Diabetes Insipidus

Group 3A
Introduction
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Results from a deficit of anti-diuretic hormone (ADH). This deficit may originate in
the neurohypophysis. Head injury or surgery may cause a temporary condition.
In some cases, the condition is considered to be nephrogenic, when the renal
tubules do not respond to the hormone. The latter may be genetic or linked to
electrolyte imbalance or drugs. The clinical manifestations include polyuria with
large volumes of dilute urine and thirst, eventually causing severe dehydration.
Replacement therapy for ADH is available.
Passage of large volumes (>3 liters/24 hours) of dilute urine (<300 mOsm/kg). it
has 2 major forms:
o Central (neurogenic, pituitary or neurohypophyseal) : characterized by
decreased secretion of ADH/vasopressin.
o Nephrogenic : characterized by decreased ability to concentrate urine
because of resistance to ADH action in the kidney.

Pathophysiology
1. Central DI may be due to : Idiopathic causes, malignant or benign tumors of the
brain or pituitary, cranial surgery or head trauma.
a. Idiopathic DI
Develops when cells in the hypothalamus are damaged/destroyed.
May be due to lymphocytic hypophysitis wherein there is a
lymphocytic infiltration of the stalk and posterior pituitary.
There may be antibodies directed against vasopressin cells.
b. Tumor-associated DI
Primary intracranial tumors include craniopharyngiomas,
germinomas, and pineal tumors.
c. DI in head trauma
Central DI can be an acute or chronic complicationof head injury or
subarachnoid haemorrhage.
d. Hereditary central DI
Autosomal dominant inheritance and results from a defect in the
AVP-NP2 gene on chromosome 20p13.
The defect results in the production of mutant prohormone that is
toxic to the neuron and eventually destroys it.
Another recessive form of central DI results from the production of
biologically inactive vasopressin.

2. Nephrogenic DI : most often develops as a result of lithium toxicity or

hypercalcemia. Impairment of urinary concentration occurs in up to 20% of
patients taking lithium, as a result of dysregulation of the aquaporin system in
principal cells of the collecting duct.
o Causes may include:
Hypokalemia
Renal disease
Hyperglycemia (osmotic diuresis)

Nephrogenic DI can be distinguished from central DI by administration of

desmopressin, the synthetic analog of ADH. Lack of prompt decrease in urine
volume and an increase in urine osmolarity within 2 hours after injection of
desmopressin is strongly suggestive of nephrogenic DI. The treatment for
nephrogenic DI is to correct the underlying renal disorder.