In a diabetic patient with mild hyperkalaemia (serum potassium 5.3 mmol/L) and an ACTH level of 51 pg/mL, how should I evaluate and manage the hyperkalaemia and assess for adrenal insufficiency?

Evaluation and Management of Mild Hyperkalemia and Elevated ACTH in a Diabetic Patient

In a diabetic patient with serum potassium 5.3 mmol/L and ACTH 51 pg/mL, the priority is to rule out adrenal insufficiency while simultaneously addressing the mild hyperkalemia through medication review and monitoring, rather than aggressive acute intervention.

Initial Assessment: Is This Adrenal Insufficiency?

The combination of mild hyperkalemia (K⁺ 5.3 mmol/L) and elevated ACTH (51 pg/mL, assuming normal range ~10-50 pg/mL) in a diabetic patient raises concern for primary adrenal insufficiency (Addison's disease) or hyporeninemic hypoaldosteronism—both can present with hyperkalemia. 1

Critical Diagnostic Steps

Immediately check:

• Serum cortisol (8 AM sample): If <3 μg/dL, adrenal insufficiency is confirmed; if >15 μg/dL, it is excluded. Values between 3-15 μg/dL require an ACTH stimulation test. 1
• Serum sodium: Hyponatremia (Na⁺ <135 mmol/L) combined with hyperkalemia strongly suggests mineralocorticoid deficiency. 1, 2
• Blood pressure: Hypotension (<90/60 mmHg) or orthostatic changes support adrenal insufficiency. 1
• Plasma renin activity (PRA) and aldosterone: Low renin with low aldosterone indicates hyporeninemic hypoaldosteronism (common in diabetics), while high ACTH with low aldosterone suggests primary adrenal insufficiency. 3, 4, 2
• Serum creatinine and eGFR: Acute kidney injury can cause hyperkalemia and may mask adrenal insufficiency. 1, 2
• Arterial or venous blood gas: Hyperchloremic metabolic acidosis (pH <7.35, HCO₃⁻ <22 mmol/L, normal anion gap) is characteristic of hypoaldosteronism. 3, 2

Do not delay cortisol measurement while treating hyperkalemia—if adrenal crisis is suspected (hypotension, hyponatremia, hyperkalemia), give hydrocortisone 100 mg IV immediately, then draw cortisol and ACTH. 1

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Hyperkalemia Management: Mild Elevation (5.3 mmol/L)

At K⁺ 5.3 mmol/L without ECG changes or symptoms, this is mild hyperkalemia and does not require emergency interventions (calcium, insulin, albuterol). 5 The focus is on identifying and reversing the cause.

Step 1: Obtain an ECG Immediately

Look for hyperkalemic ECG changes:

• Peaked/tented T waves (earliest sign, appears >5.5 mmol/L)
• Flattened P waves or prolonged PR interval (moderate, ~6.0-6.4 mmol/L)
• Widened QRS complex (severe, >6.5 mmol/L)
• Sine-wave pattern or ventricular arrhythmias (life-threatening, ≥7-8 mmol/L) 5

If any ECG changes are present, escalate immediately to acute hyperkalemia management (calcium gluconate, insulin-glucose, albuterol). 5 If ECG is normal, proceed with medication review and monitoring.

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Step 2: Medication Review—The Most Common Culprit

Immediately review and adjust these medications:

RAAS Inhibitors (ACE-I, ARBs, Aldosterone Antagonists)

• ACE inhibitors and ARBs reduce renal potassium excretion and are the most common cause of hyperkalemia in diabetics. 5, 2, 6
• Do not discontinue RAAS inhibitors permanently—they provide mortality benefit in diabetic nephropathy and cardiovascular disease. 5
• Temporarily reduce the dose by 50% (e.g., lisinopril 20 mg → 10 mg) and recheck potassium in 2-3 days. 5
• If K⁺ remains >5.5 mmol/L despite dose reduction, consider adding a potassium binder (patiromer or sodium zirconium cyclosilicate) to maintain RAAS therapy. 5

