstrual

disorders. The patient had applied to another hospital 3 years before
admission. In this center, laboratory tests and hypophysis MR imagine had
been done, prolactin level was 69 ng/ml (06-30) and hypophysis MRI showed
5x3 mm sized adenoma suspicion. The patient had been treated with
cabergoline 1 mg twice a week. After this treatment, she had regular menstrual
periods. She admitted to our endocrinology department with recurrent
menstrual disorders. Prolactin level was 94.3 (2,8-29,2). Hypophysis was
heterogeneous contrasted in hypophysis MRI but there was no obvious
adenoma. Pegylated prolactin level was in normal range. In endocrinology
council, the patient was evaluated and the council accepted the patient as
idiopathic prolactinoma. We decided monitoring the patient with cabergoline
treatment. One year later, MRI was repeated, MR imaging showed similar
results with previous MRI.
Hyperprolactinemia is very common situation that may cause menstrual
disturbances and galactrorhea. You should rule out pregnancy, drugs,
hypothyroidism, renal and hepatic failure, trauma prolactinomas and
macroprolactinemia before diagnosing idiopathic hyperprolactinemia [1, 2].
If there are symptoms, dopamine agonist is indicated [1]. Autoimmunity
may have role in idiopathic hyperprolactinemia or low resolution MRI
may miss microprolactinomas also may be responsible from idiopathic
48 Şule Canlar and Asena Canpolat
hyperprolactinemia [1]. Heterogenicity may be the result of microadenoma or

autoimmunity in our patient. Treatment should be individualized according to
symptoms.
Figure 1. Continued.
Idiopathic Prolactinoma 49
50 Şule Canlar and Asena Canpolat
Figure 1: MR imaging of pituitary.

Idiopathic Prolactinoma 51
REFERENCE
[1] Glezer A1, Bronstein MD. Approach to the patient with persistent
hyperprolactinemia and negative sellar imaging. J. Clin. Endocrinol.
MeTable 2012 Jul;97(7):2211-6.
Chapter 11
MALIGNANT PHEOCHROMOCYTOMA WITH

PAPILLARY THYROID CARCINOMA
Özgür Demir and Mustafa Şahin

Nine years ago, he admitted to a physician because of his headache, then

the headache was investigated by etiology for 2 years. After episodes of high
blood pressure, he was diagnosed as a pheochromocytoma with right adrenal
mass in a private hospital. He had right adrenalectomy there. We did not able
to get the hormonal results at that time. Pathology was consistent with
pheochromocytoma. Until 2010 he did not use any antihypertensive drugs. In
2010 cardura has been started in a private clinic because of high blood
pressure values. He did not go to doctor then. Recently, he referred to our
university hospital due to suspicion of reccurence of pheochromocytoma. At
admission his serum calcitonin level was 5.9 normal in range.
Computed tomography scan revealed a 6 cm diameter right adrenal tumor
with an irregular border. The tumor was extending to kidney and liver (Figure
1). Free urinary metaneprine, normetanephrine, 131I-MIBG scintigraphy results
were negative.
54 Özgür Demir and Mustafa Şahin
Figure 1. Dynamic CT scan of the patient.

Malignant Pheochromocytoma with Papillary Thyroid Carcinoma 55
Table 1. Serum blood levels
Normal Range
Metanephrine 87,1 74-297 mcg/st
Normetanefrine 89,1 88-444 mcg/g
VMA 4,1 1,8-6,7 mg/g
HVA 3,7 0,5-6,2
Noradrenaline 28,1 20-81 mcg/g
Dopamine 121,4 40-400 mcg/g
Renin 0.9 1.9-6 ng/ml/st
Aldosteron 10 3.4-27.3 ng/dl
DHEA-SO4 339,6 5-313 mcg/dL
ACTH 36,57
Cortisol 10,63
LIVER AND SURRENAL DYNAMIC CT: 23 06 2011

There is 10 mm nodule intense pacification of the arterial phase in the
right lobe (Metastasis) Irregular border mass continuity with the right adrenal
body (recurrence or residual tumor). Mass compress to inferior vena cava. In
mass at late phase wash out is seen.
Thyroid ultrasonography revealed thyroid nodule and fine needle
aspiration biopsy result was malignant. He underwent to total thyroidectomy
and central lymph node dissection and pathology revealed classical papillary
thyroid carcinoma 2 cm diameter. Three of the central lymph nodes were
metastatic. In 10/12/2012 150 mci RAI was given to him. He was taking
Cardura 2 x 2 mg tb; Blood Pressure 110/70 mmHg, pulse rate: 76/minute.
Table 2.
14/07/2011 N
VMA 4,1 1,8-6,7 mg/g
HVA 3,7 0,5-6,2 mg/g
5-HİAA 12,9 0,5-8,2 mcg/g
Metanefrin 221,1 74-297 mcg/st
Normetanefrin 204,4 88-444 mcg/g
Kromogranin A 14,5 0-100 ng/mL
Serotonin 116,7 50-230 mcg/L
56 Özgür Demir and Mustafa Şahin
Figure 2. Surrenal Tomography of the patient.
Iodine-131 metaiodobenzylguanidine (131I-MIBG) scintigraphy did not

show any metastatic locus.
131I-MIBG scintigraphy cannot only help localize additional extra-adrenal
tumor tissue in these patients if you suspect malignant pheochromocytoma.

Local recurrence of a pheochromocytoma can occur years after initial
surgical tumor removal due to dedifferentiation of tumor tissue excretion of
catecholamines may be decreased. Also large tumors metabolization in mass
may result in normal hormone levels.
Our endocrinology tumor board suggest him to surgery for mass in right
adrenal body. But he did not want to undergo surgery. He lost to follow up.
One year later he admitted again with tomography result with suspicious liver
metastasis. Now we hospitalized him for re-evaluation.
123I-MIBG scintigraphy may help to localize additional extra-adrenal
tumor tissue in these patients if you suspect malignant pheochromocytoma.

Local recurrence of a pheochromocytoma may be seen after initial
surgical tumor removal due to the inadequate initial surgery or possible
malignant pheochromocytomas. It is not easy to differentiate malignant
pheochromocytomas before metastasis occur. Immunohistochemistry and
proliferative markers may be helpful [1].
Our patients’ hormone values were normal but in his history first
diagnosis of pheochromocytoma was after high blood pressure presentation.
Malignant Pheochromocytoma with Papillary Thyroid Carcinoma 57
So at least for initial diagnosis we could not described our patient’s

pheochromocytoma as non-functional. Differentiation of tumor tissue
and excretion of cathecholamines may be decreased. Also large
pheochromocytomas, intratumor metabolism of catecholamine may lead to
low cathecolamine levels.
Also association of papillary thyroid cancer and pheochromocytoma has
been reported before [2, 3]. There may be common genetic origin in these
patients. Nonfunctional PCC, which refers to non-secreting PCC is reported,
but is extremely rare [3].
REFERENCES
[1] Shingo Moriyama, Hideki Takeshita, Saori Araki, Takuo Tokairin,
Makoto Kagawa, Koji Chiba, Akiko Adachi, Akira Noro Carcinoma-like
nonfunctional pheochromocytoma in the right adrenal gland: A case
report Oncol Lett. 2016 Aug; 12(2): 1489-1492.
[2] Bugalho MJ, Silva AL, Domingues R. Coexistence of
paraganglioma/pheochromocytoma and papillary thyroid carcinoma: a
four-case series analysis. Fam Cancer. 2015 Jun 14 [Epub ahead of
print].
[3] Hashiba T, Maruno M, Fujimoto Y, Suzuki T, Wada K, Isaka T,
Izumoto S, Yoshimine T (2006) Skull metastasis from papillary thyroid
carcinoma accompanied by neurofibromatosis type 1 and
pheochromocytoma: report of a case. Brain Tumor Pathol 23(2):97-100.
[4] Nasser T, Qari F (2009) Pheochromocytoma, papillary thyroid
carcinoma. Saudi Med J 30(8):1087-1090.
Chapter 12
RECURRENT PAPILLARY THYROID CANCER

AFTER PRIMARY SURGICAL RESECTION
REQUIRING RE-OPERATIONS AND
RADIOIODINE THERAPY
Şule Canlar, Mustafa Şahin and Murat Faik Erdoğan

CASE PRESENTATION
A 47 year old woman consulted to the endocrinology department because
of her thyroid nodule. Since 2004, she was followed with the diagnosis of
multinodular goiter. Physical examination revealed a nodule on the thyroid
gland, her thyroid function tests were normal in range. Fine needle aspiration
biopsy (FNAB) was done and histopathologic examination was resulted as
papillary thyroid cancer. After that, the patient underwent to bilateral
thyroidectomy, central compartment and left jugular lymph node dissection.
Histopathology was reported as multifocal papillary microcarcinoma, tumour
sizes were 7 mm in left lobe and 0.2 mm in right lobe. Pathology revealed soft
tissue infiltration. Thyroid capsule was infiltrated with tumour and there were
metastatic lymph nodes. After surgery, thyroglobulin was 21.9 ng/ml.
Radioactive iodine was administered as 150 mci and I-131 whole body
scanning was performed. Post-therapy scan detected residue focal activity on
the thyroid gland and glossal channel (Figure 1). Five months later, I-131
60 Şule Canlar, Mustafa Şahin and Murat Faik Erdoğan
whole body scanning (WBS) was repeated and was reported as normal. But
sonographic management showed suspicious lymphadenopathy 2x6 mm in
level 3 compartment. Fine needle aspiration biopsy showed papillary thyroid
cancer metastasis. Modified radical left neck dissection was performed. One of
nine lymph node showed metastasis.
Thyroglobulin levels decreased after surgery 21,9 to 3.85. Then the patient
had 200 mci radioiodine therapy. Whole body PET scanning revealed normal
physiological activity. thyroglobulin was <0.1 ng/ml.
Recurrent Papillary Thyroid Cancer after Primary Surgical Resection … 61
Figure 1. Posttherapy whole body scanning I-131.

Figure 2. Neck tomography with IV contrast.
The patient's thyroglobulin levels were followed and sonographic

assessment and I-131 whole body scanning were implemented. During this
period, elevated thyroglobulin level was established, I-131 WBS was negative.
PET scan showed increased 18F-FDG uptake in superficial cervical lymph
nodes, hyoid cartilage and pyramidal lobe. Sonography determined 13x9.6 mm
sized hypoechoic suspicious lymph node. FNAB was performed,
histopathologic examination showed papillary carcinoma metastasis. In our
endocrinology council, we decided re-operation and the patient accepted this
procedure. The patient underwent re-surgery. Pathology was concordant with
preoperative diagnosis. After surgery, 200 mci radioiodine therapy was
performed and I-131 WBS was negative. Thyroglobulin was 0.066 ng/ml. The
patient resumes her follow-up in endocrinology department.
We report a case of small papillary thyroid carcinoma (PTC) with a
jugular lymph node metastasis infiltrating soft tissue. His postoperative course
was with recurrences.
Neck sonography is important to evaluate metastatic lymh node
involvement. Also neck tomography sometimes may be necessary to evaluate
Recurrent Papillary Thyroid Cancer after Primary Surgical Resection … 63
lymph node metastasis evaluation in some patients. Neck tomography was

shown in Figure 2.
DISCUSSION
Majority of microcarcinomas have excellent prognosis for which
management should be less aggressive and conservative (for surgery and RAI
treatments) as in published guidelines [1, 2, 3]. Even lobectomy or active
surveillance without immediate surgery [3, 4]. This approach will avoid
unwanted complications.
Some cases may require more aggressive therapy. There are patients with
microcarcinoma have lymph node metastases at presentation that may increase
future recurrence risk [4]. But neck reoccurrences may not effect patient’s
survival. According to vascular invasion, extrathyroidal extension, lymph node
metastases, some microcarcinomas may require more aggressive management
or close follow-up [5, 6, 7]. Small tumor size does not always rule out future
recurrences.
REFERENCES
[1] Batori, M1; Zullino, A; Pipino, R; Eleni, C. Occult papillary thyroid
microcarcinoma manifesting only as a symptomatic lateral cervical
mass: report of a case. Surg Today., 2012 Oct, 42(10), 1010-3.
[2] Wang, TS; Goffredo, P; Sosa, JA; Roman, SA. Papillary thyroid
microcarcinoma: an over-treated malignancy? World J Surg., 2014 Sep,
38(9), 2297-303.
[3] Haugen, BR1; Alexander, EK2; Bible, KC3; Doherty, GM4; Mandel, SJ5;
Nikiforov, YE6; Pacini, F7; Randolph, GW8; Sawka, AM9;
Schlumberger, M10; Schuff, KG11; Sherman, SI12; Sosa, JA13; Steward,
DL14; Tuttle, RM15; Wartofsky, L16. 2015 American Thyroid
Association Management Guidelines for Adult Patients with Thyroid
Nodules and Differentiated Thyroid Cancer: The American Thyroid
Association Guidelines Task Force on Thyroid Nodules and
Differentiated Thyroid Cancer. Thyroid., 2016 Jan, 26(1), 1-133. doi:
10.1089/thy.2015.0020.
[4] Oda, H; Miyauchi, A; Ito, Y; Yoshioka, K; Nakayama, A; Sasai, H;

