The Endocrine System

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Tulus Panuwun, dr, MS, SpPA.

Department of Pathology
Airlangga University

I. Pituitary
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Hyperpituitarism and pituitary adenomas

Prolactinomas
Growth hormone (somatotroph cell) adenomas
Corticotroph cell adenomas
Other anterior pituitary neoplasms

Hypopituitarism
Posterior pituitary syndromes

II.Thyroid

Hyperthyroidism
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Hypothyroidism
Graves disease
Diffuse nontoxic goiter and multinodular goiter
Thyroiditis

Chronic lymphocytic (Hasmhimoto) thyroiditis

Subacute granulomatous (de Quervain) thyroiditis
Subacute lymphocytic thyroiditis
Other forms of thyroiditis

Neoplasms of the thyroid

Adenomas
Carcinomas

Papillary carcinoma
Follicular carcinoma
Medullary carcinoma
Anaplastic carcinoma

III. Parathyroid glands

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Hyperparathyroidism
Primary hyperparathyroidism
Secondary hyperparathyroidism

Hypoparathyroidism

IV. Adrenal cortex

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Adrenocortical hyperfunction (hyperadrenalism)

Hypercortisolism (cushing syndrome)
Hyperaldosteronism
Adrenogenital syndromes

Adrenal insufficiency

Chronic adrenocortical insufficiency (addison disease)

Acute adrenocortical insufficiency

Adrenocortical neoplasms

V. Adrenal medulla
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Pheochromocytoma
Neuroblastoma and other neuronal
neoplasms

VI. Multiple endocrine neoplasia

syndromes
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MEN type 1
MEN type 2
MEN 2A (sipple syndrome)
MEN 2B (william syndrome)

Figure 20-7

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Homeostasis in the hypothalamus-pituitarythyroid axis and mechanism of action of

thyroid hormones. Secretion of thyroid
hormones (T3 and T4 ) is controlled by
trophic factors secreted by both the
hypothalamus and the anterior pituitary.
Decreased levels of T3 and T4 stimulate the
release of thyrotropin-releasing hormone
(TRH) from the hypothalamus and thyroidstimulating hormone (TSH) from the anterior
pituitary, causing T3 and T4 levels to rise.
Elevated T3 and T4 levels, in turn, suppress
the secretion of both TRH and TSH. This
relationship is termed a negative-feedback
loop. TSH binds to the TSH receptor on the
thyroid follicular epithelium, which causes
activation of G proteins, and cyclic AMP
(cAMP)-mediated synthesis and release of
thyroid hormones (T3 and T4). In the
periphery, T3 and T4 interact with the thyroid
hormone receptor (TR) to form a hormonereceptor complex that
translocates to the nucleus and binds to socalled thyroid response elements (TREs) on
target genes initiating transcription.

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Disturb activity of endocrine system

Impaired synthesis / release
Abnormal interaction hormone with target
Abnormal responses of target organ

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Endocrine diseases can broadly classified

Underproduction or overproduction
Development of mass lesions

Pituitary
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Symptoms of pituitary disease can be

divided :
Hyperpituitarism
Hypopituitarism
Local mass effects

 Fig 20 - 2

I. Pituitary

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Photomicrograph of normal pituitary. The gland is populated by several distinct

cell populations containing a variety of stimulating (trophic) hormones. B, Each of
the hormones has different staining characteristics, resulting in a mixture of cell
types in routine histologic preparations. Immunostain for human growth hormone.

 Figure 20 - 1

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Hormones released by the anterior pituitary. The adenohypophysis (anterior pituitary) releases five
hormones that are in turn under the control of various stimulatory and inhibitory hypothalamic releasing
factors. TSH, thyroid-stimulating hormone (thyrotropin); PRL, prolactin; ACTH, adrenocorticotrophic hormone
corticotropin); GH, growth hormone (somatotropin); FSH, follicle-stimulating hormone; LH, luteinizing
hormone. The stimulatory releasing factors are TRH (thyrotropin-releasing factor), CRH (corticotropinreleasing factor), GHRH (growth hormone-releasing factor), GnRH (gonadotropin-releasing factor). The
inhibitory hypothalamic influences are comprised of PIF (prolactin inhibitory factor or dopamine) and growth
hormone inhibitory factor (GIH or somatostatin).

