Management of Severe Hyponatremia with High Urinary Sodium

Introduction to Severe Hyponatremia

The American College of Physicians recommends empiric hydrocortisone administration in patients with severe hyponatremia (110 mmol/l) and high urinary sodium (160 mmol/l) when clinical signs of adrenal insufficiency are present or cannot be safely excluded, as treatment is life-saving and delay through diagnostic measures must be avoided 1, 2

Severe hyponatremia (110 mmol/l) with very high urinary sodium (160 mmol/l) is highly suggestive of adrenal insufficiency, with hyponatremia occurring in 90% of newly diagnosed primary adrenal insufficiency cases 1
High urinary sodium (>20 mmol/l) in the context of hyponatremia argues against simple hypovolemia, and very high urinary sodium (160 mmol/l) suggests renal sodium loss, typical of mineralocorticoid deficiency (aldosterone deficiency in adrenal insufficiency) or cerebral salt wasting 1, 3

Hyperpigmentation of the skin is a clinical sign that suggests adrenal insufficiency 1
Hypotension or collapse, as well as nausea, vomiting, and diarrhea, are also indicative of adrenal insufficiency 1, 2

The European Society of Endocrinology suggests that empiric hydrocortisone should be given immediately in cases of suspected acute adrenal insufficiency, without waiting for diagnostic test results, especially in the presence of severe neurological symptoms (seizures, coma), hemodynamic instability (hypotension, shock), or low basal serum cortisol (<250 nmol/l) in acute illness 1, 2
Initial treatment involves hydrocortisone 100 mg i.v. bolus, followed by 100-300 mg/day as continuous infusion or every 6 hours as bolus, along with 1 liter of 0.9% NaCl over one hour 2

Cortisol deficiency leads to increased vasopressin and impaired water excretion, while aldosterone deficiency causes renal sodium loss, contributing to hyponatremia 1
Hydrocortisone corrects the sodium distribution disorder between serum and cells/interstitium, and hyponatremia often does not respond to sodium substitution alone but requires glucocorticoid replacement 2

Waiting for cortisol results or giving only sodium substitution can be harmful; empiric hydrocortisone should be started immediately in suspected adrenal insufficiency, and sodium correction should be done carefully to avoid osmotic demyelination syndrome, with a maximum correction rate of 8 mmol/l in 24 hours 1, 2, 3
"Normal" cortisol levels can be inappropriately low in acute illness, and relative adrenal insufficiency is possible despite measurable cortisol 1

Initial dosage of hydrocortisone is 100 mg i.v. as a bolus, with monitoring of serum sodium every 2 hours in severe cases, and clinical symptoms such as improvement of nausea, confusion, and hypotension 2, 3
After 48-72 hours, the dosage can be tapered to oral maintenance doses, typically 15-25 mg hydrocortisone daily in divided doses 2