Masuoka, H; Yabuta, T; Fukushima, M; Higashiyama, T; Kihara, M;
Kobayashi, K; Miya, A. Incidences of Unfavorable Events in the
Management of Low-Risk Papillary Microcarcinoma of the Thyroid by
Active Surveillance Versus Immediate Surgery. Thyroid., 2016 Jan,
26(1), 150-5.
[5] Neuhold, N; Schultheis, A; Hermann, M; Krotla, G; Koperek, O; Birner,
P. Incidental papillary microcarcinoma of the thyroid--further evidence
of a very low malignant potential: a retrospective clinicopathological
study with up to 30 years of follow-up Ann Surg Oncol., 2011 Nov,
18(12), 3430-6.
[6] Sahin, M; Sengul, A; Berki, Z; Tutuncu, NB; Guvener, ND.
“Ultrasound-guided fine-needle aspiration biopsy and ultrasonographic
features of infracentimetric nodules in patients with nodular goiter:
correlation with pathological findings”, Endocr Pathol., 17, 67-74
(2006).
[7] Mercante, G; Frasoldati, A; Pedroni, C; Formisano, D; Renna, L; Piana,
S; Gardini, G; Valcavi, R; Barbieri, V. Prognostic factors affecting neck
lymph node recurrence and distant metastasis in papillary
microcarcinoma of the thyroid: results of a study in 445 patients.
Thyroid., 2009 Jul, 19(7), 707-16.
[8] 'Aggressive papillary' thyroid microcarcinoma. Page C, Biet A, Boute P,
Cuvelier P, Strunski V. Aggressive papillary' thyroid microcarcinoma.
Eur Arch Otorhinolaryngol., 2009 Dec, 266(12), 1959-63.
Chapter 13
TWO SPORADIC MEDULLARY

THYROID CANCER CASES
Şule Canlar, Mustafa Şahin, Sevim Güllü,

Murat Faik Erdoğan and Demet Çorapcioglu
INTRODUCTION
Medullary thyroid cancer (MTC) is a neuroendocrine tumour of thyroid
gland, MTC is originated from parafollicular or C cells. Calcitonin secretion is
a characteristic of this tumour and is used as tumour marker. Most MTC are
sporadic, however they can be associated with familial syndromes (MEN2).
MTC is generally presented with a thyroid nodule. Total thyroidectomy is the
preferred initial treatment for patients with medullary thyroid cancer (MTC).
Bilateral or multifocal disease is very frequent in MTC patients [1]. The
patient should be evaluated for familial syndromes preoperatively,
measurements of serum calcium, plasma and 24-hour urine fractioned
metanephrines and catecholamines are essential for differential diagnosis of
possible pheochromacitoma and parathyroid hyperplasia associated with
MEN2. At the time of clinical diagnosis, 50% of patients with MTC have
lymph node metastases, and 10-20% have distant metastases [2].
Here, we present two MTC cases which are recurrent and require re-
operations.
66 Şule Canlar, Mustafa Şahin, Sevim Güllü et al.
CASE-1
A 48 year-old woman presented with sore and swollen throat. We
examined tenderly thyroid nodule. Ultrasound showed a 14 x 12 x 18 mm
nodule that was located to thyroid right upper lobe. Fine needle aspiration
biopsy was performed and cytology was reported as medullary thyroid
carcinoma. The patient underwent total thyroidectomy. Postoperative
pathology: tumour was 2.3 cm diameter, calcitonin ++, CEA +++,
synaptophysin +++, surgical border was negative, lymphovascular invasion
wasn’t detected and focal C cell hyperplasia was reported. Postoperative
calcitonin was 4.25 (pg/mL). She referred to our department for follow-up.
She didn’t have any relatives who had been diagnosed as medullary thyroid
carcinoma, she didn’t complain of hypertensive episodes as can be seen in
pheochromacitoma. After surgery, ultrasound was performed and a suspicious
lymph node was detected, calcitonin measurement was done from wash-out
fluid from fine-needle aspiration of thyroid nodules and was negative.
Cytology showed hemorrhagic samples. For differential diagnosis of
recurrence we carried out the pentagastrin stimulation test. Peak calcitonin
level was 39 in second minute. The patient underwent second operation and
neck exploration was performed.
CASE-2
A 52-year-old man had a complaint of swollen mass of neck in June 2008,
and admit to private clinic but until January 2009 patient was followed without
biopsy. In 2009 patient admit to our emergency department for swollen mass
in neck. Physical examination showed a nodular thyroid gland and he had
hoarseness. So urgently total thyroidectomy was performed, intraoperatively
surgeons established that vocal cords are infiltrated with tumour.
Histopathology was reported as; medullary thyroid carcinoma, tumour was 4.5
cm in diameter, capsular infiltration was positive, there are perithyroidal and
central metastatic lymph nodes and parathyroid gland was infiltrated with
tumour. His postoperative calcitonin level was 250 pg/mL and CEA level was
2.4 pg/mL. For evaluations of metastasis, thorax and abdomen CT scan were
done, no metastasis was found. One week later, complementary thyroidectomy
and left neck dissection was performed. Surgeons postponed right neck
dissection one month later. Lymph nodes’ pathology was revealed metastasis.
Two Sporadic Medullary Thyroid Cancer Cases 67
After operations, we decided performing 18F-FDG PET scan to show

metastasis. PET scan showed pathological 18F-FDG accumulations at right
paramandibular, submental and left supraclavicular lymph nodes conflicting
metastasis. At this time, calcitonin was 153 pg/mL. Lymph node dissection
was needed and histopathology was compatible with MTC metastasis.
Postoperative calcitonin decreased (33 pg/mL). One year later, the patient was
re-checked and calcitonin level was measured high (267 pg/mL) and CEA was
2.4 (pg/mL). 18F-FDG PET scan was repeated for staging and determining,
scan showed a few suspicious accumulation, biopsy was performed but
specimen was insufficient. The patient was evaluated with throat- thorax-
abdomen CT and lymph nodes were illustrated which had pathological
appearance. Then biopsy was performed after marking the lesion with
radioactive substance. Histopathology was confirmed as metastasis of MTC.
Postoperative calcitonin level was 50 pg/mL.
In first patient, initial operation was not adequate. First operation is very
important in medulary thyroid carcinoma to avoid from recurrences. In first
operation total thyroidectomy and central lymh node dissection was necessary.
In second case, late diagnosis seems to cause a recurrent local and
metastatic medullary thyroid cancer. If there is large thyroid nodule
measurement of calcitonin and fine needle aspiration is necessary.
Postoperastive serial calcitonin measurements and neck sonography are very
important for follow-up in these patients.
REFERENCES
[1] Saad MF, Ordonez NG, Rashid RK et al. Medullary carcinoma of the
thyroid. A study of the clinical features and prognostic factors in 161
patients. Medicine (Baltimore) 1984; 63:319.
[2] Medullary Thyroid Cancer: Management Guidelines of the American
Thyroid Association. The American Thyroid Association Guidelines
Task Force THYROID Volume 19, Number 6, 2009.
[3] Jung KY, Kim SM, Yoo WS, Kim BW, Lee YS, Kim KW, Lee KE,
Jeong JJ, Nam KH, Lee SH, Hah JH, Chung WY, Yi KH, Park DJ, Youn
YK, Sung MW, Cho BY, Park CS, Park YJ, Chang HS. Postoperative
biochemical remission of serum calcitonin is the best predictive factor
for recurrence-free survival of medullary thyroid cancer: a large-scale
retrospective analysis over 30 years. Clin. Endocrinol. (Oxf.). 2015 Jul.
14. doi: 10.1111/cen.12852 [Epub ahead of print].
Chapter 14
COMPOSITE PHEOCHROMOCYTOMA
Berna İmge Aydoğan, Mustafa Şahin and Rifat Emral
CASE REPORT
An 55 years old male referred to our endocrinology clinic due to adrenal
incidentaloma. His complaint was frequent urination and during the
investigation of his complaint, a-5 cm adrenal lesion was found on abdominal
ultrasonography incidentally. The cause of lower urinary tract symptoms was
benign prostatic hyperplasia. The patient indicated that he had no history of
hypertension, diabetes or typical signs or symptoms of hypercortisolism. He
was an ex-smoker and had no alcocol consumption. His family history was not
suggestive of MEN2, cancer or other genetical endocrine diseases. In his
physical examination, he seemed well nourished and healthy. His blood
pressure was 120/80 mmHg and pulse rate was 62/min. Weight: 64 kg Height:
173 cm BMI: 21.4 kg/m²; Waist circumference :86 cm; His blood pressure was
normal without treatment and with no postural decline. He had no skin lesions
suggestive of neurofibromas or café au lait spots. On laboratuary; CBC, ESR
normal, liver function tests, thyroid function tests, electrolytes and creatinin
were within the normal ranges (Table 1). Hormonal evaluation showed no
pathological finding (Table 2).
On thyroid ultrasonography right lobe was 19x23x51 mm, left lobe was
19x21x50 mm, thyroid volume was 22.09 ml. Mild parenchymal heterogeneity
and milimetric nodules in left lobe were seen and diagnosis was euthyroid
diffuse nodular goiter.
70 Berna İmge Aydoğan, Mustafa Şahin and Rifat Emral
Table 1. Laboratory investigations of patient
REFERENCE
FPG 86 60-110 mg/dL

Na 140 136 -144 mEq/dL
K 4.2 3.8 - 5.4 mEq/dL
Ca 9.1 8.5 - 10.5 mg/dL
P 3.5 2.7-4.5 mg/dL
Albumin 4.1
Creatinin 0.8 0.6 - 1.5 mg/dL
ALT 25 <34 U/L
AST 17 <41 U/L
TSH 0.9 0.34-5.6 µIU/mL
ESR 20 0-25 mm/hr
Table 2. Hormonal evaluation of patient
ACTH 29.66 10-75 pg/ml

a.m. Cortisol 14.06 5-25 µg/dl
24 h urine free 75 pg / 24 hr 19.5-115/24 hr
cortisol
Renin activity 0.66 ng/ml/hour
Aldosterone 7.7 <10
Aldosterone : renin 11 <20
ratio
DHEAS 51.5 18-391 pg/dl
24- hour urine
Vanillylmandelic asid 8.8 1.8 - 6.7 mg
Free Normetanephrine 121.8 110 - 1,050 μg
Free Metanephrine 212.3 35 – 460
Abdominal CT images revealed an enhanced cystic mass with septa [5

cm] in the region of the left adrenal gland (Figure 1).
Composite Pheochromocytoma 71
Figure 1. A 5 cm cystic mass at left adrenal gland.
Figure 2. Abdominal CT image revealed an enhanced cystic mass with septa [5 cm] in
the region of the left adrenal gland. HU: 18.
Appearance of mass on abdominal CT was not diagnostic of malignancy

and also it was evaluated non-functional. The mass was larger than 5 cm and
the choice of treatment was open unilateral adrenalectomy.
On pathological examination; left adrenal gland was measured 6.5 x 4.5 x
4.5 cm. The tumor was well circumscribed, 6 x 5 x 4 cm, soft and dark tan to
gray-yellow with focal hemorrhage. Histologically, part of tumor was

composed of large, polygonal, and pleomorphic chief cells with granular,
basophilic cytoplasm and round to oval nuclei consistent with
pheochromocytoma. The second part consisted of spindle cells and ganglion
cells with multinucleation embedded in the Schwann cell proliferation
(ganglioneuroma). Immunohistochemistry showed that the pheochromocytoma
component of the tumor stained positively for chromogranin A. The
ganglioneuroma component stained negatively for chromogranin A but
positively for S-100 protein, neurofilament antibody, and neuron-specific
enolase.
Final diagnosis was a composite tumor consisting of pheochromocytoma
and ganglioneuroma with adipose tissue invasion.
He did not have hypertensive attack during the surgery, his postoperative
urinary cathecolamine levels were within the normal ranges. I131-MIBG scan
showed no abnormal radiotracer uptake to suggest metastatic disease. Whole
body scan using 99mTc - MDP radioisotope shows physiological distribution of
radiotracer throughout the skeletal system.
No localized hot or cold area is seen which is suggestive of normal Bone
Scan.
In postoperative second year, the patient is still normotensive without
medications. There is no evidence of recurrent/metastatic disease on imaging
studies. Twenty-four hours urinary cathecolamine levels are normal and he is
on annual follow up.
DISCUSSION
To date, more than 40 cases of composite pheochromocytomas have been
reported, approximately 70% of which co-existed with ganglioneuromas
(Pheo-GN) [1].
The size of the tumors ranged from 1 to 35 cm (not more than 18 cm for
the Pheo-GN), with the average being 4 to 6 cm (1). In 9 cases, the size of the
tumor was ≥10 cm, and 4 of these 9 cases were associated with watery
diarrhea attributable. Preoperatively, functional evidence was found in roughly
(75%) of composite pheochromocytomas [1].
Our case was non-functional, non-malignant composite
pheochromocytoma.
He was recently seen for follow up in our institution and was doing well.
His BP was in normal without use of any medications.
Composite Pheochromocytoma 73
Figure 3. I131-MIBG scan shows no abnormal radiotracer uptake to suggest metastatic

disease.
Figure 4. Whole body bone scan.

