Severe hyponatremia due to hypopituitarism with adrenal insufficiency:: report on 28 cases

Objective: Severe hyponatremia due to hypopituitarism and adrenal insufficiency can be life-threatening, and treatment with glucocorticoids is very effective once the diagnosis of the underlying disorder has been made. In our experience, the diagnosis of hypopituitarism in hyponatremic patients is often overlooked. Methods: In a retrospective study we screened the files of 185 patients with severe hyponatremia (<130 mmol/l) that had been seen in one endocrinological unit of a university hospital between 1981 and 2001 in order to describe the clinical spectrum of patients with hyponatremia and hypopituitarism including secondary adrenal insufficiency. Results: In 13 9 cases it was possible to clearly ascribe the patients to the pathophysiological groups of (i) primary sodium deficiency, (ii) edematous disorders, and (iii) normovolemic disorders including the 'syndrome of inappropriate secretion of antidiuretic hormone' (SIADH). Twenty-eight patients with severe 'normovolemic hyponatremia' (serum sodium: 116+/-7 mmol/l, mean+/-S.D.) had hypopituitarism and secondary adrenal insufficiency as shown by basal cortisol measurements and dynamic tests of adrenal function. In 25 cases of this group hypopituitarism (mostly due to empty Sella, Sheehan's syndrome and pituitary tumors) had not been recognized previously, and in 12 cases recurrent hyponatremia during previous hospital admissions (up to four times) could be documented. The mean age of these patients (21 women, seven 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 the men. Frequent symptoms like nausea and vomiting, confusion, disorientation, somnolence or coma were similar to those in 91 patients with SIADH. Basal serum cortisol levels in the acutely ill state ranged from 20 to 439nmol/l (mean+/-S.D.: 157+/-123), while in 30 other severely hyponatremic patients it ranged from 274 to 1732 nmol/l (732+/-351 nmol/l). In most patients with hyponatremic hypopituitarism, plasma antidiuretic hormone levels were inappropriately high, 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 appropriately substituted subsequently. Conclusions: 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. Treatment with hydrocortisone is very effective.