Antidiuretic hormone (ADH) or vasopressin is synthesized in the hypothalamus and secreted from the posterior lobe of the pituitary gland. The normal action of ADH on the renal tubules is to promote water reabsorption and prevent diuresis. Deficiency of ADH secretion or resistance to ADH action on renal tubules causes excessive water excretion and a syndrome of diabetes insipidus.

Central diabetes insipidus is caused by deficiency of ADH secretion due to genetic abnormalities or secondary to many central nervous system disorders.

Nephrogenic diabetes insipidus results from deficiencies in the action of ADH. Nephrogenic DI can result from inherited causes, but more commonly is secondary to systemic disorders or drugs. DI results when disorders or drugs disrupt the sensitivity of the kidneys to ADH and impair concentrating ability.

Lithium is well known to cause nephrogenic DI. Lithium impairs the concentrating ability of the kidney by its action on the collecting tubule. Up to 54% patients on lithium show an impaired concentrating ability but a fewer proportion of people manifest overt polyuria [1]. With continued lithium treatment, it is estimated that about 20–40% people develop irreversible and overt polyuria that may be seen even years after lithium treatment [2]. Even though the defect in concentrating ability is initially reversible, after chronic lithium maintenance therapy, the tubular dysfunction can convert to irreversible polyuria. Renal concentrating deficit can start within weeks to months of treatment but irreversible polyuria usually takes many years to develop. The urinary concentrating ability improves immediately after lithium discontinuation but does not return to baseline in all patients [3]. Persistent renal concentrating deficit is associated with duration of lithium use, total and maximum doses of lithium administered, and simultaneous use of antipsychotics. Recurrent episodes of lithium toxicity may predispose to DI.

DI may be a risk factor for developing chronic kidney disease though the latter is much less prevalent than DI.

Some cases of DI from clozapine have also been reported but far less frequently than lithium [4].

Polyuria with large volumes of urine, even up to 20 L a day is the hallmark of DI. It is often associated with nocturia. Most people are able to compensate for the loss of fluids by an increased thirst response leading to polydipsia. Cognitively impaired individuals or elderly with dementia or those with poor access to water may develop volume depletion and resultant hypernatremia. Hypernatremia causes neurologic symptoms by water movement out of brain cells and resultant decrease in brain size. Initial symptoms are lethargy, weakness that can progress to twitching, seizures, and coma. Generally, severe symptoms do not develop unless serum sodium levels are above 150 meq/L.