REFERENCE
[1] Khan A. N., Solomon S. S., Childress R. D. Composite
pheochromocytoma-ganglioneuroma: a rare experiment of nature.
Endocr. Pract., 2010 Mar.-Apr.; 16(2):291-9.
Chapter 15
CERVICO-MEDIASTINAL MASS MIMICKING

GIANT THYROID NODULE
Asena Canpolat, Şule Canlar,

Mustafa Şahin and Sevim Güllü
We describe a middle-age woman with a cervico-mediastinal mass and

ache of her right arm that became a diagnostic challenge due to conflicting
localization of mass.
A 41-year-old Caucasian woman was admitted to out-patient clinic with
right arm pain. During the first consult in the emergency room, she described a
history of right arm pain the past three months. She had no history of
neurological deficit or chest pain. She was a non-smoker and did not take any
medications. Right partial rupture in rotator cuff was observed.
Vital signs were unremarkable. The physical examination showed limited
range of motion and tenderness of her right shoulder. The chest X-ray showed
a right-sided servical and mediastinal enlargement (Figure 1). Routine
laboratory analysis was normal.
Thoracic and neck computed tomography (CT) scan described a bulky
mass which was beginning from servical seventh vertebrae to thoracal third
vertebrae localized prevertebrally and in contact with the inferior edge of the
thyroid. The largest diameter was measured 7,5 cm (Figure 2).
A neck ultrasonograpyh was ordered, which reported the presence of a
heterogeneous mass 24 cm by 17, localized below the right lobe of the thyroid
76 Asena Canpolat, Şule Canlar, Mustafa Şahin et al.
gland. It was thought to be an exophytic thyroid nodule or a parathyroid

lesion. Her thyroid function test and parathormone level were within normal
ranges. Barium esaphagography ruled out significant narrowing.
Acid-fast bacilli (AFB) and purified protein derivative (PPD) tests were
negative and tuberculosis PCR and quantiferon blood test were also negative.
Brucella serum agglutination was negative.
Several biopsies were performed and sent to the cytology department.
Histological evaluation of the specimen revealed pleomorphic cells with
nuclear enlargement, admixed with small lymphocytes, mature squamous cells
and acellular squams which were described as suppurative brancial cleft cyst.
Mediastinal masses are located in mediastinum and can cause different
clinical presentations. They are usually asymptomatic, also they can bring on
compression complaints. The mediastinum is divided into anterior, middle,
and posterior compartments. The most common lesions in the anterior
mediastinum are thymic lesions, lymphoma, germ cell tumors, and thyroid. In
the middle mediastinum, lymphadenopathy is most common, and is usually
related to sarcoid, lymphoma, or metastatic lung cancer. In the posterior
mediastinum, Neurogenic tumors are the most common cause. Radiographic
imagines reveal the borders of the mass, but tissue sample is usually necessary
for differential diagnosis.
Branchial cleft cyst is a swelling that may develop in the neck. It results
from failed obliteration of branchial clefts. The 2-3% percent of them are
bilateral. They are usually located along the anterior border and at the junction
between the upper third and lower third of the sternocleidomastoid muscle in
general between tragus and clavicle. They are usually localized on the left side
of the neck [1, 2]. Third and fourth branchial cleft cysts are often closely
associated with the thyroid gland [3]. In patients with recurrent thyroid
abscesses, cleft cysts should be considered.
This case is interesting because of dimensions and localization of the mass
and challenging neighbourhood with the thyroid gland. This presentation is a
very rarely seen localization for branchial cysts. Branchial cyst presenting with
compression symptoms and distinguishing from tuberculosis lymphadenitis,
parathyroid adenoma or thyroid nodule with histopathological examination.
Cervico-Mediastinal Mass Mimicking Giant Thyroid Nodule 77
Figure 1: The right arm X-ray: a right-sided cervical and mediastinal enlargement.
Cervico-Mediastinal Mass Mimicking Giant Thyroid Nodule 79
Figure 2: Computed tomography (CT) scan of neck and thorax.
REFERENCES
[1] Panchbhai AS, Choudhary MS. Branchial cleft cyst at an unusual
location: a rare case with a brief review. Dento maxillo facial radiology
2012;41:696-702.
[2] Glosser JW, Pires CA, Feinberg SE. Branchial cleft or cervical
lymphoepithelial cysts: etiology and management. Journal of the
American Dental Association 2003;134:81-6.
[3] Liberman M, Kay S, Emil S et al. Ten years of experience with third and
fourth branchial remnants. Journal of pediatric surgery 2002;37:685-90.
Chapter 16
FAHR’S DISEASE WITH DYSTONIA:

A CASE REPORT
Berna İmge Aydoğan, Uğur Ünlütürk, Ferda Demir,

Mustafa Şahin and Ali Rıza Uysal
Endocrinology and Metabolism Department, Ankara University School
of Medicine, Ankara, Turkey
BACKGROUND
Fahr’s disease is a rare degenerative disorder characterized by
symmetrical and bilateral intracranial calcifications. Movement disorders are
the most common symptoms of Fahr’s disease and dystonia is an uncommon
presentation which accounts for only 8% of symptomatic patients.
CASE REPORT
A 47 years old female admitted to the emergency department with
involuntary movements of extremities and anxiety.
In her medical history, subtotal thyroidectomy was performed for
multinoduler goiter twenty-eight years ago. There was no family history of
neurological disease. She was consulted by neurology for insomnia and
anxiety five years ago. Valproic acid and haloperidol were given with the
82 Berna İmge Aydoğan, Uğur Ünlütürk, Ferda Demir et al.
diagnosis of epilepsia and insomnia. She has had involuntary movements for
two years which worsened during the last two months and her life quality
decreased rapidly. Her symptoms considered to be the side effect of
haloperidol treatment and drug was stopped, but no improvement was
observed after the discontinuation of haloperidol.
Upon neurologic examination, there were repetitive, forehead
contractions, exaggerated by voluntary movements mainly on left arm and leg.
The movement disorder was compatible with dystonia. Neurological
examination was otherwise normal.
In the laboratory results, serum calcium was 6,8 mg/dl (normal 8.4-10.6
mg/dl), phosphate 4,8 mg/dl (normal 2.3-4.7 mg/dl), albumin: 4.1 mg/dl,
parathormone was 0,25 pg/ml (normal 15-65 pg/ml), serum 25 hydroxi
vitamine D level: 13,5 µG/L (20-120 µG/L) 24 hours urine creatinin 902 mg/d
(600-1800 mg 24 h), 24 hours urine calcium: 292 mg/d (80-320), phosphate
490 mg/d (400-1300). She was euthyroid and thyroid ultrasonography was
consistent with bilateral subtotal thyroidectomy.
EMG showed 400-500 msec non-rhythmic bursts which is typical for
dystonia (Figure 1). Cranial MRI revealed massive calcifications involving
basal ganglia, thalamus and cerebellar nuclei (Figure 2). The results supported
the diagnosis of Fahr’s disease caused by hypoparathyroidism.
Figure 1. EMG study of our patient demonstrating non-rhythmic bursts.

Fahr’s Disease with Dystonia 83
Figure 2. Cranial MRI revealed bilateral symmetric calcifications in basal ganglia,

thalamus and caudat nucleus.
Levodopa ve benserazide treatment were given to provide symptomatic

relief. Serum calcium level increased to acceptable range after calcitriol and
calcium carbonate treatment and resulted in complete resolution of dystonia.
DISCUSSION
Fahr’s disease is caused by calcification and cell loss of the basal ganglia
but also thalamus, dentate nuclei, cerebral cortex, centrum ovale and
mesencephalic gray matter. In 1930 Karl Theodor Fahr reported a patient with
dementia and immobility without paralysis. Calcification of centrum ovale and
striatum was observed in autopsy of this patient [1]. Although there is
conflicting data on terminology, Striopallidodentate Calsinosis (BSPDC) is
suggested to be the most descriptive name of disease [2]. Familial, non-
familial and autosomal dominant forms of disease have been reported
previously [3].
Metabolic disturbances of calcium metabolism like hypoparathyroidism,
pseudohypothyroidism and pseudo-pseudohypothyroidism are the other causes
84 Berna İmge Aydoğan, Uğur Ünlütürk, Ferda Demir et al.
of bilateral symmetric calcification in certain areas of central nervous system

and also named as Fahr’s syndrome. The relationship between bilateral basal
ganglia calcification and hypoparathyroidism was firstly described by Eaton
and Siglin [4]. A large number of developmental, degenerative, genetic,
metabolic, neoplastic, toxic and infectious disorders must be considered for the
differential diagnosis of Fahr’s syndrome. Hypoparathyroidism may be a
feature of autoimmune polyglandular syndromes, Kenny-Caffey syndrome,
DiGeorge syndrome and may occur accidentally during thyroid surgery as
well.
The most common presentation of disease is movement disorders but
cognitive impairment, mood disorders, cerebellar signs and speech disorders
can be the other manifestations as well. Manyam et al. combined their Fahr’s
disease patients with the cases reports in the literature and observed that of the
total 99 patients, 67 were symptomatic and 32 were asymptomatic [5].
Movement disorders were present at 55% of the symptomatic patients.
We present a case of Fahr’s disease caused by longstanding
hypoparathyroidism that manifested with dystonia, an unusual presentation of
the disease. The dystonias are movement disorders which sustained muscle
contractions and can cause repetitive movements or abnormal postures. The
movements which are involuntary and sometimes painful, may affect a single
muscle or a group of muscles. Acquired dystonia results from damage to the
basal ganglia. Infections, drugs, trauma can cause dystonic symptoms.
Dystonias can also be hereditary. Bilateral striopallidodentate calcinosis is one
of the disorders that cause dystonia like our patient.
Imaging studies are essential for the assesment of patients presenting with
movement disorders. Diagnosis of the Fahr’s disease mostly depends on the
typical calcium deposits on CT or MRI. It is also principal to perform
biochemical screening for calcium metabolism disorders.
Removal of calcium deposits from the brain seems to be impossible. So,
treatment modality of Fahr’s syndrome mainly consists of symptomatic
support. Antiparkinsonian drugs and antiepileptics can releive the main
complaints of the patients [6]. On the other hand, calcium and vitamin D
supplementation for hypoparathyroidism can give up the symptoms. Our
patient experienced the complete resolution of dystonia after the resolution of
hypocalcemia.
Fahr’s Disease with Dystonia 85
CONCLUSION
Though it is rare, it is important to remember that hypoparathyroidism can
be the cause of Fahr’s disease accompanied by unusual neurological disorders.
REFERENCES
[1] Fahr I. Idiopathische verkalking der hirume fasse, Zbl. Allf. Path 1930;
50:129-33.
[2] Manyam BV. Bilateral striopallidodentate calcinosis: a proposed
classification of genetic and secondary causes. Mov. Disord. 1990;5
(Suppl. 1):94.
[3] Moskowitz MA, Winickoff RN, Heinz ER, Familial calcification of the
basal ganglia: a metabolic and genetic study. N. Engl. J. Med. 1971;285:
72-7.
[4] Eaton LM, Camp JD, Love JG 1939 Symmetric cerebral calcification
particularly of the basal ganglia,demonstrable roentgenographically;
calcification of the finer cerebral blood vessels. Arch. Neurol. Psychiatry
41:921-942.
[5] Manyam BV, Walters AS, Narla KR. Bilateral striopallidodentate
calcinosis: clinical characteristics of patients seen in a registry. Mov.
Disord. 2001 Mar;16(2):258-64.
[6] Jankovic J. Treatment of dystonia. Lancet Neurol. 2006; 5: 864-72.
Chapter 17
ADRENAL INSUFFICIENCY CASE

PRESENTING WITH HYPERCALCEMIA
AND HYPOTENSION
Şule Canlar, Rifat Emral and Mustafa Şahin

