What does acanthosis nigricans of the neck indicate and what is the appropriate work‑up and management?

Acanthosis Nigricans of the Neck: Clinical Significance and Management

Acanthosis nigricans (AN) on the neck is a clinical marker of insulin resistance and metabolic syndrome, requiring immediate screening for type 2 diabetes and evaluation for underlying endocrinopathies. 1

What Acanthosis Nigricans Indicates

Primary Association: Insulin Resistance and Metabolic Risk

• AN represents a visible cutaneous manifestation of hyperinsulinemia and insulin resistance, serving as an empirical marker for elevated risk of type 2 diabetes that can appear years before glucose intolerance develops. 2
• The presence of AN, particularly in the context of obesity, signals underlying metabolic dysfunction including dyslipidemia with elevated triglycerides, increased LDL cholesterol, and decreased HDL cholesterol. 3
• AN is strongly associated with polycystic ovary syndrome (PCOS) in women, where it appears alongside chronic anovulation, hyperinsulinemia, and decreased sex hormone binding globulin levels. 3

Critical Red Flags Requiring Urgent Investigation

• Malignancy-associated AN: When AN appears in non-obese individuals without clear metabolic risk factors, consider associated insulinoma or malignancy, particularly gastric adenocarcinoma. 3
• Rapid onset or progression of AN lesions warrants immediate evaluation for underlying malignancy. 4, 5

Appropriate Work-Up Algorithm

Step 1: Metabolic Screening (Mandatory for All Patients)

• Fasting glucose followed by 2-hour oral glucose tolerance test with 75-gram glucose load to screen for type 2 diabetes and glucose intolerance—this is the ACOG-recommended standard for patients with signs of insulin resistance. 3
• Fasting lipid and lipoprotein panel to assess for dyslipidemia (elevated triglycerides, LDL cholesterol, and low HDL cholesterol). 3
• Calculate HOMA-IR (Homeostasis Model Assessment-Insulin Resistance) using fasting glucose and insulin levels to quantify insulin resistance. 6

Step 2: Endocrine Evaluation

• Thyroid-stimulating hormone (TSH) level to exclude thyroid disease. 3
• In women: Obtain prolactin level and total/free testosterone to evaluate for PCOS and hyperandrogenism. 3
• Assess for clinical signs of Cushing's syndrome (buffalo hump, moon facies, hypertension, abdominal striae, centripetal fat distribution, easy bruising, proximal myopathy)—if present, proceed with formal Cushing's screening. 3

Step 3: Malignancy Screening (When Indicated)

• Order radiological investigations (plain radiography, ultrasonography, CT/MRI) if the patient is non-obese, has rapid onset of AN, lacks metabolic risk factors, or has constitutional symptoms suggesting malignancy. 5
• Consider upper endoscopy for gastric adenocarcinoma screening in high-risk presentations. 3

Step 4: Additional Laboratory Testing

• Hemoglobin and alanine aminotransferase (ALT) to screen for non-alcoholic fatty liver disease (NAFLD), which commonly coexists with insulin resistance. 5

Management Strategy

Primary Intervention: Weight Reduction

• Weight loss of 7-10% of excess body weight is the most effective and scientifically validated treatment for obesity-associated AN. 1, 6
• Regular physical activity and dietary modification directly reduce insulin resistance and improve AN appearance. 2

Pharmacological Management

• Metformin: Insulin-sensitizing agent that addresses the underlying hyperinsulinemia; commonly used first-line for obesity-associated AN. 5
• Saroglitazar: Dual PPAR-α/γ agonist that improves insulin sensitivity, modulates lipid metabolism, and provides anti-inflammatory effects—particularly useful when NAFLD coexists. 1
• Thiazolidinediones (PPAR-γ agonists) can improve metabolic parameters and have demonstrated benefit in NAFLD histology. 1

Topical Therapies for Cosmetic Improvement

• Topical retinoids, keratolytic agents (salicylic acid, urea), and alpha-hydroxy acids reduce plaque thickness and improve cosmesis but do not address underlying pathology. 4, 6
• Vitamin D analogs may provide modest benefit. 6
• Chemical peels (trichloroacetic acid) and lasers (long-pulsed alexandrite, fractional erbium, CO₂) are adjunctive options for refractory cosmetic concerns. 6

Treatment of Underlying Conditions

• For PCOS: Address hyperandrogenism and anovulation with appropriate hormonal therapy while managing insulin resistance. 3
• For malignancy-associated AN: Treatment of the underlying cancer typically leads to resolution of skin changes. 3

Critical Pitfalls to Avoid

Do Not Delay Diabetes Screening

• AN is an early warning sign that can precede glucose intolerance by years; failure to screen with oral glucose tolerance testing (not just fasting glucose alone) misses the opportunity for early intervention. 3, 2

Do Not Assume Benign Etiology Without Proper Evaluation

• While obesity-associated AN is most common (80% of cases), missing malignancy-associated AN has devastating consequences—always evaluate non-obese patients and those with atypical presentations thoroughly. 3, 7

Do Not Rely on Topical Therapy Alone

• Topical treatments improve appearance but do not modify the underlying metabolic disease; they should never substitute for systemic evaluation and lifestyle intervention. 4, 6

Do Not Overlook Cardiovascular Risk

• Patients with AN and insulin resistance have significantly elevated cardiovascular disease risk due to dyslipidemia and metabolic syndrome—comprehensive cardiovascular risk assessment and management is essential. 3