Special Problems

1. Hypothyroidism in pregnancy
a. Most pregnant women with primary hypothyroidism require an increase in the dose of
thyroxine of some 50 μg daily.
b. Explanation for this phenomenon is increase in serum thyroxine-binding globulin
concentration during pregnancy, resulting in a decrease in serum free thyroid hormone
concentrations which cannot be compensated for by thyroidal secretion.
2. Hypothyroid and CAD (AIPG 2011)
In the elderly, especially patients with known coronary artery disease, the starting dose of
levothyroxine should be the lowest starting dose i.e. 12.5–25 μg/d with similar increments every
2–3 weeks until TSH is normalized.
Reason for this is – in hypothyroidism the metabolic rate is low. So myocardial oxygen demand is
low. With sudden treatment with high doses, heart rate will increase and that will lead to
coronary ischemia. (Ref. Hari-18th ed., Pg-2922)
3. Myxoedema coma
a. Depressed level of consciousness
b. Body temperature may be as low as 25oC,
c. Convulsions are common
d. CSF pressure and protein content are raised.
Factors contributing to the altered consciousness level,
1. Cardiac failure
2. Chest infection
3. Dilutional hyponatremia
4. Hypoxemia
5. Hypercapnia due to hypoventilation.
Rx: Myxoedema coma is a medical emergency
1. I/V Hydrocortisone (1st to be given)
2. Parenteral
3. Slow rewarming.
4. Broad-spectrum antibiotics
5. High-flow oxygen.
Hyperparathyroid
Basic Concepts
Physiology
1. Normal serum Ca = 9 – 11 mg%,
a. Diffusible : i. Ionized Ca = 50%, ii. Ca bound to anions = 10%
b. Non Diffusible : Ca bound to protein = 40%,
Table . Distribution (mmol/L of Calcium in Normal Human Plasma).

Total diffusible

1.34
Ionized (Ca2+)
Complexed to HCO3-, citrate, etc
Total nondiffusible (protein-bound)
1.16
Bound to albumin
Bound to globulin
Total plasma calcium
2.50
2. Normal histology of the bone
It has three types of cells
a. Osteoblast - These are the bone forming cell. Whenever there is increase activity of
osteoblast it causes raised level of serum alkaline phosphatase (MCQ) That is why level of serum
alkaline phosphatase is raised in children and pregnancy (MCQ). Have receptors for PTH. Help in
forming new bone.
b. Osteocytes - They are the bone maintaining cells. They regulate bone activity.
c. Osteoclast - They cause bone resorption (MCQ). In Multiple myeloma there is increase
activity of osteoclast that is why there are lytic lesion and Hypercalcemia in MM (MCQ)
Extra Edge: In Multiple Myeloma there is no increase activity of osteoblast. That’s why serum
alkaline phosphatase level (ALP) are normal in MM and bone scan is also normal. (FAQ)
Other bone condition with increase ALP =
1. Paget disease,
2. Bone metastases,
3. Rickets, osteomalacia,
4. Osteogenesis imperfecta
5. Osteogenic sarcoma.
Extra Edge ALP level is normal in osteoporosis and multiple myeloma.
Parathyroid hormone (PTH)
Basic concept
PTH is normally secreted in response to low ionized Ca2+ levels, by 4 parathyroid glands
situated posterior to the thyroid.
PTH acts by :-
1. osteoclast activity releasing Ca2+ & PO43- from bones
2. Ca2+ & PO43- reabsorption in the kidney
3. Active 1,25 dihydroxy-vitamin D is the serum production.
Biochemical Markers of Bone Metabolism in Clinical Use
1. Bone formation
a. Serum bone-specific alkaline phosphatase
b. Serum osteocalcin
c. Serum propeptide of type I procollagen
2. Bone resorption
a. Urine and serum cross-linked N-telopeptide
b. Urine and serum cross-linked C-telopeptide
c. Urine total free deoxypyridinoline
Hyperparathyroidism (Ref. Harrison 19th ed., Pg. 2470)
Causes
1. Primary hyperparathyroidism
Ca,  PO4,  PTH
a. The most common cause of primary hyperparathyroidism is parathyroid solitary adenoma.
b. “A single solitary abnormal gland is the cause of approximately 80% of patients”
Important Point
a. Adenomas are most often located in the inferior parathyroid gland. (MCQ)
b. Chief cells are predominant in both hyperplasia and adenoma.
2. Secondary hyperparathyroidism :
Causes
a. Low vitamin D intake b. Chronic renal failure
c. Rickets d. Osteomalacia e. Malabsorption (FAQ)
Extra Edge : Lab finding secondary hyperparathyroid

Ca
PO4
PTH
Due to malnutrition



Due to CRF



Extra Edge : In CRF, serum Ca level goes down and serum PO4 level rises. This known as trade
off hypothesis.
3. Tertiary hyperparathyroidism : Ca2+, PTH (FAQ) PO4
a. Occurs after prolonged secondary hyperparathyroidism, causing glands to act autonomously
having undergone hyperplastic or adenomatous change.
b. This causes Ca2+ from secretion of PTH unlimited by feedback control.
4. Malignant hyperparathyroidism
Causes: Parathyroid-related protein (PTHrp) is produced by some cancers leading to
hypercalcemic
a. Squamous cell lung cancers
b. Breast
c. Renal cell carcinomas. (FAQ)
Extra Edge Hypercalcemia in malignancy occur due to increase level of PTHrp. In this PTH
level are not raised (AIIMS Nov 12).
Important Points Most patient’s of hyperparathyroid are “asymptomatic”.
Manifestations of Hyperparathyroidism

General
Renal feature
Bones
Abdomen
Cardiac
Calcification
∙ Anorexia
∙ Nausea
∙ Vomiting
∙ Fatigue
∙Mental confusion
(Psychic moans)
∙ Polyuria &
nocturia
∙ Renal colic
from stones
∙ Bone pain
- Bone cysts
- Brown tumor
∙ Peptic ulceration
∙Constipation (LQ 2012)
∙ Short QT interval in ECG arrhythmias
Hypertension
∙Ectopic calcification & chondrocalcinosis
Extra Edge Polyuria results from effect of hypercalcemia on renal tubules reducing their
concentrating ability, a form of nephrogenic diabetes insipidus
Tests
Serum abnormality in Hyperparathyroid
Serum Ca
Serum phosphate
Alkaline phosphatase
PTH
Primary hyperparathyroidism




