Diabetes Insipidus

Question 1

What is a diabetes insipidus and what is it aka

Answer 1

• Condition where the kidneys are unable to concentrate urine
• Arginine vasopressin deficiency (central) or resistance (nephrogenic)

Question 2

Compare cranial/central vs nephrogenic diabetes insipidus aetiology

Answer 2

Cranial DI - Insufficient levels of circulating ADH due to ‘damage’ of the hypothalamus or posterior pituitary

• Idiopathic (autoimmune),
• Infiltrations (sarcoidosis),
• Infections (TB, meningitis)
• Trauma (skull fracture, RTA, external irradiation),
• Tumour (craniopharyngioma, hypothalamic tumour)

Nephrogenic DI - Renal resistance to ADH due to ‘damage’ of the kidneys

• Idiopathic
• Familial
• Kidney disease

Question 3

What is ADH aka? Where is ADH produced, stored and release from?

Answer 3

• Anti-diuretic hormone (ADP) aka arginine vasopressin (AVP)
• Produced in the hypothalamus
• Stored & release from posterior pituitary gland

Question 4

Diabetes insipidus clinical presentation

Answer 4

Polydipsia & polyuria (dilute urine)

Question 5

Diabetes insipidus investigations

Answer 5

Water deprivation test
- Patient stops drinking water for 2-3hrs
- Patient serum & urine osmolarity is checked hourly for 8hrs
- If UR/serum osmolarity ratio <2 then DI (dilute urine)
- Patient then given DDAVP & osmolarity checked 4hrs after
- If UR/serum osmolarity ratio improves then cranial DI (AVP deficient) => CT/MRI to rule out brain tumour

Question 6

Explain the findings of a water deprivation test in diabetes insipidus

Answer 6

The failure of AVP (either due to deficiency or resistance) means that even when the patient is water deprived they fail to concentrate their urine (i.e. they don’t re absorbed water). This means their Ur/serum osmolarity is low (urine concentration is low).

If the patient has cranial DI this is due to lack of AVP and so when DDAVP is given, the Ur/serum osmolarity improves as the AVP works on the kidneys to reabsorb water. This would not be the case in nephrogenic DI where the kidney do not properly respond to AVP (despite if AVP concentration increases)

Question 7

Diabetes insipidus management

Answer 7

Cranial/Central/neurogenic DI
- Desmospray (N) or Desmopressin (O) tablets
- Desmopressin (IM) in emergency/post pituitary surgery
- I.e. AVP replacement

Nephrogenic DI
- No current drug treatment

Question 8

What is ADH/AVP and how does it work

Answer 8

ADH binds to receptors on the cell membrane of the collecting duct =>
This activates a signaling cascade that phosphorylates aquaporin-2 (AQP2) molecules =>
The phosphorylated AQP2 molecules are targeted to the apical plasma membrane =>
Water passes through the AQP2 channels and into the tissue fluid and blood plasma =>
The filtrate in the collecting duct becomes more concentrated and produces a small volume of concentrated urine.