DOI: 10.1210/js.2019-00045; PMCID: PMC6546343
Type A insulin resistance (IR) is caused by heterozygous mutations in the insulin receptor gene. It presents with mild acanthosis nigricans, severe IR, and hyperandrogenism in the absence of obesity or lipodystrophy. Treatment aims to improve insulin sensitivity and decrease androgens. An adolescent girl was evaluated for secondary amenorrhea and prominent hirsutism. She had a normal body mass index, and laboratory testing revealed an elevated LH to FSH ratio (LH 11.6 mIU/mL, FSH 4.2 mIU/mL), testosterone 96 ng/dL (reference range/dL), free testosterone 2.21 ng/dL (reference rangeA(pGly1032Asp)]. After standard treatment of hirsutism and hyperinsulinism failed, a trial of GnRH agonist therapy improved hyperandrogenism and reduced ovarian size while severe IR persisted. We describe an adolescent with type A IR who experienced resolution of clinical and biochemical hyperandrogenism during GnRH agonist treatment. Given the patient's marked reduction in testosterone and hirsutism despite persistent hyperinsulinism, this case challenges the idea that insulin increases steroidogenesis independently of gonadotropin effect. GnRH agonist therapy should be considered in the treatment of hyperandrogenism in severe cases of IR.
J Endocr Soc
GnRH; adolescent; hyperandrogenism; insulin resistance; leuprolide
Paprocki, E., Barral, R., Vanden Brink, H., Lujan, M., Burgert, T. S. GnRH Agonist Improves Hyperandrogenism in an Adolescent Girl With an Insulin Receptor Gene Mutation. J Endocr Soc 3, 1196-1200 (2019).