Secondary hyperparathyroidism due to CRF




Secondary hyperparathyroidism due to malnutrition




Extra Edge
1. 24 hrs Ca excretion in urine is increased in hyperparathyroid.
2. Serum calcitonin is not a marker of hyperparathyroid.
3. In renal osteodystrophy (CRF) calcium is low but phosphate is high but in nutritional
secondary hyperparathyroid both calcium and phosphate are low. (LQ 2012)
Pathology of Skeletal changes in hyperparathyroidism
1. Diffuse bone resorption:
a. The Howship lacunae are filled with large number of osteoclasts and the Haversian canals
are enlarged.
2. Brown tumours:
a. The "tumour" is a well circumscribed dark brown area of soft consistency, situated where
bone resorption has been severe.
3. Osteitis fibrosa cystica:
a. Healing in case of hyperparathyroidism occurs by fibrous tissue replacement or sometimes
the centre may liquefy and a bone cyst remains. (LQ 2012)
4. Deformities:
a. Intervertebral disk becomes ballooned as they indent soft vertebral bodies forming the 'Cod
Fish spine'.
5. X-Ray findings
a. Osteoporosis:
i. The early finding is that of generalized deossification.
b. Subperiosteal resorption:
i. Subperiosteal erosions are most frequently identified along the middle phalanges of the index
and middle fingers is a characteristic feature. (Tufting of the phalanges.)
ii. This x-ray feature is virtually diagnostic of hyperparathyroidism.
c. Pinhead stippling:
i. The skull displays a diffuse osteoporosis described as pinhead stippling.(pepper pot
appearance)
d. Mandible x-ray = Demineralization of mandible
e. Calciphylaxis = Metastatic calcification of blood vessel (secondary to hyperphosphatemia)
may lead to ischemic damage to skin & other organs.
Extra Edge: 1. Rugger Jersey spine is seen in CRF
2. Osteopetrosis is not a feature of Hyperparathyroid
Location of the adenoma:
a. It is done by technetium 99m scan.
b. After one hour of administration of technetium 99m, uptake is done by both thyroid and
parathyroid gland.
c. After 3 hrs uptake evidence is there only in parathyroid. So by computer subtraction
adenoma is located.
Hypercalcemia (Ref. Harrison 19th ed. pg. 2469)
Basic Concept - Vitamin D Synthesis
1. In response to ultraviolet radiation of the skin, a photochemical cleavage results in the
formation of vitamin D from 7-dehydrocholesterol.
2. Vitamin D is subsequently 25-hydroxylated in the liver.
3. The second hydroxylation, required for the formation of the mature hormone, occurs in the
kidney. (In P.C.T)
4. 1,25-dihydroxyvitamin D [1,25(OH)2D] is the major hormone involved in Ca+2 ion
homeostasis regulation.
Causes of Hypercalcemia (AIPG 10, AIIMS Nov 10)
1. Hyperparathyroidism, Hyperthyroid, Pheochromocytoma, MEN
2. Ca breast, Squamous cell Lung cancer, Renal cell carcinoma, MM, lymphoma
3. Drugs Lithium, Thiazide, Phenytoin
4. Vit D intoxication, Vit A intoxication, Aluminium intoxication
5. Milk alkali syndrome
6. Prolong Immobilization
7. Sarcoidosis
8. Familial hypercalciuric hypercalcemia
Important Points
1. Causes of Hypercalcemia with increase PTH
a. Hyperparathyroid (Primary, Secondary)
b. MEN Syndrome
c. Familial Hypocalciuru Hypercalcemia.
2. In all other causes of hypercalcemia , the PTH level is low !!!.
Extra Edge: Williams syndrome
1. Williams syndrome is developmental disorder due to deletion of genes from long arm of
chromosome 7.
2. It is characterized by a distinctive, "elfin" facial appearance, along with a low nasal bridge;
developmental delay coupled with strong language skills; and cardiovascular problems, such as
supravalvular aortic stenosis and transient Hypercalcaemia.
3. Other symptoms include failure to gain weight appropriately in infancy and low muscle
tone.
4. Most individuals with Williams syndrome are highly verbal and overly sociable, having
what has been described as a "cocktail party" type personality, and exhibit a remarkable blend of
cognitive strengths and weaknesses.
Management of Acute hypercalcemia
1. Mild hypercalcemia (up to) 12 mg/dl  Managed by hydration alone
2. More severe hypercalcemia 13 to 15 mg/dl  Hydration with saline, Forced diuresis:
saline : Loop
diuretics (Furosemide) promotes calcium excretion
Extra Edge Thiazide cause hypercalcemia so are never used in the treatment of
hypercalcemia!!!
Management of chronic hypercalcemia
1. Bisphosphonates : Bisphosphonates reduce calcium resorption
a. 1st generation Etidronate
b. 2nd generation Pamidronate
c. 3rd generation Zoledronate
2. Glucocorticoids : Effective in particular situations such as Vitamin D intoxication :
Sarcoidosis, Malignancy
3. Calcitonin
4. Phosphate:
5. Plicamycin
6. Gallium Nitrate
7. Dialysis - Quick and effective and is likely to be needed in severe cases with renal failure
8. Surgical excision of the adenoma
Extra Edge : Biphosphonate can cause intense esophagitis (AIIMS Nov 2015)
Table - Indications for Surgery in Primary Hyperparathyroidism
Symptoms related to hypercalcemia
1. Age <50 years
2. Renal manifestations
3. Renal calculi
4. Reduced creatinine clearance
5. 24-hour urine calcium excretion >400 mg/dL
6. Bone mineral density >2.5 SDs below peak bone mass (t-score)
7. Patient preference for surgery or unwillingness/inability to undergo prolonged follow-up
(SD = standard deviation)
Extra Edge: New Drugs
1. Strontium is new compound which causes both increase osteoblastic and reduce osteoclastic
activity thereby it causes both bone formation and reduces bone resorption. (AIIMS NOV 2008)
2. Cinacalcet is new drug.
a. It is a calcimimetic agent that reduces the parathormone level.
b. It is use in treatment of secondary hyperparathyroidism.
3. Risedronate
a. It is an orally administered bisphosphonate, inhibits osteoclast-mediated resorption of bone,
and modulates bone metabolism in women with postmenopausal osteoporosis.
b. The long half-life of risedronate (480 hrs) for once a –week administration.
4. Teriparatide is the recombinant human N-terminal fragment of endogenous human
parathyroid hormone, used in the treatment of some forms of osteoporosis
Hypoparathyroidism (Ref. Harrison-19th ed. Pg. 2483)
Causes of hypoparathyroid:
1. Primary (due to gland failure)
a. Idiopathic (Autoimmune) (associated with other autoimmune disorders),
Lab tests of Idiopathic hypoparathyroid - Ca2+↓, PO43-↑. (Serum ALP is not raised)
Treatment = alpha calcidiol and calcium supplement.
b. Infantile hypoparathyroidism: It is associated with thymic aplasia (Di George syndrome)
2. Secondary
a. Post operative : surgery (thyroidectomy).
b. Post radio iodine therapy
c. Hypomagnesemia – (Mg is required for PTH secretion)
3. Pseudohypoparathyroidism (PHP)
a. It is a group of disorders characterized by hypocalcemia due to renal resistance to PTH.
b. PTH levels are high.
c. Various phenotypic abnormalities may be tissues are associated—classically, short stature,
round face, obesity, short fourth metacarpals, ectopic bone formation, and mental retardation.
Cataract .
d. Treatment is same as for primary.
4. “Pseudopseudohypoparathyroidism” (PPHP)
a. Patients without hypocalcemia but sharing the phenotypic abnormalities (as of pseudo
hypoparathyroidism)..
b. These patient have normal serum calcium and high serum PTH.
c. In pseudohypoparathyroidism, defect lies at PTH receptor level. While in pseudo
pseudohypoparathyroidism defect lies at gene transcription level beyond the PTH receptors.
Mutations in pseudohypoparathyroidism is in gene for Gs-Alpha: (AIPG 2011)
1. In PHP, there is reduced synthesis of cAMP in response to PTH so there is no appropriate
increase in the urinary cAMP occurs (AIIMS Nov 2011)
2. In PPHP there is increased synthesis of cAMP in response to PTH so there is increase in the
urinary cAMP occurs.
3. Both patterns of inheritance lead to Albright’s hereditary osteodystrophy (AHO), because of
haplotype insufficiency—i.e., both copies of Gs alpha must be active in the fetus for normal bone
development.
Pseudopseudohypoparathyroidism can be best understood by comparing it to other conditions:
Condition