Hyperpituitarism and pituitary

adenomas
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In most cases, excess production of

underpituitary hormones is caused by the
presence of an adenoma

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Morphology
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Fig 20 - 4

Pituitary adenoma. This

massive, nonfunctional
adenoma has grown far
beyond the confines of the
sella turcica and has
distorted the overlying brain.
Nonfunctional
adenomas tend to be larger
at the time of diagnosis than
those that secrete a
hormone.

Prolactinomas
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Pituitary adenoma
Hyperprolactinemia causes :

Amenorrhea
Galactorrhea
Loss of libido
Infertility

Tx : Bromocriptine

Growth hormone (somatotroph cell)

adenomas
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40 % : mutation GNAS1 gene / chromosome 20q13 G

protein cAMP
Prepubertal children gigantism
Adult acromegaly
Other growth hormon excess :
-abnormal glucose tolerance
-hypertension
-arthritis
-osteoporoses
-congestive heart failure

Corticotroph cell adenomas

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Positive periodic acid-SchiffACTH

Cushing syndromeC disease
Tx of C.syndrome with removal adrenal
Nelson syndromeMSH hyp.pigmen

Other Anterior Pituitary Neoplasms

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Null cell adenomas20 % mass effect

hypopituitarism
Gonadotroph adenomas10-15%
Thyrotrophadenomas1%
Pituitary carcinomasrare

Hypopituitarism
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75% or more pituitary loss

Result of : - non secretory adenoma apoplexy
- ischemic necrosisSheehan
- ablation surgery / radiation
- inflammation : sarcoidosis,tbc,
trauma,metastatic

Empty sella syndrome : obese womenmulti

pregnancyprolactine

Fig.20-6

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Ultrastructural features of prolactinomas. A, Electron micrograph of a sparsely

granulated prolactinoma. The tumor cells contain abundant granular endoplasmic
reticulum (indicative of active protein synthesis) and small numbers of secretory
granules (6000X). B, Electron micrograph of densely granulated growth hormonesecreting adenoma. The tumor cells are filled with large, membrane-bound
secretory granules (6000X). (Courtesy of Dr. Eva Horvath, St. Michael's Hospital,
Toronto, Ontario, Canada.)

Posterior Pituitary Syndromes

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Composed of : - glial (pituicyte)

- axonal hypothalamus
Two peptides : - ADH diabetes insipidus
- Oxytocinuterus/mamma
Oncotic pressure
left atrial distention
ADH
exercise
emotional

Thyroid
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Evagination epithel pharynx

Follicle of cuboid-columnar cell
TSHthyroglubulinT4/T3Tissuecatabolism CH/LIPID +synthesis protein
C cellcalcitonin

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Fig 20 - 3
The mechanism of G-protein
mutations in endocrine neoplasia.
Mutations in the G-protein-signaling
pathway are seen in a variety of
endocrine neoplasms, including
pituitary, thyroid, and parathyroid
adenomas. G-proteins play a
critical role in signal transduction,
transmitting signals from cellsurface receptors (GHRH, TSH, or
PTH receptor) to intracellular
effectors (e.g., adenyl cyclase),
which then generate second
messengers (cAMP).

Hyperthyroidism
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T3, T4
Clinical manifestation

Constitutional symptoms: skin/heat intolerance/sympathetic-hypermetabolism

Gastrointestinal:motility/malabsorption/di-arrhea
Cardiac:palpitation/tachycardia
Neuromuscular:nervous/tremor/irritability
Ocular:sympatheticstaring gaze/lid lag
Thyroid storm:in Graves disease
Apathetic hyperthyriodism

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Fig.20-8
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A patient with hyperthyroidism. A wide-eyed, staring gaze, caused by

overactivity of the sympathetic nervous system, is one of the features
of this disorder. In Graves
disease, one of the most important causes of hyperthyroidism,
accumulation of loose connective tissue behind the eyeballs also adds
to the protuberant appearance of the eyes.

