# Acanthosis Nigricans

Acanthosis nigricans should prompt etiologic triage rather than cosmetic treatment alone: most cases reflect obesity-associated insulin resistance, but abrupt generalized, mucosal, or nonobese presentations require evaluation for medication, endocrine, autoimmune, and malignant drivers.

**Clinical question:** How should clinicians evaluate acanthosis nigricans for metabolic disease, rare insulin-resistance syndromes, and internal malignancy?

Updated: 2026-09-15T23:10:20.981266+00:00

## What matters in practice
- In an overweight patient with symmetric intertriginous plaques, prioritize assessment for insulin resistance and its metabolic comorbidities; obesity is a stronger determinant of insulin resistance than acanthosis nigricans alone. [21][22]
- Document BMI, blood pressure, fasting glucose, hemoglobin A1c, fasting lipid profile, and alanine aminotransferase when acanthosis nigricans accompanies overweight or obesity. [19][24]
- Rapidly progressive, extensive, mucosal, or nonobesity-associated acanthosis nigricans warrants a directed search for malignancy and less common endocrine, medication-related, or autoimmune insulin-resistance causes. [16][21][23]
- Treat the driver first: weight reduction, discontinuation of a causative medication, treatment of an endocrinopathy, or cancer-directed therapy may improve lesions; lesion-directed treatment is principally cosmetic. [21]

## Classify the presentation before ordering tests

The distribution, tempo, body habitus, and extracutaneous findings determine the initial workup.

Confirm the clinical phenotype: symmetric, hyperpigmented, velvety plaques with poorly defined borders, usually in intertriginous areas, support acanthosis nigricans. Skin tags commonly coexist around affected sites in insulin-resistant phenotypes. [21][23]

The common branch is obesity-associated insulin resistance. In children, adolescents, and adults with overweight or central adiposity, neck and axillary involvement should redirect the encounter toward dysglycemia, dyslipidemia, hypertension, and fatty-liver risk rather than biopsy or lesion-directed therapy. Acanthosis nigricans identifies higher metabolic risk, but obesity is more predictive of insulin resistance than the skin finding alone. [2][22][24]

Escalate beyond routine metabolic assessment when lesions are abrupt, rapidly progressive, extensive or generalized, involve oral or other mucosa, or arise in a nonobese patient without an evident insulin-resistant state. Malignant lesions can be clinically indistinguishable from benign lesions; gastrointestinal adenocarcinoma, particularly gastric carcinoma, is the classic association. [16][21][23]
- Ask about tempo: longstanding lesions tracking with weight gain favor obesity-associated disease; rapid new progression increases concern for a systemic driver. [16][21]
- Review medications and supplements because acanthosis nigricans is associated with drugs as well as insulin resistance, endocrine disorders, chromosomal abnormalities, and neoplasia. [7][21]
- Ask about menstrual irregularity, hirsutism, acne, or virilization; acanthosis nigricans can be a cutaneous marker of polycystic ovary syndrome and other hyperandrogenic states. [6][16][24]
- Ask about symptomatic hypo- or hyperglycemia and autoimmune disease when severe insulin resistance is disproportionate to adiposity; type B insulin resistance may present with either hyperglycemia or hypoglycemia. [9][11]

*Clinical patterns that change the next diagnostic step. [6][11][16][21][24]*

| Pattern | Most likely etiologic branch | Next action |
| --- | --- | --- |
| Gradual neck/axillary plaques with obesity or central adiposity | Obesity-associated insulin resistance | Measure BMI and blood pressure; obtain fasting glucose, hemoglobin A1c, fasting lipid profile, and ALT. [19][24] |
| Acanthosis nigricans with irregular menses, hirsutism, acne, or virilization | PCOS or another hyperandrogenic insulin-resistant state | Evaluate the hyperandrogenic syndrome and metabolic comorbidity burden. [6][16][24] |
| Severe generalized disease with marked hyperinsulinemia, dysglycemia, hypoglycemia, or autoimmune features | Type B insulin resistance | Obtain paired glucose and insulin/C-peptide during the glycemic phenotype and pursue insulin-receptor antibody testing through an experienced center. [9][11] |
| Abrupt, extensive, mucosal, or nonobese presentation | Malignancy-associated acanthosis nigricans | Perform symptom- and examination-directed evaluation for internal malignancy, with particular attention to gastrointestinal cancer. [16][21][23] |

## Evaluate obesity-associated acanthosis nigricans as a metabolic risk marker

The purpose of testing is to identify actionable dysglycemia and cardiometabolic comorbidity.