Potassium-Sparing Diuretics

• Spironolactone, amiloride, and triamterene must be stopped immediately if K⁺ >5.5 mmol/L. 5
• These agents are particularly dangerous when combined with RAAS inhibitors in diabetics. 6

NSAIDs

• NSAIDs impair renal potassium excretion and worsen hyperkalemia, especially in diabetics with nephropathy. 5, 2
• Discontinue all NSAIDs (including over-the-counter ibuprofen, naproxen). 5

Other Medications to Review

• Trimethoprim-sulfamethoxazole (Bactrim): Blocks renal potassium secretion. 5
• Heparin: Suppresses aldosterone synthesis. 5, 2
• Beta-blockers: Impair cellular potassium uptake. 5
• Potassium supplements or salt substitutes: Discontinue immediately. 5

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Step 3: Assess for Hyporeninemic Hypoaldosteronism

This is the most common cause of chronic hyperkalemia in diabetics, especially those with:

• Age >50 years
• Diabetic nephropathy (eGFR 30-60 mL/min)
• Mild-to-moderate renal impairment 3, 2

Diagnostic criteria:

• Low plasma renin activity (PRA) despite hyperkalemia and hyponatremia
• Low aldosterone (<5 ng/dL)
• Normal cortisol (excludes Addison's disease)
• Hyperchloremic metabolic acidosis (non-anion gap) 3, 2

If confirmed, treatment options include:

• Fludrocortisone acetate 0.1-0.2 mg daily (mineralocorticoid replacement), but monitor for sodium retention and hypertension. 3
• Loop diuretics (furosemide 40-80 mg daily) to increase renal potassium excretion. 5, 3
• Sodium bicarbonate 650-1300 mg PO TID to correct acidosis. 3

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Step 4: Rule Out Other Causes of Hyperkalemia

Check for:

• Acute kidney injury: Creatinine rise >0.3 mg/dL or eGFR drop >25% suggests AKI. 1, 2
• Diabetic ketoacidosis (DKA): Hyperglycemia >250 mg/dL, anion gap acidosis, and ketonuria cause transcellular potassium shift. 7, 2
• Insulin deficiency: Even without DKA, poor glycemic control (HbA1c >9%) impairs cellular potassium uptake. 7, 2
• Volume depletion: Dehydration reduces renal potassium excretion. 2
• Urinary tract obstruction: Hydronephrosis impairs potassium secretion. 3, 2

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Monitoring Protocol

Recheck potassium and renal function:

• Within 2-3 days after medication adjustment (RAAS inhibitor dose reduction, NSAID discontinuation). 5
• At 7 days to confirm stability. 5
• Monthly for 3 months, then every 3-6 months if stable. 5

If K⁺ remains >5.5 mmol/L despite medication adjustment, initiate a potassium binder:

• Sodium zirconium cyclosilicate (Lokelma): 10 g PO TID × 48 hours, then 5-15 g daily (onset ~1 hour). 5
• Patiromer (Veltassa): 8.4 g PO daily with food, separated from other meds by 3 hours (onset ~7 hours). 5

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When to Escalate to Acute Hyperkalemia Management

Administer IV calcium gluconate, insulin-glucose, and albuterol if:

• ECG changes (peaked T waves, widened QRS, prolonged PR)
• K⁺ ≥6.5 mmol/L
• Symptoms (muscle weakness, palpitations, paresthesias)
• Oliguria or anuria (urine output <400 mL/day) 5

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Critical Pitfalls to Avoid

• Do not assume hyperkalemia is solely due to renal failure—adrenal insufficiency can present with AKI and hyperkalemia, and the hyperkalemia is resistant to standard therapy (insulin-glucose) without steroid replacement. 1
• Do not permanently discontinue RAAS inhibitors—use potassium binders to maintain these life-saving medications in diabetic nephropathy. 5
• Do not delay cortisol measurement—if adrenal crisis is suspected, give hydrocortisone first, then draw labs. 1
• Do not use sodium polystyrene sulfonate (Kayexalate)—it is associated with bowel necrosis and lacks efficacy data. 5
• Do not rely on dietary potassium restriction alone—evidence linking dietary intake to serum levels is weak. 5