Section 18. Endocrine Disorders and the Skin

Acanthosis nigricans (AN) is a diffuse, velvety thickening and hyperpigmentation of the skin, chiefly in axillae and other body folds, the etiology of which may be related to factors of hereditary, associated endocrine disorders, obesity, drug administration, and, in one rare form, malignancy.

Classification

• Type 1—Hereditary Benign AN No associated endocrine disorder.
• Type 2—Benign AN Associated with insulin resistance (IR): IR diabetes mellitus (DM), hyperandrogenism, acromegaly, gigantism, Cushing’s disease, glucocorticoid therapy, diethylstilbestrol, oral contraceptives, growth hormone, hypogonadism, Addison’s disease, hypothyroidism.
• Type 3—Pseudo-AN Obesity-induced IR, darker skin types.
• Type 4—Drug-induced AN Nicotinic acid, stilbestrol in young males, oral contraceptives.
• Type 5—Malignant AN Paraneoplastic, usually adenocarcinoma; less commonly, lymphoma.

Epidemiology

Age Any age. Peak: puberty to adulthood.

Gender M = F.

Incidence 7% of the population.

Race African Americans > Hispanics > Caucasians.

Pathophysiology

Epidermal changes of AN are likely caused by triggers that stimulate keratinocyte and fibroblast proliferation. In type 2, benign AN, the trigger is likely insulin or an insulinlike growth factor. In type 5, malignant AN, the trigger is likely the tumor or tumor secretions.

History

AN has an asymptomatic, insidious onset. The first visible change is darkening of pigmentation which gradually progress to velvety plaques that may be pruritic.

Physical Examination

Skin Findings

Type Plaque.

Color Dark brown to black, hyperpigmented, skin appears dirty.

Palpation Velvety, rugose, mammillated.

Distribution Posterior neck (Fig. 18-1) > axillae, groin > antecubital, knuckles, submammary, umbilicus, areola.

Mucous Membranes Oral, nasal, laryngeal, and esophagus: velvety texture with delicate furrows.

Nails Leukonychia, hyperkeratosis.

Other Skin tags in same areas.

General Findings

Ocular Papillomatous lesions on the eyelids and conjunctiva.

Benign AN Obesity or underlying endocrine disorder.

Malignant AN Underlying malignancy, gastric adenocarcinoma (70%).

Differential Diagnosis

AN can be confused with confluent and reticulated papillomatosis of Gougerot and Carteaud (CRP), terre firme, hypertrichosis, Becker’s nevus, epidermal nevus, hemochromatosis, Addison’s, or pellagra.

Laboratory Examinations

Dermatopathology Papillomatosis, hyperkeratosis; epidermis thrown into irregular folds, showing varying degrees of acanthosis.

Course and Prognosis

• Type 1: Accentuated at puberty, and, at times, regresses when older.
• Type 2: Prognosis related to severity of IR. AN may regress subsequent to treatment of the IR state.
• Type 3: AN may regress subsequent to significant weight loss.
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