BY MICHAEL TESFAYE (MD, Internist)

 Introduction
 Anatomy
 Regulation
 Metabolism
 Cushing syndrome
 Mineralocorticoid excess
 Adrenal insufficiency
 Pheochromocytoma
 The adrenal cortex produces three classes of corticosteroid
hormones:

 glucocorticoids (e.g., cortisol),

 mineralocorticoids (e.g., aldosterone),and
 adrenal androgen precursors (e.g., dehydroepiandrosterone
[DHEA])
 The normal adrenal glands weigh 6–11 g each. They are
located above the kidneys and have their own blood supply
 Production of glucocorticoids and adrenal
androgens is under the control of the
hypothalamic-pituitary-adrenal (HPA) axis

 Mineralocorticoids are regulated by the

reninangiotensin-aldosterone (RAA)
system

 Diagnostic tests assessing the HPA axis

make use of the fact that it is regulated by
negative feedback
 Reflects a constellation of clinical features that result from
chronic exposure to excess glucocorticoids of any etiology.

 Can be ACTH-dependent or ACTH-independent as well as

iatrogenic

 The term Cushing’s disease refers specifically to Cushing’s

syndrome caused by a pituitary corticotrope adenoma.
 Cushing’s syndrome is generally considered a rare disease.

 It occurs with an incidence of 1–2 per 100,000 population per

year.
 The majority of clinical signs and symptoms observed in Cushing’s
syndrome are relatively nonspecific and include features such as
obesity, diabetes, diastolic hypertension, hirsutism, and depression

 A diagnosis of Cushing’s should be considered when several

clinical features are found in the same patient, in particular when
more specific features are found.

 These include fragility of the skin, with easy bruising and broad
(>1 cm), purplish striae, and signs of proximal myopathy
 In ectopic ACTH syndrome, hyperpigmentation of the knuckles,
scars, or skin areas exposed to increased friction can be
observed
 ADRENAL ADENOMA
 Unilateral laparascopic adrenalectomy

 ADRENAL CARCINOMA
 Poor PX (most die in 2 yrs); tumor removal, Mitotane

 CUSHING’S DISEASE
 Previously: bilat adrenalectomy(MR 4% & Nelson
syndrome), pitutary irradiation (Now used for failures)
 Currently: transphenoidal hypophysectomy (cure 80-90%
micro.)

 ECTOPIC ACTH SYNDROME

 Removal of tumor-curative; less favorable in SC lung Ca;
unidentified focus: bilat. Adrenal. & ffup
 Metyrapone (11β hydroxylase inhibitor)
 Aminoglutethimide (blocks earlier enzymes)
 Trilostane (more effective for adenomas, not cushing ds)
 Ketoconazole (400-800mg/d; blocks many cyt P450 depend.
enzymes)

 Mitotane (o,p`-DDD; adrenolytic, usually used in Ca; Toxic)

 Without Rx – 50% die within 5 yrs (CVD)
 Some steroid withdrawal Sxs  transient repl.
 C/f disappear 2-12 mos; HTN & DM improve, but
may not dissapear
 Ostopenia – 2yrs; Sexual F’n- 6 months
 In studies systematically screening all patients with
hypertension, a much higher prevalence is now recognized,
ranging from 5 to 12%.

 The prevalence is higher when patients are preselected for

hypokalemic hypertension.
 Patients with hypertension should be screened if
 Drug resistance,
 hypokalemia,
 an adrenal mass, or
 onset of disease before the age of 40 years
 The prevalence of well-documented, permanent adrenal
insufficiency is 5 in 10,000 in the general population.
 Adrenal insufficiency arising from suppression of the HPA axis
as
a consequence of exogenous glucocorticoid treatment is much
more
common, occurring in 0.5–2% of the population in developed
countries.

 The most obvious feature that differentiates primary from
secondary AI is skin pigmentation
 in sun-exposed areas, recent scars, axillae, nipples, creases, pressure
points, and mucous membranes (buccal, vaginal, vulval, anal).

 The cause of the pigmentation is thought to reflect

increased stimulation of the MC1R by ACTH itself.

 In autoimmune Addison's disease, there may be associated

vitiligo
 A Pigmentation in a
patient with Addison's
disease before (B)
and after (C)
treatment

 D, Similar changes in
a 60-year-old man
with tuberculous
Addison's disease
before (left) and after
(right) corticosteroid
therapy.

 E, Buccal pigmentation
 The C/Fs relate to the rate of onset and the severity of adrenal
deficiency.