INTRODUCTION
Hypercalcemia is a relatively common clinical problem and usually
asymptomatic. The most common causes of hypercalcemia are primer
hyperparathyroidism and malignancies. Other less common causes are
thyrotoxicosis, adrenal insufficiency, pheochromocytoma, immobilization,
drugs (lithium, thiazides), hypervitaminosis A, milk-alkali syndrome, familial
hypocalciuric hypercalcemia. Hypercalcemia is a rare condition in patients
with autoimmune polyglandular syndrome that is generally associated with
hypoparathyroidism and hypocalcemia. However, adrenal insufficiency may
cause hypercalcemia with different mechanisms like volume contraction,
increased tubular calcium reabsorption, and increased osteoclastic bone
resorption [1].
88 Şule Canlar, Rifat Emral and Mustafa Şahin
CASE PRESENTATION
A 47-year-old woman presented to our clinic with fatigue, weakness,
emesis and vomiting. She was admitted to the hospital with these complaints
and abdominal ultrasound was revealed. The sonography showed cholelitiasis
in biliary system. She underwent laparoscopic surgery. But her complaints
exponentially continued after surgery. Because of weight loss and lack of
appetite, upper endoscopy was performed and reported as gastritis. Proton
pump inhibitor treatment was advised. Laboratory tests were confirmed and
the patient was diagnosed as primary hypothyroidism. She was treated with
levothyroxine. She didn’t benefit this treatment, she realized her skin
hyperpigmentation and severe joint pain.
She applied with these chronic complaints, physical examination showed
orthostatic hypotension, hyperpigmentation.
On admission, her laboratory tests were : WBC 10*109 /L, PLT 299*109,
Hgb 15 g/dl, sodium 126 meq/l, potassium 5.2 meq/l, T.Calcium 11.7 mg/dl,
creatinin 1.2 mg/dl, ALT 45u/l, AST 50 u/l, TSH 3.89 mıu/ml, f T4 13.3
pmol/l, anti TPO 370 ıu/ml, PTH 7.7, 25 hydroxy vitamin D 25 mg/L. 24-hour
urine calcium excretion was 101 mg/day. Primary hyperparathyroidism was
excluded with these results.
Because of hyperpigmentation, hyperpotasemia and hyponatremia, ACTH
and cortisol levels were measured, ACTH was >2000 and plasma cortisol was
0.098 mg/dl.
She was post-menopausal for eleven years, she had two children. Her FSH
and LH levels were compatible with menopausal period.
She was diagnosed as primary adrenal insufficiency and was medicated
with prednisolone that the dose is calculated according to body surface area,
then hydrocortisone was added while decreasing prednisolone dose. Because
of having hashimoto thyroiditis, primer adrenal insufficiency, we considered
autoimmune polyglandular syndrome type 2 and performed oral glucose
tolerance test that was resulted within normal range. Vitamin B12 level was
normal.
For assessment of mineralocorticoid deficiency, renin and aldosteron
levels were measured, renin was high and aldosteron was low, we decided to
give fludrocortisone treatment because of persistence hypotension and
hyponatremia. Diet included 4 gr/day salt.
Significantly gain of appetite and weight was noticed and she expressed
herself well-being. Bone mineral density measurement was done, lomber T
Adrenal Insufficiency Case Presenting with Hypercalcemia … 89
score was established -2.3, vitamin D replacement was recommended. Her

laboratory tests before discharge were: T.Ca 9.6 mg/dl, Na 131 meq/l, K 4.2
meq/l. The patient was discharged with fludrocortison, prednisolone and
hydrocortisone treatment and acknowledged about adrenal insufficiency/crisis
symptoms.
DISCUSSION
Our patient presented with nonspecific symptoms and hypercalcemia may
be related with these symptoms. The etiology of hypercalcemia was
considered PTH related diseases in generally until an elevated ACTH level
and low cortisol level measured during her admission. Treatment with
glucocorticoids has been observe to resolve hypercalcemia in patients with
adrenal insufficiency. Various mechanisms have been proposed to explain the
casual relationship of adrenal insufficiency to hypercalcemia. Also treatment
with glucocorticoids was similarly effective in correcting the hypercalcemia in
previous cases [2]. The most important differential diagnosis of hypercalcemia
due to adrenal insufficiency is hypercalcemia secondary to lymphomas and
granulomatous diseases. In these patients, 1,25 hydroxy vitamin D3 levels are
increased. It was in normal range in our patient. Etiology of hypercalcemia in
hypoadrenalism seems to be multifactorial with alterations in the resorption of
calcium from bone. Levothyroxine may unmask the hypocortisolism and
hypercalcemia.
REFERENCES
[1] Grossmann M, Fuller P, Hunter A, Teede H. Isolated ACTH defficiency
presenting as severe hypercalcemia. Clin Endocrinol 2007;66:603-4.
[2] Katsnelson S, Cella J, Suh H, Charitou M. Hypercalcemia in a patient
with autoimmune polyglandular syndrome. Clinics and Practice
2012;2:e39.
Chapter 18
HYPERCALCEMIA DUE TO
DIABETIC KETOACIDOSIS
Şule Canlar, Mustafa Şahin and Demet Çorapcioglu

INTRODUCTION
Hypercalcemia is a relatively common clinical problem and usually
asymptomatic. The most common causes of hypercalcemia are primer
hyperparathyroidism and malignancies. Other less common causes are
thyrotoxicosis, adrenal insufficiency, pheochromocytoma, immobilization,
drugs (lithium, thiazides), hypervitaminosis A, milk-alkali syndrome, familial
hypocalciuric hypercalcemia. However, parathormon levels may be normal or
high in primer hyperparathyroidism. Tecnetium-99m sestamibi is gold
standard for imaging parathyroid glands.
CASE PRESENTATION
We present a case of a 67-year-old woman, who has been diagnosed with
type 2 diabetes mellitus, refers to emergency clinic with nausea, vomiting and
diarrhea. She has had diabetes for twenty years and hypertension for twenty-
five years, and her medications include premixed insulin analogs, metformin
and delix 10 mg/day. For four to five years, she has had neuropathy and
92 Şule Canlar, Mustafa Şahin and Demet Çorapcioglu
retinopathy. Her urinary ketone was ++++ positive and metabolic acidosis (pH
= 6.95) was detected. IV insulin infusion and IV hydration therapy was given.
The laboratory findings were: Plasma glucose, 357 mg/dl (74-100);
HbA1c 9.8% (4.5-6); serum albumin, 3.5 g/dL (normal 3.5 to 5.2); corrected
calcium 10.9 mg/dl (8,6-10,2); alkaline phosphatase 57 U/L alanine
aminotransferase, 19 U/L (<34); aspartate aminotransferase, 16U/L (<41); 25-
hydroxy vitamin D, 4.1 mg/L (10-60); intact parathormone, 38,4 pg/ml (12-
88); 24-hour urine calcium excretion 95 mg/day (80-320); and TSH 1.2
µIU/L. She had normal serum and urine protein electrophoresis. Adenoma was
not identified on parathyroid sonography.
She didn’t have any medication that was associated with hypercalcemia.
For diagnostic evaluation of hypercalcemia, thorax CT scan analysis showed
6mm diametered calcific granuloma, her ACE level 7 (8-52) was in normal
range. Serum quantiferon level was normal. There was no appearance which
can be associated with malignancy in mammographic images. Abdomen USG
was performed and was reported as hepatosteatosis and hepatomegaly. BMD
was detected as normal.
Any etiologic causes are detected on the diagnostic evaluation. Patient
was discussed in endocrinology council; the council decided to repeat the tests
and screen family members to rule out familial hypocalciuric hypercalcemia.
After urinary keton became negative, the laboratory findings in control
examination were: Total calcium, 10.1 mg/dl (8,6-10,2); serum albumin, 3.7
g/dL (normal 3.5 to 5.2). Her urine showed that her calcium/creatinine ratio
was 0.2. Her family members had normal urine calcium excretion. After the
resolution of DKA, hypercalcemia also resolved.
DISCUSSION
Hypercalcemia is a common clinical problem and may cause life-
threatening conditions. On the other hand, clinicians should consider many
drugs and diseases for diagnostic approach of hypercalcemia. It is reported that
hypercalcemia in DKA is due to metabolic acidosis, hyperglycemia and
insulin deficiency [1, 2]. Hypercalcemia is an uncommon complication of the
ketogenic diet, and these children may represent the severe end of a clinical
spectrum of disordered mineral metabolism [3]. Dehydration may be an
important factor in hypercalcemia in DKA.
Hypercalcemia Due to Diabetic Ketoacidosis 93
Adequate fluid replacement to treat the hypercalcemia is necessary. As

Makaya et al. recommended in their case report, calcium levels should be
checked routinely in all patients with DKA. We do not know the incidence of
hypercalcemia in DKA but their recommendation seems logical.
In conclusion, hypercalcemia in DKA requires early diagnosis and
treatment to prevent complications.
REFERENCES
[1] Makaya T, Chatterjee S, Arundel P, Bevan C, Wright NP. Severe
hypercalcemia in diabetic ketoacidosis: a case report. Diabetes Care.
2013 Apr;36(4):e44.
[2] Topaloglu AK, Yildizdas D, Yilmaz HL, Mungan NO, Yuksel B, Ozer
G. Bone calcium changes during diabetic ketoacidosis: a comparison
with lactic acidosis due to volume depletion. Bone 2005;37:122-127.
[3] Hawkes CP, Levine MA. Ketotic hypercalcemia: a case series and
description of a novel entity. J Clin Endocrinol Metab. 2014 May; 99(5):
1531-6.
Chapter 19
SULFASALAZINE-RELATED FALSE POSITIVE

URINARY NORMETANEPHRINE RESULT
Berna İmge Aydoğan, Pinar Kubilay,

Ali Riza Uysal and Sevim Güllü
CASE REPORT
A 50-year-old female patient was admitted to the Endocrinology
Departmentwith adrenal incidentaloma. In her medical history, she has had
ulcerativite colitis for nine years and ankylosing spondylitis for two years.
During her colonoscopy, a stricture was found and abdominal CT was
performed. Upon performing an abdominal CT, a left adrenal mass, 29 mm in
diameter was diagnosed. She was receiving sulfasalazine 3 gr/day for
ankylosing spondilitis.
The 24-hour urinary catecholamines and metabolites were measured by
high-performance liquid chromatography after urine specimens were acidified
and hydrolyzed. Normetanephrine levels were measured twice and both were
higher than the normal ranges (790.5 and 698 μg/d; normal range 88-444 μg/d,
929 and 1290 mg/d creatinin). Urinary metanephrine and adrenaline levels
remained normal. Urinary noradrenaline levels were higher than the normal
(69,7 and 96,4 μg/d; normal range 20-81 μg/d). Plasma chromogranin A level
was normal. The patient was normotensive without antihypertensive
96 Berna İmge Aydoğan, Pinar Kubilay, Ali Riza Uysal et al.
medication. He had no history of hypertensive attacks, massive perspiration,

palpitation, pallor or flushing. A false positive result in 24 hour urinary
normetanephrine level was suspected. Patient’s urinary normetanephrine level
was measured two times after the cessation of sulfasalazine and both were
between the normal ranges (198.5 and 141 μg/d).
Figure 1. Abdominal CT revealed a 29 mm left adrenal mass.
CONCLUSION
Initial evaluation for adrenal incidentaloma includes measurements of
fractionated metanephrines in urine and provide a highly sensitive test for
diagnosis of pheochromocytoma, but false-positive results remains as a
problem. We report a biochemical misdiagnosis of pheochromocytoma in two
patients being treated with sulfasalazine. Sulfasalazine is reported to cause
false positive urinary cathecolamines [1]. Recognition of drugs that may
interfere with assays of urinary normetanepfrine can avoid unnecessary
surgical and diagnostic interventions.
Sulfasalazine Related False Positive Urinary Normetanephrine 97
REFERENCE
[1] 1-Bouhanick B, Fauvel J, Pont F. Biochemical misdiagnosis of
pheochromocytoma in patients treated with sulfasalazine. JAMA. 2010
Nov 3;304(17):1898-901.
Chapter 20
A 55-YEAR-OLD WOMAN
WITH HEMANGIOPERICYTOMA-
ASSOCIATED HYPOGLYCEMIA

A 55-year-old women was admitted with cold sweats, chills, occasional

confusion even loss of consciousness. They occurred especially in the early
morning hours and had been increasing in severity and frequency.
Hypoglycemia has been documented by measuring blood testing. Her
symptoms have resolved after iv dextrose administration. Since 1994, she was
followed with diagnosis of intra-abdominal hemangiopericytoma and had
undergone surgery several times. One year ago, splenectomy, omentectomy,
removal of peritoneal implants, and cauterization were performed.
Pathological examination were consistent with multiple round cell
malignant mesenchymal tumor nodules. She was receiving no medications
except proton pump inhibitors and reported no drug or alcohol abuse. In
clinical follow-up the patient's blood sugar levels were not elevated and iv
dextrose infusion was continued. Laboratory evaluation showed mild anemia,
increase in acute phase reactants and unremarkable abnormalities in blood
chemistry. Her insulin growth factor -1 (IGF-1) level was low, IGF-2 level
was high and Insulin-like growth factor-binding protein -3 (IGFBP-3) level
was within normal limits (Table 1). Abdominal computed tomography
revealed multiple masses in the liver and peritoneum. These findings were
consistent with progressive disease. Patients were considered in-operable by

the department of general surgery. Then, she did not benefit from sandostatin
or glucagon treatment. We did not plan whole body positron emission
tomography because there was not any pathological uptake in Ga-68
DOTATATE. During the follow-up with the reasons that hypoglycemia was
continued and carbohydrate-rich diet could not prevent more hypoglycaemia.
We had started steroid treatment for a while to prevent episodes. Also we have
consulted her for evaluation for chemotherapy chance by oncology
department. But she did not want to take chemotherapy.
Finally, the patient underwent palliative surgery. Plasma glucose levels
remained normal in the postoperative period with normalized IGF-2 levels and
no hospital admissions due to hypoglycemia.
Table 1. Laboratory Data
Variable Reference Range Results

