HORMONAL PHENOTYPE AND HLA-GENOTYPE IN FAMILIES OF PATIENTS WITH CONGENITAL ADRENAL-HYPERPLASIA (21-HYDROXYLASE DEFICIENCY)

被引:41
作者
LORENZEN, F [1 ]
PANG, S [1 ]
NEW, MI [1 ]
DUPONT, B [1 ]
POLLACK, M [1 ]
CHOW, DM [1 ]
LEVINE, LS [1 ]
机构
[1] SLOAN KETTERING INST CANC RES, TISSUE TYPING LAB, NEW YORK, NY 10021 USA
关键词
D O I
10.1203/00006450-197912000-00011
中图分类号
R72 [儿科学];
学科分类号
100202 ;
摘要
The response of 17-hydroxyprogesterone (17-OHP) and cortisol (F) to a 6-hr ACTH stimulation in families of patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency was studied. These studies demonstrated that siblings who should be heterozygous carriers of the 21-hydroxylase deficiency gene based on HLA genotyping are hormonally different from the general population. In pre- and early pubertal children predicted to be heterozygous carriers of the gene based on HLA genotyping, the 17-OHP level (13.1 ± 4.5 ng/ml), the rate of increase of 17-OHP (0.03 ± 0.01), and the ratio of 17-OHP/F at 6 hr (0.27 ± 0.07) were significantly higher (P < 0.001) than in the control population, (3.9 ± 1.9, 0.009 ± 0.005, and 0.08 ± 0.04 ng/ml, respectively). In late and postpu- bertal males, these hormonal parameters in the heterozygotes (17 ± 9.7, 0.04 ± 0.026, 0.42 ± 0.33 ng/ml, respectively) were significantly higher (P < 0.001) than in the general population (5.3 ± 1.6, 0.009 ± 0.004, and 0.1 ± 0.03 ng/ml, respectively). In postmenarchal females, the mean hormone responses in the heterozygotes (12.1 ± 9.7, 0.03 ± 0.02, and 0.27 ± 0.24 ng/ml, respectively) were significantly higher (P< 0.005, < 0.01, < 0.005, respectively) than in the general population (5.2 ± 2.5, 0.01 ± 0.007, and 0.1 ± 0.04 ng/ml, respectively). However, the overlapping values did not permit a clear differentiation of the hormonal responses in these two groups. Another (ACTH) stimulation in one family demonstrated that a father of a patient probably is a previously unrecognized homozygous affected patient and, thus, revision of the congenital adrenal hyperplasia (CAH) genotype for this family was required. Speculation: In families of patients with CAH due to 21-hydroxylase deficiency, siblings predicted to be heterozygous carriers of the gene for 21 hydroxylase deficiency based on HLA genotyping, will express a mild enzyme deficiency by hormonal testing. © 1979 International Pediatric Research Foundation, Inc.
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页码:1356 / 1360
页数:5
相关论文
共 20 条
[1]   CHROMATOGRAPHIC SEPARATION OF STEROID-HORMONES FOR USE IN RADIOIMMUNOASSAY [J].
ABRAHAM, GE ;
BUSTER, JE ;
TELLER, RC ;
LUCAS, LA ;
CORRALES, PC .
ANALYTICAL LETTERS, 1972, 5 (08) :509-&
[2]  
BERGADA C, 1965, EXCERPTA MED INT 99, pE130
[3]   VIRILIZING ADRENAL HYPERPLASIA - GENETIC AND HORMONAL STUDY [J].
CHILDS, B ;
GRUMBACH, MM ;
VANWYK, JJ .
JOURNAL OF CLINICAL INVESTIGATION, 1956, 35 (02) :213-222
[4]   RESPONSE TO AN 11BETA-HYDROXYLASE INHIBITOR (SU-4885) IN MALES WITH ADRENAL HYPERPLASIA AND IN THEIR PARENTS [J].
CLEVELAND, WW ;
NIKEZIC, M ;
MIGEON, CJ .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1962, 22 (03) :281-+
[5]  
DUPONT B, 1977, LANCET, V2, P1309
[6]   LINKAGE STUDIES BETWEEN HLA-A,B,D ALLELES AND CONGENITAL ADRENAL-HYPERPLASIA (CAH) [J].
GROSSEWILDE, H ;
WEIL, J ;
ALBERT, E ;
SCHOLZ, S ;
BIDLINGMAIER, F ;
KNORR, D .
PEDIATRIC RESEARCH, 1978, 12 (11) :1088-1088
[7]   DETECTION OF HETEROZYGOUS CARRIER FOR CONGENITAL VIRILIZING ADRENAL-HYPERPLASIA [J].
GUTAI, JP ;
KOWARSKI, AA ;
MIGEON, CJ .
JOURNAL OF PEDIATRICS, 1977, 90 (06) :924-929
[8]   A STUDY OF PARENTS OF PATIENTS WITH CONGENITAL ADRENAL HYPERPLASIA - DETECTION OF HETEROZYGOTE [J].
HALL, R ;
SMITH, PA ;
HARKNESS, RA ;
SMART, GA .
PROCEEDINGS OF THE ROYAL SOCIETY OF MEDICINE-LONDON, 1970, 63 (10) :1040-&
[9]  
HOMOKI J, 1977, CONGENITAL ADRENAL H, P479
[10]   PROGRESS IN TESTING FOR HETEROZYGOSITY IN CONGENITAL ADRENAL-HYPERPLASIA (CAH) [J].
KNORR, D ;
BIDLINGMAIER, F ;
BUTENANDT, O ;
SIPPELL, WG ;
WEIL, J .
PEDIATRIC RESEARCH, 1978, 12 (11) :1100-1100