A CONTRIBUTION TO THE CLASSIFICATION OF CASES OF NONCLASSIC 21-HYDROXYLASE-DEFICIENT CONGENITAL ADRENAL-HYPERPLASIA

The aim of this study war to classify the degree of 21 alpha-hydroxyla se deficiency inpatients suspected for nonclassic 21-hyduoxylase-defic ient congenital adrenal hyperplasia (CAH). In 66 selected subjects (45 young women with polycystic ovary (PCO)-like symptoms and members of their families, of whom 12 were men), progesterone, 17-hydroxyprogeste rone (17-OHP) and cortisol were measured at 0, 15, 30, 45 and 60 min a fter adrenocorticotropic hormone (ACTH) stimtulation. The markers [(17 -OHP at 30 min - 17-OHP at a min) + (progesterone at 30 min - progeste rone at 0 min)]/30 proposed by Gutai and the ratio of cortisol to 17-O HP at 30 min (cortisol(30)/(17)-OHP30) were calculated and cluster ana lysis was performed using the above two markers and 17-OHP at 60 min ( 17-OHP60) Our patients were grouped by cluster analysis into four Grou ps: I II, III and IV (n = 3, 11, 35 and 16, respectivelyl with Gutai ( ($) over bar x +/- SE) 107.0 +/- 21.7, 29.9 +/- 4.4, 10.5 +/- 0.54 and 4.0 +/- 0.37 ng/dl per min, respectively, (2) 17-OHP60 169.7 +/- 28.3 , 10.8 +/- 1.3, 4.6 +/- 0.2 and 3.7 +/- 0.4 ng/ml, respectively, and ( 3) cortisol/17-OHP(30)0.97 +/- 0.28, 38.5 +/- 6.9, 82.3 +/- 5.5 and 11 2.0 +/- 8.9, respectively. All three markers showed highly significant differences between the four groups (p < 0.0001). The patterns of 17- OHP, cortisol and cortisol/17-OHP ratio following ACTH testing reveale d the degree of 21-hydroxylase deficiency in every group. HLA typing e ffected in 20 studied individuals confirmed the classification derived from cluster analysis. Thus, it seems that Groups I, II and III inclu de, respectively, patients with severe, mild and minimal forms of non- classic 21-hydroxylase-deficient CAH, while in patients of Group IV th e hyperandrogenemic symptoms are of different etiology. In conclusion, the concurrent evaluation of the three markers together with the vari ations of 17-OHP, cortisol and the cortisol/17-OHP ratio after ACTH re sting enhance the accurate identification of a patient suspected for n on-classic 21-hydroxylase-deficient CAH in relation to the severity of the enzymatic defect.