PTHlevels
Calcium
(Pattern of inheritance)
Imprinting
Hypoparathyroidism
Low
Low
Not applicable
Pseudohypoparathyroidism
Increase
Low
Gene defect from mother
Pseudopseudohypoparathyroidism
Increase
Normal
Gene defect from father
Tetany
Definition: Increase excitability of peripheral nerve due either to a low serum calcium or low
serum magnesium or alkalosis
Causes of tetany
1. Due to hypocalcemia
a. Malabsorption
b. Osteomalacia
c. Hypoparathyroidism
d. Acute pancreatitis
2. Due to alkalosis (LQ 2012)
a. Repeated vomiting
b. Hyperventilation
c. Primary hyperaldosteronism
3. Hypomagnesemia
Clinical feature of tetany
1. In children a characteristic triad of
a. Carpopedal spasm
b. Stridor
c. Convulsions.
2. In adults complain of tingling in the hands, feet and around the mouth. Carpopedal spasm
(Main d’accoucheur position)
Latent tetany signs are
1. Trousseau’s sign
2. Chvostek sign
Treatment of tetany
1. Injection calcium gluconate I/V
2. In case of persistent vomiting – I/V saline
3. In hyperventilation – Re breath from same bag
Magnesium disorders
Basic physiology
Normal serum magnesium = 1.5 to 2.3 mg%
Extra Edge
1. Serum Ca and Serum Mg level always go parallel in the body.
2. The notable exceptions are CRF (Hypocalcemia and Hypermagnesemia), Gitelman syndome
(Normocalcemia and hypomagnesemia)
3. Magnesium is required for PTH secretion and for PTH action (Ref. Oxford Hand book of
medicine, 7th ed., Pg-206)
Hypomagnesemia (Ref. Harrison-19th ed. Pg. 2483)
Causes of hypomagnesemia
1. Reduce intake especially common in alcoholic patient and on TPN
2. GI losses - chronic diarrhea
3. Kidney loss – diuretics, Gitelman syndrome.
4. Acute pancreatitis
5. Drugs - Foscarnet (It is an anti herpes group of drug used generally in zoster ophthalmitis).
Extra Edge The clinical feature and ECG finding of hypomagnesemia are same as of
hypocalcemia, i.e. ↑QT
Treatment of hypomagnesemia = Replacement
Hypermagnesemia : (Ref. Harrison-19th ed. Pg. 2462)
Causes:
1. ARF, CRF
2. Addison disease
3. Magnesium containing drugs.
4. Hemolysis
Clinical features.
a. Occur due to vasodilatation and neuromuscular blockage.
b. There is paradoxical Bradycardia, Hypotension,
c. Altered sensorium, respiratory depression.
Treatment: 1. Injection calcium gluconate for heart (LQ 2012) 2. Diuretics
(Frusemide)
3. Dialysis
Tumor lysis syndrome
1. Tumor lysis syndrome occurs during-the treatment of malignancies.
2. Destruction of large number of rapidly proliferating neoplastic cells leads to release of a
number of intracellular electrolytes which causes following effect:
a. Hyperuricemia
b. Hyperphosphatemia
c. Hypocalcemia (LQ 2012)
d. Hyperkalemia
e. Lactic acidosis
f. Dehydration
Bony lesion in vitamin A intoxication
Vitamin A. intoxication produces following bony manifestation: (MCQ)
1. Bone demineralization
2. Bone pain
3. Hypercalcemia
4. Hyperostosis
Vitamin D intoxication
Vitamin D intoxication (delayed effect) causes persistent hypercalcemia and hyperphosphatemia
which may produce:
1. Urinary Lithiasis.
2. Metastatic calcification which affects kidneys, bronchi, pulmonary alveoli, muscles, arteries
and gastric mucosa & Renal failure leading to death.
Hypophosphatemia & Hyperphosphatemia
Causes of hypophosphatemia (Ref. Harrison-19th ed. Pg. 2458)
A. Reduced renal tubular phosphate reabsorption
1. PTH/PTHrP -dependent
a. Hyperparathyroidism
b. PTHrP-dependent hypercalcemia of malignancy
c. Familial hypocalciuric hypercalcemia
2. PTH/PTHrP-independent
a. Genetic hypophosphatemia i. X-linked hypophosphatemia rickets ii. Wilson disease
b. Other systemic disorders i. Poorly controlled diabetes mellitus ii. Alcoholism
c. Drugs i. Diuretics
ii. Cisplatin
iii. Ifosfamide
iv. Foscarnet
v. Calcitonin
vi. Pamidronate
B. Impaired intestinal phosphate absorption
1. Aluminum-containing antacids
C. Shifts of extracellular phosphate into cells
1. Insulin therapy of prolonged hyperglycemia or diabetic ketoacidosis
Causes of hyperphosphatemia (Ref. Harrison 19th ed. pg. 2460)
A. Decreased renal phosphate excretions
1. ARF,
2. CRF,
3. Hypoparathyroidism,
4. Pseudo Hypoparathyroidism,
5. Bisphosphonates,
6. Acromegaly
B. Others
1. Vitamin D intoxication
2. Acidosis,
3. Rhabdomyolysis,
4. Cytotoxic therapy
5. Tumourlysis Syndrome
6. Fulminant hepatitis
Multiple Endocrine Neoplasia (MEN)
The MEN syndromes are a group of genetic syndromes inherited in an autosomal dominant
manner.
They comprise of:
1. MEN l & 2
2. Von Hippel Lindau syndrome.
3. Peutz-Jeghers' syndrome
4. Carney complex: This consists of spotty skin pigmentation, schwannomas, myxoma of skin,
mucosa or heart (especially atrial myxoma), and endocrine tumours: eg pituitary adenoma,
adrenal hyperplasia, testicular tumour.
MEN type-l: (Wermer syndrome) (AIPG 10) (LQ 2012) √√√√√√√√√√√√√√√√√√√√√√√√√
1. Parathyroid hyperplasia/adenoma (most common feature).
2. Pancreatic endocrine tumours -usually gastrinoma
3. Pituitary adenoma
MEN 2a: Sipple syndrome (LQ 2012) MEN 2b:(LQ 2012)
1. Thyroid: Medullary thyroid carcinoma 1. Thyroid: Medullary thyroid carcinoma
2. Pheochromocytoma 2. Pheochromocytoma
3. Parathyroid hyperplasia 3. Mucosal neuromas and Marfanoid appearance
Important points Cutaneous findings in:
1. MEN-I :-
2. Cutaneus angio fibromas
3. MEN –2a :- Cutaneous lichen amyloidosis.
4. MEN 2b :- Cutaneous neuromas.
Extra Edge
1. MEN-I is caused by MEN-I gene which is a tumour suppressor gene. Menin, its protein
alters transcription activation.
2. Gene involved in MEN 2a and 2b is RET – proto oncogene, a receptor tyrosine kinase.
3. RET mutation do not contribute to parathyroid tumor.
Von Hippel – Lindau disease (VHL)
a. It is a autosomal dominant, characterize by abnormal angiogenesis, leading to retinal
angioma, CNS hemangioblastoma, pheochromocytoma & renal cell carcinoma. (AIIMS May 11).
b. There is increase erythropoietin secretion so it causes polycythemia.
Autoimmune polyendocrine syndromes
Autoimmune disorders cluster into two defined syndromes:
Type 1: (APECED Syndrome) Autosomal recessive, due to mutation in AIRE (Auto immune
Regulator) Gene in chromosome 21.
Features:
a.
Addison's disease
b. Hypoparathyroidism
c. Type 1 diabetes
d. Primary hypothyroidism
e.
Chronic mucocutaneous candidiasis
f. Nail dystrophy
g. Dental enamel hypoplasia
Important Points: APECED Syndrome:- Autoimmune Poly Endocrinopathy Candidiasis
Ectodermal Dystrophy
Type 2: (Schmidt's syndrome) DR3 & DR4 linked (common)
Features:
a. Addison's disease
b. Primary hypothyroidism
c. Graves' disease
d. Pernicious anaemia
e. Primary hypogonadism
f. Type 1 diabetes
g. Vitiligo
h. Coeliac disease
i. Myasthenia gravis
Cushing’s Syndrome (Ref. Harrison-19th ed. Pg. 2314)
Physiology
The adrenal cortex produces steroids:
1. Glucocorticoids (eg cortisol)
2. Mineralocorticoids
3. Androgens
Cushing's syndrome:
1. This is chronic glucocorticoid excess.
2. The commonest cause is exogenous steroid treatment.
3. Endogenous causes are much rarer
4. 85% are due to  ACTH, of these a pituitary adenoma (Cushing's disease) is the
commonest endogenous cause.
Causes of Cushing Syndrome
1. ACTH-dependent causes: ( ACTH)
a. Cushing's disease Bilateral adrenal hyperplasia due to an ACTH secreting pituitary adenoma
b. Ectopic ACTH production Especially small cell lung cancer and carcinoid tumors Q)
Pancrease Ca, bronchial adenoma.
2. ACTH-independent causes: (ACTH due to -ve feedback).
a. Iatrogenic Pharmacological doses of steroids (most common cause of cushing).
b. Adrenal adenoma or carcinoma may be associated with abdominal pain and virilization in
women
c. Adrenal nodular hyperplasia
Extra Edge-: The most common histopathologic classification of adrenocortical carcinoma is the
Weiss score.
Summary of Causes
Cause S. ACTH Diagnosis Rx
1. Iatrogenic Reduce History Reduce dose
2. Pituitary adenoma Raise CT (Head) Surgery
3. Ectopic ACTH secreting tumor Raise CT (Chest) Surgery
4. Adrenal adenoma / Cancer Reduce CT (abdomen) Surgery
Extra Edge:
1. Adrenal adenoma has size less than 6cm and adrenal carcinoma has size more than 6 cm.
2. Loss of diurnal variation of steroid hormones in the body is the first feature of Cushing
syndrome.
Clinical Features of Cushing’s syndrome (Ref. Harrison-19th ed. Pg. 2315)
1. Symptoms due to excess of glucocorticoid
a. The loss of proteins from the muscle in particular causes severe weakness of proximal
muscles (Proximal myopathy)
b. The protein collagen fibres in the subcutaneous tissue are diminished so that the
subcutaneous tissue tear easily resulting in development of large purplish striae where they have
torn apart.
c. Elevated blood glucose concentration . Insulin resistance can occur
d. Mobilization of fat from the lower part of the body with concomitant extra deposition of fat
in the thoracic and upper abdominal regions (Centripetal obesity) giving rise to a buffalo torso.
The excess secretion of steroid also leads to an edematous appearance of the face. ("moon
facies").
2. Symptoms due to excess of mineralocorticoid
a. Salt and water retention leads to sustained hypertension.
b. Significant K+ depletion (Hypokalemia)
Extr Edge: Episodic hypertension occurs in pheochromocytoma
3. Symptoms due to excess of androgen
a. Hirsutism b. Facial acne c. Oligomenorrhea d. Amenorrhea
4. Other Symptoms
a. Psychosis, insomnia, euphoria b. Osteoporosis
Investigation of Suspected Cushing’s syndrome
1. Loss of diurnal variation of cortisol level is the earliest features of Cushing syndrome.
2. Diagnosis: The diagnosis of Cushing’s syndrome depends on the demonstration of increased
cortisol production and failure to suppress.
a. Increase 24h urinary free cortisol
b. Dexamethasone (DM) suppression test
i. Low dose DM suppression test is done to differentiate between Cushing syndrome and
simple obesity.
ii. High dose suppression test is done to differentiate between Cushing syndrome due to
pituitary adenoma and ectopic secretion of ACTH
Treatment Modalities for Patients with Adrenal Hyperplasia Secondary to Pituitary ACTH
Hypersecretion

