Causes of Acanthosis Nigricans
Acanthosis nigricans is primarily caused by insulin resistance, with obesity being the most common underlying factor, though it can also result from genetic defects in insulin action, endocrinopathies, medications, and rarely, internal malignancy. 1, 2
Primary Causes
Insulin Resistance and Obesity
- Obesity is the most common cause of acanthosis nigricans, particularly in children and adolescents 3
- Insulin resistance leads to compensatory hyperinsulinemia, which stimulates keratinocyte and dermal fibroblast proliferation 2
- The obesity syndrome with insulin resistance is particularly common in pigmented ethnic groups 4
Genetic Causes
- Mutations in the insulin receptor gene can cause acanthosis nigricans 5
- Specific genetic syndromes associated with acanthosis nigricans include:
Endocrinopathies
- Excess hormones that antagonize insulin action can cause acanthosis nigricans 5:
- Acromegaly (excess growth hormone)
- Cushing's syndrome (excess cortisol)
- Glucagonoma (excess glucagon)
- Pheochromocytoma (excess epinephrine)
- These typically occur in individuals with preexisting defects in insulin secretion 5
- Hyperglycemia usually resolves when the hormone excess is treated 5
Autoimmune Conditions
- Anti-insulin receptor antibodies can cause acanthosis nigricans by:
- Blocking insulin binding to receptors in target tissues
- Sometimes acting as insulin agonists (causing hypoglycemia)
- These antibodies are found in patients with systemic lupus erythematosus and other autoimmune diseases 5
- This was formerly called type B insulin resistance 5
Medication-Induced
- Various medications can impair insulin action or secretion, leading to acanthosis nigricans 5:
- Nicotinic acid
- Glucocorticoids
- α-interferon
- Other medications that cause insulin resistance
Malignancy-Associated
- Rarely, acanthosis nigricans can be a sign of internal malignancy 3
- Adenocarcinomas, particularly of the pancreas, can be associated with acanthosis nigricans even when involving only a small portion of the organ 5
Clinical Presentation and Diagnosis
Acanthosis nigricans presents as symmetric, velvety, hyperpigmented plaques with ill-defined borders, typically in intertriginous areas such as:
- Neck
- Axillae
- Inframammary regions
- Groin
Diagnostic Approach
For patients with acanthosis nigricans, screening should include:
- Fasting plasma glucose
- 2-hour glucose tolerance test
- Hemoglobin A1C
- Fasting lipid panel
- Insulin levels 1
Additional tests based on clinical presentation:
- For women with menstrual irregularities: Total testosterone or free testosterone and sex hormone binding globulin
- Thyroid-stimulating hormone (TSH)
- In cases of suspected malignancy: Age-appropriate cancer screening 1
Management Considerations
The primary approach to treating acanthosis nigricans is addressing the underlying cause:
- Weight reduction for obesity-associated cases (target 7-10% decrease in excess weight) 1, 2
- Discontinuation of causative medications
- Treatment of underlying endocrinopathies
- Treatment of malignancy if present 3
For cosmetic improvement:
- Topical retinoids (first-line therapy)
- Vitamin D analogs
- Keratolytics
- Combination therapies to reduce irritation 1, 6
For insulin resistance:
- Metformin may improve both insulin resistance and acanthosis nigricans 7
- Oral retinoids and octreotide for extensive or resistant cases 7
Important Considerations
- Early recognition is crucial as acanthosis nigricans can signal serious underlying metabolic disorders
- Complete resolution of lesions is difficult to achieve even with treatment
- Regular follow-up is necessary to monitor for metabolic abnormalities, with repeat testing at minimum 3-year intervals or more frequently if BMI increases 1