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.