Laboratory Workup for Acanthosis Nigricans
When evaluating a patient with acanthosis nigricans, order fasting plasma glucose (or A1C), fasting insulin level, and lipid panel as the core laboratory tests to screen for insulin resistance, diabetes, and metabolic syndrome.
Essential Laboratory Tests
The presence of acanthosis nigricans (AN) is a clinical marker of insulin resistance and warrants systematic metabolic screening 1, 2, 3. The following tests should be ordered:
Primary Screening Tests
- Fasting plasma glucose (FPG) or A1C: Screen for diabetes (FPG ≥126 mg/dL or A1C ≥6.5%) and prediabetes (FPG 100-125 mg/dL or A1C 5.7-6.4%) 1, 3
- Fasting insulin level: Elevated fasting insulin (>15 mU/L, with >20 mU/L considered high) indicates insulin resistance 4. Research consistently shows that all patients with AN have elevated fasting insulin levels and exaggerated insulin responses to glucose loads 5
- Lipid profile: Check HDL cholesterol (<35 mg/dL) and triglycerides (>250 mg/dL), as dyslipidemia commonly accompanies insulin resistance 1, 2
Calculate HOMA-IR
Use fasting glucose and insulin to calculate the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). Values >2.5 indicate significant insulin resistance 6, 7. Studies show that 71.8% of obese children with AN have HOMA-IR >2.5, and when AN is combined with elevated BMI, the incidence of insulin resistance reaches 80% 6, 7.
Additional Screening Based on Clinical Context
For Women with AN
- Testosterone and androstenedione: Screen for polycystic ovary syndrome (PCOS), which frequently coexists with AN 8, 5, 9
- LH/FSH ratio: Elevated LH with normal FSH suggests PCOS 9
- Prolactin: Check if menstrual irregularities or galactorrhea present 5
For All Patients with AN
- TSH and free T4: Hypothyroidism was present in 15% of patients with AN in one series 5
- Liver enzymes (AST, ALT): Screen for metabolic dysfunction-associated steatotic liver disease (MASLD), as AN predicts higher grades of hepatic steatosis 10. AST levels are significantly higher in patients with AN 6
- Blood pressure measurement: Hypertension commonly accompanies AN and insulin resistance 1, 4
Age-Specific Considerations
In Children and Adolescents (≥10 years or after puberty onset)
The same metabolic screening applies when AN is present with overweight/obesity (BMI ≥85th percentile) 1, 3. The combination of AN and elevated BMI has 80% predictive value for insulin resistance in children 7.
Repeat Testing Intervals
- If initial tests show prediabetes: annually 3
- If tests are normal but AN persists: every 3 years minimum, or more frequently if BMI increases 1, 3
Important Clinical Pearls
Do not routinely measure C-peptide or perform euglycemic clamp studies in the evaluation of AN—these are research tools, not clinically necessary 11. The simple combination of fasting glucose, fasting insulin, and physical examination (BMI, presence of AN) provides adequate assessment of insulin resistance 11.
AN precedes metabolic comorbidities in the majority of cases 12, making it an excellent early screening opportunity. In one study, 67.6% of obese children had AN, and most had significant insulin resistance 6.
The neck is the most reliable location for detecting AN with high interobserver reliability 13. AN at the knuckles specifically predicts higher grades of hepatic steatosis (OR 2.09) 10.
Malignancy screening (particularly gastric adenocarcinoma) should be considered in adults with sudden-onset, rapidly progressive AN without obesity or metabolic risk factors 5, 14, though this represents a minority of cases.