 A medical emergency manifesting as hypotension and acute circulatory

failure typically resistant to catecholamine and IVF resuscitation

 Anorexia may be an early feature; it progresses to N & V, diarrhea,

sometimes, abdominal pain. Fever and hypoglycemia may occur.

 Difficult to diagnose, but evidence of occult hemorrhage (rapidly

falling hemoglobin), progressive hyperkalemia, and shock
should alert the clinician to the diagnosis.
 In a previously undiagnosed
with1ryAI who has serious
infection or other acute,
major stress.

 with known 1ry AI who does

not take more glucocorticoid
during an infection

 In patients who are abruptly

withdrawn from doses of
glucocorticoid that 2ry AI.
 The patient may present with vague features of chronic AI—weakness,
tiredness, weight loss, muscle cramps, postural hypotension …

 Salt craving ,low-grade fever may be present.

 Adrenal androgen secretion is lost, more apparent in women - loss of

axillary and pubic hair ,dry and itchy skin.

 Psychiatric symptoms in long-standing cases - memory impairment,

depression, and psychosis.

 Tiredness is often profound & Low quality-of-life measures

 In secondary AI due to hypopituitarism, the presentation may relate to
deficiency of other hormones -LH/FSH (infertility, amenorrhea, poor
libido) and TSH (weight gain, cold intolerance).

 Fasting hypoglycemia occurs because of loss of the gluconeogenic

effects of cortisol.

 Rare in adults unless concomitant alcohol abuse or GH deficiency.

 hypoglycemia is a common feature in childhood.

 In addition, patients with ACTH deficiency present with malaise, weight

loss, and other features of chronic adrenal insufficiency.

 Rarely, the presentation is more acute in patients with pituitary apoplexy.

 Emergency precautions
- Medic Alert bracelet or necklace
- Emergency Medical Information Card
-Patient education for self medication

 Glucocorticoid replacement therapy

- Hydrocortisone - 15–25 mg in two to three divided doses
- 2/3 Am & 1/3 Pm
 Long acting Glucocorticoids:
- Dexamethasone - 0.25 – 0.5 mg/day

- prednisolone - 5 -7.5 mg/day

 Minealocorticoid replacement

- Fluidricortisone - 0.1 mg/day

 Androgen replacement

- DHEA – 25 – 50 mg/day for 3 -6 months

 Evaluation & Rx of other hormone deficiencies

 Pheochromocytomas and paragangliomas are catecholamine-
producing tumors derived from the sympathetic or
parasympathetic nervous system.
 Pheochromocytoma is estimated to occur in 2–8 of 1 million
persons
per year
 ∼0.1% of hypertensive patients harbor a pheochromocytoma.
 The mean age at diagnosis is ∼40 years, although the tumors
can
occur from early childhood until late in life.
 The classic “rule of tens” for pheochromocytomas states that
∼10% are bilateral, 10% are extraadrenal, and 10% are
malignant.
 The World Health Organization (WHO) restricts the term
pheochromocytoma to adrenal tumors and
applies the term paraganglioma to tumors at all other sites
 The etiology of sporadic pheochromocytoma is unknown
 25–33% of patients have an inherited condition, including
germ-line mutations in the classically recognized RET, VHL, NF1,
SDHB, SDHC, and SDHD genes
 so variable
 episodes of palpitation, headache, and profuse sweating are
typical
 The dominant sign is hypertension. Classically, patients have
episodic hypertension
 Catecholamine crises can lead to heart failure, pulmonary edema,
arrhythmias, and intracranial hemorrhage.
 paroxysms generally last <1 h and may be precipitated by surgery,
positional changes, exercise, pregnancy, urination (particularly
with bladder pheochromocytomas), and various medications
 Complete tumor removal
 Preoperative preparation of the patient is important.
 Classically, blood pressure has been controlled by α-adrenergic
blockers
 phenoxybenzamine, 0.5–4 mg/kg of body weight
 Minimally invasive techniques (laparoscopy or
retroperitoneoscopy) have become the standard approaches in
pheochromocytoma surgery.
 Synthesis and release of thyroid hormone is controlled by TSH
released from the anterior pituitary
 TSH is controlled by the release of thyroid releasing hormone
(TRH) from the hypothalmus and a negative feedback loop to
the pituitary
 Thyroid hormone production is dependent on adequate iodine
intake
 Thyroid hormone is reversible bound to various proteins
including thyronine-binding globulin (TBG)
 Free unbound portions are biologically active
 T4 is the predominant circulating hormone
 T4 is deiodinated to t3
 T3 is biologically more active than T4 but has a shorter half-life
 Occurs in in all ages
 Uncommon under the age of 15
 10 x’s more common in women (1/10,000)
 Graves disease is the most common etiology
 80% of cases in the U.S.
 Common in the 3rd and 4th decades
 Caused by autoimmune thyroid-stimulating
antibodies
 Associated with diffuse goiter, opthalmopathy, and
local dermopathy
 Toxic multinodular and toxic nodular goiters are the next most
common etiologies
 Usually occurs in older populations
 Commonly with previous history of goiter
 Often with milder symptoms of thyrotoxicosis
 Amiodarone-induced thyrotoxicosis (AIT)
 Amiodarone is iodine rich and may cause both hyper and
hypothyroidism
 Difficult to treat because of incomplete understanding of
mechanism
 Two major forms exists
 Type 1 occurs with a normal thyroid
 Type 2 occurs with a abnormal thyroid
 Tx. Varies based on the the type
 Hyperthyroidism resembles a state of increased adrenergic
activity despite a normal or low serum cortisol level
 Classic complaints include heat intolerance, palpitations,
weight loss, sweating, nervousness, and fatigue
Symptoms Signs
Weakness Goiter/thyroid burit

