In a diabetic patient with hyponatremia, hyperkalemia, and a mildly elevated ACTH level, what is the most likely diagnosis and how should it be acutely managed?

Primary Adrenal Insufficiency (Addison's Disease)

The combination of hyponatremia, hyperkalemia, and mildly elevated ACTH in a diabetic patient is diagnostic of primary adrenal insufficiency until proven otherwise, and you must immediately administer 100 mg IV hydrocortisone plus 0.9% saline at 1 L/hour without waiting for confirmatory testing if the patient is hemodynamically unstable. 1

Immediate Clinical Assessment and Action

The triad of hyponatremia, hyperkalemia, and elevated ACTH strongly indicates primary adrenal insufficiency with combined glucocorticoid and mineralocorticoid deficiency. 1 This presentation occurs because:

• Hyponatremia is present in approximately 90% of newly diagnosed adrenal insufficiency cases 1, 2
• Hyperkalemia occurs in approximately 50% of cases—its presence strongly supports primary adrenal insufficiency, but its absence does not exclude the diagnosis 1, 2
• The combination of hyponatremia plus hyperkalemia specifically points to primary adrenal insufficiency rather than secondary adrenal insufficiency, where mineralocorticoid production remains intact 1

Critical Decision Point: Stable vs. Unstable Patient

If the patient shows any signs of hemodynamic instability (hypotension, altered mental status, severe vomiting, collapse):

• Give 100 mg IV hydrocortisone immediately as a bolus 1, 3
• Start 0.9% saline infusion at 1 L/hour (at least 2 L total) 1, 3
• Draw baseline serum cortisol and plasma ACTH before hydrocortisone if feasible, but never delay treatment to obtain labs 1, 3
• If you need to preserve diagnostic testing capability while treating, use dexamethasone 4 mg IV instead of hydrocortisone, as it does not interfere with cortisol assays 1

If the patient is clinically stable:

• Draw early-morning serum cortisol and plasma ACTH immediately 1, 2
• Obtain basic metabolic panel to document sodium, potassium, and assess for renal function 1
• Proceed with confirmatory testing based on initial results 1, 2

Diagnostic Interpretation

Baseline Hormone Levels

• Serum cortisol < 250 nmol/L (< 9 µg/dL) with elevated ACTH in the setting of acute illness is diagnostic of primary adrenal insufficiency 1, 2
• Cortisol 250–400 nmol/L (9–14 µg/dL) with elevated ACTH raises strong suspicion and warrants confirmatory testing 1, 2
• Elevated ACTH with low cortisol distinguishes primary from secondary adrenal insufficiency, where ACTH would be low or inappropriately normal 2

Confirmatory Testing: Cosyntropin Stimulation Test

When baseline cortisol is indeterminate, the cosyntropin stimulation test is the gold standard: 1, 2

• Administer 250 µg cosyntropin IM or IV 1, 2
• Measure serum cortisol at baseline, 30 minutes, and 60 minutes 1, 2
• Peak cortisol < 500 nmol/L (< 18 µg/dL) confirms adrenal insufficiency 1, 2
• Peak cortisol > 550 nmol/L (> 18–20 µg/dL) excludes adrenal insufficiency 1, 2

Critical pitfall: Do not perform this test in patients actively receiving corticosteroids, as HPA-axis suppression yields falsely low results. 1 Glucocorticoids and spironolactone should be stopped on the day of testing. 1

Important Differential Consideration: SIADH vs. Adrenal Insufficiency

Before diagnosing SIADH, you must exclude adrenal insufficiency because both present with nearly identical laboratory findings: 1, 2

• Euvolemic hyponatremia 1, 2
• Serum sodium < 134 mEq/L 1, 2
• Plasma osmolality < 275 mOsm/kg 1, 2
• Inappropriately high urine osmolality 1, 2
• Elevated urinary sodium 1, 2

The cosyntropin stimulation test is required to rule out adrenal insufficiency in patients with hypo-osmolar hyponatremia. 1, 2 Treatment differs fundamentally: adrenal insufficiency requires glucocorticoid replacement, whereas SIADH requires fluid restriction. 1, 2

Determining the Underlying Cause

Once primary adrenal insufficiency is confirmed, determine etiology:

1. Measure 21-hydroxylase (anti-adrenal) antibodies first—autoimmune adrenalitis accounts for approximately 85% of primary adrenal insufficiency in Western populations 1, 2

2. If antibodies are negative, obtain adrenal CT imaging to evaluate for hemorrhage, metastatic disease, tumors, tuberculosis, or other structural abnormalities 1, 2

3. In male patients with negative antibodies, assess very long-chain fatty acids (VLCFA) to screen for adrenoleukodystrophy 1, 2

Additional Laboratory Findings to Expect

• Plasma renin activity is typically elevated in primary adrenal insufficiency 1
• Mild hypercalcemia occurs in 10–20% of patients 1
• Anemia, mild eosinophilia, and lymphocytosis are common 1
• Elevated liver transaminases are frequently observed 1
• TSH may be modestly elevated (4–10 IU/L) due to loss of cortisol-mediated inhibition 1

Special Consideration: Diabetes and Hyperkalemia

Be aware that diabetic patients may have baseline predisposition to hyperkalemia from hyporeninemic hypoaldosteronism (Type 4 RTA), which can confound the clinical picture. 4 However, the combination of hyponatremia with hyperkalemia and elevated ACTH still strongly favors primary adrenal insufficiency over isolated diabetic hyperkalemia. 1, 5

One case series documented severe hyperkalemia developing in diabetic patients after cosyntropin administration, emphasizing the need for close monitoring during diagnostic testing in this population. 4

Acute Management Protocol Summary

For suspected adrenal crisis (unstable patient):

• Hydrocortisone 100 mg IV bolus immediately 1, 3
• 0.9% saline at 1 L/hour 1, 3
• Draw cortisol and ACTH before steroids if possible, but do not delay treatment 1, 3

For stable patient with strong suspicion:

• Morning cortisol and ACTH 1, 2
• Cosyntropin stimulation test if baseline indeterminate 1, 2
• Begin stress-dose steroids if test confirms diagnosis 3

Critical pitfall to avoid: Never delay treatment of suspected acute adrenal crisis for diagnostic procedures—mortality is high if untreated. 1, 2, 3 The absence of hyperkalemia cannot rule out adrenal insufficiency, as it is present in only about 50% of cases. 1, 2, 3