The mechanism in hypothyroidism is incompletely understood, but felt to relate mainly to a reduction in cardiac output, increased activity of baroreceptors and subsequent non-osmotic release of ADH. Often, a reduction in GFR is noted in hypothyroid patients, thereby reducing the quantity of free water that reaches the distal nephron. Correction can be achieved by the administration of exogenous thyroid hormone.
In adrenal insufficiency, the reduction in cortisol may cause reduced cardiac output and blood pressure, again via a poorly understood mechanism. This can result in non-osmotic ADH release and tendency towards free water retention. Perhaps more importantly, ADH release from the posterior pituitary is under the control of CRH from the hypothalamus. CRH in turn is under negative feedback control from cortisol. So, in states of low cortisol, the negative feedback on CRH is lost and, in turn, ADH release is stimulated.
Why do thiazides cause more hyponatraemia than loop diuretics?
The efficacy of ADH depends on the generation of the medullary concentration gradient via NaCl reabsorption, without water, in the thick ascending limb of the loop of Henle. This creates a gradient for water reabsorption via aquaporin-2 insertion in the luminal membranes of the cortical and outer medullary collecting tubules.
With this in mind, it becomes clearer why thiazide diuretics are more likely to cause hyponatraemia than loop diuretics. Loop diuretics, by inhibiting the sodium reabsorption in the thick ascending limb of Henle’s loop, interfere with the generation of the hypertonic medullary interstitium; so, despite inducing a mild increase in ADH secondary to volume depletion, the ADH is less effective because there is a reduced concentration gradient for water reabsorption. Thiazide diuretics act on the distal tubule, having no effect on the medullary concentration gradient, thereby allowing ADH induced by volume depletion to promote water reabsorption unabated.
Posted by Finnian McCausland M.D.