Fatigue Hyperkinesis

Heat intolerance Opthalmopathy

Nervousness Lid retraction/stare

Increased sweating Lid lag

Tremors Tremor

Palpitations Warm moist skin

Weight loss Hyperreflexia

Hyperdefication Tachycardia/arrhythmia

Dyspnea Systolic hypertension

Menstrual abnormalities Widened pulse pressure

 Confirmed by thyroid function test
 Elevated free T4 and Low TSH
 In some cases of graves disease T4 may be normal and TSH
decreased but the patient appears thyrotoxic
 T3 level should be done to rule out T3 toxicosis
 Hypothyroidism secondary to pituitary adenoma will have elevated
TSH levels
 Treatment
 Palliative treatment of mild hyperthyroidism is accomplished using
B-blockers
 Most commonly used is propanolol
 Treatment of Graves diseases include long-term use of antithyroid
medications, radioactive iodine, or subtotal thyroidectomy
 Type I AIT is treated with methimazole and potassium perchlorate
 Type II AIT is treated with glucocorticoids
 Treatment cont.
 Toxic multinodular goiter and solitary adenomas may be treated
with radioiodine therapy
 Thryoiditis is usually self limited and therapy is rarely needed
 A life threatening hypermetabolic state due to
hyperthyroidism
 Mortality rate is high (10-75%) despite treatment
 Usually occurs as a result of previously unrecognized
or poorly treated hyperthyroidism
 Thyroid hormone levels do not help to differentiate
between uncomplicated hyperthyroidism and
thyroid storm
 Precipitants of Thyroid Storm