At the initial visit, record height, weight, BMI, waist or hip circumference when useful for adiposity assessment, and blood pressure. Examine for skin tags, hirsutism, goiter, abdominal tenderness or hepatomegaly, and broad pink striae when the history suggests endocrine disease. [19][24]

Obtain fasting plasma glucose and hemoglobin A1c to detect dysglycemia, and obtain a fasting lipid profile to identify atherogenic dyslipidemia. Add ALT when obesity-associated metabolic dysfunction or hepatic steatosis is a concern; overweight and obese children with acanthosis nigricans have demonstrated higher fasting glycemia, insulin, HOMA index, triglyceride-related metabolic abnormalities, and aminotransferase levels than peers without lesions. [19][24]

Do not use acanthosis nigricans as a stand-alone proxy for insulin resistance or type 2 diabetes. In obese children, the presence of lesions is associated with insulin resistance, but obesity itself remains the more important determinant; a normal glucose result does not negate the need to address excess adiposity and longitudinal metabolic risk. [18][22]
- For youth with obesity plus acanthosis nigricans, recognize the lesion as a sign of insulin resistance that strengthens concern for type 2 diabetes risk. [2][6]
- When fasting glucose and hemoglobin A1c do not explain the clinical phenotype but concern for glucose intolerance remains high, consider an oral glucose tolerance test; OGTT has been used to characterize glucose tolerance and insulin resistance in obese children with acanthosis nigricans. [18][19]
- In patients with obesity-associated disease, use the laboratory results to manage dysglycemia, hypertension, dyslipidemia, and suspected fatty liver rather than treating pigment alone. [19][24]

## Recognize endocrine, autoimmune, and malignancy-associated patterns

Rare causes matter when phenotype severity or clinical context is discordant with ordinary obesity-associated disease.

Consider endocrine-associated acanthosis nigricans when there are syndrome-specific findings. Hyperandrogenic and hypogonadal states, Cushing disease, Addison disease, hypothyroidism, and diabetes-related insulin resistance have been reported associations. In a patient with corresponding symptoms or examination findings, test for the suspected disorder rather than applying a broad endocrine panel. [10][16]

Type B insulin resistance is an autoimmune syndrome caused by insulin-receptor autoantibodies and can produce severe insulin resistance with hyperglycemia or, less often, hypoglycemia. During a spontaneous hypoglycemic event, obtain glucose with insulin, proinsulin, and C-peptide; confirmation requires insulin-receptor autoantibody detection. The coexistence of acanthosis nigricans, extreme hyperinsulinemic biochemistry, autoimmune features, and hyperandrogenism or female virilization should prompt urgent endocrinology involvement. [9][11]

For suspected malignant acanthosis nigricans, use history and examination to direct cancer testing rather than assuming that lesion morphology distinguishes malignant from metabolic disease. Gastric carcinoma is the most common reported tumor association, and adenocarcinomas of the gastrointestinal tract, ovary, lung, and breast have been described. Mucosal involvement may include the oral cavity, nasal or laryngeal mucosa, or esophagus. [16][23]
- A nonobese patient with new acanthosis nigricans and no evident insulin-resistant phenotype needs malignancy assessment and medication review. [16][21]
- Mucosal lesions or widespread papillomatous disease increase the need to investigate a paraneoplastic pattern, while recognizing that mucosal lesions have also been reported in acanthosis nigricans generally. [16][23]
- Do not infer that correction of hypothyroidism alone will resolve acanthosis nigricans or hyperinsulinemia; reported cases showed persistence after thyroid correction. [10]

## Treat the underlying driver before cosmetic therapy

Improvement in plaques follows reduction of the pathogenic stimulus more reliably than lesion-only treatment.

