Late Onset Adrenal Hyperplasia (21-Hydroxylase Deficiency): 17-OH Progesterone Response to ACTH Stimulation and HLA Typing

Late-onset 21-hydroxylase deficiency (21OHD) presents biochemical evidence of 21OHD and virilization in peri-or postpubertal age; it has been demonstrated that late-onset 21OHD is linked to HLA system. We present the HLA typing, the baseline and the ACTH-stimulated hormonal levels in 5 patients with late-onset 21OHD and in their family members. We identified 3 HLA identical male sibs within their respective families, 2 sibs sharing one haplotype with the affected member and 2 homozygous normal sibs. We observed elevated baseline (greater than 4 ng/ml) and ACTH-stimulated 17-hydroxyprogesterone levels, increased baseline Androstenedione levels, slightly elevated or normal DHEA-S and Testosterone values and subnormal response of Cortisol levels to ACTH in patients and in the HLA-identical sibs, reduced SHBG levels in patients but not in their identical sibs. The heterozygous family members presented hyperresponsiveness of 17-hydroxyprogesterone but not of androgens after ACTH. We confirm that late-onset of 21OHD is an autosomal recessive disease linked to HLA-B; there is in fact biochemical evidence of mild 21OHD in patients and in their HLA identical sibs and 17-hydroxyprogesterone levels in the range of heterozygotes for classical 21OHD in parents and sibs predicted by HLA to be carriers. Thus HLA typing and hormonal data, particularly 17-hydroxyprogesterone, are useful, also in this form of congenital hyperplasia, in detecting heterozygotes.

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Nonclassical Congenital Adrenal Hyperplasia and the Polycystic Ovarian Syndromea

New

1993

Annals of the New York Academy of Sciences

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PCOS has a hormonal pattern that includes an apparent dysfunction in ovarian steroidogenesis, although the sequence (or sequences) of endocrine changes, possibly with inherent paracrine abnormalities that can establish PCOS, are only postulated. Development of PCOS in the setting of androgen overproduction (or persistent disturbances of the hypothalamic-pituitary-adrenal axis even after normalization of androgen levels) points to adrenal enzyme defects, but the precise interaction of gonad and adrenal cortex via serum steroids remains open. Several interesting schemas for the development of PCOS have been proposed, but the subject remains controversial. Sonographic abnormalities of the ovaries may be similar in women with PCOS and women with adrenal enzyme defects, and differentiation of PCOS from nonclassical 21-hydroxylase deficiency on the basis of pituitary gonadotropin response to LHRH is also nonspecific. The 17-OHP response to ACTH testing is necessary to make the diagnosis (see nomogram). The preliminary data on the subgroup of women with PCOS and nonclassical 21-hydroxylase deficiency indicate that (1) the size of cystic changes of ovaries on sonography and (2) LH:FSH ratios may improve with dexamethasone treatment. Identification of an adrenal enzymatic disorder by ACTH testing is cost-effective in patients with symptoms of androgen excess, offers a good prognosis for improved fertility in couples, and as well is informative in family genetic studies.

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Late Onset Adrenal Hyperplasia (21-Hydroxylase Deficiency): 17-OH Progesterone Response to ACTH Stimulation and HLA Typing

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Endocrinology

Endocrinology

HLA and hormonal studies in 5 patients with late-onset 21-hydroxylase deficiency syndrome (21 OHDS)

Nonclassical Congenital Adrenal Hyperplasia and the Polycystic Ovarian Syndromea

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