1. Treatments to reduce pituitary ACTH production

a. Transsphenoidal resection of microadenoma

b. Radiation therapy
2. Treatments to reduce or eliminate adrenocortical cortisol secretion
a. Bilateral adrenalectomy
b. Medical adrenalectomy:- i.e. Drugs used to reduce steroid synthesis.
i. Metyrapone ii. Mitotane iii. Aminoglutethimide iv. Ketoconazole
v. Mifepristone vi. Trilostane vii. Cyproheptadine viii. Etomidate. (Ref.
Hari. 18th ed., Pg - 2899)
Pseudo Cushing’s syndrome:
1. Some patient resemble like Cushing’s syndrome (Pseudo Cushing syndrome).
2. These are patient with obesity, chronic alcoholism, depression and acute illness of any type.
Incidentalomas:
1. Many incidental masses (so called incidentalomas) are discovered during radiographic
testing for another condition, rather than testing performed because of suspected adrenal disorder.
2. Many of them turn out to be adrenocortical adenoma. Especially in the patient above the age
of 30 yrs.
Nelson Syndrome:
1. It is the rapid enlargement of apituitaryadenoma that occurs after the removal of bothadrenal
glands.
2. Most aggressive growing pituitary tumor.
3. Removal of both adrenals eliminates production ofcortisol, and the lack of cortisol
‘snegative feedbackcan allow any preexisting pituitary adenoma to grow unchecked.
4. Continued growth can causemass effectsdue to physical compression of brain tissue, along
with increased production of ACTH and MSH.
5. Very high serum ACTH (> 100 micro gram/ml) causing hyperpigmentation and due to mass
effect causes headache. It can invade cavernous sinus.
6. Treatment of Nelson Syndrome: Pituitary surgery is performed in some cases. The risk can
also be minimized by pituitary irradiation.
Adrenal insufficiency (Ref. Harrison-19th ed. Pg. 2323)
Adrenocortical insufficiency or hypofunction may be
1. Primary adrenal Disease
2. Secondary hypoadrenalism (decreased stimulation of ACTH due to deficiency of ACTH).
Table - Classification of Adrenal Insufficiency (Ref. Harrison-19th ed. Pg. 2323)