For obesity-associated acanthosis nigricans, make weight reduction and treatment of insulin resistance the primary intervention. Weight loss can improve obesity-related disease, and control of hyperinsulinemia through dietary change may reduce lesion severity. Treat documented diabetes, dyslipidemia, hypertension, polycystic ovary syndrome, or suspected fatty-liver disease according to the relevant disease pathway. [14][16][21]

When an identifiable medication is implicated, discontinue or substitute it when clinically feasible. If a defined endocrinopathy or internal malignancy is driving the lesions, direct treatment to that disorder; this approach may improve acanthosis nigricans and avoids ineffective escalation of cosmetic therapies. [21]

Use lesion-directed therapy only after addressing the driver and clarifying that evidence is largely symptomatic or cosmetic. Localized lesions may be treated with topical retinoids, vitamin D analogs, chemical peels, or other keratolytics; systemic oral retinoids have been considered for extensive, generalized, or topical-treatment–unresponsive disease. Laser therapy, dermabrasion, and surgical removal are less common options. [21]
- Metformin has been reported to improve insulin resistance and acanthosis nigricans after treatment for at least 6 months, but the reviewed material does not establish a lesion-specific dose or make it a substitute for indication-based metabolic treatment. [15][22]
- Tazarotene has been reported as symptomatic treatment in juvenile familial obesity-associated acanthosis nigricans; select topical therapy for cosmetic goals, not to exclude or treat systemic disease. [4]
- Reassess lesion trajectory alongside body weight and the identified metabolic or systemic driver; continued rapid progression should reopen evaluation for an alternative cause. [16][21]

*Management priorities by etiologic branch. [14][15][16][21][22]*

| Etiology | Primary intervention | Role of skin-directed therapy |
| --- | --- | --- |
| Obesity-associated insulin resistance | Weight reduction and treatment of documented metabolic comorbidities. [14][16][21] | Consider topical retinoids, vitamin D analogs, peels, or keratolytics for residual cosmetic concern. [21] |
| Medication-associated disease | Discontinue or replace the causative medication when feasible. [21] | Use only if lesions remain bothersome after medication review. [21] |
| Endocrinopathy or PCOS-associated disease | Treat the identified endocrine or hyperandrogenic disorder and associated insulin resistance. [16][21][24] | Adjunctive only. [21] |
| Malignancy-associated disease | Treat the underlying malignancy after directed diagnostic evaluation. [21] | Do not allow cosmetic treatment to delay cancer evaluation. [21] |
| Type B insulin resistance | Confirm insulin-receptor autoantibodies and manage with specialized endocrinology input. [11] | No primary role until the systemic disorder is addressed. [21] |

## Use biopsy selectively and refer for discordant disease

Histology may support the diagnosis but does not replace etiologic assessment.

Clinical diagnosis is usually sufficient when the morphology and metabolic context are typical. Consider dermatology evaluation and biopsy when morphology is atypical, distribution is unusual, facial pigmentation raises competing diagnoses, or a mimicker such as an acanthosis nigricans-like variant of mycosis fungoides is plausible. Patch-stage mycosis fungoides may require multiple skin biopsies. [13][17]

Refer urgently to endocrinology for suspected type B insulin resistance or severe dysglycemia with disproportionate hyperinsulinemia, and coordinate expedited malignancy evaluation for rapid, generalized, mucosal, or nonobese disease. The referral question should specify the phenotype, lesion tempo, glucose pattern, insulin/C-peptide results when obtained, medication exposures, and systemic cancer symptoms. [9][11][16][21]
- Biopsy does not distinguish benign from malignant acanthosis nigricans reliably because malignant lesions may be clinically indistinguishable from benign lesions. [23]
- For facial hyperpigmentation, reconsider facial acanthosis nigricans and competing pigmentary disorders before initiating depigmenting or keratolytic treatment. [17]

## References
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13. Mycosis fungoides: a review - Oxford Academic — academic.oup.com — https://academic.oup.com/ced/advance-article-pdf/doi/10.1093/ced/llaf341/63867538/llaf341.pdf
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15. An approach to acanthosis nigricans : Indian Dermatology Online Journal — journals.lww.com — https://journals.lww.com/idoj/fulltext/2014/05030/an_approach_to_acanthosis_nigricans.1.aspx
16. Acanthosis Nigricans - an overview | ScienceDirect Topics — www.sciencedirect.com — https://www.sciencedirect.com/topics/medicine-and-dentistry/acanthosis-nigricans
17. Facial acanthosis nigricans − a narrative review : Pigment International — journals.lww.com — https://journals.lww.com/pigi/fulltext/2023/10020/facial_acanthosis_nigricans___a_narrative_review.2.aspx
18. Acanthosis nigricans is a reliable cutaneous marker of insulin resistance in obese Japanese children - PubMed — www.ncbi.nlm.nih.gov — https://www.ncbi.nlm.nih.gov/pubmed/14651545
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## Editorial note

Prepared from cited clinical literature using Astra's research workflow. Verify recommendations against current guidance and patient-specific factors.