Acanthosis Nigricans, Hirsutism, Insulin Resistance and Insulin Receptor Defect

Abstract

A 24-year-old negress with the triad of acanthosis nigricans, hirsutism associated with polycystic ovaries and insulin resistance is reported. Metabolic studies were done 3 years after a bilateral ovarian wedge resection. Partial remission of the hirsutism and return of menstrual cycles occurred after surgery. Extreme resistance to endogenous and exogenous insulin was observed. Three studies of insulin receptors on circulating red blood cells (RBC) showed abnormal inhibition-competition curves, characterized by increased percentage insulin binding at higher unlabelled insulin levels. Scatchard plots suggested an apparent increase in the number of low affinity receptors. Despite the changes in receptor-insulin interaction, the defect does not seem to explain the insulin resistance since binding of insulin to a target tissue (RBC) appeared to be quantitatively normal at physiological insulin levels, suggesting a simultaneous post receptor defect.

Adipose tissue, hepatic, and skeletal muscle insulin sensitivity in extremely obese subjects with acanthosis nigricans

“…In fact, defects in insulin binding [21] and post-insulin receptor function [22], and genetic defects within the insulin receptor gene have been documented in patients with AN [23,24]. These abnormalities are consistent with data from several studies showing both impaired insulin-receptor autophosphorylation [25 -27] and reduced numbers of insulin receptors in subjects with AN [13,28].…”

Remission of Acanthosis Nigricans, Hypertrichosis, and Hashimoto's Thyroiditis with Thyroxine Replacement

“…Of the endocrine disorders, insulin resistance is frequently associated with AN, and may occur on the basis of receptor or postreceptor defects (11,12). Hyperinsulinism stimulates production of androgens in the ovarian stroma and may lead to significant hirsutism (5).…”