1. Primary Adrenal Insufficiency

a. Anatomic destruction of gland (chronic or acute)
i. Surgical removal
ii. Infection (tuberculous, fungal, viral—especially in AIDS patients)
iii. Hemorrhage
iv. "Idiopathic" atrophy (autoimmune)
v. Invasion: metastatic (The most common site of primary in a patient presenting with
secondries to adrenals is Melanoma.) Lung, Breast, lymphoma, RCC
b. Metabolic failure in hormone production
i. Enzyme inhibitors (metyrapone, ketoconazole, aminoglutethimide)
ii. Congenital adrenal hyperplasia
iii. Cytotoxic agents (mitotane)
iv. Adrenal hypoplasia congenital
2. Secondary Adrenal Insufficiency
a. Hypopituitarism due to hypothalamic-pituitary disease
b. Suppression of hypothalamic-pituitary axis
i. By endogenous steroid from tumor
ii. By exogenous steroid
Basic Physiology of Addison disease (Primary adrenocortical insufficiency)

Symptoms:
1. Fatigue, weakness, anorexia, weight loss
2. Dizziness, fainting, Asthenia is most common symptoms (MCQ)
3. Myalgia, arthralgia.
4. Mood: depression, psychosis, low self-esteem. Enhancement of the sensory modalities of
taste, olfaction, and hearing is reversible with therapy.
5. Nausea or vomiting, abdominal pain, diarrhea or constipation. Note: Both diarrhea or
constipation can occur
Note: Due to low BP & hypoglycemia, the commonest symptom of Addison’s disease is
Asthenia.
Extra Edge
1. The increased MSH in Addison's causes melanocytes to disperse melanin in the epidermis
thus increasing pigmentation.
2. Hyper pigmentation due to increase ACTH which is a precursor of MSH. But Vitiligo may
be associated.
3. GI: nausea or vomiting, abdominal pain, diarrhea or constipation.
Extra Edge: Both diarrhea or constipation can occur
This increased pigmentation is diffuse but may be accentuated in the
1. Palmer crease
2. Sites of friction & pressure areas - Knuckles, elbows, knees, nail beds
3. Scars
4. Oral mucosa, gums & conjunctival
5. Areolae of nipples
Extra Edge:
1. Increase in ACTH occurs only in primary Addison’s disease.
2. It is not seen in secondary Addison disease as it is caused due to decrease in ACTH.
3. Therefore, pigmentation can not occur in secondary Addison's disease.
Extra Edge 1. Primary Addison’s disease both aldosterone and glucocorticoid are deficient,
2. In secondary Addison’s disease only glucocorticoid deficiency is seen.
Tests of adrenal insufficiency
1. Na+ & K+ 2. Glucose 3. Ca2+,(MCQ) 4. Eosinophilia,
(MCQ)
Extra Edge
1. Hyponatremia is a characteristic feature in primary adrenal insufficiency. Hyperkalemia is
also a feature.
2. Hyponatremia is primarily caused by mineralocorticoid deficiency but can also occur in
secondary adrenal insufficiency due to diminished inhibition of ADH by cortisol, resulting in
mild SIADH.
Note: The commonest symptom of Addison’s disease is Asthenia due to low BP &
hypoglycemia.
Diagnosis (Ref. Harrison-19th ed. Pg. 2325)
1. ACTH stimulation test (Most confirmatory Test)
The diagnosis of adrenal insufficiency should be made only with ACTH stimulation testing to
assess adrenal reserve capacity for steroid production. In brief, the best screening test is the
cortisol response 60 min after 250 μg of cosyntropin given IM or IV. Cortisol levels should be 18
μg/dL.
2. 21-Hydroxylase adrenal autoantibodies: +ve in autoimmune disease in >80%.
3. In Addison disease - Increased Plasma renin and reduced plasma aldosterone level:
In secondary adrenal insufficiency both plasma renin and plasma aldosterone level are raised.
4. Addison’s disease is associated with serum cortisol <3 mcg/dl
Extra Edge Low plasma cortisol (<3 mcg/dl) at 8:00 AM is diagnostic especially if
accompanied by simultaneous elevation of plasma ACTH level (usually >200 pg/ml)
Treatment of Addison disease
1. Replace steroids: 15-25mg hydrocortisone daily, in 2-3 divided doses.
2. Mineralocorticoid replacement is needed if postural hypotension: fludrocortisone from 50-
200 micro μg daily.
Recent advances
Eflornithineis used in the treatment of facialhirsutism (excessive facial hair growth) as well as in
African trypanosomiasis(sleeping sickness).
Hyperaldosteronism (Ref. Harrison-19th ed. Pg. 2318)
A. Primary hyperaldosteronism is excess production of aldosterone, independent of the renin-
angiotensin system, causing sodium and water retention, and renin release.
Causes of primary hyperaldosteronism
1. Adrenal adenoma (Conn’s syndrome)- Usually unilateral. It is the most common cause of
primary hyperaldosteronism.
2. Adrenal carcinoma:
3. Bilateral adrenal cortical hyperplasia
Clinical features of Conn’s syndrome :
1. Weakness, cramps, paraesthesia,
2. Polyuria, (Impaired concentrating ability of kidney causes polyuria) due to nephrogenesis
diabetes insipidus.
3. Polydipsia
4. Hypernatremia
5. Hypertension
6. Hypokalemia
7. Metabolic Alkalosis (AIIMS Nov 2011) (Ref. Hari 18th Pg. 342, 247)
8. Ventricular arrhythmia
9. Muscle wasting (Proximal myopathy),
MCQ: In Conn syndrome Polyuria occur Because of hypokalemia which leads to nephrogenic
diabetes insipidus.
Extra Edge Oedema feet is not a feature of primary hyperaldosteronism & SIADH (LQ 2012)
Tests
1. Primary hyperaldosteronism a. Aldosterone b.  Renin
2. Secondary hyperaldosteronism a.  Aldosterone b.  in Renin
Extra Edge In Addison disease Renin and  Aldosterone
Recent Advances Primary Aldosteronism
1. The ratio of plasma hyper aldosterone to plasma renin activity (PA/PRA) is a useful
screening test.
2. Bilateral adrenal venous sampling for measurement of plasma aldosterone is the most
accurate means of differentiating unilateral from bilateral forms of primary aldosteronism.
3. The sensitivity and specificity of adrenal venous sampling (95% and 100%, respectively) for
detecting unilateral aldosterone hypersecretion are superior to those of adrenal CT.
Treatment:
a. Conn’s : Adrenalectomy.
b. Hyperplasia: Treated medically: spironolactone, Eplerenone
1. Secondary hyperaldosteronism
Cause:
a. CCF b. Hepatic failure c. Nephrotic syndrome
Treatment: a. Spironolactone, b. Eplerenone
Recent Advances
Eplerenone: A new selective aldosterone receptor antagonist, which does not cause gynecomastia
(PQ)
Extra Edge: : In Conn syndrome Polyuria occur Because of hypokalemia which leads to
nephrogenic diabetes insipidus.
Pheochromocytoma (Ref. Harrison-19th ed. Pg. 2329)
Adrenal Medulla
1. Normally adrenal medulla secretes 80% epinephrine and 20% norepinephrine.
2. In adrenal pheochromocytoma mainly epinephrine is secreted, in extra adrenal
norepinephrine is secreted exclusively.
3. Malignant pheochromocytoma secretes epinephrine, norepinephrine and dopamine.
4. Pheochromocytomas roughly follow the 10% rule: 10% are malignant, 10% are extra-
adrenal, 10% are bilateral, and 10% are familial.
Associations -90% are sporadic. 10% are part of a hereditary cancer syndrome eg MEN2a and 2b,
neurofibromatosis, von Hippel-Lindau syndrome.
Pheochromocytoma
Clinical Features of
Symptoms produced
1. Hypertension
a. M.C. manifestation of pheochromocytoma
b. 60% of the patients have sustained hypertension
c. 40% have paroxysmal hypertension
2. Arrhythmia, Sinus tachycardia, or Sinus bradycardia
3. Angina and myocardial infarction even in the absence of coronary artery disease.
4. Profuse sweating (LQ 2012)
5. Mild to moderate Weight loss
6. Impaired carbohydrate tolerance
7. Orthostatic hypotension
8. Hypercalcemia, Abdominal pain
9. Increase hematocrit
Extra Edge
1. Wheezing is not a feature.
2. Headache, palpitation & sweating are the classic triad of pheochromocytomas (LQ 2012)
3. Symptoms may be precipitated by straining, exercise, stress, pressure on the abdomen,
surgery, or parturition-or by agents such as beta-blockers, IV contrast agents, or the tricyclic
(MCQ)
Complications:
a. Heart failure
b. Dilated cardiomyopathy
c. Arrhythmias
d. Stroke
e. Death due to hypertensive crisis.
Note: Pheochromocytomas is a highly vascular tumor that is why FNAC is not done in this case.
(LQ)
FNAC is also not done in case of thymomas (It is inconclusive)
Diagnosis of pheochromocytoma :
1. Screening test: phentolamine test (MCQ):
2. The diagnosis can usually be made by analysis of a single 24 h urine sample.
a. Urinary total metanephrine: Most sensitive & specific screening test for pheochromocytoma
(LQ 2012)
b. Urinary VMA measurements: Less sensitive and specific than urinary metanephrine
measurements.
c. Urinary catecholamines
3. Localization: Abdominal CT/MRI, or meta-iodobenzylguanidine (MIBG-Chromaffin-
seeking isotope) scan: 111In somatostatin analogue or 18F-dopa PET scan useful for detection of
extra-adrenal tumours.
Table - Biochemical and Imaging Methods Used for Pheochromocytoma and Paraganglioma
Diagnosis

