Most Appropriate Initial Laboratory Test
For a patient with persistent hypertension and acanthosis nigricans, the most appropriate initial laboratory test is fasting blood glucose (or HbA1c) to screen for insulin resistance and diabetes mellitus type 2, as acanthosis nigricans is a dermatologic marker of hyperinsulinemia and insulin resistance—not a sign of secondary hypertension from endocrine tumors. 1, 2, 3
Clinical Reasoning
The presence of acanthosis nigricans fundamentally changes the diagnostic approach in this case:
Acanthosis nigricans is a thickening and hyperpigmentation of the skin (commonly on neck and axillae) that indicates hyperinsulinemia and insulin resistance, which are primary risk factors for type 2 diabetes, dyslipidemia, and hypertension 2, 3, 4
Studies demonstrate that 62-80% of patients with acanthosis nigricans have high insulin resistance, with the highest rates occurring when AN is combined with obesity 3, 5
The American Diabetes Association recommends screening for type 2 diabetes in patients with signs of insulin resistance, specifically listing acanthosis nigricans as a key clinical indicator 1
Why Not the Other Options?
Plasma Renin Activity (Option B) - Not First-Line Here
While the aldosterone-to-renin ratio is appropriate for screening primary aldosteronism in resistant hypertension:
The American Heart Association recommends paired morning plasma aldosterone and plasma renin activity for patients with resistant hypertension, defined as BP >140/90 mmHg despite optimal doses of at least three antihypertensive drugs including a diuretic 1, 6
However, acanthosis nigricans is NOT a clinical feature of primary aldosteronism—which typically presents with hypokalemia, muscle weakness/cramps, or family history of early-onset hypertension 1, 6
The ESC 2024 guidelines now recommend measuring renin and aldosterone in all adults with confirmed hypertension, but this represents screening for a different pathophysiologic process than what acanthosis nigricans suggests 6
Urinary Metanephrines (Option C) - Wrong Clinical Picture
Measurement of plasma or urinary metanephrines is indicated for screening pheochromocytoma, but this condition presents with episodic symptoms (sweating, palpitations, headaches) and labile hypertension—not persistent hypertension with acanthosis nigricans 1
The clinical presentation described does not suggest catecholamine excess 1
Cortisol Level (Option D) - Less Likely
Hypercortisolism (Cushing syndrome) may present with obesity, diabetes, and hypertension, but the classic features include abdominal striae, moon facies, and intrascapular fat deposition—not acanthosis nigricans 1
While midnight salivary cortisol or late-night cortisol can screen for Cushing syndrome, acanthosis nigricans is not a typical feature of this condition 1, 7
Complete Initial Workup
After obtaining fasting glucose/HbA1c, the comprehensive evaluation should include:
Basic metabolic profile (sodium, potassium, creatinine, eGFR) to assess for kidney disease and electrolyte abnormalities 1
Lipid profile since insulin resistance is associated with dyslipidemia 1, 2
Urinalysis with albumin-to-creatinine ratio to detect early kidney damage 1, 8
Calculate HOMA-IR (Homeostatic Model Assessment of Insulin Resistance) using fasting glucose and insulin levels to quantify insulin resistance 2, 3
Common Pitfalls to Avoid
Do not pursue expensive workup for rare endocrine tumors (pheochromocytoma, primary aldosteronism) when the clinical presentation clearly suggests metabolic syndrome with insulin resistance 6
Acanthosis nigricans is often overlooked or misinterpreted—it should prompt immediate screening for diabetes and metabolic syndrome, not secondary hypertension from adrenal or renal causes 3, 5, 4
The combination of hypertension, acanthosis nigricans, and likely obesity represents metabolic syndrome, which affects 40% of hypertensive patients and requires lifestyle intervention alongside pharmacologic management 1