How does adrenal insufficiency cause hyponatremia (low sodium levels)?

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From the Guidelines

Adrenal insufficiency causes hyponatremia primarily through aldosterone deficiency, which impairs sodium reabsorption in the kidneys, and cortisol deficiency, which allows increased secretion of antidiuretic hormone (ADH) and promotes water retention. In adrenal insufficiency, the adrenal glands fail to produce adequate amounts of cortisol and aldosterone. Aldosterone normally acts on the distal tubules and collecting ducts of the kidneys to promote sodium reabsorption and potassium excretion. Without sufficient aldosterone, excessive sodium is lost in the urine while water is retained, leading to dilutional hyponatremia. Additionally, cortisol deficiency contributes to hyponatremia by allowing increased secretion of ADH, which promotes water retention. Cortisol normally suppresses ADH, so when cortisol levels are low, ADH levels rise inappropriately, causing further water retention and dilution of serum sodium. The combination of renal sodium wasting and increased water retention results in hyponatremia, as noted in a study published in the Journal of Internal Medicine 1.

Some key points to consider in the diagnosis and treatment of adrenal insufficiency include:

  • The diagnosis of primary adrenal insufficiency (PAI) should be considered in all patients presenting with unexplained collapse, hypotension, vomiting, or diarrhea, and hyperpigmentation, hyponatremia, hyperkalemia, acidosis, and hypoglycemia increase clinical suspicion of PAI 1.
  • Treatment involves hormone replacement therapy with hydrocortisone (typically 15-25 mg daily in divided doses) and fludrocortisone (usually 0.05-0.2 mg daily) to replace cortisol and aldosterone, respectively, which corrects the underlying hormonal imbalance and resolves the hyponatremia 1.
  • Patients with PAI should be reviewed at least annually, with assessment of health and well-being, measurement of weight, blood pressure, and serum electrolytes, and occasional monitoring for the development of new autoimmune disorders, particularly hypothyroidism 1.

Overall, the management of adrenal insufficiency requires careful attention to the underlying hormonal imbalance and its effects on sodium and water balance, as well as regular monitoring and adjustment of hormone replacement therapy to prevent complications and improve quality of life.

From the Research

Adrenal Insufficiency and Hyponatremia

  • Adrenal insufficiency can lead to hyponatremia (low sodium levels) due to the decreased production of cortisol and aldosterone 2, 3.
  • The underlying mechanisms for the development of hyponatremia in glucocorticoid deficiency include:
    • Impaired renal water handling in the absence of circulating cortisol 4.
    • Increased plasma concentrations of arginine vasopressin (AVP), despite hypo-osmolality 4.
  • Hyponatremia in adrenal insufficiency can be severe and life-threatening, and treatment with glucocorticoids is very effective once the diagnosis of the underlying disorder has been made 2, 5.
  • The diagnosis of hypopituitarism in hyponatremic patients is often overlooked, and a high level of suspicion is the best way to recognize the underlying disorder 5.
  • Patients with primary adrenal insufficiency usually develop skin hyperpigmentation and crave salt, in addition to hyponatremia 6.

Clinical Presentation

  • The clinical presentation of hyponatremia in adrenal insufficiency can be non-specific, with symptoms such as nausea, vomiting, confusion, disorientation, somnolence, or coma 5.
  • Patients with hypopituitarism and secondary adrenal insufficiency may exhibit missing or scanty pubic and axillary hair, pale and doughy skin, and small testicles in men 5.
  • Hyponatremia in adrenal insufficiency can be euvolemic, with a similar biochemical picture to syndrome of inappropriate antidiuresis (SIAD) 4.

Treatment

  • Treatment with hydrocortisone is very effective in correcting hyponatremia and improving clinical symptoms in patients with adrenal insufficiency 2, 5.
  • Patients with adrenal insufficiency require active and repeated education on managing their condition, including advice on how to increase medication during intercurrent illness, medical or dental procedures, and profound stress 6.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Hyponatremia and Glucocorticoid Deficiency.

Frontiers of hormone research, 2019

Research

Adrenal insufficiency.

Lancet (London, England), 2021

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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