Acanthosis Nigricans, insulin action, and hyperandrogenism: clinical, histological, and biochemical findings

Acanthosis nigricans (AN) is a frequent clinical finding in hyperandrogenic women. Its presence has been used to subgroup such women. We performed this study in order to determine the actual histological prevalence of AN and its relationship to sex hormone levels and insulin action. Insulin-mediated glucose disposal was determined by the euglycemic clamp technique, and neck or axillary skin biopsies were graded blind for the presence and severity of AN in lean and obese women with the polycystic ovary syndrome (PCO) and in age- and weight-matched normal ovulatory controls. AN was present on clinical examination in 11 of 13 obese PCO, 3 of 6 lean PCO, 4 of 14 obese normal, and 0 of 4 lean normal women. AN was present on histological examination in 13 of 13 obese PCO, 5 of 6 lean PCO, 13 of 14 obese normal, and 1 of 4 lean normal women. The severity of histological AN was most highly correlated with insulin-mediated glucose disposal (r = -0.61; P less than 0.001) rather than fasting (r = 0.46; P less than 0.05) or glucose-stimulated insulin levels (r = 0.48; P less than 0.01). The only sex steroid correlated with histological AN was dehydroepiandrosterone sulfate (r = 0.46; P less than 0.01). We conclude that 1) clinical skin examination was very insensitive for detecting AN; 2) the best biochemical correlate of histological AN was decreased insulin action, rather than insulin or androgen levels per se; and 3) AN is a very common epiphenomenon of insulin resistance, and its clinical presence should not be used as a criterion for stratifying hyperandrogenic women.