Hyperandrogenism, insulin resistance, and acanthosis nigricans syndrome: a common endocrinopathy with distinct pathophysiologic features.

The HAIR-AN syndrome that consists of hyperandrogenism (HA), insulin resistance (IR), and acanthosis nigricans (AN) is an underdiagnosed endocrinopathy, because hyperandrogenic women are not commonly screened for insulin resistance or acanthosis nigricans. The distinct pathophysiologic features of the HAIR-AN syndrome are discussed in detail. In this syndrome, the primary pathophysiologic derangements are the insulin resistance and the hyperandrogenism. The acanthosis nigricans is an epiphenomenon of these primary processes. In patients with the HAIR-AN syndrome, the degree of severity of the insulin resistance is positively correlated with the degree of severity of the hyperandrogenism. In patients with adequate pancreatic beta-islet cell reserve, insulin resistance results in a long-term increase in circulating insulin levels. The hyperinsulinemia probably directly stimulates ovarian androgen production. In turn, hyperandrogenism itself produces insulin resistance. This positive feedback loop between insulin resistance and hyperandrogenism propagates the disease, and increases its severity over time. The relationship between insulin resistance and hyperandrogenism may explain the hyperandrogenemia seen in the following disease processes: obesity, acromegaly, lipoatrophic diabetes, leprechaunism, and Kahn types A and B insulin resistance.