IGFBP-3 2020-3990 ng/ml 2440
IGF-1 94-284 ng/ml 10
IGF-2 459-1123 ng/ml 1276
GH 0-3,5 ng/ml 0,25
Insulin (fasting) 4-16 µIU/ml 1
C-peptide 1,1-4,4 ng/ml <0,01
Cortisol (morning) 6,2-19,4 µg/dl 15
ACTH 7,2-63,3 pg/ml 22,9
TSH 0,34-5,6 µIU/ml 1,88
sT4 7-16 pmol/l 13,6
sT3 3,8-6 pmol/l 3,9
DISCUSSION
We present a case of a woman with non-islet cell tumor (NICTH)
hypoglycemia due to a metastatic hemangiopericytoma. These tumours are
often large, slow growing, well differentiated [1-4]. Most common tumours
causing tumor induced hypoglycemia are mesenchymal origin, mesotholioma
8%, Haemangiopericytoma 7% [2]. If patient with mesenchymal or malignant
epithelial tumour suffering from hypoglycemic episodes or unconsciousness,
non-islet cell tumor hypoglycemia (NICTH) should be considered [1, 2].
A 55-Year-Old Woman with Hemangiopericytoma … 101
Production of hormones with insulin-like activity is main cause of

hypoglycemia in these tumors. A high normal IGF-2 undetectable IGF-1 and
GH and low IGFBP-3 levels strongly suggest tumor-induced hypoglycemia [4,
5, 6]. Generally with surgical cure hypoglycemia resolve. Even in cases that
are considered surgically inoperable palliative surgical treatment should be
considered for resolving hypoglycemia and to improve quality of life [6].
REFERENCES
[1] Daughaday, W.H., Hypoglycemia in patients with non-islet cell tumors.
Endocrinol. Metab. Clin. North Am., 1989. 18(1): p. 91-101.
[2] de Groot JW1, Rikhof B, van Doorn J, Bilo HJ, Alleman MA, Honkoop
AH, van der Graaf WT. Non-islet cell tumour-induced hypoglycaemia: a
review of the literature including two new cases. Endocrine related
cancer 2007 14 979-993.
[3] Zapf, J., Role of insulin-like growth factor II and IGF binding proteins in
extrapancreatic tumor hypoglycemia. Horm. Res., 1994. 42(1-2): p. 20-
6.
[4] Cariani, E., et al., Expression of insulin-like growth factor II (IGF-II) in
human primary liver cancer: mRNA and protein analysis. J. Hepatol.,
1990. 11(2): p. 226-31.
[5] Lawson, E.A., et al., Hypoglycemia from IGF2 overexpression
associated with activation of fetal promoters and loss of imprinting in a
metastatic hemangiopericytoma. J. Clin. Endocrinol. Metab., 2009.
94(7): p. 2226-31.
[6] Mechanisms of tumor induced hypoglycemia with intraabdominal
hemangiopericytoma (JCEM 1996 81(3):919-25.
[7] Treatment of hemangiopericytoma-induced hypoglycemia with growth
hormone and corticosteroids. (JCEM 1999 may 84(5):1758-98.
Chapter 21
A 58-YEAR-OLD WOMAN WITH

ANKYLOSING SPONDYLITIS WHO
DEVELOPED PAPILLARY THYROID CANCER

INTRODUCTION
A 58-year-old woman with a history of ankylosing spondylitis and uveitis
was found to have a thyroid nodule in sonography. In 2005, the patient
underwent a total thyroidectomy due to the diagnosis of nodular goiter.
Pathological examination was consistent with differentiated follicular cell
neoplasia. Postoperatively patient had consulted to nuclear medicine
department for radioiodine therapy but because of there was not absolute
malignancy criteria (Unknown potential malignancy of well differentiated
thyroid cancer) radioactive iodine treatment was not given to the patient. In
2013 pathological specimens were re-evaluated at another hospital and they
were consistent with follicular variant of papillary carcinoma.
Since 2000, the patient was followed with the diagnosis of ankylosing
spondylitis. She was treated with methotroxate for several years followed by
sulfasalazine. She was taking steroid for 1.5 years. She had no history of
cancer or neck irradiation, no family history of TCA (thyroid cancer). Her
sedimentation was 32 mm/hour, her C-reactive protein (CRP) level was 19;
HLA-B-27 was positive.
Because of did not respond to conventional treatment, anti-TNF therapy
planned for patient at rheumatology clinic. She was consulted from
rheumatology clinic to us for anti-TNF treatment. The physical examination
revealed tenderness of the sacroiliac joints and limited range of spinal motion.
Thyroid ultrasound showed bilaterally residual tissue and TSH-stimulated RAI
whole-body scan demonstrated no abnormal uptake except mild focal
accumulation in right thyroid bed. In 02/01/2014, her serum TSH, sT4, sT3,
thyroglobulin and antithyroglobulin antibody levels were 0.02 µIU/ml, 19.2
pmol/l, 4.1 pmol/l, 0,293ng/ml and <0.9IU/ml respectively. At the time of
admission, she was receiving levothyroxine 175 mcg/day, leflunomide 20
mg/day, hydroxychloroquine 400 mg/day, methylprednisolone 16 mg/day and
methotrexate therapy. Additional medical treatment or radioiodine therapy was
not recommended by our department of endocrinology and follow-up was
recommended. As additional recommendation, if there will be recurrence of
thyroid malignancy under anti-TNF therapy then treatment alternatives may be
considered.
DISCUSSION
Anti-TNF (Anti-Tumor necrosis factor) antibody therapies may increase
the risk of infections and malignancies. During anti TNF treatment, one of the
most feared topics is malignancy risk so the patients that receiving this
treatment should be kept under close follow up. In patients with previously
known malignancy these drugs should be used with more caution [1-3].
The cancers found in children treated with anti-TNF therapy included
gastrointestinal lymphomas, leukemia, malignant melanoma and thyroid
cancer [4]. Does patient’s immunocompromized state increase her risk of
reccurency of papillary thyroid cancer (PTC)? Immune suppressive treatment
may increase the risk of papillary thyroid cancer. Patients have undergone
transplantation have higher risk for malignanacy [5, 6]. We must have higher
degree of suspicion. Also we do not know the effect of AS or anti-TNF
treatment on thyroid cancer recurrence.
Also steroid therapy may effect prognosis and follow-up of these patients,
TSH measurements may be effected by steroid therapy.
A 58-Year-Old Woman with Ankylosing Spondylitis… 105
We have also consulted the pathology preps for capsule re-evaluation

because if it is non-invasive follicular variant papillary thyroid cancer its
prognosis will be very good [7]. So it may also change TSH suppression level
and time of controls.
There may be difficulty in treatment decisions because of the potential risk
of additional surgery or RAI treatment. We do not know if more invasive
initial treatment may be required in these patients. But close follow-up
especially with neck sonography and thyroglobulin measurement is helpful.
REFERENCES
[1] Dixon, W.G., et al., Influence of anti-tumor necrosis factor therapy on
cancer incidence in patients with rheumatoid arthritis who have had a
prior malignancy: results from the British Society for Rheumatology
Biologics Register. Arthritis Care Res (Hoboken), 2010. 62(6): pp. 755-
63.
[2] Maini, R., et al., Infliximab (chimeric anti-tumour necrosis factor alpha
monoclonal antibody) versus placebo in rheumatoid arthritis patients
receiving concomitant methotrexate: a randomised phase III trial.
ATTRACT Study Group. Lancet, 1999. 354(9194): pp. 1932-9.
[3] Keystone, E.C., et al., Radiographic, clinical, and functional outcomes of
treatment with adalimumab (a human anti-tumor necrosis factor
monoclonal antibody) in patients with active rheumatoid arthritis
receiving concomitant methotrexate therapy: a randomized, placebo-
controlled, 52-week trial. Arthritis Rheum, 2004. 50(5): pp. 1400-11.
[4] Onel K, Onel KB, Anti-TNF Therapy and Cancer Risk in Patients with
Autoimmune Disorders, Arthritis Care and Research doi10.1002/acr.
20228.
[5] Engels EA, Pfeiffer RM, Fraumeni JF Jr, Kasiske BL, Israni AK, Snyder
JJ, Wolfe RA, Goodrich NP, Bayakly AR, Clarke CA, Copeland G,
Finch JL, Fleissner ML, Goodman MT, Kahn A, Koch L, Lynch CF,
Madeleine MM, Pawlish K, Rao C, Williams MA, Castenson D, Curry
M, Parsons R, Fant G, Lin M. Spectrum of cancer risk among US solid
organ transplant recipients. JAMA. 2011 Nov 2;306(17):1891-901.
[6] Tisset H, Kamar N, Faugeron I, Roy P, Pouteil-Noble C, Klein M,

Mourad G, Drui D, Do Cao C, Leenhardt L, Allix I, Bonichon F,
Morelon E, Leboulleux S, Kelly A, Niccoli P, Toubert ME, Frimat L,
Vantyghem MC, Bournaud C, Schlumberger M, Borson-Chazot F;
TUTHYREF network. Is thyroid cancer recurrence risk increased after
transplantation? J Clin Endocrinol Metab. 2013 Oct;98(10):3981-8.
[7] Rosario PW, Mourão GF, Nunes MB, Nunes MS, Calsolari MR. thyroid
neoplasm with papillary-like nuclear features (NIFTP). Endocr Relat
Cancer. 2016 Sep 22. pii: ERC-16-0379.
Chapter 22
A 35-YEAR-OLD WOMAN WITH LEFT

NON-FUNCTIONAL ADRENAL ADENOMA
AFTER RIGHT ADRENALECTOMY
FOR PHEOCHROMOCYTOMA

A 35-year-old woman presented with hypertension, headaches and limb

pain. She was well until three months prior to admission, her blood pressure at
that time was 160/90 mm Hg and was started low dose of amlodipine. During
follow up blood pressure continued high and alpha-blocker therapy was added
to treatment. Regulation of blood pressure was achieved with dual
antihypertensive therapy. The physicial examination revealed any pathological
finding except cachexia. In fundus examination grade 3 retinopathy was
detected. Thyroid function tests and levels of urine catecholamines were
within normal limits. In 2005, she had similar complaints and at that time
urine catecholamines were very high (urinary free normetanephrine 13476
μg/day and free metanephrine 410 μg/day) and surrenal imaging showed
right adrenal adenoma and she had undergone right adrenalectomy.
Pathological examination was consistent with pheochromocytoma (5.5x5x4
cm in diameter) and in immunohistochemistry exam chromogranin and
synaptophysin expressions were positive. In 2009 for intraabdominal bleeding
and bleeding from right renal parenchyme diagnostic laparotomy was made in
another clinic. During the operation hypertension attack was reported. In her
examination grade 3 retinopathy and 24 hour urinary noepinephrine was
reported as 750 μg//day. I-131- MIBG was reported as negative. In 2010 upper
abdominal MR showed left adrenal adenoma 23x33x28 mm in size.
Metaiyodobenzilguanidin scintigraphy revealed no pathological uptake and
urine of urine catecholamines were within normal limits. Serum aldosterone to
renin activity ratio and plasma basal cortisol –ACTH values were within
normal limits. Glucagon stimulation test was also negative. According to
ambulatory blood pressure measurement; her blood pressure maximum
measurement was 163 mmhg and in 75 % it was higher than 135 mmhg. Her
renal arteries were patent. Calcitonin and PTH levels were normal, gastrin
level was 81.9 pg/mL. During the follow-up in our clinic amlodipin treament
was given 8 mg and patient’s blood pressure was regulated with only alpha-
blocker treatment and then adrenal imaging of the patients was repeated.
Adrenal MRI showed 2.3 cm diameter adenoma in left adrenal gland and T2-
weighted image was not consistent with pheochromocytoma. Follow-up with
6-months interval was recommended by the endocrinology department.
History is important for diagnosis of reccurence. In 2009; acute abdomen
status may be an attack due to anesthesia induction. Negative glucagon
provacation test does not rule out pheochromocytoma. In addition, negative
biochemical results also does not rule out pheochromocytoma always. All
tests were done on alpha blocker therapy. It is unclear if I-131 MIBG
scintigraphy is useful for diagnosis of reccurence. Catecholamine secretion is
largely varible among patients with pheochromocytoma. Even some
pheochromocytoma tumors may be non-functional [1]. Tumours due to
succinate dehydrogenase subunit B mutations are often non-functional and
malignant. But still these tumors may be fatal because of abrupt release of
cathecolamine bolus [1]. Becasue of bilateral adrenal mass and young age it is
better to make genetical analysis especially for SDHB mutation. In fact it is
more logic to make genetical analysis in all pheochromocytoma patients.
MEN (Multiple endocrine Neoplasia) 2A/2B, VHL (Von Hippel–Lindau),
Neurofibromatosis type 1 (NF1), familial pheochromocytoma may be possible
genetical syndromes related to pheochromocytomas. Also for prognosis of
these tumors, genetical analysis is very important [2]. If diagnosis will be
reccurence in follow-up, it may be possible to make cortex sparing adrenal
surgery to right side. This surgery may avoid life long cortisol defficiency.
Reccurence of pheochromocytoma is possible in the other adrenal gland years
after adrenalectomy. Long term follow-up is necessary after surgery for a
pheochromocytoma. Even benign pheochromocytomas may reccur years later.
A 35-Year-Old Woman … 109
REFERENCES
[1] Mannelli M., Lenders J. W., Pacak K., Parenti G., Eisenhofer G.
Subclinical phaeochromocytoma. Best Pract. Res. Clin. Endocrinol.
Metab., 2012 Aug.; 26(4):507-15.
[2] Bausch B, Wellner U, Bausch D, Schiavi F, Barontini M, Sanso G, Walz
MK, Peczkowska M, Weryha G, Dall'igna P, Cecchetto G, Bisogno G,
Moeller LC, Bockenhauer D, Patocs A, Rácz K, Zabolotnyi D,
Yaremchuk S, Dzivite-Krisane I, Castinetti F, Taieb D, Malinoc A, von
Dobschuetz E, Roessler J, Schmid KW, Opocher G, Eng C, Neumann
HPLong-term prognosis of patients with pediatric pheochromocytoma.
Endocr Relat Cancer. 2013 Dec 16;21(1):17-25.
Chapter 23
A 22-YEAR-OLD WOMAN WITH TYPE 1