Infection Trauma

DKA MI

CVA PE

Surgery Withdrawal of thyroid

med
Iodine administration Palpation of thyroid
gland
Ingestion of thyroid Unknown etiology (20-
hormone 25%)
 Clinical features
 The most common signs are fever, tachycardia
out of proportion to the fever, altered mental status,
and diaphoresis
 Clues include a history of hyperthyroidism,
exophthalmoses, widened pulse pressure and a
palpable goiter
 Patients may present with signs of CHF
 Clinical features cont.
 Common GI symptoms include diarrhea and hyperdefication
 Apathetic thyrotoxicosis is a distinct presentation seen in the
elderly
 Characteristic symptoms include lethargy, slowed mentation, and
apathetic facies
 Goiter, weight loss , and proximal muscle weakness also present
 Diagnosis
 Thyroid storm is a clinical diagnosis based upon suspicion and
treated empirically
 Lab work is non specific and may include Leukocytosis,
hyperglycemia, elevated transaminase and elevated bilirubin
 Treatment
 Initial stabilization includes airway protection, oxygenation, fluids and
cardiac monitoring
 Treatment can then be divided into 5 areas:
 General supportive care
 Inhibition of thyroid hormone synthesis
 Retardation of thyroid hormone release
 Blockade of peripheral thyroid hormone effects
 Identification and treatment of precipitating events
 Drug Treatment of Thyroid Storm (table 216-6)
 Decrease de novo synthesis:
 Porpythiouracil 600-1000mg PO initially, followed by 200-250 mg q 4 hrs
 Methimazole 40 mg PO initial dose, then 25 mg PO q6h
 Prevent relases of hormone (after synthesis blockade intiated)
 Iodine Iaponoric acid (Telepaque) 1 gm IV q8h for the first 24 h, then
500 mg bid or Potassium iodide (SSKI) 5 drops PO q6h or Lugol
solution 8-10 drops PO q6h
 Lithuim 800-1200 mg PO every day
 Prevent peripheral effects:
 B-Blocker Propanolol (IV) titrate 1-2 mg q 5min prn (may need 240-480mg
PO q day) or Esmolol (IV) 500 mcg/kg IV bolus, then 50-200
mcg/kg per min maintenance
 Guanethidine 30-40 mg PO q 6 h
 Reserpine 2.5-5 mg IM q4-6h
 Other consideration:
 Corticosteroids Hydrocortisone 100 mg IV q 8 h or
dexamethosone 2 mg IV q 6 hr
 Antipyretics Cooling blanket
acteaminophen 650 mg PO q 4-6h
 Treatment cont
 Propranolol has the additional effects or blocking perpheral
conversion of T4-T3
 Avoid Salicylates because it may displace T4 from TBG
 If the patient continues to deteriorate despite appropriate
therapy circulating thyroid hormone may be removed by
plasma transfusion, plasmapheresis, charchoal
plasmaperfusion
 Remember you must not administer iodine until the
synthetic pathway has been blocked
 Disposition
 Admit to the ICU
 Occurs when there is insufficient hormone
production or secretion
 Occurs more frequently in women (0.6 to 5.9 %)
 The most common etiologies are
 Primary thyroid failure due to autoimmune diseases
(Hashimoto thyroiditis is the most common)
 Idiopathic causes
 Ablative therapy
 Iodine deficiency
 May be transient
 Pathophysiology is unclear but may be viral in nature
 Etiologies of Hypothyroidism
 Primary
 Autoimmune etiologies
 Hashimotos is the most common
 Idopathic
 Post ablation (surgical, radioiodine)
 Post external radiation
 Thryoiditis (subacute, silent, postpartum)
 Postpartum thyroiditis occurs within 3-6 months and occurs in 2- 16
% of women
 Self limited etiologies, often prededed by hyperthroid phase
 Infiltrative disease (lymphoma, sarcoid, amyloidosis,
Tuberculosis
 Congenital
 Etiologies of Hypothyroidism
 Post Partum
 Occurs 3-6 months post partum and occurs in 2-16% of
women
 Secondary (pituitary)
 Neoplasm
 Infiltrative Dz.
 Hemorrhage
 Tertiary (hypothalamic)
 Neoplasm
 Infiltrative Dz.
Etiologies of Hypothyroidism
 Drugs
 Amiodarone
 Occurs in 1-32% of patients
 Most likely due to the large amount of iodine released in the
metabolism of the drug which inhibits thyroid hormone
synthesis, release, and conversion of T4 to T3
 Lithium
 Acts similarly to iodine and inhibit thyroid hormone release
 Iodine (in patients with pre-existing autoimmune disease)
 Antithyroid medication
 Clinical Features
 The typical symptoms of hypothyroidism include fatigue,
weakness, cold intolerance, constipation, weight gain, and
deepening of voice.
 Cutaneous signs include dry, scaly, yellow skin, non-pitting,
waxy edema of the face and extremities (myxedema): and
thinning eyebrows
 Clinical Features cont.
 Cardiac findings include bradycardia, enlarged heart, and low-
voltage electrocardiogram
 Paresthesia, ataxia, and prolongation or DTR’s are characteristic
neurologic findings
 Symptoms and Signs or Hypothyroidism