Hypothyroidism
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Clinical manifestation of
hypothyroidism
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Cretinism infancy/childhood-endemic
-inborn
*Skeletal/CNS/Short stature/Coarse facial
/Protruding tongue/Umbilical hernia
Myxedemachildren/adult
*Apathy/Cold intolerant/Obese/Constipation/Pericardial effusions
ScreeningTSH

Graves Disease
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Triad Manifestation :
-ThyrotoxicosisStruma
-Ophthalmopathy
-Dermopathy
20-40 year old/women 7x/HLA-DR3

Pathogenesis of Graves
Autoimmune disorder
-TSH Receptor AbTSI/TGI/TBII
-Thyroid peroxisomes Ab
-Thyroglobulin Ab
CD4+helper T cellBcellAntibody
Thyrotropin receptorhelper T cellinterferon-/tumor necrosis factor
HLA class II/T cellThyroid AgT cell
HLA DR3 dan CTLA 4Helper T cell

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Infiltrative Ophthalmopathy
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Orbital FibroblastTSH receptor

Anti TSH rec.Ab.FibroblastAdipocyte/
glycosaminoglycansexophthalmos

Morphology

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Hyperplasia , hypertrophy .
Smooth , soft , capsule intact .
Epithel : tall,columnar,crowded,papillae,
pale colloid,scalloped margins.
Lymphoid infiltrate,germinal centers .
Orbit : edematous,lymphocyte,fibrosis.
Dermis : thickening,lymphocyte.

Fig 20-12
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Diffusely hyperplastic thyroid in a case of Graves disease. The follicles are

lined by tall, columnar epithelium. The crowded, enlarged epithelial cells
project into the lumens of the follicles. These cells actively resorb the colloid in
the centers of the follicles, resulting in the scalloped appearance of the edges
of the colloid.

Diffuse Nontoxic Goiter and

Multinodular Goiter
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Endemic ( 10 % more ), Non endemic

Impaired synthesis : iodine deficiency
TSH rise
Female is common , puberty/young adult

Morphology
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TSHhypertrophy , hyperplasiacrowded
columnarcolloid goiter
Diffuse/symmetriccrowded columnar cell
Colloid goiterflattened/cuboidal cell,colloid rich
Multinodularmore nodulebrown,fibrosis,hemorrhage,calcification,
cystic change

Fig . 20-13

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Nodular goiter. The gland is coarsely nodular and contains areas of fibrosis and
cystic change.

Thyroiditis
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Chronic lymphocytic thyroiditis

(Hashimoto)
Subacut granulomatous thyroiditis
(de Quervain)
Subacut lymphocytic thyroiditis

Chronic Lymphocytic (Hashimoto)

Thyroiditis
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Cause of hypothyroidism
Autoimmune inflammatory
Related case : SLE , Rheumatoid arthritis
Most prevalent : 45-65 Y , female 10-20 x
Paintless , sometime hashitoxicosis
Increased riskNHL B cell

Fig.20-9

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Pathogenesis of Hashimoto thyroiditis. Three proposed models for mechanism of

thyrocyte destruction in Hashimoto disease. Sensitization of autoreactive CD4+ T
cells to thyroid antigens appears to be the initiating event for all three mechanisms
of thyroid cell death. See the text for details.

Pathogenesis
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CD4+TcellCD8+c.toxicTcellParenchym
Bcellinhib.antiTSHrec.AbHypothyroid
Antithyroglob./ Antithyroid peroxidase
Ab.destruction
GeneticHLA DR3 , DR5

Fig.20-10

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Hashimoto thyroiditis. The thyroid parenchyma contains a dense lymphocytic infiltrate

with germinal centers. Residual thyroid follicles lined by deeply eosinophilic Hrthle cells
are also seen.

