Diagnostic Workup for Buffalo Hump or Acanthosis Nigricans
Screen immediately for insulin resistance and diabetes with fasting glucose followed by a 2-hour oral glucose tolerance test (75-gram glucose load), as these physical findings are strong markers of metabolic dysfunction. 1, 2
Initial Laboratory Evaluation
Essential Metabolic Screening
- Fasting plasma glucose followed by 2-hour oral glucose tolerance test (75-gram load) to detect diabetes and impaired glucose tolerance 1, 2
- Fasting insulin levels (normal <15 mU/L; borderline 15-20 mU/L; high >20 mU/L) to directly assess insulin resistance 3
- Hemoglobin A1C (values 5.7-6.4% indicate prediabetes) 3
- Fasting lipid panel including total cholesterol, LDL, HDL, and triglycerides 1, 3
Endocrine Evaluation
- Thyroid-stimulating hormone (TSH) to exclude thyroid disease 1, 4
- Total testosterone or free/bioavailable testosterone to evaluate for hyperandrogenism, particularly in women 1
- Prolactin level if clinical features suggest hyperprolactinemia 1
When Buffalo Hump is Present
If buffalo hump is identified, immediately screen for Cushing's syndrome with appropriate testing (24-hour urinary free cortisol, late-night salivary cortisol, or low-dose dexamethasone suppression test), as this represents a potentially serious endocrine disorder requiring urgent evaluation. 1
Additional considerations for buffalo hump:
- HIV status and antiretroviral medication history if risk factors present, as HIV-associated lipodystrophy is a common cause 5
- Duration of HIV infection, viral load, and CD4 counts if HIV-positive 5
Physical Examination Focus
Key Clinical Features to Document
- Body mass index (BMI) and waist-hip ratio calculation 1
- Distribution and extent of acanthosis nigricans (neck, axillae, groin, beneath breasts, vulva) 1
- Signs of hyperandrogenism: acne, hirsutism, male-pattern balding, clitoromegaly 1, 2
- Signs of Cushing's syndrome: moon facies, hypertension, abdominal striae, centripetal fat distribution, easy bruising, proximal muscle weakness 1
- Pelvic examination for ovarian enlargement if PCOS suspected 1
Malignancy Screening
In patients with rapidly progressive or extensive acanthosis nigricans, particularly with "tripe palms" (palmar involvement), pursue age-appropriate cancer screening with emphasis on gastric and intra-abdominal malignancies. 1, 6, 7
- Acanthosis nigricans associated with malignancy most commonly involves gastric adenocarcinoma 1
- Consider upper endoscopy if rapid onset, extensive disease, or tripe palms present 6
- In women, evaluate for endometrial cancer risk, especially with obesity, chronic anovulation, and hyperinsulinemia 1, 6
- Age-appropriate cancer screening based on clinical history and examination 1
Differential Diagnosis Considerations
Polycystic Ovary Syndrome (PCOS)
When acanthosis nigricans occurs with menstrual irregularities or hyperandrogenism in women:
- Document menstrual history and onset/duration of androgen excess signs 1
- Exclude other causes: nonclassic congenital adrenal hyperplasia, androgen-secreting tumors, acromegaly 1
- Screen for type 2 diabetes given demonstrated increased risk in PCOS 1
Pediatric Considerations
In children and adolescents with acanthosis nigricans:
- Serves as early marker for insulin resistance and type 2 diabetes risk 2
- Distinguishing type 1 from type 2 diabetes can be challenging, as obesity and acanthosis nigricans may occur with either type 1, 2
- Consider islet autoantibodies if diabetes type unclear 1
Common Pitfalls
- Do not assume benign etiology based solely on obesity; always screen for diabetes and other endocrine disorders 4
- Insulin resistance testing must be performed fasting to avoid postprandial variations 3
- Rapidly progressive acanthosis nigricans warrants urgent malignancy workup, not reassurance 6, 7
- Buffalo hump requires Cushing's syndrome exclusion before attributing to obesity alone 1
- In HIV-positive patients, lipodystrophy changes are often permanent despite antiretroviral modification 5