Symptoms Signs
Fatigue Hoarseness
Weight Gain Hypothermia
Cold intolerance Periobital puffiness
Depression Delayed relaxation of ankle
jerks
Menstrual irregularities Loss of outer third of eyebrow
Constipation Cool, rough, dry skin
Joint Pain Nonpitting edema
Muscle cramps Bracycardia
Infertility Peripheral Neuropathy
 Treatment
 Most patient with uncomplicated symptomatic Hypothyroidism may
be referred to the primary physician for further evaluation and
initiation of treatment
 If hypothyroidism is due to a secondary etiology initiation of thyroid
hormone therapy may exacerbate preexisting adrenal insufficiency
 Myxedema is a rare life threatening decompensation of
hypothyroidism
 Usually in individuals with long-standing hypothyroidism
 Most often seen in the winter months
 More common in elderly women with underdiagnosed or
undertreated hypothyroidism
 Precipitating events include
 Infection
 CHF
 Trauma
 CVA
 Exposure to cold
 Drugs
 Sedatives
 Lithium
 Amiodarone
 In addition to the clinical features of hypothyroidism
patients may present with
 Hypothermia
 Altered mental status
 Coma, delusions, and psychosis (myxedema maddness)
 Hyponatremia
 Dilutional secondary to decreased free-water clearance
 Hypoglycemia
 Secondary to impaired gluconeogenesis
 Hypotension
 Bradycardia
 Respiratory Failure
 Secondary to decreased strength of respiratory muscle
 Hypercapnia and hypoxia is common
 Diagnosis
 Must have high clinical suspicion
 Commonly has Hx. Of hypothyroidism
 Delcine in function is usually insidious in onset
 Diagnosis cont
 Laboratory evaluation may reveal
 Anemia
 Hyponatremia
 Hypoglycemia
 ↑ Transaminases
 ↑ CPK
 ↑ LDH
 ↓Po2 and ↑PCo2 on ABG’s
 Diagnosis cont.
 EKG may reveal
 Sinus Bradycardia
 Prolonged QT interval
 Low voltage
 Flattened or inverted T waves
 Treatment
 Airway stabilization with adequate oxygenation and
ventilation or vital
 Cardiovascular status must be monitored closely
 Hypothermic patients should be gradually
rewarmed with gentle passive external rewarming
 Hypotension from reversal of hypothermic
vasoconstriction should be avoided
 Treatment cont.
 Hyponatremia typically responds to fluid restrictions. Severe cases
may require hypertonic saline with lasixs
 Vasopressors are usually ineffective and should only be used in
severe hypotension
 Lovothyroxine 300-500 mcg slow IVP followed by 50-100 mcg daily
 Treatment cont.
 L-triiodothyronine 25 mcg IV or orally q 8 h is a
alternative
 This dose should be halved in patients with cardiovascular
disease
 Hydrocortisone 100 mg IV q 8 hours should be given
 Send baseline cortisol level to lab if possible
 Precipitating causes should be sought and treated
 Recognition
 Supportive therapy including ventilatory support
 Thyroid replacement
 Lovothyroxine 300-500 mcg slow IVP followed by 50-100 mcg daily or
 T3 25 mcg IV or PO q 8 hrs

 Glucocorticoid
 Hydrocortisone: 100 mg IV q8h

 Hypothermia
 Prevent additional loss
 Passive external rewarming

 Electrolyte correction
 Gentle fluid restriction for dilutional hyponatremia
 Hypertonic saline for severe hyponatremia

 Hypoglycemia
 Dextrose-containing IV fluids
 Monitoring

 Aggressive treatment of presipitating causes

 Admit patient to a monitored setting
 Disposition
 Admit to appropiately monitored bed
 Parathyroids consist of 4 glands located adjacent to the thyroid
gland
 Each gland weighs approximately 40 mg
 The two superior glands are usually found near the posterior
aspect of the capsule
 The inferior glands are most often located near the inferior
thyroid margin
 The size of the gland ranges from 2-7 mm (thickness)
 Kidney shaped, soft and brown-rust colored
 Composed of chief cells, oxyphil cells, fibrous stroma and
variable amounts of fat
The Parathyroid Gland
 The parathyroid glands develop from the third and fourth
pharyngeal pouches
 The third pharyngeal pouch migrates downwards until the
inferior parathyroids attain their normal location
 The fourth pharyngeal pouch remains attached to the upper
poles of the thyroid
 PTH gene is located in chromosome 11
 PTH is synthesized as a 110 amino acid polypeptide called pre-
pro-PTH
 It is cleaved to pro-PTH (90 amino acids) and then PTH (84
amino acids)
 PTH is the major storage, secreted and biologically active form
of the hormone.
 Ca regulates synthesis, release and degradation of PTH
 Once secreted, PTH is rapidly taken up by the
liver and kidney (PTH cleaved into amino and
carboxyl fragment) and cleared by the kidney
 Half life of PTH is 2-4 minutes
 The biologic activity of PTH resides in its amino
terminus
 The effects of PTH are initiated by binding of
PTH to PTH receptors in the target tissues (type
1)
 Type 2 receptors have been found in brain and
intestines (function unknown)
The PTH response to hypocalcemia
 Seconds to minutes- exocytosis of PTH
 Minutes to 1 hour- reduction in intracellular PTH degraded
 Hours to days- increase in PTH gene expression
 Days to weeks- proliferation of parathyroid cells
 Important that serum ionized calcium concentration
be maintained within a very narrow range
 PTH and calcitriol are the major hormones
modulating calcium and phosphate homeostasis
 Increase in serum ionized calcium leads to calcium
receptor complex acting via one or more guanine
nucleotide binding protein and second messengers
leading to inhibition of PTH
 Decreased serum ionized calcium leads to
deactivation of receptors, which leads to stimulation
of PTH
1.Skeletal actions of PTH
 PTH acts on bone to mobilize Calcium from readily available
skeletal stores (immediate effect)
 Later it stimulates Calcium and phosphate release by bone
resorption
2. Renal actions of PTH
 PTH acts on distal tubules to stimulate calcium absorption
 It inhibits proximal resorption of phosphorus
3.Synthesis of calcitriol (1,25
dihydroxyvitamin D)
 Stimulates the synthesis of 1-alpha
hydroxylase in proximal tubules leading to
conversion of calcidiol to calcitriol
4.Intestines
 Indirect effect of PTH
 Produces calcitriol which leads to ↑ intestinal
absorption of calcium and phosphorus
 A clinical syndrome causing signs and symptoms that result
from ↑ PTH, PTH induced bone resorption and hypercalcemia
 Three types of hyperparathyroidism
- Primary
- Secondary
- Tertiary
 A common and usually asymptomatic disorder
 Underlying disorder is in the parathyroid gland
Epidemiology
 Overall incidence is 42 in 100,000
 Incidence increases with age
 Prevalence is 1:1000
 Female to male ratio is 2-3:1
 Primary hyperparathyroidism is caused by
…..parathyroid adenoma – 80%
…..parathyroid hyperplasia – 15%
…..parathyroid carcinoma – 1-2%
 It can occur as part of at least three familial
endocrinopathies
…..MEN 1
…..MEN 2A
…..Isolated familial hyperparathyroidism
 Etiology unknown.Both monoclonal and polyclonal origins
possible
 Gene abnormality has been mapped to 11q13
 Associated with the oncogene PRAD-1
 Gene causing MEN 1 has been cloned, and is called MENIN
1.Renal – hypercalciuria
- nephrolithiasis
- nephrocalcinosis
- polyuria and polydipsia
- renal insufficiency

