Diabetes Insipidus Flashcards
What is diabetes insipidus (DI)?
A metabolic disorder characterised by an absolute or relative inability to concentrate urine, resulting in the production of large quantities of dilute urine.
Briefly describe the pathophysiology of DI
It may result from an absolute or relative deficiency of arginine vasopressin (AVP), also known as antidiuretic hormone (ADH), which is produced by the hypothalamus and secreted via the posterior pituitary, or by resistance to its action within the renal collecting ducts.
What are the different types of DI?
- Central
- Nephrogenic
Briefly differentiate between central and nephrogenic DI
Central: DI caused by absence/ decreased secretion/ production of antidiuretic horomone (ADH) by posterior pituitary
Nephrogenic: kidneys unresponsive to ADH secreted by posterior pituitary
Give examples of central causes of DI
- Idiopathic
- Acquired:
- Pituitary surgery
- Craniopharyngioma
- Post-traumatic head injury
- Pituitary stalk lesions
- Autoimmune disorders→ Hashimoto’s thyroiditis and diabetes mellitus type 1
- Subarachnoid haemorrhage
- Infection→ meningioencephalitis
- Congenital:
- Wolfram syndrome (WS)
Give examples of nephrogenic causes of DI
- Acquired:
- Medications→ lithium therapy
- Systemic disease, electrolyte imbalance, and post-obstructive uropathy→ chronic kidney disease, renal sarcoidosis and renal amyloidosis
- Congenital:
- Mutations in the AVPR2 receptor, which mediates the antidiuretic action of AVP in the collecting duct
What are the signs of DI?
- Signs of volume depletion: dry mucous membranes, poor skin turgor, tachycardia, hypotension and shock
- Hypotension
What are the symptoms of DI?
- Polyuria
- Increased thirst/ polydipsia
- Nocturia
- Dehydration
What investigations should be ordered for DI?
- Urine osmolality
- Serum osmolality
- Serum glucose
- Serum sodium
- Serum potassium
- Serum urea nitrogen
- Serum calcium
- Urine dipstick
- 24 hour urine collection for volume
- Water deprivation test
- AVP (desmopressin) stimulation test
Why investigate urine osmolality?
A low urine osmolality in conjunction with high serum osmolality or elevated sodium strongly suggests DI.
Low: typically <300 mmol/kg (<300 mOsm/kg).
Why investigate serum osmolality?
The predicted serum osmolality can be calculated on the basis of the serum sodium, potassium, glucose, and blood urea nitrogen.
Normal or elevated.
Why investigate serum glucose?
Order as baseline investigation, and to exclude diabetes mellitus as a cause of polyuria.
Normal.
Why investigate serum sodium?
Serum sodium may be normal if patients have an intact thirst mechanism and have unrestricted access to fluids. Elevated serum sodium in association with hypotonic urine (urine osmolality <300 mmol/kg [<300 mOsm/kg]) strongly suggests DI.
Normal or elevated.
Why investigate serum potassium?
Hypokalaemia is associated with nephrogenic DI.
Normal or low.
Why investigate serum urea nitrogen?
Elevated in patients with volume depletion or co-existent renal disease.
Normal or elevated.
How does water deprivation test (desmopressin stimulation test) differentiate between central, nephrogenic and primary diabetes insipidus?
In cranial diabetes insipidus the patient lacks ADH. The kidneys are still capable of responding to ADH. Therefore initially the urine osmolality remains low as it continues to be diluted by excessive water secretion in the kidneys. Then when synthetic ADH is given the kidneys respond by reabsorbing water and concentrating the urine so the urine osmolality will be high.
In nephrogenic diabetes insipidus the patient is unable to respond to ADH. They are diluting their urine with the excessive water secretion by the kidneys. Therefore the urine osmolality will be low initially and remain low even after the synthetic ADH is given.
In primary polydipsia the 8 hours of water deprivation will cause the urine osmolality to be high even before the synthetic ADH is given. A high urine osmolality after 8 hours of water deprivation indicates no diabetes insipidus.
