Late-onset adrenal steroid 3 beta-hydroxysteroid dehydrogenase deficiency. I. A cause of hirsutism in pubertal and postpubertal women.
To investigate the adrenal cause of hyperandrogenism in peri- and postpubertal hirsute women, baseline and ACTH-stimulated serum concentrations of delta 5-17-hydroxypregnenolone (delta 5-17P), dehydroepiandrosterone (DHEA) and its sulfate, 17-hydroxyprogesterone (17-OHP), cortisol, delta 4-androstenedione, and testosterone were determined in 116 women with hirsutism or acne of peri- and postpubertal onset with or without menstrual abnormalities. The results were compared with the same steroid concentrations in 30 normal age-matched women. Sixteen of the 116 women with hirsutism whose ACTH-stimulated 17-OHP levels (mean +/- SD, 5404 +/- 3234 ng/dl; normal, 334 +/- 194) were markedly elevated while their ratios of delta 5-17P to 17-OHP (0.4 +/- 0.2; normal, 3.4 +/- 1.5) were low were diagnosed as having nonclassical symptomatic 21-hydroxylase deficiency. Seventeen other hirsute women, including 3 siblings, had very high responses of delta 5-17P (2276 +/- 669 ng/dl; normal, 985 +/- 327) and DHEA (2787 +/- 386 ng/dl; normal, 1050 +/- 384) to ACTH stimulation, with significantly elevated ratios of delta 5-17P to 17-OHP (11 +/- 2.0; normal, 3.4 +/- 1.5) and DHEA to delta 4-androstenedione (7.5 +/- 2.3; normal, 4.6 +/- 1.5). In these hirsute women, the morning serum delta 5-17P and DHEA concentrations were elevated, had a diurnal variation, and were suppressed with dexamethasone administration. We propose that partial adrenal 3 beta-hydroxysteroid dehydrogenase deficiency is the cause of hirsutism in these women. This may represent an allelic variant at the genetic locus for 3 beta-hydroxysteroid dehydrogenase deficiency similar to that reported for symptomatic nonclassical 21-hydroxylase deficiency producing peripubertal excess androgen syndrome.
Pang
S Y
SY
Lerner
A J
AJ
Stoner
E
E
Levine
L S
LS
Oberfield
S E
SE
Engel
I
I
New
M I
MI
D015096:3-Hydroxysteroid Dehydrogenases / Q000172:deficiency*; D000293:Adolescent; D000311:Adrenal Glands / Q000201:enzymology*; D000312:Adrenal Hyperplasia, Congenital; D000324:Adrenocorticotropic Hormone; D000328:Adult; D000367:Age Factors; D002940:Circadian Rhythm; D003907:Dexamethasone; D005260:Female; D006628:Hirsutism / Q000201:enzymology*; D006801:Humans; D011085:Polycystic Ovary Syndrome / Q000097:blood; D011627:Puberty; D013256:Steroids / Q000097:blood
D013256:Steroids; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D015096:3-Hydroxysteroid Dehydrogenases