2.Neuromuscular – weakness
- myalgia
3.Neurologic and psychiatric
- Memory loss - Confusion
- Depression - Lethargy
- Psychosis - Fatigue
- Neurosis - paresthesias

4.Skeletal
- Bone pain
- Osteoporosis
- Subperiosteal skeletal resorption
5.GI
- Abdominal pain
- Nausea
- Peptic ulcer
- Constipation
- Pancreatitis

6.Hypertension
7.Arthralgia, synovitis, arthritis
8.Band keratopathy
9.Anemia
 Classic phrase of these features is “stones, bones, abdominal
groans and psychic moans”
 Hypercalcemia is universal
 Serum phosphorus is low normal (<3.5
mg/dl) or low (<2.5 mg/dl)
 Mild hyperchloremic metabolic acidosis
 PTH is elevated or high normal
 Modern assays of intact PTH use
immunoradiometric assay (IRMA) or
immunochemiluminescent assay (ICMA)
 Alkaline phosphatase may be increased
 Definitive treatment is surgical parathyroidism
 Cure rate for adenomais >95% (less for
hyperplasia)
 No value in pre-op studies to localize
parathyroid tumors
 The only localization study needed is to locate
an experienced parathyroid surgeon
 No definitive medical therapy for
hyperparathyroidism
 In the asymptomatic patient, who should undergo surgery?
 Serum calcium of 1 mg/dl or more above upper limit of normal
 Hypercalciuria
 Creatine clearance 30% or less than age matched normal
subjects
 Osteoporosis
 Age < 50 years
 Difficult follow up
 Excessive secretion of PTH in response to hypocalcemia,
hyperphosphatemia, ↓ calcitriol eg. Renal failure,
malabsorption, vitamin D deficiency
 Hypercalcemia and parathyroid overactivity in the presence of
a condition that would be expected to cause secondary
hyperparathyroidism
 PTH Calcium

Primary N↑ ↑

Secondary ↑ ↓N

Tertiary ↑↑ ↑
 Protein with 141 amino acid
 Produced by malignant cells
 Interacts with the PTH receptor and mimics action of PTH

 Biochemical abnormalities are ↑PTHrP, ↑Ca, ↓ PTH, ↓ PO4, ↓

Calcitriol
 Intact PTHrP Calcitriol Calcium
PTH
Primary ↑ ↓ ↑ ↑
HPT
PTHrP ↓ ↑ ↓ ↑
Malig
Non PTHrP ↓ ↓ ↓ ↑
Malig
Etiology
a.Surgical hypoparathyroidism
 Most common cause is neck surgery eg.total
thyroidectomy

b.Idiopathic hypoparathyroidism
 Age of onset is 2-10 years
 Female preponderance
 Circulating parathyroid antibodies common
c.Autoimmune hypoparathyroidism
 Hypoparathyroidism is a prominent
component of autoimmune polyglandular
syndrome
 Associated with primary adrenal
insufficiency, mucocutaneous candidiasis
 Age of onset 5-9 years

d.Familial hypoparathyroidism
 Autosomal dominant
 Mutation in PTH gene leads to defective PTH
e.DiGeorge’s syndrome
f.Congenital aplasia of the parathyroids
g.Iron deposition in the glands
h.Copper deposition
i.Aluminium deposition
j.Infiltration with metastatic carcinoma
k.Magnesium depletion
 Ca PO4 PTH 25-Vit D Calcitriol

