A 31-year-old woman with infertility and polycystic ovaries diagnosed with non-classic congenital adrenal hyperplasia due to a novel CYP21 mutation.

A 31-yr-old woman presenting with a history of hirsutism, amenorrhea, and infertility was previously assumed to have polycystic ovary syndrome. A new gynecological-endocrine evaluation demonstrated elevated testosterone/SHBG ratio, serum 17-hydroxyprogesterone (17-OHP), and urinary pregnantriol. She was diagnosed with non-classic congenital adrenal hyperplasia. In spite of treatment with dexamethasone and fludrocortisone in doses that suppressed adrenal androgens and 17-OHP into normal range or below, she did not ovulate. Clomiphene citrate and then FSH/hCG treatment in several cycles gave no consistent ovulation. Progesterone levels remained elevated throughout the cycles indicating a possible contribution from the adrenals. Oral glucose tolerance was normal, but the homeostasis model assessment index indicated insulin resistance. With metformin 1500 mg daily the index decreased remarkably from 2.77 to 0.96 with a few ovulations but no pregnancy occurred. Three cycles of IVF treatment thereafter were unsuccessful. Three months after the last in vitro fertilization (IVF) cycle, still on dexamethasone, fludrocortisone, and metformin, her menstruations became regular and she thereafter became pregnant. During pregnancy metformin was discontinued and dexamethasone replaced with prednisolone. Mild gestational diabetes developed and insulin was given. A healthy boy was born at term by elective Cesarean section. A CYP21- gene analysis had not indicated any of the known mutations but after gene sequencing a novel mutation was found, namely R233G. This case confirms the necessity of adding an analysis of 17-OHP when evaluating women with hirsutism and menstrual disturbances and if an elevated value is found, the advantage of performing a mutation analysis to facilitate counseling and decisions on treatment.