DHEA-S was ~400mcg/dL(280-640). No test for DHEA. My endo is retesting my blood now(don't know if pregnenolone is being retested, but I assume that it is).
I would ask for intermediaries, more specifically mention "Type II 3{beta}-Hydroxysteroid Dehydrogenase Deficiency."
Frank-Raue K, Raue F, Korth-Schutz S, Vecsei P, Ziegler R.
[Clinical features and diagnosis of mild 3-beta-hydroxysteroid dehydrogenase deficiency in men]. Dtsch Med Wochenschr 1989;114(9):331-4.
3 beta-hydroxysteroid dehydrogenase (HSD) deficiency was demonstrated in six males, aged between 18 and 24 years, who had gynaecomastia, hypogonadism or infertility. The predominant laboratory finding was a striking elevation of dehydroepiandrosterone sulphate (DHEAS) levels. The diagnosis of HSD deficiency was confirmed by finding a marked rise in dehydroepiandrosterone (DHEA) and 17-hydroxypregnenolone levels. In contrast to these findings in late-onset enzyme deficiency, in four males with the classical form of 21-hydroxylase deficiency the only sign was a reduction in adult height. The prevalence of late-onset HSD deficiency in men is not known and may be more relevant in patients with gynaecomastia or abnormal gonadal function than has hitherto been realized.
Cavanah SF, Dons RF.
Partial 3 beta-hydroxysteroid dehydrogenase deficiency presenting as new-onset gynecomastia in a eugonadal adult male. Metabolism 1993;42(1):65-8.
The postpubertal clinical presentation of 3 beta-hydroxysteroid dehydrogenase deficiency (3B-HSD deficiency) is less well-defined for adult males than for adult females, who often present with hirsutism. We describe a male with normal puberty who presented with new-onset gynecomastia at age 24. Common causes of gynecomastia were excluded. Dehydroepiandrosterone-sulfate (DHEA-S), estradiol, estrone, and 24-hour urinary 17-ketosteroid levels were elevated. A feminizing tumor was considered; biochemical tumor markers, chest x-ray, ultrasound of testes, and abdominal computed tomography (CT) scan were negative.
Dexamethasone-suppression testing showed normal suppression of 24-hour urinary adrenal steroids. Cosyntropin-stimulation testing showed normal cortisol, 11-deoxycortisol, 17-OH progesterone (17-OHP), and aldosterone levels,
but significant elevations of pregnenolone (preg), 17-OH preg, progesterone, DHEA, and androstenedione (A) levels. The sperm count was high and gonadotropin-releasing hormone (GnRH)-stimulation testing showed a normal increase in testosterone (T) level, suggesting that the defect did not involve the testes.
It is concluded that this patient's gynecomastia is due to 3B-HSD deficiency with an associated alteration in sex hormone ratios. To our knowledge, this is the first well-described adult male with normal gonadal function presenting with postpubertal gynecomastia due to 3B-HSD deficiency. This defect may be a frequently unrecognized cause of gynecomastia.
Lutfallah C, Wang W, Mason JI, et al.
Newly Proposed Hormonal Criteria via Genotypic Proof for Type II 3{beta}-Hydroxysteroid Dehydrogenase Deficiency. J Clin Endocrinol Metab 2002;87(6):2611-22.
To define the hormonal criteria via genotypic proof for 3{beta}-hydroxysteroid dehydrogenase (3{beta}-HSD) deficiency in the adrenals and gonads, we investigated the type II 3{beta}-HSD genotype in 55 patients with clinical and/or hormonal presentation suggesting compromised adrenal with or without gonadal 3{beta}-HSD activity.
Fourteen patients (11 males and 3 females) had ambiguous genitalia with or without salt wasting and with or without premature pubarche. One female neonate had salt wasting only. Twenty-five children (4 males and 21 females) had premature pubarche only. Fifteen adolescent and adult females had hirsutism with or without menstrual disorder.
The type II 3{beta}-HSD gene, including the promoter region up to -1053 base, all exons I, II, III, IV, and exon and intron boundaries, was sequenced in all subjects. Eight patients had a proven or predictably deleterious mutation in both alleles of the type II 3{beta}-HSD gene, and 47 patients had no apparent mutation in the gene.
ACTH-stimulated (1 h post iv bolus of 250 {micro}g Cortrosyn) serum 17-hydroxypregnenolone ({Delta}5-17P) levels and basal and ACTH-stimulated ratios of {Delta}5-17P to cortisol (F) in the genotypic proven patients were unequivocally higher than those of age-matched or pubic hair stage matched genotype-normal patients or control subjects (n = 7-30 for each group). All other baseline and ACTH-stimulated hormone parameters, including dehydroepiandrosterone (DHEA) levels, ratios of {Delta}5-17P to 17-OHP and DHEA to androstenedione in the genotype-proven patients, overlapped with the genotype-normal patients or control subjects.
The hormonal findings in the genotype-proven patients suggest that the following hormonal criteria are compatible with 3{beta}-HSD deficiency congenital adrenal hyperplasia (numeric and graphic reference standards from infancy to adulthood are provided):
ACTH-stimulated {Delta}5-17P levels in 1) neonatal infants with ambiguous genitalia at or greater than 378 nmol/liter equivalent to or greater than 5.3 SD above the control mean level [95 {+/-} 53 (SD) nmol/liter]; 2) Tanner I children with ambiguous genitalia at or greater than 165 nmol/liter equivalent to or greater than 35 SD above the control mean level [12 {+/-} 4.3 (SD) nmol/liter]; 3) children with premature pubarche at or greater than 294 nmol/liter equivalent to or greater than 54 SD above Tanner II pubic hair stage matched control mean level [17 {+/-} 5 (SD) nmol/liter]; and 4) adults with at or greater than 289 nmol/liter equivalent to or greater than 21 SD above the normal mean level [25 {+/-} 12 (SD) nmol/liter].
ACTH-stimulated ratio of {Delta}5-17P to F in 1) neonatal infants at or greater than 434 equivalent to or greater than 6.4 SD above the control mean ratio [88 {+/-} 54 (SD)]; 2) Tanner I children at or greater than 216 equivalent to or greater than 23 SD above the control mean ratio [12 {+/-} 9 (SD)]; 3) children with premature pubarche at or greater than 363 equivalent to or greater than 38 SD above the control mean ratio [20 {+/-} 9 (SD)]; and 4) adults at or greater than 4010 equivalent to or greater than 221 SD above the normal mean ratio [29 {+/-} 18 (SD)]. Conversely, the hormonal data in the genotype-normal patients suggest the following hormonal criteria are not consistent with 3{beta}-HSD deficiency congenital adrenal hyperplasia:
ACTH-stimulated {Delta}5-17P levels in children with premature pubarche up to 72 nmol/liter equivalent to up to 11 SD above the control mean level, and in hirsute females up to 150 nmol/liter equivalent to up to 12 SD above the normal female mean level [28 {+/-} 10 (SD) nmol/liter]; and ACTH-stimulated {Delta}5-17P to F ratio in children with premature pubarche up to 67 equivalent to up to 5 SD above the control mean ratio, and in hirsute females up to 151 equivalent to up to 10 SD above the normal mean ratio [32 {+/-} 12 (SD)].
These findings help define newly proposed hormonal criteria to accurately predict inherited 3{beta}-HSD deficiency.
