Less than 10% of DI is hereditary. X-linked nephrogenic DI (NDI) accounts for 90% of cases of congenital NDI
Associated with inadequate arginine vasopressin (AVP) or antidiuretic hormone (ADH) secretion or renal response to AVP, resulting in hypotonic polyuria and a compensatory/underlying polydipsia.
All four forms of polyuria–polydipsia syndrome result in a water diuresis due to an inability to maximally concentrate urine
Central DI (hypothalamic/neurogenic DI) (M/C form):
Results from inadequate secretion and usually deficient synthesis of arginine vasopressin (AVP) in the hypothalamic–neurohypophyseal system in response to osmotic stimulation
Usuyally secondary to surgery or head injury which causes traumatic injury to the hypothalamus or posterior pituitary gland and destruction/degeneration of neurons originating in the supraoptic and paraventricular nuclei of the hypothalamus
Result of an inadequate response of the kidneys to AVP, either due to mutations in AVP receptor 2 (AVPR2) or aquaporin 2 (AQP2) (hereditary nephrogenic DI) or as an adverse effect of various drugs, most commonly lithium, or due to electrolyte disorders, such as hypercalcaemia or hypo-kalaemia (acquired nephrogenic DI).
Children usually present with the inherited form whereas adults present with the acquired form of NDI. In most cases (90%), inherited NDI is an X-linked condition caused by a loss-of-function mutation in the V2R gene.
Results from the enzymatic breakdown of endogenous AVP by increased placental vasopressinase levels in pregnancy.
Onset of CDI can be abrupt (due to insult to the body) or gradual (due to tumor or idiopathic causes). The age of onset and the severity of the disease can differ among patients who have congenital disease.
Polyuria: Excessive urination
Compared with other forms of DI, patients with central DI more often describe nocturia and a sudden onset of symptoms, as urinary concentration can often be maintained fairly well until the residual neuronal capacity of the hypothalamus to synthesize AVP falls below 10–15% of normal capacity, after which urine output increases dramatically
Polyuria: > 50 ml/kg body-wt/24 h | osmolality <300 mOsm/L)
Most patients with an intact hypothalamic thirst centre maintain their fluid balance by drinking water. But patient who are unable to access free water as seen in neonates and elderly present with clinical features of hypernatremia and dehydration
Excessive drinking: > 3 l/day
Dizziness, weakness, nocturia, fatigue
Signs of dehydration: Fever, dry skin and mucus membranes, weight loss, poor skin turgor
Severe dehydration, vomiting, constipation, fever, irritability, sleep disturbances, retardation of growth, and failure to thrive
Mental retardation (caused by repeated and unrecognized dehydration)
Water deprivation test “Hare-Hickey test” and desmopressin (DDAVP) trial:
Indirect assessment of AVP activity by measurement of the urine concentration capacity during a prolonged period of dehydration and again after a subsequent injection of an exogenous synthetic AVP analogue, desmopressin
During water deprivation, hourly measurements of body weight and urine osmolality are made, until 2–3 samples vary by <30 mOsm/kg (or <10%), or until the patient loses 5% of his/her body weight. Serum ADH is then measured and ADH/desmopressin (5 units) is injected. Urine osmolality is measured 30–60 min after this. The test is discontinued if the patient loses >5% of his/her body weight and/or plasma Na+ exceeds 143 mEq/L and/or urine osmolality increases to normal. Response to the administration of desmopressin distinguishes between CDI and NDI.
Hypertonic saline infusion:
Alternative to water restriction test
Baseline copeptin levels:
Copeptin, the C- terminal segment of the AVP prohormone, is an easy- to-measure AVP surrogate that is very stable ex vivo. As the serum copeptin level reflects the osmosensitive circulating AVP concentration, it is a promising biomarker for differential diagnosis of polyuria–polydipsia syndrome.
Central DI (partial and complete): <4.9 pmol/L (after hypertonic saline infusion)
Mild cases of DI may not even need treatment and sufficient water intake may suffice. The removal of aggravating factors (e.g.,: reductions in glucocorticoids that directly cause free water clearance) improves polyuria.
DDAVP (1-deamino-8-arginine vasopressin):
DRUG OF CHOICE for the long-term management of central DI. It is a synthetic, long-acting vasopressin analog with minimal pressor activity but has nearly two-fold antidiuretic potency of arginine vasopressin.
Treatment involves pharmacological management with salt restriction