- Etiology: - 1/3 of cases are primary (idiopathic/ hereditary) - 2/3 of cases come from damage to the [[hypothalamus]]-posterior pituitary axis - Pathophys: - Arginine vasopressin (AVP, chemical name vs the functional name of antidiuretic hormone (ADH)) trigger aquaporin incorporation into the collecting duct for water reabsorption - It's produced in the hypothalamus and secreted in the posterior pituitary - A deficiency of AVP (or AVP resistant receptor in the case of nephrogenic DI) cause water loss and subsequent **hyperosmotic volume contraction** (e.g. hypernatremia, high serum osmolality) as intracellular water continue to diffuse into the extracellular space to equilibrate osmolarity - Clin features: - polyuria, nocturia, polydipsia - dehydration - Dx and dDx: - Ruling out common dDx: BMP and urinalysis - osmotic diuresis: hyperglycemia and glucouria - acquired AVP-R: hypercalcemia, hypokalemia - Initial testing: serum sodium, plasma osmalality, urine osmolality - If serum Na and plasma osmalality normal: Water deprivation test (collect urine osmolality every 1-2 hrs) - Urine osmolality increases to > 800 mOsm/kg: Primary polydipsia is confirmed. - Urine osmolality remains ≤ 800 mOsm/kg: AVP disorders are likely - Administer desmopressin (a synthetic AVP analogue) - Initial urine osmolality 300–800 mOsm/kg and: Significant increase (≥ 10%) after desmopressin: partial AVP-D No or minimal increase (< 10%) after desmopressin: primary polydipsia - Initial urine osmolality < 300 mOsm/kg and: Significant increase (> 50%) after desmopressin: complete AVP-D (indicating intact renal AVP receptors) No or moderate increase (< 50%) after desmopressin: AVP-R (indicating defective renal AVP receptor - Plasma coeptin testing (c-terminus of AVP, more stable ex vivo) - ≥ 21.4 pmol/L: AVP-R is confirmed. - < 21.4 pmol/L: Obtain stimulated plasma copeptin testing, e.g., hypertonic saline infusion test. - > 4.9 pmol/L: primary polydipsia - ≤ 4.9 pmol/L: AVP-D | Condition | Arginine vasopressin deficiency (central DI) | Arginine vasopressin resistance (nephrogenic DI) | Primary polydipsia (psychogenic polydipsia) | | --------------------- | -------------------------------------------- | ------------------------------------------------ | ------------------------------------------- | | **Initial studies** | | | | | **Serum sodium** | Mild hypernatremia | Mild hypernatremia | Hyponatremia | | **Plasma osmolality** | High-normal or high | High-normal or high | Low | | **Urine osmolality** | Low (Urine specific gravity <1.006) | Low (Urine specific gravity <1.006) | Low | Mgmt: - desmopressin