What workup should be done for a 13-year-old patient with acanthosis nigricans, aside from checking the Hemoglobin A1c (HbA1c) level?

Workup for a 13-Year-Old with Acanthosis Nigricans

Beyond A1c, immediately perform a 2-hour oral glucose tolerance test with 75-gram glucose load and fasting insulin level, as these are the most sensitive tests for detecting insulin resistance and impaired glucose tolerance in adolescents with acanthosis nigricans. 1

Essential Metabolic Screening

Glucose Metabolism Assessment

• Perform a 2-hour oral glucose tolerance test (75-gram glucose load) following fasting glucose measurement, as this is more sensitive than A1c alone for detecting prediabetes and impaired glucose tolerance in youth 1
• Measure fasting insulin levels to directly assess insulin resistance (normal <15 mU/L; borderline 15-20 mU/L; high >20 mU/L) 1
• Calculate HOMA-IR (Homeostatic Model Assessment of Insulin Resistance) using fasting glucose and insulin values to quantify insulin resistance 2, 3

The rationale here is critical: A1c can miss early insulin resistance and impaired glucose tolerance in adolescents. The OGTT captures glucose handling abnormalities that A1c may not detect, and direct insulin measurement confirms the underlying pathophysiology 1, 2.

Lipid and Metabolic Panel

• Obtain a fasting lipid panel including total cholesterol, LDL, HDL, and triglycerides, as dyslipidemia commonly accompanies insulin resistance in youth with acanthosis nigricans 1
• Measure liver transaminases (ALT/AST) to screen for non-alcoholic fatty liver disease, which frequently coexists with insulin resistance 4

Endocrine Evaluation

Thyroid Assessment

• Check thyroid-stimulating hormone (TSH) to exclude thyroid dysfunction, which is more common in youth with metabolic disorders 1
• Consider antithyroid peroxidase and antithyroglobulin antibodies if TSH is abnormal, as autoimmune thyroid disease can coexist 5

Hyperandrogenism Screening (Particularly in Females)

• Measure total testosterone or free/bioavailable testosterone to evaluate for polycystic ovary syndrome (PCOS) or other hyperandrogenic states 1
• Document menstrual history in females, as irregular menses combined with acanthosis nigricans strongly suggests PCOS 1
• Check prolactin level if clinical features suggest hyperprolactinemia 1

Diabetes Type Differentiation

This is a critical pitfall to avoid: In an overweight 13-year-old with acanthosis nigricans, distinguishing type 1 from type 2 diabetes can be challenging, as obesity is increasingly common in type 1 diabetes and autoantibodies can be present in youth with clinical features of type 2 diabetes 5.

• Test pancreatic autoantibodies (GAD-65, IA-2, insulin autoantibodies, ZnT8) if diabetes is diagnosed or strongly suspected, as their presence indicates type 1 diabetes and predicts faster progression to insulin dependence 5
• The presence of ketosis or ketoacidosis does not definitively distinguish type 1 from type 2, as approximately 6% of youth with type 2 diabetes present with DKA 5

Physical Examination Documentation

Acanthosis Nigricans Characteristics

• Document the distribution and extent of acanthosis nigricans (neck, axillae, groin, beneath breasts, antecubital/popliteal fossae) 1, 4
• Look specifically for "tripe palms" (palmar involvement), which when present with rapidly progressive or extensive acanthosis nigricans raises concern for underlying malignancy 1

Associated Physical Findings

• Calculate BMI and waist-hip ratio to quantify obesity severity 1
• Examine for signs of hyperandrogenism: acne, hirsutism, male-pattern balding in females 1
• Screen for Cushing's syndrome features: moon facies, hypertension, abdominal striae, centripetal fat distribution, easy bruising, proximal muscle weakness, buffalo hump 1
• Perform pelvic examination for ovarian enlargement if PCOS is suspected 1

When to Consider Additional Testing

Malignancy Screening (Rare but Critical)

Age-appropriate cancer screening with emphasis on gastric and intra-abdominal malignancies should be pursued if acanthosis nigricans is rapidly progressive, extensive, or involves the palms, as malignancy-associated acanthosis nigricans most commonly involves gastric adenocarcinoma 1

Cushing's Syndrome Evaluation

If buffalo hump or other cushingoid features are present, immediately screen with 24-hour urinary free cortisol, late-night salivary cortisol, or low-dose dexamethasone suppression test 1

Common Pitfalls to Avoid

• Do not rely on A1c alone for diabetes screening in this population, as it misses early insulin resistance and impaired glucose tolerance 1
• Do not assume type 2 diabetes based solely on obesity and acanthosis nigricans—always check autoantibodies to exclude type 1 diabetes 5
• Do not dismiss acanthosis nigricans as purely cosmetic—it is a clinical marker requiring metabolic evaluation, as 62-80% of children with acanthosis nigricans (especially when combined with elevated BMI) have significant insulin resistance 2
• Do not overlook the possibility of malignancy in rapidly progressive cases, particularly with palmar involvement 1

Monitoring Strategy

• If initial screening is normal but BMI is increasing, repeat testing at minimum 3-year intervals or more frequently 5
• The presence of acanthosis nigricans alone predicts hyperinsulinemia and insulin resistance in approximately 7% of overweight adolescents, making it a valuable noninvasive screening tool 3