CONGENITAL GENERALIZED LIPOATROPHY

A 22-year-old woman who first admitted to hospital in 2004 with thirst

and polyuria has been diagnosed with type 1 diabetes mellitus. In 2009 the
patient was also diagnosed with hypertriglyceridemia, fenofibrate and niacin
therapy had been started. At that time she began using an insulin pump but
because of development of local infection intensive insulin treatment was re-
started again and insülin pump therapy was interrupted. She needs very high
doses of insulin. In 2010 she admitted to hospital again with alopecia, weight
loss, menstrual irregularity. She had also iron deficiency and insulin
resistance. Laboratory tests revealed AGPAT-2 (that encodes 1 acylglycerol-3-
phosphate O-acyltransferase 2 = key enzyme in triglyceride metabolism)
homozygous mutation and her leptin level was <0.1 µg/dl (upper limit 0.7
µg/dl). With these finding she was diagnosed with type 1 congenital
generalized lipoatrophy. In 2012 she underwent five sessions of
plasmapheresis because of severe hypertriglyceridemia. After plasmapheresis
plasma TG level decreased from 6603 mg/dl to 1400 mg/dl. Due to negative
effects on blood glucose regulation her niacin treatment was stopped. She had
been diagnosed with celiac disease. Her thyroid autoantibodies were positive.
Thyroid sonography and thyroid function tests revealed chronic autoimmune
thyroiditis and levothyroxine replacement was started. Her vitamin B 12 level
were also low. She had oligomenorhea and her estradiol levels were low which
may be related to deficiency of fat tissue. Recently used drugs of patients was
metformin, pioglitazone, gemfibrozil, pregabalin, omega-3, alpha lipoic acid,
ramipril, atorvastatin and levothyroxine.
Recombinant human leptin treatment was planned for the patient. Also
intermittent plasmapheresis was continued.
DISCUSSION
Congenital generalized lipoatrophy or Seip-Berardinelli syndrome is an
autosomal recessive disease which is characterized by generalized absence of
fat within the first year of life, followed by insulin resistance, acanthosis
nigricans, diabetes mellitus before adolescence; severe hypertriglyceridemia
accompanied by frequent pancreatitis; high basal metabolic rate and increased
appetite [1]. Generally the major clinical problems requiring treatment in
lipoatrophy syndromes are diabetes and hypertriglyceridemia. Achieving good
glycemic control is difficult for most patients with lipoatrophic diabetes.
Leptin analogs can be used for diabetes control and for high hypertriglyceride
levels [2]. Leptin increase insulin sensitivity and secretion and decrease
hypertriglyceridemia and decrease ectopic fat accumulation. And it may
improve glycemic lability.
Thiazolinediones increase subcutanous fat, leptin replacement has been
shown to improve hyper glycemia and hypertriglyceridemia [3, 4]. Patient may
also be treated with fenofibrate for congenital generilized lipodistrophy and
severe hypertriglyceridemia. Also we think that plasmapheresis has very
mandatory role in lowering elevated triglyceride levels in such cases.
REFERENCES
[1] Copeland, K.C., et al., Discordant metabolic actions of insulin in
extreme lipodystrophy of childhood. J. Clin. Endocrinol. Metab.,1993.
77(5): p. 1240-5.
[2] Agarwal, A.K. and A. Garg, Genetic basis of lipodystrophies and
management of metabolic complications. Annu. Rev. Med., 2006. 57: p.
297-311.
A 22-Year-Old Woman … 113
[3] Moon HS1, Dalamaga M, Kim SY, Polyzos SA, Hamnvik OP, Magkos
F, Paruthi J, Mantzoros CS. Leptin's role in lipodystrophic and
nonlipodystrophic insulin-resistant and diabetic individuals. Endocr.
Rev. 2013 Jun; 34(3):377-412.
[4] Owen KR1, Donohoe M, Ellard S, Hattersley AT. Response to treatment
with rosiglitazone in familial partial lipodystrophy due to a mutation in
the LMNA gene. Diabet. Med. 2003 Oct; 20(10):823-7.
Chapter 24

HURTHLE CELL CARCINOMA AND
RECURRENT LYMPH NODE METASTASES
Çağlar Keskin, Mustafa Şahin and Seher Demirel

INTRODUCTION
A 38-year-old women had been followed as toxic multinodular goiter
since 2001 in one university hospital and he had taken intermitant
propylthiouracil therapy for 10 years. The was no fine needle aspiration
procedure history. She presented to another clinic with neck swelling and
dysphagia in 2011. Thyroid ultrasonography of the patient showed
multinodular goiter and she underwent bilateral total thyroidectomy in 2011.
There was not a personal history of head and neck irradiation or a family
history of thyroid cancer.
Pathological examination was consistent with minimally invasive
follicular carcinoma (Hurthle cell carcinoma), tumor was 3.5 cm in diameter.
There was not lymphovascular invasion but minimally capsular invasion was
present. Focal galectin and CD19 (+) and HBMC-1 was negative. After
surgery she did not undergo RAI therapy and TSH-stimulated RAI whole-
body scan demonstrated on focal increased activity in the right submandibular
region and TSH, sT4, sT3, Tg, anti-Tg levels were 7.2 µIU/ml, 4.56 pmol/l,
116 Çağlar Keskin, Mustafa Şahin and Seher Demirel
3.8 pmol/l, 25.5 ng/ml and <10 IU/ml respectively. Postoperatively thyroid
ultrasonography revealed solid hypoechoic lymph node that was containing
microcalcifications in the right submandibular region 27 x 19 x 17 mm in
diameter and fine-needle aspiration biopsy (FNAB) results showed no
malignancy findings. Additionally thyroglobulin washout results were
negative (Tg < 0,1 ng/ml). After all examinations she underwent surgery for
central neck dissection and right lymph node dissection. Pathological
examination revealed that all lymph nodes were reactive (22/22) and there was
not metastatic lymph node. One year later the patient admitted to our hospital
with recurrent right cervical lymph node. Positron emission tomography
showed increased 18F-FDG uptake in right submandibular lymph node
(SUVmax:2.5) and left axillary lymph node (SUV max:4.85). For her
persistence high thyroglobulin levels and without detected focus, because she
recieved 150 mci radioactive Iodine I-131 therapy. For differential diagnosis
calcitonin level were measured (Calcitonin level was 5 ng/L).
DISCUSSION
Hurthle cell carcinoma (HCC) of the thyroid gland is rare type of thyroid
cancer according to other well-differentiated ones. Hurthle cell cancer tends to
be more aggressive than papillary and follicular thyroid cancers. They have
higher frequency of metastasis and mortality [1-3]. According to other
differentiated thyroid carcinomas, HCC has a lower uptake of radioactive
iodine and treatment with radioactive iodide has limited benefit [3]. Hürthle
cell carcinoma (HCC) is regarded as an aggressive variant of follicular thyroid
carcinoma based in part on its propensity to metastasize regionally and recur
locally [4]. We presented a case of 38 year old women with metastatic hurthle
cell carcinoma and resistance to RAI therapies.
Many patients with hyperthyroidism may have thyroid cancer [5].
Frequently, generally there may be late diagnosis of thyroid cancer in
hyperthyroidism because of lack of suspicion and proper evaluation. In this
patient, diagnosis seems to be so late.
Hurthle cell carcinoma is resistance to radioactive iodine lymph node
follow up may be more appropriate fort his patient. Nowadays, we are trying
to find a focus by other imaging techniques that are magnetic resonance
imaging and multislice tomography and PET.
A 38-Year-Old Woman with Hurthle Cell Carcinoma … 117
REFERENCES
[1] DeGroot, L.J. et al., Morbidity and mortality in follicular thyroid cancer.
J. Clin. Endocrinol. Metab., 1995. 80(10): p. 2946-53.
[2] Kutun, S. et al., The predicting factors for clinical outcomes in patients
with Hurthle cell carcinoma: how we do it. Clin. Otolaryngol., 2011. 36
(1): p. 73-7.
[3] Kushchayeva, Y. et al., Comparison of clinical characteristics at
diagnosis and during follow-up in 118 patients with Hurthle cell or
follicular thyroid cancer. Am. J. Surg., 2008. 195(4): p. 457-62.
[4] Bishop JA, Wu G, Tufano RP, Westra WH. Histological patterns of
locoregional recurrence in Hürthle cell carcinoma of the thyroid gland.
Thyroid. 2012 Jul;22(7):690-4.
[5] Sahin M, Guvener ND, Ozer F, Sengul A, Ertugrul D, Tutuncu NB.
Thyroid cancer in hyperthyroidism: incidence rates and value of
ultrasound-guided fine-needle aspiration biopsy in this patient group. J.
Endocrinol. Invest. 2005 Oct;28(9):815-8.
Chapter 25

AN ELEVATED PARATHORMONE LEVEL
AFTER THE SURGERY FOR
SECONDARY HYPERPARATHYROIDISM

A 56-year-old women presented with generalized bone pain and itching.

In laboratory test parathyroid hormone levels was found to be 1470 pg/ml. In
the patient's past medical history she had been undergoing hemodialysis since
2000 for chronic kidney disease secondary to pyelonephritis. In 2006, she
admitted to our hospital with multinodular goiter and high parathyroid
hormone level (PTH: 1088 pg/ml) and then she had bilateral subtotal
thyroidectomy for nodular goiter and parathyroidectomy. She has no history of
neck irradiation. Pathological examination was consistent with 16 mm
oncocytic variant papillary thyroid cancer and right parathyroid nodular
hyperplasia. There was not thyroid capsular invasion. After the surgery
radioiodine therapy had not been given because of re-surgery plan. Serum
thyroglobulin and antithyroglobulin antibody measurement was found 1.78
ng/ml and 1274 IU/ml respectively. Thyroid function tests were within the
normal range and the patient was not using levothyroxine. During the follow-
up parathyroid hormone levels has been remained high and calcium level was
normal. In 2009 hypoechoic lesion with 05x06 mm diameter was seen in right
thyroid bed in thyroid sonography. In the same ultrasonographic examination

did not revealed parathyroid adenoma and parathyroid scintigraphy also
revealed no pathological findings. At that time in laboratory tests, PTH,
calcium and phosphate level was found 1440 pg/ml, 8.6 mg/dl and 6.4 mg/dl
respectively. In 2011 the patient was treated with cinacalcet but after the three
months treatment was discontinued because of continued epistaxis.
Coagulation analyses were within normal ranges. Previously renal hemorrhage
has been reported due to cinacalcet [1].
End stage renal disease (ESRD) patients with secondary
hyperparathyroidism (HPT) are at greater risk of thyroid cancer [2]. It is not
clear if thyroid cancer in these patients is more aggressive. Specific
immunological functional defects may be responsible in part. In addition to
relation between primary hyperparathyroidism and thyroid cancer. Secondary
hyperparathyroidism may also be related to thyroid cancer.
DEXA scan results was consistent with osteoporosis (femur neck T-
score:-4.8, lumbar spine total T-score:-3.7)
Recommended target values for serum PTH (150–300 pg/ml) in secondary
hyperparathyroidism [3]. Parathyroidectomy is not required for patients with a
mild form of secondary hyperparathyroidism. Parathyroidectomy is generally
required for severe secondary hyperparathyroidism which are not controlled
by medical therapy. Especially, surgery can be carried out in young patients
with precisely localized lesion in sonographic evaluation [4, 5, 6].
There is no consensus or guideline on the treatment and the radioactive
iodine dosages that should be administered in end stage renal disease patients.
Empirically 40-50% of routine doses would be enough in such patients. It is
better to perform dialysis sessions immediately before and at 48 hours after
131I administration [7]. Also there is no specific recommendation for TSH
suppression in these patients.
REFERENCES
[1] Wada K, Wada Y, Iino Y. Two cases of acute renal hemorrhage
undergoing maintenance hemodialysis after concurrent administration of
cinacalcet. Clin. Exp. Nephrol. 2011 Oct;15(5): 783-7.
A 56-Year-Old Woman with an Elevated Parathormone Level … 121
[2] Lin SY1, Lin WM2, Lin CL3, Yang TY4, Sung FC3, Wang YH5, Kao
CH6.The relationship between secondary hyperparathyroidism and
thyroid cancer in end stage renal disease: a population based cohort
study. Eur. J. Intern. Med. 2014 Mar;25(3): 276-80.
[3] National Kidney Foundation (2003) K/DOQI clinical practice
guidelines: bone metabolism and disease in chronic kidney disease. Am.
J. Kidney 42: S1–S201.
[4] Messa P1, Regalia A, Alfieri CM, Cresseri D, Forzenigo L, Gandolfo
MT, Rastaldi MP. Current indications to parathyroidectomy in CKD
patients before and after renal transplantation. J. Nephrol. 2013 Nov-
Dec;26(6): 1025-32.
[5] Dewberry LK1, Weber C, Sharma J. Near total parathyroidectomy is
effective therapy for tertiary hyperparathyroidism. Am. Surg. 2014
Jul;80(7): 646-51.
[6] Blomme RA1, Blomme AM, Rinkes IH, Meerwaldt R, van der Wal MB,
Valk GD, Vriens MR. Surgical strategy in patients with secondary and
tertiary hyperparathyroidism. A bi-institutional series. Acta Chir. Belg.
2010 Jan-Feb;110(1): 35-9.
[7] Alevizaki C, Molfetas M, Samartzis A, Vlassopoulou B, Vassilopoulos
C, Rondogianni P, Kottou S, Hadjiconstantinou V, Alevizaki M. Iodine
131 treatment for differentiated thyroid carcinoma in patients with end
stage renal failure: dosimetric, radiation safety, and practical
considerations. Hormones (Athens). 2006 Oct-Dec;5(4): 276-87.
EDITOR CONTACT INFORMATION
Editor-in-Chief
Dr. Mustafa Sahin

