| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Departamento de Clinica Medica (L.M.M., A.C.M., M.d.C.) and Departamento de Fisiologia (L.L.K.E.), School of Medicine of Ribeirao Preto, University of São Paulo, Ribeirao Preto, São Paulo, Brazil 14049-900; and Unidade de Endocrinologia do Desenvolvimento, Laboratorio de Hormonios e Genetica Molecular (S.M., B.B.M.), School of Medicine of University of São Paulo, São Paulo, Brazil 01060-970
Address all correspondence and requests for reprints to: Margaret de Castro, M.D., Ph.D., Departamento Clinica Medica, Faculdade de Medicina de Ribeirao Preto, University of São Paulo, Avenida Bandeirantes, 14049-900, Ribeirao Preto, São Paulo, Brazil. E-mail: castrom{at}fmrp.usp.br.
Congenital adrenal hyperplasia due to 3ß-hydroxysteroid dehydrogenase/
5-4-isomerase (3ßHSD), a rare autosomal recessive disorder that affects both sexes, has a heterogeneous clinical presentation ranging from the severe salt-wasting to the non-salt-wasting forms and results from mutations in the HSD3B2 gene. The hormonal criteria for diagnosing the mild variant of 3ßHSD deficiency have been controversial because the initial studies were not based on genetic evidence. We investigated the relationship between the hormonal phenotype and HSD3B2 genotype in 22 patients with clinical and/or biochemical features suggestive of 3ßHSD2 deficiency, including nine female children with premature pubarche, 12 hirsute females, and one boy with salt-wasting and ambiguous genitalia. Serum 17-hydroxypregnenolone (5-17P), cortisol (F), 17-hydroxyprogesterone, dehydroepiandrosterone, and androstenedione levels were determined by RIA and were compared with Tanner pubic hair stage-matched control groups. The genomic DNA was extracted, and the entire HSD3B2 gene was amplified by PCR followed by automatic sequencing. Besides two different mutations previously observed in three patients (T259M and G129R/P222Q mutations), we observed the P222Q mutation in the male patient with salt-wasting form of 3ßHSD2 deficiency. Basal and ACTH-stimulated 5-17P levels (nanomoles per liter) ranged from 4–41 (–0.2 to 14 SD) and 36–97 (3.5–15.5 SD), respectively, in patients without mutation in HSD3B2 and from 69–153 (25–57 SD) and 201–351 (36–65 SD), respectively, in patients with mutation in HSD3B2. Basal and ACTH-stimulated 5-17P to F ratios ranged from 11–159 (0.5–25 SD) and 42–122 (2.4–11.3 SD), respectively, in patients without mutation in HSD3B2 and from 181-1700 (29–282 SD) and 487-1523 (52–167 SD), respectively, in patients with mutation in HSD3B2. The hormone findings in the genotype-proven patients suggest that the following hormonal criteria are compatible with 3ßHSD2 deficiency in children with premature pubarche: ACTH-stimulated 5-17P and 5-17P to F ratios at or greater than 201 and 487 nmol/liter, respectively, equivalent to or greater than 36 and 52 SD above matched control mean. Basal and ACTH-stimulated 5-17P and 5-17P to F ratios in all genotype-proven patients in childhood were unequivocally higher than the levels of either genotype-normal patients. All the other parameters overlapped between the patients with and without mutations in the HSD3B2 gene. In conclusion, genotyping more patients in the present study, we confirm that patients with mutations in the HSD3B2 gene have extremely elevated basal and ACTH-stimulated 5-17P levels and 5-17P to F ratios. Therefore, these data refine the hormonal criteria proposed to predict more accurately 3ßHSD2 deficiency.
This article has been cited by other articles:
 |
|
 |
|
  F. C. Soardi, J. Y. Penachioni, G. Z. Justo, T. A. S. S. Bachega, M. Inacio, B. B. Mendonca, M. de Castro, and M. P. de Mello Novel Mutations in CYP11B1 Gene Leading to 11{beta}-Hydroxylase Deficiency in Brazilian Patients J. Clin. Endocrinol. Metab., September 1, 2009; 94(9): 3481 - 3485. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Welzel, N. Wustemann, G. Simic-Schleicher, H. G. Dorr, E. Schulze, G. Shaikh, P. Clayton, J. Grotzinger, P.-M. Holterhus, and F. G. Riepe Carboxyl-Terminal Mutations in 3{beta}-Hydroxysteroid Dehydrogenase Type II Cause Severe Salt-Wasting Congenital Adrenal Hyperplasia J. Clin. Endocrinol. Metab., April 1, 2008; 93(4): 1418 - 1425. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. K Ong, F. de Zegher, A. Lopez-Bermejo, D. B Dunger, and L. Ibanez Flutamide metformin for post-menarcheal girls with preclinical ovarian androgen excess: evidence for differential response by androgen receptor genotype Eur. J. Endocrinol., November 1, 2007; 157(5): 661 - 668. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Ibanez, A. Lopez-Bermejo, L. del Rio, G. Enriquez, C. Valls, and F. de Zegher Combined Low-Dose Pioglitazone, Flutamide, and Metformin for Women with Androgen Excess J. Clin. Endocrinol. Metab., May 1, 2007; 92(5): 1710 - 1714. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Ibanez, A. Jaramillo, G. Enriquez, E. Miro, A. Lopez-Bermejo, D. Dunger, and F. de Zegher Polycystic ovaries after precocious pubarche: relation to prenatal growth Hum. Reprod., February 1, 2007; 22(2): 395 - 400. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Ibanez, K. Ong, C. Valls, M. V. Marcos, D. B. Dunger, and F. de Zegher Metformin Treatment to Prevent Early Puberty in Girls with Precocious Pubarche J. Clin. Endocrinol. Metab., August 1, 2006; 91(8): 2888 - 2891. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Ibanez, C. Valls, and F. de Zegher Discontinuous low-dose flutamide-metformin plus an oral or a transdermal contraceptive in patients with hyperinsulinaemic hyperandrogenism: normalizing effects on CRP, TNF-{alpha} and the neutrophil/lymphocyte ratio Hum. Reprod., February 1, 2006; 21(2): 451 - 456. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