Diagnostic Method

Sensitivity
Specificity
1. Plasma tests
a. Free metanephrine
++++
+++
b. Catecholamines
+++
++
c. Chromogranin A
+++
++
2. 24-h urinary tests
a. Total metanephrine
+++
++++
b. Vanillylmandelic acid
++
++++
c. Catecholamines
+++
+++
d. Fractionated metanephrine
++++
++
3. CT scan
++++
+++
4. MRI scan
++++
+++
5. Somatostatin receptor scintigraphy
++
++
6. MIBG scintigraphy
+++
++++
7. Dopa (dopamine) PET (preliminary data)
++++
++++
Extra Edge
1. For localization of tumour, contrast CT/MRI and MIBG scintigraphy is used
2. Pheochromocytomas is a highly vascular tumor that is why FNAC is not done in this case.
(LQ)
3. FNAC is also not done in case of thymomas (It is inconclusive)
Treatment of pheochromocytoma
1. Alpha blocker alone or alpha + beta blocking drug like labetalol.
2. Surgery to Remove the tumour most common post operative complication is hypotension
which is treated by normal saline infusion.
Extra Edge
1. Beta blocker alone are contraindicated in pheochromocytomas (AIPG 10)
2. Most common post operative complication is Hypotension which is managed by giving
normal saline.
Treatment of malignant pheochromocytoma
1. Aver-Buch’s chemotherapy protocol includes dacarbazine, cyclophosphamide and
vincristine.
2. 131I MIBG treatment using 200-mCi doses at monthly interval.

