Endocrinology - Diabetes Insipidus

Question 1

what is DI? what are the 2 major forms?

Answer 1

Condition caused by hyposecretion of ADH (cranial DI) or insensitivity to its effects (nephrogenic GI).

Results in AQP insertion in luminal membrane of DCT and CD principal cells… inability to concentrate urine… passage of copious volumes of dilute urine.

Question 2

describe the symptoms of DI

Answer 2

Onset can be vague and insidious.

• marked polyuria (usually >3L/24hrs of low osmolality urine)
• polydipsia and chronic thirst
• nocturia
• +/- urinary incontinence if damage to bladder from chronic overdistension

Question 3

suggest common causes of cranial DI

Answer 3

Most common:

1. brain tumours, e.g. hypothalamic mets, large pituitary tumours, germinomas…
2. severe head injuries (damage hyothalamus or pit. gland)
3. intracranial surgery
4. idiopathic

Other causes:

• infections, e.g. meningitis
• granulomata, e.g. sarcoidosis, TB, GPA
• vascular disorders, e.g. stroke, sickle cell disease, Sheehan’s syndrome
• Wolfram’s syndrome: autosomal recessive combination of DI, DM, optic atrophy and deafness

Question 4

suggest common causes of nephrogenic DI

Answer 4

Acquired:

• lithium ADR
• hypercalcaemia or hypokalaemia
• ureteral obstruction
• idiopathic

Inherited:

• X-linked AVPR2 mutation (ADH R) - 90%
• autosomal recessive AQP2 mutation - 10%

Question 5

which tests would you use to establish Dx of DI

Answer 5

1. Bloods
   - plasma osmolality: >295 mOsmol/kg
   - UandEs: often increased Na+ due to excess free water loss
   - plasma glucose: rule of DM
2. Urinalysis
   - urine osmolality: <700 mOsmol/kg
   - 24hr urine collection: >3L/24hrs
3. Fluid deprivation test + desmopressin response: pt is fluid-deprived for up to 8hrs after which 2 ug (IM) desmopressin is given:
   - urine osmolality after fluid deprivation <300 mOsm/kg in both cranial and nephrogenic DI
   - urine osmolality after desmopressin: >800 in cranial DI and <300 in nephrogenic DI

Question 6

which tests may help determine cause of DI?

Answer 6

1. MRI of hypothalamis, pit. gland and surrounding tissue

2. KUB USS or IV pyelogram: assess for obstructive complications

Question 7

how would you manage a pt with cranial DI?

Answer 7

i) Mild cases (UO 3-4L/24 hrs): water ingestion to quench thirst
ii) desmopressin (e.g. intranasal spray) - long-acting ADH analogue that acts on DCTs and CDs of kidney to increase water absorption.
iii) 1-3 mthly measurement of serum Na+ due to risk of hyponatraemia from chronic desmopressin overdose

Question 8

how would you manage a pt with nephrogenic DI

Answer 8

i) if UO <4L/24 hrs and pt does not have severe dehydration, definitive therapy not always necessary. Important to always drink enough to satiate thirst.
ii) Correct any underlying cause, e.g. stop lithium, correct electrolyte abnormalities
iii) High-dose desmopressin may be used with in mild-moderate cases. Combination Tx with thiazide diuretic and NSAID may be effective in reduce urine volume produced.
iv) pts with genetic cause of severe DI may need o practice clean, intermittent catheterisation to reduce urinary tract back-pressure complications.