What is the first investigation for a patient presenting with hypertension, acanthosis nigricans, and a family history of diabetes mellitus and hypertension?

First Investigation for Hypertension with Acanthosis Nigricans

The first investigation should be fasting blood glucose (or HbA1c) to screen for diabetes mellitus and insulin resistance, which is the most likely underlying diagnosis given the clinical presentation of acanthosis nigricans, hypertension, and family history of both conditions.

Clinical Reasoning

The presence of acanthosis nigricans in a hypertensive patient is a critical clinical clue that points toward insulin resistance and metabolic syndrome rather than a primary endocrine cause of secondary hypertension 1, 2. This skin finding fundamentally changes the diagnostic approach:

• Acanthosis nigricans is strongly associated with insulin resistance, obesity, and type 2 diabetes, with studies showing prevalence rates of 67.6% in obese children and strong associations with family history of diabetes and hypertension 3, 2
• The combination of hypertension, acanthosis nigricans, and family history of diabetes creates a high-risk phenotype for undiagnosed diabetes, with prevalence of undiagnosed diabetes in hypertensive patients ranging from 15-20% 4
• Acanthosis nigricans is a visible marker of conditions associated with insulin resistance including hypertension, dyslipidemia, and polycystic ovarian syndrome 1, 5

Why Not the Other Options?

Plasma Renin (Option A)

• While the European Society of Cardiology 2024 guidelines recommend measuring renin and aldosterone in all adults with confirmed hypertension (Class IIa recommendation), this is a screening approach for primary aldosteronism 6
• Primary aldosteronism typically presents with resistant hypertension, hypokalemia, and muscle weakness—not acanthosis nigricans 6
• The clinical picture here points toward metabolic/insulin resistance rather than mineralocorticoid excess 4, 6

Plasma Catecholamines (Option B)

• Plasma catecholamines and urinary metanephrines are appropriate for screening pheochromocytoma, which presents with episodic symptoms, labile hypertension, headaches, and palpitations 6
• The American Heart Association states that measurement of plasma or urinary metanephrines is indicated only when pheochromocytoma is specifically suspected based on clinical features 6
• This does not fit the clinical presentation of acanthosis nigricans with stable hypertension 6

Kidney Ultrasound (Option C)

• Renal ultrasound is indicated when renovascular disease or renal parenchymal disease is suspected, typically with abrupt onset hypertension, flash pulmonary edema, history of urinary tract infections, or early-onset hypertension in young women (fibromuscular dysplasia) 6
• While renal function assessment (serum creatinine and eGFR) should be part of the initial workup, imaging is not the first-line investigation in this metabolic presentation 1, 4

Ambulatory Blood Pressure (Option D)

• Ambulatory blood pressure monitoring (ABPM) is valuable for confirming the diagnosis of hypertension, detecting white coat hypertension, masked hypertension, and assessing nocturnal dipping patterns 1, 7
• The European Society of Hypertension recommends ABPM to confirm hypertension diagnosis and maximize prediction of cardiovascular risk 1
• However, ABPM does not address the underlying metabolic etiology suggested by acanthosis nigricans 1, 7
• In diabetic patients, ABPM can detect masked hypertension (prevalence 66% in one study) and non-dipping patterns associated with target organ damage, but this is a secondary consideration after establishing the metabolic diagnosis 7

Comprehensive Initial Workup

After establishing the presence or absence of diabetes/prediabetes, the complete initial evaluation should include 1, 4:

• Fasting blood glucose and HbA1c to screen for diabetes or prediabetes 1, 4
• Lipid profile (total cholesterol, LDL, HDL, triglycerides) as insulin resistance is associated with dyslipidemia 1, 4
• Serum creatinine with eGFR to assess kidney function 1, 4
• Serum electrolytes (sodium and potassium) 1, 6
• Urinalysis with albumin-to-creatinine ratio to detect proteinuria 1, 4
• 12-lead ECG to assess for left ventricular hypertrophy 1, 4
• Thyroid-stimulating hormone (TSH) to screen for thyroid disorders 4

Important Clinical Pitfalls

• Do not pursue expensive secondary hypertension workup before completing basic metabolic screening when clinical features point toward insulin resistance 6
• The American Diabetes Association recommends that overweight patients with acanthosis nigricans should be tested for type 2 diabetes every 2 years starting at age 10 or at puberty onset 1
• Obesity combined with hypertension creates a synergistic effect that accelerates both cardiovascular disease and diabetes onset, highlighting the importance of early screening 4
• Even if glucose is normal initially, these patients require ongoing surveillance given their high-risk phenotype 1, 4