What etiologies give rise to euvolemic hyponatremia with less than maximally dilute urine?
Most commonly, euvolemic hyponatremia with less than maximally dilute urine arises from the syndrome of inappropriate antidiuretic hormone secretion (SIADH, discussed below). Other potential causes include exercise-associated hyponatremia (EAH), methylenedioxy- N -methamphetamine (MDMA or ecstasy) ingestion, hypothyroidism, and glucocorticoid insufficiency. EAH is classically observed among marathon runners, who become overhydrated in the face of excessive water ingestion coupled with impaired water excretion from non-osmotically driven ADH release. By stimulating both ADH secretion and polydipsia via activation of serotonergic pathways, MDMA ingestion can lead to acute, severe hyponatremia and death if not promptly addressed. Although the mechanism is not definitively clear, the negative systemic effects of profound thyroid hormone deficiency on cardiac output and peripheral vascular resistance appear to trigger nonosmotic ADH secretion and hyponatremia. Since cortisol suppresses ADH release, isolated glucocorticoid deficiency can result in hyponatremia from uninhibited vasopressin secretion. This entity is distinct from Addison disease or other causes of adrenal gland destruction where mineralocorticoid deficiency and consequent volume depletion are present along with glucocorticoid lack.