Diabetes Insipidus

Question 1

What is DB insipidus

Answer 1

disease in where the secretion of/ response to vasopressin (ADH)is impaired, resulting in production of very large quantities of dilute urine leading to dehydration and insatiable thirst.

Question 2

Type of DBI

Answer 2

Central (most common form): caused by 1)insufficient or absent hypothalamic synthesis
2) insufficient or absent secretion of antidiuretic hormone (ADH) from the posterior pituitary

Nephrogenic (rare): defective ADH receptors in the distal tubules and collecting ducts

Question 3

Causes of CDI

Answer 3

Primary (∼ ⅓ of cases)

• Usually idiopathic.
• hereditary form is rare.

Secondary (∼ ⅔ of cases)

• Brain tumors (especially craniopharyngioma)
• cerebral metastasis (most common: lung cancer)
• Neurosurgery:after removal of large adenomas
• TBI, pituitary bleeding, subarachnoid hemorrhage
• Pituitary ischemia (e.g., Sheehan syndrome)
• Infection (e.g., meningitis)

Question 4

What is Sheehan’s syndrome

Answer 4

Sheehan syndrome is postpartum necrosis of the pituitary gland.

Usually occurs afterpostpartum hemorrhage, but clinical evidence of haemorrhage isn’t required for sheehan syndrome to be present

Prolactin production increases During pregnancy, causing hypertrophy of prolactin-producing regions of the pituitary

This increases the size of the pituitary gland,
makes it very sensitive to ischemia.

So blood loss during delivery/postpartum hemorrhage
→ hypovolemia
→ vasospasm of hypophyseal vessels
→ ischemia of the pituitary gland and necrosis

Question 5

Causes of NDI

Answer 5

Hereditary (very rare)

Acquired
medications interfering w/ADH action on kidney (lithium, demeclocycline)

Hypokalemia, hypercalcemia causes reduced sodium reabsorption and reduced response to ADH

Renal disease causes da,age and reduces renal sensitivity to ADH (e.g., autosomal dominant polycystic kidney disease, renal amyloidosis)

Pregnancy causes transient resistance to ADH known as Gestational diabetes

Question 6

PP of DBI

Answer 6

NORMALLY

• ADH signals the integration of aquaporins into the plasma membrane of collecting duct cells
• Allows the reabsorption of free water through these pores

DBI

• CDI:↓ ADH (central DI)’ no aquaporins,
• NDI: defective renal ADH receptors

-kidneys cant concentrate urine by water reabs
→ dilute urine d/2 increased water
(low urine osmolarity)

Urine osmolality changes

Normal: 500–800 mOsmol/kg

Complete DI (< 300 mOsmol/kg, often < 100 mOsmol/kg)

Partial DI (300–500 mOsmol/kg)

Question 7

Sx of DBI

Answer 7

Polyuria with dilute urine
Nocturia → Restless sleep, daytime fatigue
Polydipsia
If low water intake →
severe dehydration (altered mental status, lethargy, seizures, coma)
-hypotension

In the absence of nocturia, diabetes insipidus is very unlikely!

Question 8

Dg of DBI

Answer 8

sodium, plasma osmolality, and urine osmolality values are tested

Water deprivation test to confirm suspicions and dx CDI vs NDI

CT if CDI suspected to rule out craniopharyngioma/ metastasis

Question 9

What is the water deprivation test and how is it performed

Answer 9

1) obtainin baseline lab values
2) patients stop drinking water for 2–3 hours before the first measurement
3) After 2–3 hours w/o water test :
- urine volume and osmolality every hour
- sodium and plasma osmolality every two hours

4)Water deprivation continues until:
-Urine osmolality becomes normal (> 600 mOsmol/kg) =primary polydipsia NOT DI
OR
-No change in urine osmolality despite a rising plasma osmolality (> 290 mOsmol/kg)
OR
-Plasma osmolality > 295–300 mOsmol/Na+ decreases

5)If latter two situations give desmopressin (synthetic ADH)I sx bet/w CDI/NDI

6) urine osmolality testing every 30 minutes for 2 hours
- CDI: Urine osmolality rises after desmopressin administration (renal ADH receptors are intact).
- NDI: Urine osmolality remains low after desmopressin administration (defective renal ADH receptors).i

Question 10

Dx of DBI

Answer 10

Excessive water intake

Diabetes mellitus

Beer potomania: Dilutional hyponatremia secondary to limited renal free water excretion caused by intake of large amounts of beer. Malnutrition in patients with alcohol abuse contributes to low body sodium stores.

Question 11

Rx of DBI

Answer 11

Central diabetes insipidus

• Desmopressin: (causes hyponatremia)
• Chlorpropamide ( increases secretion and strength of ADH)

Nephrogenic diabetes insipidus

• Thiazide diuretics (depletes sodium so promotes reabsorption of sodium and water before water reaches collecting ducts)
• NSAIDs
• Amiloride:blocks entry of lithium in lithium induced NDI