Endocrine Abstracts

Diabetes insipidus (DI) is a syndrome caused by various defects in the secretion or action of the antidiuretic hormone, arginine vasopressin (AVP). They include impaired AVP production (pituitary DI), increased AVP degradation (gestational DI), suppression of AVP secretion by excessive water intake (primary polydipsia) or decreased antidiuretic effect due to various abnormalities in the kidney (nephrogenic DI). In all four types, the severity of the defect varies between patients. This complicates differential diagnosis by traditional methods based on the urinary response to fluid restriction and injection of AVP or its analogue, desmopressin. An alternative approach is now available. It begins with measurement of basal plasma AVP. If it is normal or elevated (>2 pg/ml), the patient has nephrogenic DI and further testing can focus on the pathogenesis. If basal plasma vasopressin is low (<2 pg/ml), nephrogenic DI is excluded and a brain MRI to determine the absence or presence of the normal posterior pituitary ‘bright spot’ distinguishes pituitary DI from primary polydipsia. This method is more than 90% accurate as judged by the response to standard therapeutic doses of AVP or desmopressin. Hyponatremia is also due to several different defects in the osmoregulation of antidiuresis. They include impaired suppression of AVP secretion due to non-osmotic stimuli (‘effective’ hypovolemia, true hypovolemia, nausea or cortisol deficiency) as well as inappropriate secretion of AVP (SIADH) due to ectopic production or primary defects in osmoregulation. The latter take various forms including downward resetting of the osmostat. There is also an AVP-independent type of inappropriate antidiuresis caused by an activating mutation of the V2 receptor or other unidentified abnormalities. Differentiation between the various causes of hyponatremia is a necessary part of the decision whether to treat with hypertonic saline, antiemetic, cortisol or an antagonist of the AVPR2 receptor.