Hyponatremia and Glucocorticoid Deficiency

Hyponatremia is the commonest electrolyte deficiency in clinical practice. Of the many causes of hyponatremia, syndrome of inappropriate antidiuresis (SIAD) is the commonest. Glucocorticoid deficiency, due to central/secondary adrenal insufficiency, is the key differential diagnosis for SIAD, as it presents with a similar biochemical picture of euvolemic hyponatremia and inappropriate urinary concentration. The underlying mechanisms for the development of hyponatremia in glucocorticoid deficiency are: (1) impaired renal water handling in the absence of circulating cortisol and (2) increased plasma concentrations of arginine vasopressin (AVP), despite hypo-osmolality. The original diagnostic criteria for SIAD emphasized that normal adrenal reserve was essential for its diagnosis, in recognition of the similar biochemical presentation of SIAD and glucocorticoid deficiency. This has been emphasized in all of the recently published clinical guidelines. However, data from the literature suggest that clinicians ignore the measurement of plasma cortisol concentration in both clinical practice and research protocols. The reported prevalence of glucocorticoid deficiency in patients presenting with euvolemic hyponatremia may, therefore, be underestimated and patients with a dangerous, but treatable cause of hyponatremia are inevitably missed. In this chapter, we will review the physiopathology of hyponatremia in the setting of glucocorticoid deficiency. We will discuss the differential diagnosis of euvolemic hyponatremia and review the prevalence of glucocorticoid deficiency in patients with hyponatremia.