Endocrinology and Metabolism Department
Ankara University School of Medicine, Turkey
Email: drsahinmustafa@yahoo.com
Co-Editors
Dr. Demet Çorapçioğlu,

Dr. Nilgün Başkal,
Dr. Ali Riza Uysal,
Dr. A. Vedia Tonyukuk Gedik,
Dr. Murat Faik Erdoğan,
Dr. Sevim Güllü
and Dr. Rifat Emral
Endocrinology and Metabolism Department
Ankara University School of Medicine, Turkey
INDEX
alcohol abuse, 99
A aldosterone, 21
aldosteronism, 24
acid, 12, 81, 112
alkaline phosphatase, 11, 25, 92
acid-fast bacilli (AFB), 76
alopecia, 111
ACTH, 18, 55, 70, 88, 89, 100
ALT, 70, 88
adalimumab, 105
anemia, 25, 99
adenoma, 12, 17, 18, 21, 22, 31, 47, 76, 92,
ankylosing spondylitis, 95, 103
107, 120
antibody, 72, 104
adipose tissue, 72
antihypertensive drugs, 53
adrenal, ix, 11, 15, 17, 18, 20, 21, 22, 23,
antithyroglobulin antibody, 104, 119
24, 31, 53, 55, 56, 57, 69, 70, 71, 87, 88,
antithyroid therapy, 1
89, 91, 95, 96, 107
anxiety, 81
adrenal adenoma, 18
appetite, 88, 112
adrenal cortical adenomas, 11
ascites, 37
adrenal gland, 18, 57, 70, 71
aspartate, 92
adrenal hyperplasia, 22
aspiration, 2, 4, 7, 9, 39, 45, 55, 59, 62, 64,
adrenal incidentaloma, 17, 20, 69, 95, 96
66, 115, 116, 117
adrenal insufficiency, 87, 88, 89, 91
assessment, 62
adrenal lesion, 22, 69
asymptomatic, 76, 84, 87, 91
adrenalectomy, 19, 21, 22, 24, 53, 71, 107
atorvastatin, 1, 112
adrenaline, 95
autoantibodies, 111
adrenocortical carcinoma (ACC), 17
autoimmune disease, 26
age, 75
autoimmunity, 48
agglutination, 76
autopsy, 17, 83
aggressive therapy, 63
autosomal dominant, 83
aggressiveness, 4
autosomal recessive, 112
alanine, 92
azotemia, 36
alanine aminotransferase, 92
albumin, 11, 82
alcocol consumption, 69
126 Index
carcinoids, 11
B carcinoma, 5, 6, 7, 9, 17, 39, 44, 45, 55, 57,
62, 66, 67, 103, 115, 116, 117, 121
basal ganglia, 82, 83, 84, 85
cartilage, 62
basal metabolic rate, 112
catecholamines, 56, 65, 95
benign, 2, 5, 17, 21, 22, 36, 69
category b, 36
benign cyst, 17
cauterization, 99
benign prostatic hyperplasia, 69
CBC, 69
Bible, 6, 63
central nervous system, 84
bilateral, 2, 3, 8, 22, 25, 26, 27, 59, 76, 81,
cerebral cortex, 83
82, 83, 84, 115, 119
cervico-mediastinal mass, 75
biopsy, 2, 4, 5, 26, 39, 55, 59, 62, 64, 66,
chemosis, 1, 3
116, 117
chemotherapy, 100
bleeding, 11, 12
chest pain, 75
blood, 1, 3, 11, 21, 35, 53, 55, 69, 76, 85,
childhood, 112
99, 111
children, 88, 92, 104
blood glucose regulation, 111
cholesterol, 3, 22
blood pressure, 1, 3, 11, 21, 53, 69
chronic kidney disease, 119, 121
blood urea nitrogen, 11
cirrhosis, 37
blood vessels, 85
CKD, 121
BMI, 3, 4, 69
classification, 37, 85
body mass index (BMI), 1, 18, 35
clavicle, 76
bone, 18, 25, 28, 40, 73, 87, 89, 119, 121
clinical diagnosis, 65
bone metastasis, 25
clinical presentation, 37, 76
bone pain, 119
clinical problems, 112
bone resorption, 87
cognitive impairment, 84
brain, 84
colitis, 95
brancial cleft cyst, 76
collaboration, ix
brucella, 76
collagenomas, 11
buffalo, 18
colonoscopy, 44, 95
common symptoms, 81
C compilation, ix
complete blood count, 2
café au lait spots, 69 compliance, 3
calcification, 39, 42, 81, 82, 83, 84, 85 complications, 63, 93, 112
calcinosis, 84, 85 compression, 76
calcitonin, 8, 9, 53, 65, 66, 67, 116 computed tomography, 21, 75, 99
calcium, 1, 3, 11, 12, 18, 26, 36, 65, 82, 83, conjunctival injection, 1
84, 87, 88, 89, 92, 93, 119 consensus, 24, 120
calcium carbonate, 83 consumption, 69
cancer, 4, 5, 60, 65, 69, 101, 103, 104, 105, contracture, 3
116, 117, 120, 121 controversial, 17
capsular invasion, 115, 119 correlation, 64
capsule, 2, 59, 105 corticosteroids, 5, 101
carbohydrate, 100 cortisol, 17, 18, 70, 88, 89
Index 127
c-peptide, 36
creatinin, 69, 70, 82, 88, 95
E
creatinine, 1, 3, 11, 92
ECG, 21
creative thinking, ix
edema, 1, 3, 4
cribriform morular variant, 44, 45
electrolytes, 69
CRP, 104
electrophoresis, 26, 92
CT scan, 8, 18, 25, 35, 54, 66, 92
emergency, 66, 75, 81, 91
cure, 101
EMG, 82
Cushing Syndrome, v, 17, 20
emission, 116
cyst, 17, 76, 80
end stage renal disease, 120, 121
cytology, 4, 7, 39, 66, 76
endocrine, ix, 11, 12, 14, 15, 18, 26, 69
cytology department, 39, 76
endocrine disorders, 26
cytoplasm, 72
endocrinologists, ix, 20
endocrinology, ix, 1, 15, 17, 20, 37, 47, 56,
D 59, 62, 69, 81, 92, 95, 104, 123
endoscopy, 8, 11, 88
defects, 120 enlargement, 75, 76, 78
deficiency, 92, 111 enzyme, 111
deficit, 75 epigastric pain, 8, 11
dementia, 83 esophagus, 39
deposits, 84 ESR, 69, 70
dexamethasone suppression test, 18 ESRD, 120
diabetes, ix, 2, 12, 69, 91, 93, 112 etiology, 53, 80, 89
diabetic ketoacidosis, 93 euthyroid diffuse nodular goiter, 69
dialysis, 120 evidence, 36, 64, 72
diarrhea, 72 examinations, 116
diet, 92, 100 excretion, 56, 88, 92
differential diagnosis, 14, 26, 65, 84, 89 exophytic thyroid nodule, 76
diseases, ix, 1, 26, 69, 89, 92 expertise, ix
disorder, 81, 82
distribution, 40, 72
diuretic, 18
F
dopamine, 47
facial angiofibromas, 11
dopamine agonist, 47
false positive, 96
drugs, 47, 84, 87, 91, 92, 96, 104, 112
familial hypocalciuric hypercalcemia, 87,
duedenal ulcers, 11
91, 92
duedenopancreatic neuroendocrine tumors,
family history, 7, 21, 25, 69, 81, 103, 115
11
family members, 12, 92
dyslipidemia, 1, 17, 18
fasting, 1, 2, 3, 11, 12, 35, 36, 70, 100
dysphagia, 7, 115
fasting glucose, 11
dysphonia, 7
fasting plasma glucose (FPG), 1, 2, 3, 70
dyspnea, 7
fat, 18, 112
dystonia, 81, 82, 83, 84, 85
femur, 12, 120
fenofibrate, 111, 112
128 Index
fine needle aspiration biopsy (FNAB), 2, 39, hemorrhage, 72, 120

