Neurohypophysial disorders

Question 1

Recall the pathophysiology of diabetes insipidus

Answer 1

• Central (cranial): absence/lack of circulating vasopressin
• Nephrogenic: end-organ (kidneys) resistance to vasopressin

Cycle:

• Lack of VP
• Increased urine excretion (polyuria)
• Reduction in EC fluid volume
• Increase in plasma osmolarity
• Osmoreceptors trigger VP release
• Triggers thirst
• Increased drinking (polydipsia)
• Decrease in plasma osmolarity
• Expansion of EC fluid volume
• Increased urine excretion (polyuria)

Question 2

What are the principle causes of diabetes insipidus?

Answer 2

Cranial:

• Damage to neurohypophysial system: injury, surgery, cerebral thrombosis, tumours, granulomatous infiltration of median eminence
• Idiopathic
• Familial (rare) - receptor gene mutations

Nephrogenic:

• Familial (rare)
• Drugs - lithium, dimethyl chlortetracycline

Question 3

What are the clinical features of diabetes insipidus?

Answer 3

• Polyuria
• Hypo-osmolar urine (v dilute)
• Polydipsia
• Dehyration if fluid intake not maintained (can –> death)
• Possible sleep disruption
• Possible electrolyte imbalance

Question 4

How is diabetes insipidus diagnosed?

Answer 4

1. Water deprivation test - should stimulate VP system - no/little change in urine osmolarity/VP
2. Desmopressin (DDAVP) - like giving extra VP
   - Central - urine osmolarity increases bc VP receptors work fine and are stimulated by DDAVP
   - Nephrogenic - no effect bc they have VP anyway, it just has no effect

Question 5

How is diabetes insipidus treated?

Answer 5

• Desmopressin (DDAVP) for cranial - oral

- Thiazide diuretics for nephrogenic

Question 6

Recall the pathophysiology of SIADH

Answer 6

• Plasma [VP] is inappropriately high for existing plasma osmolarity
• Increased water reabsorption
• Decreased plasma osmolality (hyponatraemia)
• Decreased urine volume
• Compensatory “escape” phenomenon - natriuresis + attempted restoration of urine output?

Question 7

What are the principle causes of SIADH?

Answer 7

• Tumours (ectopic secretion)
• Neurohypophysial malfunction (meningitis, cerebrovascular disease)
• Thoracic disease (pneumonia)
• Endocrine disease (Addison’s)
• Physiological (hypovolaemia, pain, surgery)
• Drugs (carbamezapine, SSRI)
• Idiopathic

Question 8

What are the principle clinical features of SIADH?

Answer 8

Signs:

• Raised urine osmolarity
• Decreased urine volume (initially)
• ***Hyponatraemia - decrease in plasma [Na] due to increased water reabsorption

Symptoms:

• Can be asymptomatic
• When [Na] falls <120mM - generalised weakness, poor mental function, nausea
• When <110mM - confusion, coma, death

Question 9

How is SIADH treated?

Answer 9

• Once cause is identified, provide appropriate treatment, e.g. surgery
• If someone already hyponatraemic, must treat this immediately: immediate fluid restriction; longer term, use drugs that prevent VP action in kidneys (lithium, dimethyl chlortetracycline, V2R antagonist - vaptans)

Question 10

What are the principle actions of vasopressin?

Answer 10

• Acts on renal cortical and medullary CDs
• Stimulates synthesis and assembly of aquaporin 2
• Increased water transport
• Increased water reabsorption
• Anti-diuretic effect
• All above = V2
• Vasoconstrictor activity - V1a
• ACTH release - V1b
• Factor VIII + VWF - V2
• Central effects

Question 11

Which receptors does vasopressin act on

Answer 11

V2 receptors

Question 12

What are the neurohypophysial hormones?

Answer 12

Vasopressin

Oxytocin