Hypoparathyr ↓ ↑ ↓ N ↓
oidism
Pseudohypopr ↓ ↑ ↑ N ↓N
arthyroidism
Liver disease ↓ ↑ ↓ ↓N

Renal disease ↓ ↑ ↑ N ↓N
 Main treatments available are calcium salts, vitamin D
 Acute hypocalcemia
- IV Calcium
- Oral or IV Calcitriol
 Chronic hypocalcemia
- Oral calcium
- Calcitriol or vitamin D


 Controlled by Trophic and inhibitory factors from Hypothalamus

 Anterior Pituitary Hormones

 GH, LH, FSH, TSH, ACTH, PRL

 Posterior Pituitary (Hypothalamic) Hormones

 Antidiuretic hormone (ADH) and Oxytocin
GROWTH HORMONE (GH)

 Polypeptide, secreted in bursts

 Acts indirectly through serum factors synthesized in liver
 Insulin-like growth factors (IGF)
 IGF shares some insulin-like actions
 Regulation
 Stimulated by GHRH, Sleep, Exercise, Insulin,
Hypoglycemia, Arginine, L-dopa, Propranolol
 Inhibited by Somatostatin, Glucocorticoids, Hyperglycemia,
Hypothyroidism, “Long loop” negative feedback by IGF-1
(Somatomedin-C)
 Decreased GH
 Not very significant in adults but important in children
 Treatment: recombinant human growth hormone

 Increased GH
 Hyper secretion causes Gigantism in children, Acromegaly in
adults
 Causes
 Pituitary adenomas most common
 Rarely Carcinoid tumors and pancreatic islet tumors make GHRH
CLINICAL FEATURE OF ACROMEGALY

– Acral bony overgrowth results in frontal bossing, increased hand

and foot size, mandibular enlargement with prognathism, and
widened space between the lower incisor teeth.

– Soft tissue swelling results in increased heel pad thickness,

increased shoe or glove size, ring tightening, characteristic coarse
facial features, and a large fleshy nose.

– Other commonly encountered clinical features include

hyperhidrosis, deep and hollow-sounding voice, oily skin,
arthropathy, kyphosis, carpal tunnel syndrome, proximal muscle
weakness and fatigue, acanthosis nigricans, and skin tags.

– Generalized visceromegaly occurs, including cardiomegaly,

macroglossia, and thyroid gland enlargement.
 most significant clinical impact of GH excess occurs with
respect to the cardiovascular system.
 Coronary heart disease, cardiomyopathy with arrhythmias
 Left ventricular hypertrophy, decreased diastolic function
 Hypertension occur in about 30% of patients.

 UAO with sleep apnea occurs in >60% of patients and is

associated with both soft tissue laryngeal airway
obstruction and central sleep dysfunction.
 DM -25% most patients are intolerant of a glucose load
(as GH counteracts the action of insulin).
 Increased risk of colon polyps and mortality from colonic
malignancy; polyps are diagnosed in up to one-third of
patients.

 Overall mortality is increased about threefold and is due

primarily to cardiovascular and cerebrovascular disorders and
respiratory disease.

 Uncontrolled, survival is reduced by an average of 10 years

compared with an age-matched control population.`

11/25/2018 132
 Screening- serum IGF-I levels
 Due to the pulsatility of GH secretion, measurement of a single
random GH level is not useful for the diagnosis or exclusion
 PRL elevated in ~25%
 Thyroid function, gonadotropins, and sex steroids may be
attenuated because of tumor mass effects.
 Definitive diagnosis: increase in GH with oral glucose
tolerance test
(failure of GH suppression to <1 g/L within 1–2 h of an oral
glucose load 75 g)
 Treatment: surgery, radiation, Bromocriptine, Octreotide
PROLACTIN (PRL)

