Diabetes Insipidus (Cranial and Nephrogenic)

Vasopressin, also called antidiuretic hormone (ADH)= arginine vasopressin (AVP) is as a nonapeptide synthesised in the hypothalamus and is the key regulator of water reabsorption in the distal nephron. In healthy adults, the osmotic threshold for AVP secretion ranges from 280-285 mOsm/kg H2O. Small rises in plasma osmolality of as little as 1% are sufficient to trigger AVP release with proportional increases in urine concentration, and maximal antidiuresis is achieved after increases in plasma osmolality of only 5 to 10 mOsm/kg H2O above the threshold for AVP secretion.

About

• AVP is made in the hypothalamus and stored and released from posterior pituitary
• Diabetes Inspidus is due to the lack of action of ADH (AVP)
• This is due to either a failure to produce ADH(Cranial) or failure of its action (Nephrogenic)
• NDI results from the failure of the kidney to respond to AVP.
• Urine production in patients with NDI is typically 12 L/day.

Physiology

• AVP system maintains water balance based on serum osmolality and arterial blood volume via the vasopressin-2-receptor (V2R)
• AVP activates V2R at the basolateral membrane of the principal cells in the distal convoluted tubule and collecting duct of the kidney.
• This activates protein kinase A which in turn phosphorylates aquaporin 2 (AQP2) water channels in the intracellular vesicles.
• Exocytic insertion of AQP2 vesicles into the cell membrane follows, and the collecting duct becomes water permeable, thus concentrating the urine.

Nephron Structure

Aetiology

• Loss of ADH secretion or effectiveness is the result is free water loss at the collecting tubules
• Patient if water access restricted rapidly becomes dry and hypernatraemic
• Cranial DI is the commonest after 80-90% of the magnocellular neurons in the hypothalamus are damaged

Cranial DI (Central DI due to impaired secretion of arginine vasopressin )

• Idiopathic, Head injury, Craniopharyngioma
• Histiocytosis X, Sarcoid, TB, DIDMOAD
• Interventricular haemorrhage, Aneurysms
• Meningitis, Post encephalitis
• Familial (autosomal dominant)

Nephrogenic DI (Nephrogenic DI due to impaired action on the collecting tubules)

• Lithium, Hypercalcaemia , Hypokalaemia
• Genetic, Demeclocycline, Sickle cell disease
• Pyelonephritis, Post obstruction uropathy
• Sarcoidosis, Amyloidosis, Polycystic disease

Clinical

• Polyuria despite clinical dehydration
• Hypernatraemia If water intake fails to match water loss
• Polydipsia, Confusion, hypervolaemia with progressive hypernatraemia
• May be a risk of venous thromboembolism

Investigations

• FBC, U&E: hypernatraemia
• Raised plasma osmolality
• Inappropriately low serum osmolality
• Inappropriately low urine osmolality
• Inappropriate high urine volume

Differential of Polyuria

• Hyperglycaemia, Hypercalcaemia
• Diuretics, Hypokalaemia, Diabetes Insipidus
• Potomania, Renal failure
• Post SVT and ANP release

Management

• Cranial DI: is with des-amino-des-aspartate-arginine Vasopressin (desmopressin, DDAVP) an analogue of ADH with a longer half-life. It is given usually IM or intranasal metered-dose spray. Be careful of hyponatraemia and water intoxication
• Nephrogenic DI: Polyuria is helped by Bendroflumethiazide 2.5-5 mg / Amiloride 5-10 mg/day. The role of Amiloride is to avoid hypokalaemia which can worsen polyuria. Some add NSAID Indomethacin and a Low Sodium diet
• Nephrogenic Diabetes Insipidus due to Lithium: Treat with Amiloride 2.5-10 mg/day which reduces lithium entry into the principal cells in the distal nephron. NSAIDs have also been used

References

• Diabetes Insipidus Anne Klibanski, MD, Janet Schlechte, MD, Nicholas Tritos, MD The Journal of Clinical Endocrinology & Metabolism, Volume 98, Issue 7, 1 July 2013, Pages 35A-36A,
• Diabetes insipidus: The other diabetes