| Fall 2002 CARES Foundation, Inc. | |
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Research Summary in Non Classical 21- Hydroxylase Deficiency Dr. Naomi Weintrob |
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Institute for Endocrinology and Diabetes, Schneider Children’s Medical Center of Israel, Petah-Tikva, Israel |
| We have run several studies over the past few years involving patients with nonclassical CAH (NC21-OHD) at our clinic. In the first study by our team, published in the European Journal of Endocrinology (volume 136: 188-195, 1997), we investigated the relationship of pubertal and bone age (BA) maturation at the start of glucocorticoid therapy with the course of puberty and the final height in subjects with NC21OHD. We found that patients in whom therapy was initiated at least one year before the onset of true puberty and/or bone age of 9 years reached their genetic adult height, whereas those who started therapy during active puberty or at BA more than 9 years, had a final height below their mid-parental height range.
To determine if the clinical variability in NC21OHD is due to genotype differences, our next study was done in collaboration with Dr. Shosh Israel and Dr. Haiim Brautbar from the Tissue Typing Unit of the Hadassah Medical Organization in Jerusalem, who developed the setup for genotyping the CYP21 gene in Israel. The possible association of genotype with ethnic origin was also investigated. The results were published in the European Journal of Endocrinology, (Volume 143, 397-403, 200). Our findings suggest that males with NC21OHD may be under diagnosed. Further, we believe that genotyping is justified in patients with the non-classical form of steroid-21 hydroxylase deficiency owing to the existence of a subgroup (about 30% in our study population) with compound heterozygosity for one mild and one severe mutation. In patients carrying a severe mutation, future genetic and prenatal counseling is advocated as there is a chance of approximately 1:1000-1600 that they will have a daughter affected with classic 21OHD compared to 1:15000 prevalence in the general population and prenatal treatment with dexamethasone for fetuses carrying two severe mutations is now feasible.In our third study, published in the July/August 2002 issue of The Journal of Pediatric Endocrinology and Metabolism, we assessed cortisol response in patients with NC21OHD before and during hydrocortisone therapy, and the findings were related to genotype. We concluded that coverage with a stress dose of hydrocortisone during serious intercurrent illness or surgery should be considered in patients with documented cortisol deficiency. In conclusion, NC21OHD is a rather frequent entity with a large variability in presentation. A difference in genotype (2 mild mutations vs. one mild and one severe mutation) might explain some of the variance, with the more severe form being associated with earlier chronological age and more advanced bone age at diagnosis, relatively taller stature, and higher frequency of precocious puberty. We do not yet know if the group with more severe disease ends up shorter. |
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