Morphology
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Diffuse,symmetric,asymmetric,capsule
intact
Cut surfacepale,gray-tan,firm,friable
Microscopiclymphocyte,plasma cell,germinal center,atrophic follicle,Hurthle/oxyphil cell

Subacute Granulomatous (de

Quervain) Thyroiditis
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30-50 Year.; More in women.; Suggesting

viral
Acute.; Neck pain.;Fever.;Malaise.;
Thyroid enlargement.;Self limited ,6-8 wks.

Morphology
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Uni/bilaterally.;Firm.;Intact capsule
Disruption of follicles.;PMN infiltrate,
lymphocyte,plasma cell,macrophage.;
giant cell.;fibrosis

Fig.20-11
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Subacute thyroiditis. The thyroid parenchyma contains a chronic inflammatory

infiltrate with a multinucleate giant cell (above left) and a colloid follicle (bottom
right).

Subacute Lymphocytic Thyroiditis

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Silent/painles .; postpartum .; autoimmune

Women .; middle age .; T3-T4 excess
Lymphocytic infiltration.; germinal center

Riedel thyroiditis
Fibrosis , contiguous neck structure
Susp. autoimmune

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Palpation thyroiditis
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Multifocal follicular disruptionchronic

inflammatory + giant cell

Neoplasms of The Thyroid

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Solitary nodules >< multiple nodules

Solid nodule >< cystic nodules
Younger patients >< older patients
Males >< females
Cold nodules >< hot nodules

Adenomas
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Follicular epitheliumFollicular Adenomas

Painless nodules.; difficulty in swallowing
Toxic adenomashot nodules in scan
USG , FNA preoperative evaluation

Morphology
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Solitary compresses adjacent

Well-formed capsule
Uniform follicles.; oxyphil/Hurthle cell

Fig. 20-14
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Follicular adenoma of the thyroid. A solitary, well-circumscribed nodule is seen.

Fig. 20-15
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Follicular adenoma. The photomicrograph shows well-differentiated

follicles resembling normal thyroid parenchyma.

Fig. 20-20
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Capsular integrity in follicular neoplasms. Evaluating the integrity of the capsule is critical in
distinguishing follicular adenomas from follicular carcinomas. In adenomas (A), a fibrous
capsule, usually thin but occasionally more prominent, circumferentially surrounds the
neoplastic follicles and no capsular invasion is seen (arrowheads); compressed normal thyroid
parenchyma is usually present external to the capsule (top of the panel). In contrast, follicular
carcinomas demonstrate capsular invasion (B, arrow-heads) that may be minimal, as in this
case, or widespread with extension into local structures of the neck. The presence of vascular
invasion is another feature of follicular carcinomas.

Fig. 20-16

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Hrthle cell tumor. A high-power view showing that the tumor is

composed of cells with abundant eosinophilic cytoplasm and small
regular nuclei. (Courtesy of Dr. Mary Sunday, Brigham and Women's
Hospital, Boston, MA.)

Toxic Adenoma
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Adenomasnonfunctional
Toxic adenomasindependent of TSH
Autonomous nodulesmutations
- TSH receptor gene / GNAS 1

Carcinomas
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Papillary Ca.
Follicular Ca.
Medullary Ca.
Anaplastic Ca.