55, 59, 62, 66, 116 hepatic failure, 47
fine needle aspiration cytology (FNA), 4, 7 hepatomegaly, 92
fluid, 26, 66, 93 heterogeneity, 69
force, 12 high blood pressure, 18, 53, 56
histological examination, 8
histology, 7
G history, 7, 14, 17, 21, 25, 35, 36, 56, 69, 75,
96, 103, 115, 119
galactorrhea, 47
HLA, 104
galactrorhea, 47
hoarseness, 39, 66
ganglion, 72
hormone, 12, 56, 101, 119
ganglioneuroma, 17, 72, 74
hormone levels, 119
gastrin, 12, 14
human, 101, 105, 112
gastrinoma, 12, 14
Hunter, 89
gastritis, 8, 11, 88
Hurthle Cell Carcinoma, 115, 116, 117
gastrointestinal tract, 8
hydrocortisone, 88, 89
general surgery, 100
hyoid, 62
genitourinary malignancies, 7
hyperactivity, 2
gland, 7, 18, 40, 59, 66, 76
hyperaldosteronism, 21, 22, 24
gliclazide, 1
hyperandrogenism, 18
glucagon, 100
hypercalcemia, 14, 18, 25, 26, 28, 29, 87,
glucocorticoids, 1, 5, 89
89, 91, 92, 93
glucose, 1, 2, 3, 12, 17, 18, 35, 36, 70, 88,
hypercortisolism, 18, 69
92, 100, 111
hyperglycemia, 1, 92
glucose regulation, 111
hyperinsulinemia, 37
glucose tolerance, 17, 18, 88
hyperlipidemia, 17, 25
goiter, 2, 7, 59, 64, 69, 81, 103, 115, 119
hyperparathyroidism, 11, 14, 18, 25, 26, 29,
gonadal, ix
87, 88, 91, 119, 120, 121
granulomas, 26, 28
hyperplasia, 11, 12, 14, 22, 65, 66, 119
gray matter, 83
hyperprolactinemia, 47, 51
growth factor, 99, 101
hypertension, ix, 17, 18, 21, 22, 24, 25, 69,
growth hormone, 101
91
guidance, 4
hyperthyroidism, 1, 6, 116, 117
guidelines, 4, 20, 63, 121
hypertriglyceridemia, 111, 112
gynecomastia, 3, 22
hypertrophy, 1, 3
hypervitaminosis, 87, 91
H hypervitaminosis A, 87, 91
hypoglycemia, 35, 36, 37, 99, 100, 101
HCC, 116 hypokalemia, 21, 22
headache, 53 hyponatremia, 88
hemangiopericytoma, 99, 100, 101 hypoparathyroidism, 82, 83, 84, 85, 87
hematochezia, 11 hypophosphatemia, 25
hemodialysis, 119, 120 hypotension, vi, 87, 88
hemoglobin, 11 hypothyroidism, 47, 88
Index 129
I L
idiopathic, 47 laboratory tests, 12, 25, 37, 47, 88, 89, 120
images, 27, 36, 70, 71, 92 lactic acid, 93
immobilization, 87, 91 laparoscopic surgery, 37, 88
implants, 99 laparoscopy, 19
imprinting, 101 LDL, 1, 2, 3
incidence, 4, 17, 93, 105, 117 lead, 57
individuals, 113 legs, 4
infection, 111 leptin, 111, 112, 113
infectious disorders, 84 lesions, 22, 44, 69, 76
inferior vena cava, 55 leukemia, 104
inflammation, 22 levothyroxine, 88, 89, 104, 111, 119
inheritance, 12 libido, 22
inherited disorder, 11 life quality, 82
inhibitor, 18, 88 lipoatrophy, 111, 112
initiation, 22 lipodystrophy, 112, 113
injections, 37 lipomas, 11
insomnia, 81 liquid chromatography, 95
insulin, 2, 3, 12, 25, 35, 36, 37, 91, 92, 99, lithium, 87, 91
100, 101, 111, 112, 113 liver, 53, 56, 69, 99, 101
insulin pump, 111 liver cancer, 101
insulin resistance, 111, 112 liver function tests, 69
insulin sensitivity, 112 lobectomy, 63
insulinoma, 35, 36, 37 localization, 14, 75, 76
internal medicine specialists, ix locus, 56
intracranial calcifications, 81 loss of consciousness, 99
iodine, 2, 5, 44, 59, 103, 116, 120 lumbar spine, 120
iron, 111 lung cancer, 26
iron deficiency, 111 lymph, 4, 7, 25, 39, 44, 55, 59, 62, 63, 64,
irradiation, 103, 115, 119 65, 66, 76, 116
itching, 119 lymph node, 7, 39, 44, 55, 59, 62, 63, 64,
65, 66, 116
lymph node metastases, 63, 65
J lymphadenitis, 76
lymphadenopathy, 4, 25, 60, 76
joint pain, 88
lymphocytes, 76
joints, 104
lymphoma, 26, 76
lymphovascular invasion, 12, 66, 115
K
M
kidney, 12, 53
kidney disease, 119, 121
magnesium, 11
majority, 22
130 Index
malignancy, 24, 26, 39, 63, 71, 92, 103, multiple endocrine neoplasia type 1
104, 105, 116 (MEN1), 11, 14, 15
malignant melanoma, 104 multiple myeloma, 25
management, ix, 2, 5, 20, 60, 63, 80, 112 muscle contraction, 84
mass, 4, 7, 12, 14, 18, 21, 22, 36, 39, 42, 53, muscles, 84
55, 56, 63, 66, 70, 71, 75, 76, 95, 96 mutation, 44, 111, 113
mediastinum, 40, 43, 76 myelolipomas, 17
medical, ix, 18, 20, 21, 22, 81, 95, 104, 119,
120
medical history, 21, 22, 81, 95, 119 N
medication, 3, 21, 92, 96
nausea, 91
medicine, ix, 29, 103
necrosis, 104, 105
medullary thyroid cancer (MTC), 65, 67
negative effects, 111
mellitus, 12, 25, 35, 91, 111, 112
neoplasm, 106
MEN2, 65, 69
nephrocalcinosis, 12
menstrual disorders, 47
nephropathy, 25
Metabolic, 1, 83
neuroendocrine tumour, 65
metabolic acidosis, 92
neurofibromas, 69
metabolic alkalosis, 21
neurological deficit, 75
metabolic diseases, ix, 1
neurological disease, 81
metabolic-related diseases, ix
neuropathy, 25, 91
metabolism, 15, 18, 37, 57, 83, 84, 92, 111,
niacin, 111
121
nocturia, 4
metabolites, 95
nodes, 40, 55, 59, 66, 116
metanephrines, 65, 96
nodules, 2, 7, 39, 40, 43, 64, 66, 69, 99
metaneprine, 53
normetanephrine, 53, 70, 95, 96
metastasis, 4, 9, 25, 44, 56, 57, 60, 62, 63,
North America, 37
64, 66, 116
nuclei, 72, 82, 83
metastatic disease, 72, 73
metastatic lung cancer, 76
metastatic lymph nodes, 39, 59, 66 O
metformin, 91, 112
methylprednisolone, 104 obesity, ix, 18, 37
microcarcinoma, 2, 59, 63, 64 omega-3, 112
milk-alkali syndrome, 87, 91 omentectomy, 99
mineralocorticoid, 22, 88 opacity, 27
monoclonal antibody, 105 operations, 65, 67
mood disorder, 84 ophtalmopathy, 1, 2, 5
Moon, 113 organ, 105
mortality, 116, 117 orthostatic hypotension, 88
movement disorders, 81, 84 osteoporosis, 12, 17, 18, 120
MRI, 12, 14, 47, 82, 83, 84 outpatient, 17
mRNA, 101 overweight, 35
multinodular goiter, 59, 115, 119
multiple endocrine neoplasia, 15
Index 131
positron, 100
P positron emission tomography, 100
potassium, 11, 88
pain, 8, 11, 75, 119
pregnancy, 47
palliative, 100, 101
primary hyperparathyroidism, 11, 25, 120
pallor, 96
prognosis, 44, 63, 104, 105
palpitations, 35
prolactin, 12, 36, 47
pancreas, 7, 8, 12, 14, 36
prolactinoma, 11, 14, 47
pancreatitis, 112
proliferation, 72
papillary thyroid carcinoma, 5, 39, 44, 45,
prophylactic, 5
55, 57, 62
propranolol, 36
paralysis, 83
proptosis, 3, 4
parathormone, 12, 25, 76, 82, 92, 119
propylthiouracil, 115
parathormone level, 25, 76
protein analysis, 101
parathyroid, 7, 12, 14, 18, 28, 29, 65, 66, 76,
proteins, 101
91, 92, 119
proton pump inhibitors, 12, 99
parathyroid glands, 91
purified protein derivative (PPD), 76
parathyroid hormone, 28, 29, 119
pyelonephritis, 119
parathyroid lesion, 7, 76
parathyroidectomy, 14, 119, 121
pathology, 2, 8, 22, 55, 66, 105 Q
patient care, ix
PCR, 76 quality of life, 101
pelvis, 28
peptide, 12, 29, 35, 36, 37, 100
periorbital edema, 1, 3 R
peritoneum, 99
personal history, 115 radiation, 121
PET, 60, 62, 67, 116 radio, 6, 40, 44, 60, 62, 103, 104, 119
PET scan, 60, 62, 67 radioactive iodine, 2, 5, 44, 59, 103, 116,
pH, 92 120
pheochromacitoma, 65, 66 radioiodine therapy, 44, 60, 62, 103, 104,
pheochromocytoma, 17, 53, 56, 57, 69, 72, 119
74, 87, 91, 96, 97, 107 radioisotope, 40, 72
phosphate, 11, 82, 111, 120 reactants, 99
phosphorus, 1 receptor, 4, 22
pioglitazone, 112 recurrence, 2, 3, 55, 56, 63, 64, 66, 67, 104,
pituitary, ix, 11, 50 106, 117
pituitary tumors, 11 relatives, 66
placebo, 105 relief, 83
plasmapheresis, 111, 112 remission, 67
pleomorphic cells, 76 renal cell carcinoma, 7, 9
polycystic ovary syndrome, ix renal failure, 121
polydipsia, 25 renin, 21, 22, 70, 88
polyuria, 25, 111 resection, 17
population, ix, 121 residue, 59
132 Index
resistance, 116 suppression, 2, 3, 5, 18, 40, 120

resolution, 47, 83, 84, 92 surface area, 88
retinopathy, 25, 92 surgical intervention, 12
rheumatoid arthritis, 105 surgical removal, 36
risk, 5, 14, 36, 37, 63, 104, 105, 106, 120 surgical resection, 18
rosiglitazone, 113 survival, 63, 67
rotator cuff, 75 swelling, 76, 115
symptoms, 7, 26, 29, 47, 69, 76, 82, 84, 89,
99
S syndrome, ix, 17, 18, 20, 22, 44, 84, 87, 88,
89, 112
safety, 121
sarcoidosis, 25, 26, 28, 29
scapula, 40 T
secretion, 65, 112
sedimentation, 104 target, 120
serum, 4, 26, 36, 53, 65, 67, 76, 82, 92, 104, Task Force, 6, 63, 67
120 testing, 99
serum albumin, 92 thalamus, 82, 83
sex, 14 therapy, 1, 2, 3, 5, 14, 15, 18, 22, 28, 40, 44,
SGOT, 2, 3 59, 60, 62, 92, 103, 104, 105, 111, 115,
SGPT, 1, 2, 3 120, 121
showing, 27, 28 thiazide, 18
sibling, 14 thiazides, 87, 91
siblings, 14 thoracotomy, 44
side effects, 22 thorax, 44, 66, 78, 79, 80, 92
signs, 29, 69, 75, 84 thyroglobulin, 3, 4, 40, 59, 60, 62, 104, 105,
sine wave, 21 116, 119
skin, 69, 88 thyroid, ix, 1, 2, 3, 4, 5, 6, 7, 9, 12, 39, 40,
smoking, 25 44, 45, 53, 55, 57, 59, 62, 63, 64, 65, 66,
sodium, 11, 88 67, 69, 75, 76, 82, 84, 103, 104, 105,
specialists, ix 106, 111, 115, 116, 117, 119, 120, 121
speech, 84 thyroid cancer (TCA), 4, 5, 57, 59, 65, 103,
spindle, 72 104, 105, 106, 115, 116, 117, 119, 120,
splenectomy, 99 121
squamous cell, 76 thyroid disorders, ix
state, 36, 104 thyroid function tests, 59, 69, 111, 119
statin, 18 thyroid gland, 7, 9, 39, 59, 65, 66, 76, 116,
stenosis, 17 117
sternocleidomastoid, 76 thyroid malignancy, 39, 104
sternum, 28 thyroidectomy, 2, 3, 4, 8, 39, 44, 55, 59, 65,
stimulation, 66 66, 67, 81, 82, 103, 115, 119
strabismus, 1, 3 thyroiditis, 2, 88, 111
striae, 18 thyrotoxicosis, 87, 91
striatum, 83 tissue, 3, 4, 12, 22, 40, 56, 59, 62, 76, 104,
supplementation, 84 112
Index 133
TNF, 104, 105

toxic multinodular goiter, 7, 115
U
transformation, 22
ulcer, 14
transplant, 105
ulcerativite colitis, 95
transplant recipients, 105
ultrasonography, 4, 7, 12, 17, 36, 55, 69, 82,
transplantation, 104, 106, 121
115, 116
trauma, 47, 84
ultrasound, 7, 66, 88, 104, 117
treatment, 2, 3, 17, 22, 24, 26, 36, 40, 44,
urinary tract, 69
47, 65, 69, 71, 82, 83, 84, 88, 89, 93,
urine, 65, 70, 82, 88, 92, 95, 96
100, 101, 103, 104, 105, 111, 112, 113,
uveitis, 103
116, 120, 121
tremor, 3
trial, 105 V
triglycerides, 1
TSH, 2, 3, 4, 5, 25, 40, 70, 88, 92, 100, 104, vein, 24
105, 115, 120 vertebrae, 75
tuberculosis, 76 vitamin D, 12, 18, 25, 26, 84, 88, 89, 92
tuberculosis PCR, 76 vomiting, 91
tumor, 2, 4, 7, 8, 12, 14, 17, 22, 36, 39, 44,
53, 55, 56, 63, 71, 72, 99, 100, 101, 105,
115 W
tumor necrosis factor, 105
tumor progression, 4 weakness, 35, 88
tumors, 9, 11, 14, 44, 56, 72, 76, 100, 101 weight loss, 88, 111
Turkey, 1, 7, 11, 17, 21, 25, 31, 35, 39, 47, well-being, 88
53, 59, 65, 69, 75, 81, 87, 91, 95, 99, withdrawal, 5
103, 107, 111, 115, 119
type 1 congenital generalized lipoatrophy, Z
111
type 1 diabetes mellitus, 25, 111 ZES, 11, 14
type 2 diabetes mellitus, 35, 91

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ENDOCRINOLOGY RESEARCH AND CLINICAL DEVELOPMENTS

Additional books in this series can be found on Nova’s website

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Library of Congress Cataloging-in-Publication Data

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Chapter 8 A Case of Insulinoma Presented with

Chapter 18 Hypercalcemia Due to Diabetic Ketoacidosis 91

Endocrine and metabolic diseases involve very common diseases like

MICROPAPILLARY THYROID CANCER IN

Mustafa Şahin and Rifat Emral

Compliant: Dry Mouth at Night, Nocturia

According to these results, the patient's insulin dose was recommended as

Tiroid USG: Total thyroidectomy. No enlarged cervical

 In right cervical 3 cm LAP was detected. Left eye predominant

Aspiration biopsy under ultrasonography guidance of the probable LN

FNA: Non Diagnostic

According to these wash-out results according to serum thyroglobulin

Concomitant papillary thyroid carcinoma may complicate the

Asena Canpolat and Mustafa Şahin

A 47-year-old man with a 4-year history of non-toxic multinodular goiter

Figure 1. CT scan of neck and abdomen.

synaptophysin, but has not calcitonin expression with 1.5 cm in diameter.

A CASE OF MEN PRESENTING WITH ZES

Asena Canpolat, Mustafa Şahin,

Multiple endocrine neoplasia type 1 (MEN1) is an inherited disorder

After his hemodynamic parameters were restored and active bleeding

This case is interesting because of localization of gastrinoma and bening

Asena Canpolat and Mustafa Şahin

The incidence of adrenal incidentaloma is 8.7% reported in autopsy series.

inhibitor plus thiazide diuretic and calcium channel bloker) and

surgery for patients with SCS is minimally invasive adrenalectomy with

Figure 1. Adrenal adenoma on the left side of the patient.

A RELAPSING CONN’S SYNDROME

Asena Canpolat and Mustafa Şahin

A 50-year-old white male with hypertension was admitted to our hospital

Figure 1. Computed tomography (CT) scanning for adrenal imaging.

Asena Canpolat and Mustafa Şahin

Figure 1. Chest radiograph revealing bilateral hilar masses.

Figure 2. Chest radiograph revealing bilateral reticulonodülar opacity.

Five to ten percent of sarcoidosis patients may have hypercalcemia [3].

Çağlar Keskin and Mustafa Şahin

A 44- year-old women presented with uncontrolled hypertension despite

anteroapical and anterior wall. Coronary anjiography showed non-critical

Figure 1. Adrenal adenoma on the right side of the patient.

tumors. We could not able to make ACTH staining in immunohistochemistry

A CASE OF INSULINOMA PRESENTED WITH

Asena Canpolat, Mustafa Şahin,

A 63-year-old morbid obese woman has a 3-year history of episodic

Table 1. Insulin –glucose-c peptide levels

Insulin Glucose c-peptide

She had Child B criptogenic chirosis with ascites. He is more prone to

METASTATİC PAPİLLARY THYROİD

Berna İmge Aydoğan, Mustafa Şahin and Sevim Güllü

Figure 1a. Lung X-Ray: Trachea shifted to right

Figure 1b. Continued.

Figure 1b. Neck CT: left calcification mass; 4 cm metastatic.

Figure 1c. Thorax CT revealed lymphadenopathies greater than 3 cm located in

Figure 1d. Posttherapy Scan.

We recommend patient to have surgery for mediastinal lesions with thorax

Şule Canlar and Asena Canpolat

A 32 year-old woman presented with galactorrhea and menstrual

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