What is the management for a patient presenting with acanthosis nigricans and a probable buffalo hump?

Management of Acanthosis Nigricans with Buffalo Hump

Immediately screen for Cushing's syndrome with 24-hour urinary free cortisol, late-night salivary cortisol, or low-dose dexamethasone suppression test, as buffalo hump represents a potentially serious endocrine disorder requiring urgent evaluation. 1

Immediate Diagnostic Workup

Priority Testing for Buffalo Hump

• Perform Cushing's syndrome screening first using one of three tests: 24-hour urinary free cortisol, late-night salivary cortisol, or low-dose dexamethasone suppression test, as this is the most critical diagnosis to exclude given the buffalo hump presentation 1
• Document physical examination findings including moon facies, hypertension, abdominal striae, centripetal fat distribution, easy bruising, and proximal muscle weakness to support or refute Cushing's diagnosis 1

Metabolic and Insulin Resistance Evaluation

• Obtain fasting plasma glucose followed by 2-hour oral glucose tolerance test with 75-gram glucose load to detect diabetes and impaired glucose tolerance 1
• Measure fasting insulin levels (normal <15 mU/L; borderline 15-20 mU/L; high >20 mU/L) to directly assess insulin resistance 1
• Check hemoglobin A1C, with values 5.7-6.4% indicating prediabetes 1
• Order fasting lipid panel including total cholesterol, LDL, HDL, and triglycerides 1

Additional Endocrine Screening

• Measure thyroid-stimulating hormone (TSH) to exclude thyroid disease 1
• Assess total testosterone or free/bioavailable testosterone to evaluate for hyperandrogenism, particularly in women 1
• Check prolactin level if clinical features suggest hyperprolactinemia 1
• Calculate body mass index (BMI) and waist-hip ratio 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, as gastric adenocarcinoma is the most common malignancy associated with acanthosis nigricans 1

HIV and Lipodystrophy Consideration

• Assess HIV status and antiretroviral medication history, as buffalo hump is a characteristic feature of HIV-associated lipodystrophy occurring as a complication of antiretroviral treatment, particularly protease inhibitors 2
• Consider dual-energy X-ray absorptiometry to assess fat distribution patterns if lipodystrophy is suspected 2

Management Strategy

Primary Treatment: Address Underlying Cause

Weight reduction is the most effective and scientifically validated strategy for obesity-associated acanthosis nigricans, with a target of 7-10% decrease in excess weight. 3

For Insulin Resistance/Prediabetes/Type 2 Diabetes

• Initiate lifestyle modification program including nutrition counseling and physical activity 4
• Start metformin as first-line pharmacologic therapy at diagnosis if diabetes or significant insulin resistance is confirmed 4, 5
• Monitor HbA1c concentrations every 3 months and intensify treatment if goals are not met 4
• Encourage at least 60 minutes daily of moderate-to-vigorous exercise and limit nonacademic screen time to less than 2 hours daily 4

For Cushing's Syndrome

• Refer urgently to endocrinology for definitive management, which may include surgical resection of pituitary adenoma, adrenal tumor, or ectopic ACTH-producing tumor depending on etiology 1
• Be aware that systemic corticosteroids can cause acanthosis nigricans as a side effect, so if patient is on exogenous steroids, taper appropriately under supervision 4

For PCOS/Hyperandrogenism

• Treat underlying endocrinopathy with appropriate hormonal management 3
• Metformin improves insulin sensitivity and may benefit both metabolic and hyperandrogenic features 5
• Document menstrual history and exclude other causes including nonclassic congenital adrenal hyperplasia and androgen-secreting tumors 1

For HIV-Associated Lipodystrophy

• Recognize that lipodystrophy changes are often permanent despite antiretroviral modification 1
• Avoid antiretroviral drugs with strong metabolic adverse effects when possible to prevent or partially reverse lipodystrophy 2
• Focus management on screening for and treating metabolic complications such as insulin resistance and diabetes mellitus 2

Cosmetic Treatment Options (If Underlying Cause Not Amenable to Treatment)

First-Line Topical Therapy

• Topical retinoids are first-line therapy for hyperpigmented plaques, though skin irritation is a limiting factor 6, 7
• Vitamin D analogs can be used as alternative or adjunctive topical therapy 6
• Keratolytics may help reduce hyperkeratosis 6

Second-Line Options

• Chemical peels with trichloroacetic acid for localized lesions 6
• Oral retinoids for extensive or generalized acanthosis nigricans unresponsive to topical therapy 8
• Laser therapy including long-pulsed alexandrite, fractional 1550-nm erbium fiber, or CO2 lasers 6

Critical Pitfalls to Avoid

• Do not dismiss buffalo hump as simple obesity without ruling out Cushing's syndrome, as this represents a life-threatening condition if untreated 1
• Do not overlook malignancy screening in rapidly progressive acanthosis nigricans, especially with tripe palms, as this may be the presenting sign of gastric adenocarcinoma 1
• In children and adolescents, recognize that acanthosis nigricans serves as an early marker for insulin resistance and type 2 diabetes risk, requiring aggressive metabolic screening 1, 3
• Be aware that distinguishing type 1 from type 2 diabetes can be challenging in pediatric patients with acanthosis nigricans; consider checking islet autoantibodies if diabetes type is unclear 1
• Understand that complete cure of acanthosis nigricans is difficult to achieve even with treatment; set realistic expectations with patients 6, 8