75-85 %
10-20 %

5 %
<5 %

Papillary Carcinoma
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Occur at any age

Ionizing radiation
Nonfunctional
Cervical metastasis > , Lung metastasis <
10 year survival 85 %

Pathogenesis
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Genetic factors
Ionizing radiation
Preexisting thyroid disease

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Morphology
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Solitary / multifocal
Encapsulated / infiltrative
Fibrosis / calcification / cystic
Cut surfacegranular , papillary
Nuclear featuresoptically cleargroundglass / orphan annie
intranuclear inclusions
Psammoma bodies

Fig.20-17
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Papillary carcinoma of the thyroid. A, The macroscopic appearance of a papillary carcinoma with
grossly discernible papillary structures. This particular example contains well-formed papillae (B),
lined by cells with characteristic empty-appearing nuclei, sometimes termed "Orphan Annie eye"
nuclei (C). D, Cells obtained by fine-needle aspiration of a papillary carcinoma. Characteristic
intranuclear inclusions are visible in some of the aspirated cells.

Follicular Carcinoma
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Middle adultiodine deffnodular goiter

Solitary cold / hot nodule
Bloodstreamlungs,bone,liverRx.activ
Txsurgical
TSH

Morphology
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Circumscribed / infiltrative
Demarcated,minimal invasionadenomas
Small follicles , Hurthle variants
Invasion capsular / vascular
Molecular abnormalityPAX8-PPAR 1

Fig. 20-18
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Follicular carcinoma. Cut surface of a follicular carcinoma with

substantial replacement of the lobe of the thyroid. The tumor has a
light-tan appearance and contains small foci of hemorrhage.

Fig. 20-19

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Follicular carcinoma of the thyroid. A few of the glandular lumens contain

recognizable colloid.

Medullary Carcinoma
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NeuroendocrineC cell
ElaborateCalcitonin , Ca.embryonic Ag,
Somatostatin ,Serotonin , VIP.
80% sporadically5th-6th
20% familialMEN synd.2A/2Byounger
non MEN
Dysphagia , hoarseness , diarrhea ,

Fig. 20-21
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Medullary carcinoma of thyroid. These tumors typically show a solid pattern of

growth and do not have connective tissue capsules. (Courtesy of Dr. Joseph
Corson, Brigham and Women's Hospital, Boston, MA.)

Fig. 20-22

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Medullary carcinoma of the thyroid. These tumors typically contain

amyloid, visible here as homogeneous extracellular material, derived
from calcitonin molecules secreted by the neoplastic cells.

Fig. 20-23

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Electron micrograph of medullary thyroid carcinoma. These cells contain

membrane-bound secretory granules that are the sites of storage of
calcitonin and other peptides (30,000X).

Anaplastic Carcinoma
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Elderly age , endemic goiter

Grow rapidly , metastases , 1 year SR

Morphology
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Bulky mass
Anaplastic cells-giant cells , pleomorph
-spindle cells , sarcoma
-squamoid

Parathyroid Glands
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Pharyngeal pouches Ca+PTH

PTH : -Osteoclasts
-Reabsorption Ca in tubular
-Vit D active dehydroxy in kidneys
-Phosphate excretion in urine
-Calcium absorption in GI tract

Primary Hyperparathyroidism
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Adenoma >>/ hyperplasia / Carcinoma<<

Adult > ; Women >
PTH : - bone resorption, renal disease, hypercalcemia

Clinical signs :
- GI constipation,nausea,peptic ulcers,pancreatitis,gallstones
- CNS depression,lethargy,seizures
- Neuromuscularhypotonia,weakness
- Polyuria , polydipsia

Morphology
80-90%adenoma
, 0,5-5
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grm
Tan nodule ,soft , well-circumscribed
Chief cell >>uniform,polygonal,central nuclei

Oxyphil cell <cell with granular cytoplasm

10-20%hyperplasiamultiglandular
Carcinoma5 grm >chief cells
Morphologic changes in other organs :
- skeletalosteoclastsosteoblast>osteitis fibrosa cys
tica brown tumors
- kidney nephrolithiasis
- other site stomach,lungs,myocardium,blood vessels

Fig. 20-24
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Parathyroid adenomas are almost always solitary lesions. Technetium-99msestamibi radionuclide scan demonstrates an area of increased uptake
corresponding to the left inferior parathyroid gland (arrow). This patient had a
parathyroid adenoma. Preoperative scintigraphy is useful in localizing and
distinguishing adenomas from parathyroid hyperplasia, where more than one
gland would demonstrate increased uptake.