 Promotes milk production and antagonizes sex steroids

peripherally.
 Regulation
 Stimulation
 Physiologic: sleep, stress, pregnancy, mid-menstrual cycle, breast
feeding, TRH
 Pharmacologic: Psychotropics, Anti-hypertensives, Opiates,
Estrogens, Metoclopramide, Cimetidine
 Pathologic
 Primary hypothyroidism (increased TRH)
 Chronic renal failure, Liver cirrhosis (secondary to reduced clearance)
❏ Inhibition
• Physiologic: tonic inhibition by dopamine
• Pharmacologic: dopamine agonists (e.g. Bromocriptine)
Pathology
❏ Hypo-prolactinemia
• Inability to lactate
• May be the first sign of Sheehan’s syndrome
❏ Hyper-prolactinemia
 Galactorrhea, Infertility, Hypogonadism (women and men)
 Serum prolactin levels > 100 µg/L often of Prolactinoma
 Treatment includes Bromocriptine, Surgery +/– Radiation
 These tumors are very slow-growing and sometimes
require no Rx
 ANTIDIURETIC HORMONE (ADH)

• Major secretory stimulus is serum osmotic pressure detected by

Osmoreceptors in hypothalamus
• Hypovolemia, stress, fever, pain may also stimulate ADH
Pathology
1. Diabetes Insipidus (DI)
 Definition: passage of large volumes of dilute urine
 Central vs. Nephrogenic
 Central DI: insufficient ADH due to dysfunction of hypothalamus
 Nephrogenic DI: collecting tubules in kidneys resistant to ADH
 Psychogenic polydipsia must be ruled out
 Diagnosis
 Fluid deprivation will differentiate true DI from psychogenic DI
 Response to exogenous ADH distinguish central from nephrogenic DI
 Treatment
 DDAVP (Vasopressin) for Central DI
 Nephrogenic DI treated with solute restriction and Thiazides
SYNDROME OF INAPPROPRIATE ADH
SECRETION (SIADH)
ADH excess associated with Hyponatremia without edema
 Causes
 Malignancy (lung, pancreas, lymphoma)
 CNS disease (inflammatory, hemorrhage, tumor, GBS)
 Chest disease (TB, pneumonia, empyema)
 Drugs (Vincristine, Chlorpropamide, Cyclophosphamide, Carbamazepine,
Nicotine, Morphine)
 Stress (post-surgical)
 Diagnosis
 Euvolemic hyponatremia with inappropriately concentrated urine
 Normal thyroid, adrenal and renal functions
 Treatment
 Treat underlying cause
 fluid restriction
 Demeclocycline
Causes uterine contractions
 Causes breast milk secretion
 Secretion stimulated by suckling, distention of the female
genital tract
PITUITARY PATHOLOGY

 Pituitary Adenoma
 Related to size and location
 Visual field defects, Oculomotor palsies, Increased ICP
 Skull radiograph: “double floor” (large Sella or erosion), calcification
 CT and MRI far more sensitive for diagnosis
 Related to destruction of gland
 • Hypopituitarism
 Related to increased hormone secretion
 Prolactinoma is most common pituitary tumor
- Galactorrhea
 Acromegaly in adults, Gigantism in children
 Cushing’s disease = Cushing’s syndrome caused by a pituitary tumor
 Tumors secreting LH, FSH and TSH are rare

•
Craniopharyngioma
 From Rathke’s pouch
 Usually mass lesion with compressive effect

Empty Sella Syndrome

 Sella turcica appears enlarged on x-ray
 Generally eupituitary - no treatment necessary

Pituitary Apoplexy
 Acute hemorrhage/infarction of pituitary
 Note: Ophthalmoplegia with pituitary tumor likely
indicates apoplexy since tumor rarely gets big enough to
encroach on cranial nerves
Etiology
❏ Mnemonic: eight “I”s
 Invasive: generally primary tumors
 Infarction: e.g. Sheehan’s syndrome
 Infiltrative disease e.g. Sarcoidosis, Hemochromatosis,
Histiocytosis
 Iatrogenic: following surgery or radiation
 Infectious: e.g. syphilis, TB
 Injury: severe head trauma
 Immunologic: autoimmune destruction
 Idiopathic: familial forms, congenital midline defects
Typical clinical progression in panhypopituitarism
 laboratory
 low levels of trophic hormones in the setting of low target hormone
levels.
 Diagnosis by Triple Bolus Test
 ❏ Rapid sequence IV infusion of Insulin, LHRH and TRH
 Insulin ––> hypoglycemia ––> increased GH and ACTH
 LHRH ––> increased LH and FSH
 TRH ––> increased TSH and PRL
HYPOPITUITARISM: TREATMENT

 Hormone replacement therapy, including glucocorticoids, thyroid

hormone, sex steroids, growth hormone, and vasopressin
Thank you