Adrenal Insufficiency Related Hyponatraemia

Hyponatraemia is a common and frequently missed presenting feature of adrenal insufficiency.

Two mechanisms operate: cortisol deficiency removes the normal inhibition of antidiuretic hormone release, producing water retention in a pattern that closely mimics SIADH, and, in primary adrenal insufficiency, aldosterone deficiency additionally causes renal sodium loss with hyperkalaemia and volume depletion.

This matters clinically because adrenal insufficiency is treatable and, untreated, can progress to adrenal crisis and death.

Any unexplained hyponatraemia should prompt consideration of it, and the diagnosis is easy to miss precisely because it so often looks like SIADH on the initial biochemistry.

• The combination of hyponatraemia with hyperkalaemia should raise adrenal insufficiency prominently, since SIADH does not cause hyperkalaemia. In secondary adrenal insufficiency, however, aldosterone is preserved and potassium may be normal, so a normal potassium does not exclude the diagnosis
• Morning (8–9 am) serum cortisol is the initial screening test; a clearly low value supports the diagnosis and a clearly normal one largely excludes it, with intermediate values requiring dynamic testing
• Short Synacthen (ACTH stimulation) test is confirmatory
• ACTH level distinguishes primary (high ACTH) from secondary (low or inappropriately normal ACTH) disease
• Additional supporting features: hypoglycaemia, eosinophilia, mild hypercalcaemia, and a raised urea reflecting volume depletion
• In primary disease, look for hyperpigmentation of skin creases, buccal mucosa and scars, and consider adrenal autoantibodies, and imaging or infective causes such as tuberculosis where relevant

Critically, treatment should not be delayed for confirmatory testing in a patient who is unwell. Take the cortisol sample, then treat.

• Hydrocortisone is the definitive treatment and corrects the hyponatraemia by restoring normal suppression of antidiuretic hormone. In suspected adrenal crisis, give 100 mg intravenously immediately, followed by regular dosing or an infusion
• Intravenous fluid resuscitation with isotonic saline for volume depletion, which is a prominent feature of primary adrenal insufficiency
• Correct hypoglycaemia
• Note that hyponatraemia in this setting can correct rapidly once glucocorticoid is given, because removing the ADH stimulus produces a prompt water diuresis. This creates a genuine risk of overcorrection and osmotic demyelination, so sodium must be monitored closely during the first 24 hours and the usual 8–10 mmol/L limit still applies
• Fludrocortisone is added for primary adrenal insufficiency once the acute phase settles, but is not needed in secondary disease
• Identify and treat the precipitant, most often infection
• Provide steroid sick-day rules, a steroid emergency card and, where appropriate, an emergency hydrocortisone injection kit before discharge

Referral: endocrinology for all newly diagnosed adrenal insufficiency, for confirmatory testing, long-term replacement and education.