Fig 20-25

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Parathyroid adenoma. A, Solitary chief cell parathyroid adenoma (lowpower photomicrograph) revealing clear delineation from the residual
gland below. B, High-power detail of a chief cell parathyroid adenoma.
There is some slight variation in nuclear size but no anaplasia and
some slight tendency to follicular formation.

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Fig. 20-26

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Cardinal features of hyperparathyroidism. With routine

evaluation of calcium levels in most patients, primary
hyperparathyroidism is often detected at a clinically silent
stage. Hypercalcemia from any other cause can also give
rise to the same symptoms.

Secondary Hyperparathyroidism
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Renal failurephosphate excretion<<

Calcium<< parathyroidPTH >>
Clinical features :
-renal-osteodystrophy
-vascularischemic of skincalciphylaxis

Morphology
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Hyperplasticchief cell, water-clear cell

Bone changes , metastasis calcification

Hypoparathyroidism
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Surgical ablation
Congenital absence
Autoimmune : parathyroid,thyroid,pancreas,adrenals
Clinical manifestation :hypoPTHCa.<<
-neuromuscular: tingling,spasms,tetany
-cardiac arrhythmias
-cranial pressure>> , seizures
-cataracts, calcification basal ganglia

Adrenal Cortex
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Hyperfunction / Hypofunction
Mass lesion : - nonfunctional
- hyperfunction

Adrenocortical Hyperfunction
(Hyperadrenalism)
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Steroid hormon :
1. Glucocorticoids cortisol
2. Mineralocorticoidsaldosteron
3. Adrenocortical
androgen

Hypercortisolism
( Cushing Syndrome )
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1. Hypothalamic-pituitary ( Cushing
disease )
2. Adrenocortical hyperplasia/neoplasia
3. Ectopic ACTH nonendocrine
4. Iatrogenic / exogenous

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Fig 20-20 buku lama

Figure 24-43 A schematic representation of the various forms of

Cushing syndrome, illustrating the three endogenous forms as well
as the more common exogenous (iatrogenic) form. ACTH,
adrenocorticotropic hormone.

Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 3 August 2009 05:23 AM)
2007 Elsevier

1.Cushing Disease
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50 % of Cushing syndrome
Third-fourth of life , women 3x
Pituitary microadenomaACTH
Corticotroph cell hyperplasiaACTH
HypothalamusCRH

2.Primary adrenocortical neoplasia

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25-30 %
Adrenal cushing syndrome / ACTH indepent Cushing
syndrome
Most casesunilateraladenoma >>
carcinoma<<
Primary bilateral hyperplasia :
macronodule >3 mm
micronodule <3 mmprimary pigmented nodular
adrenocortical disease

3.Ectopic ACTH Non Endocrine

Neoplasia
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Small cell carcinoma of the lung

Carcinoid tumors
Medullary carcinoma of the thyroid
Islet cell tumor of the pancreas

Clinical Features of Cushing

Syndrome
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Hypertension , Weight gain , Truncal obesity ,

moon facies , buffalo hump
Atrophy of fast-twitch myofibers
muscle mass << , weakness
Diabetes mellitus : hyperglycemia , glucosuria , polydipsia
Skin : thin , fragile , bruised , striae
Bone : osteoporosis
Hirsutism , menstrual abnormalities , pigmentation

Morphology
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Exogenous : atrophy bilateral of cortices

Endogenous : hyperplasia
bilateralthickened , yellow 25-40 grm
Adrenocortical neoplasm : lipid rich cell
encapsulated,expansile,yellow,30 grm

Pituitary Crooke hyaline change

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Fig 20-21 buku lama

Figure 24-47 Nodular hyperplasia of the adrenal contrasted with

normal adrenal gland. In cross-section, the adrenal cortex is yellow,
thickened, and multinodular, owing to hypertrophy and hyperplasia
of the lipid-rich zonae fasciculata and reticularis.

