A 55-year-old woman presented with
androgenetic alopecia which had started at age 40. Her clinical history revealed that, unlike her younger sister, she was unable to conceive and was diagnosed as being sterile at age 30. At age 45,
21-hydroxylase deficiency (late-onset CAH) was assumed and
glucocorticoid treatment suggested, but not initiated. There was slight
hirsutism, but no other sign of
virilization. Retesting of plasma
steroids revealed elevated 17-OH-progesterone and free
testosterone. Treatment with
prednisone,
cyproterone acetate, and
spironolactone was started with significant clinical success. Surprisingly, the analyses of urinary
steroid metabolites revealed a pattern that did not support the diagnosis of
21-hydroxylase deficiency (
pregnanetriolone absent,
pregnanediol, 17-
OH-
pregnanolone and
pregnanetriol not increased). Abdominal CT showed bilateral adrenal
hyperplasia and masses in both ovaries. Bilateral adnexectomy was performed, and cystic
teratomas were diagnosed. Postoperative urinary
steroid analyses showed a decreased
tetrahydrocortisol/
tetrahydrocortisone ratio (values around 0.08 as compared to age- and sex-matched controls with a ratio of about 0.5-0.8). Plasma
cortisol appeared to be repeatedly elevated with exogenous sources excluded. Mass spectrometry showed that, while the tetrahydro metabolites were mainly
cortisone-derived, the metabolites not reduced in A ring were mostly
cortisol derivatives. This constellation clearly indicates
cortisone reductase deficiency, a defect of hepatic
11 beta-hydroxysteroid dehydrogenase (11 beta-HSD1). This
enzyme catalyzes the oxidation of
cortisol to
cortisone and the reduction of
cortisone to
cortisol. In contrast to the corresponding kidney
enzyme (11 beta-HSD2), its primary activity is, however, reductive. Although this is only the fifth reported case of that defect, more attention should be paid to this condition in hyperandrogenic women, even if elevated 17-OH-progesterone and
testosterone suggest a more frequent cause.