Anterior Pituitary
Hypopituitarism (Ref. Harrison-19th ed. Pg. 2255)
In hypopituitarism hormone are affected in the following order: GH (First to decrease) FSH and
LH, prolactin (PrL), TSH, and ACTH (Last to decrease). (MCQ)
Causes are from 3 levels
1. Hypothalamus: Kallmann’s syndrome , tumor, inflammation, infection (eg meningitis, TB),
ischemia.
2. Pituitary stalk: Trauma, craniopharyngioma, meningioma.
3. Pituitary: Tumour, irradiation, inflammation, infiltration (hemochromatosis, amyloidosis,
metastatic ca), ischemia (pituitary apoplexy, Sheehan's syndrome).
Pituitary apoplexy occur in pregnancy, DM, HT, Sickle cell anemia . (AIIMS May 12) It does not
occur in hyperthyroidism.
Features are due to
A.  hormones B. Mass effect
A. Hormone:
1. GH deficiency
2. Gonadotrophin deficiency (FSH; LH) oligomenorrhea or amenorrhea
3. Thyroid deficiency: As for hypothyroidism .
4. Corticotrophin deficiency: As for adrenal insufficiency . (MCQ: No hyper pigmentation as
ACTH is reduced)
5. Prolactin deficiency: failure of lactation.
Extra Edge
1. DI is not a feature of hypopituitarism i.e. transection of pituitary stalk does not lead to
diabetes insipidus)
2. Insulin is a pancreatic hormone and is not under the control of pituitary.
3. Transection of the pituitary stalk does not lead to diabetes mellitus.
B. Mass effect: eg pituitary tumour , causing mass effect, (Headache, Bitemporal hemianopia)
1. Tests:
Insulin tolerance test: In this test I/V insulin is given to induce hypoglycemia causing stress to
increased cortisol and increased GH secretion. In hypopituitarism, G H level does not increase on
including hypoglycemia.
2. Treatment involves hormone replacement and treatment of underlying cause.
a. Hydrocortisone for secondary adrenal failure.
b. Thyroxine if hypothyroid.
c. Hypogonadism (for symptoms and to prevent osteoporosis).
Extra Edge
1. Sheehan’s syndrome is post-partum infarction of the pituitary, leading to hypopituitarism.
2. Treatment consists of hormone replacement therapy including Glucocorticoids, thyroid
hormone, sex steroids, growth hormone, vasopressin, etc.
3. Thus multiple hormones must be replaced, but cortisol replacement is most important &
should be the first to be replaced.
4. Steroids are given before thyroxine, otherwise thyroxine may precipitate an adrenal crisis.
Pituitary tumours
1. Pituitary tumours (almost always benign adenomas) account for 10% of intracranial
tumours.
2. They may be divided by size: a microadenoma is a tumour< 1cm, and a macroadenoma is >
1cm.
3. Symptoms are caused by local pressure, hormone hyper secretion, or hypopituitarism
4. Features of local pressure (Especially if size is more than 10 mm)
a. Headache,
b. Visual field defects (bilateral temporal hemianopia, due to compression of the optic
chiasma),
c. Palsy of cranial nerves III,IV, VI (pressure or invasion of the cavernous sinus).
d. Diabetes insipidus (DI) more likely from hypothalamic disease)
e. Disturbance of hypothalamic centres sleep, and appetite
f. Erosion through floor of sella leading to CSF rhinorrhea.
5. Treatment of hypopituitarism
a. In hypopituitarism start hormone replacement as needed. Ensure steroids are given before
thyroxine, as thyroxine may precipitate an adrenal crisis.
b. Surgery: pituitary surgery is trans-sphenoidal
c. Radiotherapy: Post-op if complete removal of the tumour has not been possible.
Craniopharyngioma (Ref. Harrison-19th ed. Pg. 2483)
1. It does not secrete any hormone.
2. Bimodal age of presentation – childhood and above 60 years.
3. Commonest childhood intracranial tumour
4. Most common cause of hypopituitarism in children
5. Benign pituitary tumor derived from Rathke's pouch remnants
6. Located above the sella turcica i.e. supra sellar mass.
7. Extends into sella turcica and destroys the gland. Can also damage the pituitary stalk,
causing raised prolactin.
8. Cystic tumor with hemorrhage and calcification.
9. Commonly causes bitemporal hemianopia
10. Over 50% present in childhood with growth failure;
11. Adults may present with amenorrhoea, ↓libido, hypothalamic symptoms (eg central
diabetes insipidus, hyperphagia, sleep disturbance) or tumour mass effect.
Tests: CT/MRI (calcification in 50%, may also be seen on skull XR).
Treatment: Surgery ±post-op radiation.
Hyperprolactinemia (Ref. Harrison-19th ed. Pg. 2266)
Hyperprolactinemia may result from
1. Excess production from the pituitary, eg prolactinoma. (A prolactinoma is the most
common hyperfunctioning pituitary adenoma).
2. Administration of a dopamine antagonist
Causes of hyperprolactinemia
1. Physiological: Pregnancy; breast-feeding; stress eg post-seizure.
2. Drugs (most common cause): Phenothiazine; metoclopramide; haloperidol, methyldopa;
estrogens.
3. Diseases: Prolactinoma: micro- or macroadenoma;
4. Stalk damage: pituitary adenomas, surgery, trauma; craniopharyngioma,;
5. Other: hypothyroidism, CRF.
Symptoms: Females:
1. Amenorrhea
2. Oligomenorrhea;
3. visual field defect,
4. infertility;
5. Galactorrhea
6. Men have decreased libido and erectile dysfunction and infertility, due to hypogonadism.
7. Hypopituitarism occurs in 50% and it is caused by mass effect of the tumor
Tests :
1. Serum prolactin level estimation (It is the most important investigation)
a. If serum prolactin >100 microgram/ml it is strongly suggestive of macroadenoma. Levels
more than 200 micro gram per ml occur only in prolactinoma.
2. CT / MRI
Diagnosis is by MRI/CT for confirmation of tumor.
a. Microprolactinomas: A tumour <10mm on MRI
b. Macroprolactinomas: A tumour> 10 mm diameter on MRI.
Treatment:
1. Bromocriptine, a dopamine agonist. ↓ PRL secretion, restores menstrual cycles and ↓tumour
size.
An alternative dopamine agonist is cabergoline: more effective and less side effects.
2. Trans-sphenoidal surgery
3. Radiation therapy for non resectable macroadenomas
Growth Hormone
Basic physiology
1. Growth hormone is also known as somatotropin.
2. Growth hormone releasing inhibitory factor (GHRIF) is also known as somatostatin.
3. Somatomedin (LQ 2012) are a group of hormone produced when stimulated by
somatotropin (i.e. GH) to mediate its effects. They are:
a. Somatomedin A - also known as IGF – 2
b. Somatomedin B - Derived from vitronectin
c. Somatomedin C - also known as IGF – 1. It is a potent growth and differentiation factor.
4. Increase GH release by occur by
a. Fasting
b. L arginine
c. alpha agonist
d. dopamine
e. apomorphine
f. beta blocker
Extra Edge
1. GH is released by GHRF 2. Ghrelin is agonist for GHRF so increases GH
release.
3. Somatostatin inhibits GH secretion. 4. GH exerts its action directly or via IGF-1
Extra Edge : Mecaserminisrecombinanthumaninsulin-like growth factor 1(IGF-I), which is used
for the long-term treatment ofgrowth failure in children with severe primary IGF-I deficiency.
This drug is not to be confused with Mecasermin rinfabate, which is a combination of
recombinant human IGF-1 (rhIGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3).
IGFBP-3 serves to prolong the action of IGF-1 in the human body. These are new drugs
Acromegaly (Ref. Harrison-19th ed. Pg. 2269)
1. Almost always due to pituitary adenoma secreting growth hormone
2. If GH secretion occurs in childhood prior to skeletal epiphyseal closure it leads to gigantism
3. If secretion begins after epiphyseal closure it leads to acromegaly.
4. Clinical Feature
a. There is excessive growth of hands, feet b. Jaw (prognathism) c. Voice
deepening
d. Joint erosions e. Carpal tunnel syndrome f. Proximal muscle weakness
Local effects of pituitary tumor-amenorrhea, headaches, visual field loss, weakness.
Complications:
1. DM as GH is counter-regulatory to insulin
2. Vascular: ↑BP, LVH, cardiomyopathy.
3. Malignancy: ↑development of colon cancer;
Tests
Screening test
1. Increase heal pad thickness seen on X-ray lateral view of the heal
Extra Edge Most common cause of increase heal pad thickness is heal injury (AIIMS Nov
2010).
2. Elevated IGF-I. Usually > 5 times normal.
3. Serum GH not suppressed following oral glucose. OGTT test (75 gms of glucose given .
After 1 hour if GH>1 ng/ml- suggestive of GH tumor.) It is the most definite test.
4. Confirmation- MRI/CT neoplasm
Treatment.
1. Medical:
a. Somatostatin analogues eg octreotide & Lanreotide.
b. Dopamine agonist – Bromocriptine & cabergoline are also used.
c. GH Receptor Antagonist, Pegvisomant
It endogenous GH action by blocking peripheral GH binding to its receptor.
Consequently, serum IGF-I levels are suppressed, reducing the deleterious effects of excess
endogenous GH. (PNQ)
2. Surgery - Trans-sphenoidal surgery: Usually the treatment of choice.
3. Radiotherapy: If surgery inappropriate or as adjuvant; may take years to work,
Extra Edge:
1. Carney syndrome is characterized by spotty skin pigmentation, myxomas, and endocrine
tumors, including testicular, adrenal, and pituitary adenomas. Acromegaly occurs in about 20% of
these patients.
2. McCune-Albright syndrome consists of polyostotic fibrous dysplasia, pigmented skin patches,
and a variety of endocrine disorders, including acromegaly, adrenal adenomas, and autonomous
ovarian function.
Recent Advances
1. GH Receptor Antagonist, Pegvisomant, antagonizes endogenous GH action by blocking
peripheral GH binding to its receptor.
2. Consequently, serum IGF-I levels are suppressed, reducing the deleterious effects of excess
endogenous GH. (PNQ) (Ref. Hari. 18th ed., Pg - 2896)
Octreotide
Octreotide is an octapeptide that mimics natural somatostatin pharmacologically, though it is a
more potent inhibitor of growth hormone, glucagon, and insulin than the natural hormone.
Actions
Since octreotide resembles somatostatin in physiological activities, it can:
1. Inhibit secretion of many hormones, such as gastrin, cholecystokinin, glucagon, growth
hormone, insulin, secretin, pancreatic polypeptide, TSH, and vasoactive intestinal peptide,
2. Reduce secretion of fluids by the intestine and pancreas,
3. Reduce gastrointestinal motility and inhibit contraction of the gallbladder,
4. Inhibit the action of certain hormones from the anterior pituitary,
5. Cause vasoconstriction in the blood vessels, and
6. Reduce portal vessel pressures in bleeding varices.
Uses of Octreotide:
1. Zollinger-Ellison syndrome, 2. Acromegaly 3. Carcinoid syndrome
4. Diarrhea 5. Dumping syndrome 6. Glucagonoma
7. Hepatorenal syndrome 8. Insulinoma 9. Intestinal obstruction
10. Metastatic neuroendocrine tumors 11. Nausea and vomiting 12. Oncogenic
osteomalacia
13. Orthostatic hypotension 14. Pancreatitis 15. Thymoma
16. TSH-secreting adenomas, 17. Variceal bleeding 18. VIPoma
Diabetes insipidus (Ref. Harrison-19th ed. Pg. 2275)
Anti Diuretic hormone (ADH) (DESMOPRESSIN)
Basic concepts
Desmopressin acts via V1 and V2 receptors.
1. Actions Via V1 are
a. Blood vessel = Constricts, causes increase BP in high doses.
b. Smooth muscle constriction, causes increases GIT movement
c. Liver increase hepatic glycogenolysis
d. Increase platelet aggregation
2. Action Via V2 are
a. Collecting tubules – action by regulating aquaporin 2, 3, 4 (Reabsorb water)
b. Liver : release of factor VIII ( that’s why it is used in hemophilia)
c. Endothelium : causes release of V.W. Factor
Diabetes insipidus (DI)
This is the passage of big volumes [polyuria (>3L/day) of dilute urine due to impaired water
resorption by the kidney, because of reduced ADH secretion from the posterior pituitary (cranial
DI), or impaired response of the kidney to ADH (nephrogenic DI).
Causes of cranial DI .
1. Idiopathic (>50%) . 2. Congenital: X-link recessive, DIDMOAD syndrome
3. Tumour: craniopharyngioma 4 Trauma: hypophysectomy, head injury.
5. Infiltration: histiocytosis, sarcoidosis. 6. Vascular: Sheehan's syndrome.'
haemorrhage
7. Infection: meningoencephalitis,
Important Point Multiple sclerosis is not a cause of DI
Causes of nephrogenic DI
1. Drugs:
a. Lithium (FAQ), b. Demeclocycline, c. Methoxyflurane, d. Amphotericin B,
e. Aminoglycosides, f. Cisplatin, g. Rifampin, h. Foscarnet
2. Chronic renal disease.
3. Post-obstructive uropathy.
4. Hypokalemia
5. Hypercalcemia (FAQ)
Diagnosis of DI
The water deprivation test.
1. In this test patient is hospitalized and his water intake is stop completely.
2. If patient urine out put is reduce that indicates psychogenic cause of polyuria.
3. If still urine out put is high then injection ADH is given.
4. Now If patient’s urine output is reduce that indicate cranial cause of diabetes insipidus.
5. If still urine output is high than it is most likely nephrogenic diabetes insipidus. In that case
treat the basic cause.
Laboratory differentiation of polyuria (LQ 2012)
Lab parameters