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Fig 20-22
buku lama

Figure 24-45 Adrenal cortical adenoma. The adenoma is

distinguished from nodular hyperplasia by its solitary, circumscribed
nature. The functional status of an adrenal cortical adenoma cannot
be predicted from its gross or microscopic appearance.

Hyperaldosteronism
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Sodium retention , potassium excretion

hypertension , hypokalemia
Primaryautonomousrenin angiotensin <
neoplasm , hyperpasia
Secondaryactivation renin-angiotensin>
*renal perfusion <<
*arterial hypovolemia,edema
Conn syndromeneoplasmmiddle adult , female
2xTx. : surgical
Primary hyperplasiachildren, young adultsTx. :
spironolacton

Morphology
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80 % primaryaldosterone secreting

adenomaConn syndrome
Solitary , < 2 cm , encapsulated
Hyperplasiaproliferation zona glomerulosa

Adrenogenital Syndromes

Androgen excess : 1.gonadal, 2.adrenal

0010
ACTHadrenalandrogen
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21 hydroxylase deficiencycong.adrenal.hyperplasia.( 95 %)

Congenital adrenal hyperplasia

chrom.6 mutation21 hydroxylase gene

Clinical symptoms : perianal / childhood / adulthood

Androgenic>>in womenmasculinizationclitoral
hypertrophy/pseudohermaphroditism/oligomenorrhoe/ hersutism/acne
in malesexternal genitalia enlarge/precocious
puberty/oligospermia

17 hydroxylase deficiency :
Androgenic << in femalesecondary sexual <
in malespseudohermaphrodite

11 hydroxylase deficiency
Mineralocorticoid>sodium retension / hypertension

Adrenal insufficiency
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Primary hypoadrenalism :
1. Addison disease
2. Acute primary adrenal insufficiency
Secondary hypoadrenalism :
1. Sheehan syndrome
2. Adenoma non functional
3. Lesion of hypothalamus / suprasellar

Chronic Adrenocortical
Insufficiency ( Addison Disease )
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1855 Thomas Addison

Autoimmune adrenalitis (75-90%)
1. restricted to the adrenal
2. polyglandular syndrome : a.type 1 :autosomal recessive
b.type 2 : HLA-B8;HLA-DR3;HLA-DQ5
Infections : - tuberculosis ; - fungal
Metastatic neoplasms

Weakness,fatigability,anorexia,nausea,vomiting,weight
loss,diarrhea,hyperpigmentation.
Hyperkalemia,hyponatremia,volume depletion,hypotention.
Hypoglycemia.

Morphology
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Secondary hypoadrenalism :
-Adrenal are small,flattened,yellow
-Cell atrophyzonae fasciculata/reticularis
Primary autoimmune adrenalitis :
-Shrunken glands
-Scattered cell in connective tissue
Tuberculosis , fungal :
-Granulomatous infection

Tabel 20-8.
CAUSES OF ADRENAL INSUFFICIENCY
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Acute

Waterhouse-Friderichsen syndrome
Sudden withdrawal of long-term corticosteroid therapy
Stress in patients with underlying chronic adrenal insufficiency

Chronic
Major Contributors
Autoimmune adrenalitis
Tuberculosis
Acquired immunodeficiency syndrome
Metastatic disease

Minor Contributors
Systeminc amyloidosis
Fungal infection
Hemochromatosis
Sarcoidosis

Acute Adrenocortical Insufficiency

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Chronic adrenocortical
insufficiencystressacute state
Tx.anticoagulantacute state
Waterhouse-Friderichsen syndrome of Neisseria meningitis

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Fig 20-24 buku lama

Figure 24-50 Waterhouse-Friderichsen syndrome. At autopsy, the

adrenals were grossly hemorrhagic and shrunken; microscopically,
little residual cortical architecture is discernible.

