Potential mechanisms of hypothyroidism-induced hyponatremia.

the pathophysiology in hypothyroidism, involving impaired renal and cardiovascular functions as well as distortion of hypothalamo-adrenal systems , antidiuretic hormone (ADH)and atrial natriuretic peptide (ANP) release, which play important roles in water and electrolyte metabolisms (2, 3). In hypothyroidism, decreases in free water formation and urine volume, especially following an acute water load, were consistently noticed, irrespective of the presence or absence of hyponatremia (3). Diminished ability of the kidney to excrete free water fails to produce maximumurine dilution, leading to water retention with consequent hyponatremia. Several mechanisms may be given to explain the diminished free water formation. First, ADHhas been reported to enhance renal water reabsorption in the collecting duct via the action mediated by ADHV2-receptors (4). Increases in plasma ADH decrease free water excretion, thereby resulting in water retention which leads to hyponatremia. Increases in plasma osmolality and decreases in plasma volumestimulate the release of ADH,respectively via osmoreceptors and via volumereceptors. Whenthe situation is vice versa, ADHrelease is restrained. Therefore, a reduction in plasma osmolality and a rise in plasma volume inhibit ADHrelease, thus leading to water diuresis with subsequent normoVolemiaand eunatremia. Whenthere is an increased ADHrelease, associated with the presence of hypervolemic hyponatremia with impaired urine dilution, it is well knownthat the pathological state is coined as the syndrome of inappropriate secretion of ADH(SIADH). Skowsky and Kikuchi (5) showed that plasma ADHwas elevated and was not sufficiently suppressed in response to decreases in plasma osmolality in hypothyroidism. Laczi et al (6) reported that patients with severe hypothyroidism had high plasma ADH and decreases in osmotic threshold ADHrelease. Onthe other hand, plasma ADHhas been shown to be low, and ADHresponses to changes in plasma osmolality are attenuated in hypothyroidism (3, 7). In particular, Ota et al (3) showed that plasma ADHis decreased in hypothyroidism, but it did not decrease in response to a fall in plasma osmolality after an acute water load. These findings strongly suggest that there is impaired osmoregulation of ADHrelease and/or a decrease in the metabolic clearance rate (MCR)ofADH. Indeed, the MCR of circulating hormones has been known to fall in hypothyroidism.