Can a patient with hyponatremia and a low morning cortisol level have adrenal insufficiency?

Can Hyponatremia with Low Morning Cortisol Indicate Adrenal Insufficiency?

Yes, a patient with hyponatremia and a low morning cortisol level can absolutely have adrenal insufficiency, and this diagnosis must be actively excluded before attributing hyponatremia to other causes like SIADH. 1, 2

Why This Combination is Highly Suspicious

• Hyponatremia is present in 90% of newly diagnosed adrenal insufficiency cases, making it one of the most common presenting features of both primary and secondary adrenal insufficiency 1, 2
• The clinical picture of adrenal insufficiency can be nearly identical to SIADH, with both conditions presenting with euvolemic hypo-osmolar hyponatremia, inappropriately high urine osmolality, and elevated urinary sodium 1, 2
• Low morning cortisol (<250 nmol/L or <9 μg/dL) is diagnostic of adrenal insufficiency when accompanied by appropriate ACTH levels: high ACTH indicates primary adrenal insufficiency, while low or inappropriately normal ACTH indicates secondary adrenal insufficiency 1, 2, 3

Critical Diagnostic Algorithm

Step 1: Obtain Morning Cortisol and ACTH Simultaneously

• Draw both tests at 8 AM to capture peak physiological cortisol secretion 1, 3
• Morning cortisol <250 nmol/L (<9 μg/dL) with elevated ACTH in acute illness is diagnostic of primary adrenal insufficiency 1
• Morning cortisol 140-275 nmol/L (5-10 μg/dL) with low or inappropriately normal ACTH suggests secondary adrenal insufficiency 1, 2, 3

Step 2: Perform Cosyntropin Stimulation Test if Cortisol is Indeterminate

• The 0.25 mg cosyntropin stimulation test is medically necessary to rule out adrenal insufficiency in patients with hypo-osmolar hyponatremia, as adrenal insufficiency cannot be reliably distinguished from SIADH without this test 1
• Administer 0.25 mg cosyntropin (tetracosactide) intramuscularly or intravenously 1
• Measure serum cortisol at baseline and 30 minutes (and/or 60 minutes) post-administration 1
• **Peak cortisol <500 nmol/L (<18 μg/dL) is diagnostic of adrenal insufficiency**, while >550 nmol/L (>18-20 μg/dL) is normal and excludes the diagnosis 1, 2, 3

Step 3: Distinguish Primary from Secondary Adrenal Insufficiency

• Primary adrenal insufficiency: Low cortisol + high ACTH, often with hyperkalemia (though present in only ~50% of cases) and metabolic acidosis 1, 2
• Secondary adrenal insufficiency: Low cortisol + low or inappropriately normal ACTH, characteristically presents with hyponatremia without hyperkalemia or metabolic acidosis because aldosterone secretion remains intact 2

Common Pitfalls to Avoid

• Never diagnose SIADH without first excluding adrenal insufficiency via cosyntropin stimulation testing, as both conditions are clinically indistinguishable 1, 2
• The absence of hyperkalemia cannot rule out adrenal insufficiency—it is present in only 50% of primary cases and is typically absent in secondary adrenal insufficiency 1, 2
• Never delay treatment of suspected adrenal crisis for diagnostic procedures—if the patient is clinically unstable with hypotension, altered mental status, or severe symptoms, give IV hydrocortisone 100 mg immediately plus 0.9% saline infusion at 1 L/hour 1, 4
• Exogenous steroids (including prednisone, dexamethasone, and inhaled fluticasone) suppress the HPA axis and confound cortisol testing—if diagnostic testing is needed but treatment cannot be delayed, use dexamethasone 4 mg IV instead of hydrocortisone, as dexamethasone does not interfere with cortisol assays 1

Mechanism of Hyponatremia in Adrenal Insufficiency

• Cortisol deficiency impairs free water clearance and causes inappropriately elevated vasopressin secretion, leading to water retention and dilutional hyponatremia 2, 5
• In primary adrenal insufficiency, aldosterone deficiency causes renal sodium wasting, further contributing to hyponatremia 4, 3
• In secondary adrenal insufficiency, aldosterone secretion remains intact through the preserved renin-angiotensin-aldosterone system, so hyponatremia occurs without hyperkalemia or significant sodium wasting 2
• Sodium supplementation alone is often ineffective in treating hyponatremia caused by adrenal insufficiency—the underlying problem is cortisol deficiency, not absolute sodium deficiency 5

Treatment Implications

• If adrenal insufficiency is confirmed, lifelong glucocorticoid replacement therapy is required: hydrocortisone 15-25 mg daily or prednisone 3-5 mg daily 1, 3
• For primary adrenal insufficiency, add fludrocortisone 0.05-0.1 mg daily for mineralocorticoid replacement 1, 3
• All patients need education on stress dosing, should wear a medical alert bracelet, and must be prescribed an emergency injectable hydrocortisone 100 mg IM kit with self-injection training 1, 3
• Hyponatremia and associated symptoms (nausea, vomiting, fatigue) typically resolve with glucocorticoid replacement without requiring sodium supplementation 5, 6, 7