Adrenocortical Neoplasms
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Adrenocortical neoplasm :
- hyperaldosteronism ; -Cushing syndrome
- non functional

Morphology
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Adrenocortical Adenoma :
-neoplams of functional state
-yellow to yellow-brown
-small , 1-2 cm
-normal adrenal cortex - atypic

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Fig 20-25 buku lama

Figure 24-46 Histologic features of an adrenal cortical adenoma.

The neoplastic cells are vacuolated because of the presence of
intracytoplasmic lipid. There is mild nuclear pleomorphism. Mitotic
activity and necrosis are not seen.

Morphology
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Adrenocortical Carcinomas :
-occur at any age
-some inherited : -Li-Fraumeni
-Beckwith-Wiedemann
Functional / non functional

Large , some is small

Cell like adenoma , bizarre , pleomorphic

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Figure 24-52 Adrenal carcinoma. The hemorrhagic and necrotic

tumor dwarfs the kidney and compresses the upper pole.

Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 3 August 2009 08:37 AM)
2007 Elsevier

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Figure 24-53 Adrenal carcinoma (A) revealing marked anaplasia,

contrasted with normal cortical cells (B).

Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 3 August 2009 08:37 AM)
2007 Elsevier

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Figure 24-53 Adrenal carcinoma (A) revealing marked anaplasia,

contrasted with normal cortical cells (B).

Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 3 August 2009 08:37 AM)
2007 Elsevier

Adrenal Medulla
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Neural crestchromaffin cell

catecholamines
Tumorsneuronal-neuroblastomas
-mature ganglion cell
pheochromocytomas

Pheochromocytoma
Chromaffin cell catecholamineshypertension
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ACTH , Somatostatin
rule of 10s :
- 10% arise in one of familial syndromes
MEN2a,2b/von Hippel-Lindau/Sturge-Weber

- 10% extra-adrenal : carotid body (paraganglioma)

- 10% bilateral , in familial up to 50%
- 10% biologically malignant
Hypertension,tachycardia,palpitation,headache,sweating,trem
or,apprehension
Abdomen/chest pain,nausea,vomiting

Morphology
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Small,circumscribedlarge,hemorrhagic,
several kilograms
Yellow-tan , hemorrhagic , necrotic , cystic
Polygonal-spindle chromaffine cell ,
cytoplasma granular , supporting cell , vascular network , Zellballen
Malignancymetastasis

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Fig 20-27 buku

lama

Figure 24-55 Pheochromocytoma. The tumor is enclosed within an

attenuated cortex and demonstrates areas of hemorrhage. The
comma-shaped residual adrenal is seen below.

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Fig 20-28 buku lama

Figure 24-56 Pheochromocytoma demonstrating characteristic nests of cells

("zellballen") with abundant cytoplasm. Granules containing catecholamine
are not visible in this preparation. It is not uncommon to find bizarre cells
even in pheochromocytomas that are biologically benign, and this criterion by
itself should not be used to diagnose malignancy.

Neuroblastoma
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Extracranial tumor of childhood

First 5 years
Sympathetic of brain ,abdomen

Multiple Endocrine Neoplasia

Syndromes
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Inherited diseases
MEN syndromes :- younger age
- multiple endocrine
- asymptomatichyperplasia
-aggressive

MEN type 1
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Autosomal dominant
Tumor suppresor gene11q13
Parathyroid 95 %hyperplasia
Pancreas 45 %functionalZollinger-Ellison

Hypoglycemia
Pituitary 30%prolactinomas
somatotrophinoma

MEN type 2
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RET protooncogene mutations10q11.2

Autosomal dominant

MEN 2a ( Sipple Syndroma)

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1. Thyroid : Medullary Carcinoma

2. Adrenal : Pheochromocytomas
3. Parathyroid : Hyperplasia

MEN 2b (William Syndrome)

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Do not develop primary hyperparathyroid

Develop extraendocrine :
-ganglioneuromas of mucosal
-marfanoid habitus