Psychogenic Polydipsia
Central DI
Nephrogenic DI
(LQ 2012)
Osmotic Diuresis
Serum Na
N or 

 (LQ 2012)
N or 
Posm
N, 


N, 
Uosm


 (LQ 2012)

Plasma ADH


↑

Uosm after ADH
Increase
Increase
Nil (LQ 2012)
Slight increase
How to approach a cause of Polyuria (>3L / 24 hrs)
Urine osmolality (Should be first to be checked in cases of polyuria)
1. Urine osmolality < 250 mosmol = diabetes insipidus
a. Low serum sodium, · Plasma osmolality Normal or Low = Psychogenic polydipsia
b. Increased serum sodium, Increased plasma osmolality (LQ 2012)
i. ↑ plasma ADH & no response in urine osmolality after ADH administration = Nephrogenic
DI
ii. ↓ plasma ADH & increase in urine osmolality after ADH administration = Central DI
2. Urine osmolality (>300 mosm/kg) = Solute Diuresis
Serum Sodium / Serum Osmolality is usually increased
During solute diuresis more water is lost than sodium thereby causing hypernatremia and
hypertonicity.
Solute Diuresis
a. Glucose (Diabetes Mellitus)
b. Mannitol (Osmotic Diuretic)
c. Urea (High protein feeding)
d. Resolving ATN
e. Medullary Cystic Disease

TABLE Response to Water Deprivation Test

Diagnosis

Increase in Urine Osmolality above 280 mOsm/kg with Dehydration

Further Increase in Urine Osmolality in Response to ADH
Normal
+
-
Central DI
-
+
Nephrogenic DI
-
-
Treatment
1. Cranial DI: desmopressin (LQ 2012), a synthetic analogue of ADH.
2. Nephrogenic:
a. Treat the cause-
b. Treatment with conventional doses of a thiazide diuretic and/or amiloride in conjunction
with a low-sodium diet and a prostaglandin synthesis inhibitor (e.g., indomethacin) usually
reduces the polyuria and polydipsia (Ref. Hari. 18th ed., Pg-2907)
Endocrine Paraneoplastic Syndrome (FAQ)
Syndrome Chiefly associates with
1. SIADH (Hyponatremia) (LQ 2012) . Small cell lung Ca,
. Head & Neck cancer
2. Cushing's syndrome . Small cell lung Ca
. Carcinoid Tumour
3. Hypercalcemia of malignancy . Non small cell lung Ca (squamous)
. Breast Ca, Renal Ca, Myeloma, Bladder Ca, Head & Neck Ca
4. Acromegaly . Carcinoid tumour, Small cell Lung Ca, Pancreatic Islet tumour
5. Gynecomastia . Testicular Ca,. Lung Ca, Carcinoid Tumour of lung and GIT
6. Hypoglycemia . Sarcomas, Hepatoma
Note: Hypercalcemia occur in squamous cell lung cancer. it does not occur in small cell lung
cancer.