Clinical Picture of Severe Hyponatremia in Patients with Hypopituitarism Including Secondary Adrenal Insufficiency

Severe hyponatremia due to hypopituitarism and adrenal insufficiency can be life-threatening, and glucocorticoid treatment is very effective once a diagnosis of the underlying disorder has been reached. In our experience, the diagnosis of hypopituitarism in hyponatremic patients is often overlooked. In a retrospective study, we screened the files of 185 patients with severe hyponatremia (< 130 mmol/l) in order to describe the clinical spectrum of patients with hyponatremia and hypopituitarism including secondary adrenal insufficiency.

In 139 cases, clear allocation of patients to pathophysiological groups representing 1) primary sodium deficiency, 2) edematous disorders, and 3) normovolemic disorders including the syndrome of inappropriate ADH secretion (SIADH) was possible. Twenty-eight patients with severe normovolemic hyponatremia (mean serum sodium: 116 ± 7 mmol/l, mean ± SD) had hypopituitarism and secondary adrenal insufficiency as shown by basal cortisol measurements and dynamic tests of adrenal function (the latter performed after recovery from hyponatremia). Hypopituitarism (mostly due to empty sella, Sheehan’s syndrome, and pituitary tumors) in 25 cases from this group had not been recognized previously, while recurrent hyponatremia during previous hospital admissions (up to four times) could be documented in 12 cases. The mean age of these patients (21 women, 7 men) was 68 years. The most frequently occurring clinical signs were missing or scanty pubic and axillary hair, pale and doughy skin, and small testicles in men. Frequent symptoms such as nausea and vomiting, confusion, disorientation, somnolence or coma were similar to those in 91 SIADH patients. Basal serum cortisol levels in the acutely ill state ranged from 20 to 439 nmol/l (mean 157 ± 123), ranging from 274 to 1732 nmol/l (732 ± 351) in 30 other severely hyponatremic patients. In most patients with hyponatremic hypopituitarism, plasma ADH levels were inappropriately high, which was probably due to a failure of endogenous cortisol to suppress the hormone in a stressful situation. All patients recovered after low-dose hydrocortisone substitution. Most patients had other pituitary hormone deficiencies and were subsequently administered appropriate substitute treatment.

Hypopituitarism, including secondary adrenal insufficiency, seems to be a frequently overlooked cause of severe hyponatremia. A high level of suspicion is the best way to recognize the underlying disorder. Hydrocortisone treatment is very effective.