Posterior Pituitary Disorders

Question 1

ADH is synthesized in the _______ & then migrates in __________ __________ along the axonal pathways to the _____ pituitary.

Answer 1

hypothalamus, neurosecretory granules, posterior

Question 2

Pituitary disease alone without hypothalamic involvement does or doesn’t lead to ADH deficiency?

Answer 2

No, it doesn’t lead to ADH deficiency.

Question 3

Factors that increase ADH/vasopressin release

Answer 3

• increases osmolality
• hypovolemia
• hypotension
• hypothyroidism
• adrenaline (epinephrine)
• cortisol
• nicotine
• angiotensin II
• antidepressants

Question 4

Factors that decrease ADH/vasopressin

Answer 4

• decreased osmolality
• hypervolemia
• hypertension
• ethanol
• alpha-adrenergic stimulation

Question 5

3 disorders of ADH secretion

Answer 5

1. Cranial diabetes insipidus (DI)
2. Nephrogenic DI = renal tubules are insensitive to ADH
3. Syndrome of Inappropriate Antidiuretic Hormone (SIADH) = inappropriate excess of ADH

Question 6

Diabetes Insipidus (DI)

Answer 6

Pathological state in which large amounts of hypotonic, dilute urine are passed (polyuria).

Question 7

Causes of DI (2)

Answer 7

1. Deficiency of ADH secretion (cranial DI)
2. An inappropriate renal response to ADH (nephrogenic DI)

• As a result, fluid reabsorption at the kidneys is impaired causing the characteristic signs & symptoms.

Question 8

Clinical Features of DI

Answer 8

• Polydipsia = deficiency of ADH or insensitivity to its action —– excess excretion of dilute urine with a compensatory increase in thirst.
• Polyuria =up to 20L of water can be passed in a day.
• Severe dehydration = can lead to unconsciousness.

Question 9

Familial isolated vasopressin deficiency

Answer 9

• causes DI from early childhood
• dominantly inherited
• caused by a mutation in the AVP-NPII gene

Question 10

DIDMOAD (Wolfram’s) Syndrome

Answer 10

• rare autosomal recessive disorder
• 4 most common features = DI, DM, Optic atrophy & Deafness.
• caused by mutations in the WFS1 gene on c/some 4
• MRI may show an absent or poorly developed posterior pituitary.

Question 11

Diagnosis of DI

Answer 11

Clinical history + increased plasma osmolality (>300 mOsm/kg) + low urine osmolality (<600 mOsm/kg).

Question 12

ADH stimulation test is used to?

Answer 12

Distinguish between cranial DI & nephrogenic DI

Question 13

ADH stimulation test results

Answer 13

• Cranial DI = inability to concentrate urine after fluid restriction alone, but the ability to concentrate urine after administration of ADH.
• Nephrogenic DI = inability to concentrate urine even after administration of ADH.

Question 14

Osmolality

Answer 14

The concentration of dissolved particles
- normal = 285 - 295 mOsm/kg
- dissolved particles (major) = glucose, sodium, blood urea nitrogen (BUN).

Question 15

Water Deprivation Test Results
- Normal response

Answer 15

Normal response
- serum osmolality = remains within normal range (275 - 295 mOsm/kg)
- urine osmolality = rises to >600 mOsm/kg

Question 16

Water Deprivation Test Results
- Diabetes Insipidus (DI)

Answer 16

Diabetes Insipidus (DI)
- serum osmolality = rises above normal without adequate concentration of urine osmolality.
- serum osmolality >300 mOsm/kg
- urine osmolality <600 mOsm/kg

Question 17

Water Deprivation Test Results
- Nephrogenic DI

Answer 17

If desmopressin doesn’t concentrate urine

Question 18

Water Deprivation Test Results
- Cranial DI

Answer 18

If urine osmolality rises by >50% after desmopressin.

Question 19

Nephrogenic DI may be:
(2)

Answer 19

1. Inherited
   - rare sex-linked recessive, with an abnormality in the vasopressin-2 receptor.
   - an autosomal post-receptor defect in aquaporin-2 (ADH-sensitive water channel)
2. Acquired (more common)
   - as a result of renal disease, sickle cell disease, drug ingestion (lithium), hypercalcemia, or hypokalemia.

Question 20

Syndrome of Inappropriate Anti-diuretic Hormone (SIADH) leads to:
(2)

Answer 20

1. Retention of water
2. Hyponatremia

Question 21

Clinical Features of SIADH

Answer 21

Presentation is usually vague, with confusion, nausea, irritability & later, fits & coma.

Question 22

Mild symptoms of SIADH

Answer 22

Na+ <125 mmol/L

Question 23

Serious manifestations

Answer 23

Likely Na+ <115 mmol/L

Question 24

Investigations of SIADH

Answer 24

• dilutional hyponatremia (drinking too much water)
• low plasma osmolality
• euvolemia
• inappropriate urine osmolality >100 mOsm/kg
• continued urinary sodium excretion >30 mmol/L
• absence of hypokalemia (hypotension)
• normal function of renal, adrenal, thyroid.

Question 25

Common causes of SIADH (5)

Answer 25

1. Tumors = small-cell carcinoma of lung, prostate, thymus.
2. Pulmonary lesions = pneumonia, tuberculosis (TB), lung abscess.
3. CNS = meningitis, tumors, head injury.
4. Metabolic = alcohol withdrawal, porphyria
5. Drugs = carbamazepine, chlorpropamide

Question 26

Management of SIADH = Treat the cause
(5)

Answer 26

1. Fluid Restriction = 500-100 mL OD (once daily), correct the biochemical abnormalities in almost every case.
2. Frequent measurement of plasma osmolality, serum Na+ & body weight.
3. Demeclocycline (600-1200 mg OD) is given if water restriction is poorly tolerated or ineffective.
4. Hypertonic saline = may be indicated when very severe, but potentially dangerous & should only be used with extreme caution.
5. Vasopressin V2 antagonists