Evidence for Partial 21-Hydroxylase Deficiency Among Heterozygote Carriers of Congenital Adrenal Hyperplasia

Abstract

Concentrations of 17-hydroxyprogesterone are significantly greater in heterozygous carriers of CVAH than in controls 30 and 60 minutes after an infusion of 25 units of synthetic ACTH 1-24 and 2 hours after beginning a 4-hour infusion of 50 units ACTH. The majority of carriers were clearly above the control range at these collection times. Hence, heterozygous carriers have a partial enzyme deficiency although all cannot be diagnosed based on 17-hydroxyprogesterone levels after ACTH stimulation.

Heterozygotes and Cryptic Patients in Families of Patients with Congenital Adrenal Hyperplasia (21-Hydroxylase Deficiency)

“…3.2 pg/1 [27], The upper limit in non-affected siblings was 1.7 pg/1 -at the same level as found in other studies: 1.5 [22,27] and 2.0 pg/1 [25].…”

“…As no control values from the general population were available and the non-affected siblings were so few, it is not possible to draw any significant conclusion. But the lower limit of ACTH-stimulated 17-OHP in all heterozy gotes was 2.3 pg/1 -this is at the same level as found in other studies: 2.5 [22,25] and Plasma concentrations are given before and 60 min after ACTH administration. Urinary excretions are given before and on the 3rd day of ACTH administration.…”

“…has been demonstrated. Urinary excretion of metabolites and later 17-OHP determination have been used, especially during ACTH stimulation or in combination with dexamethasone suppression [1,[21][22][23]. However, there has been a considerable overlap be tween the heterozygotes and the control pop ulation, making it difficult to predict which siblings are carriers.…”

Late-Onset 21-Hydroxylase Deficiency Is an Allelic Variant of Congenital Adrenal Hyperplasia Characterized by Attenuated Clinical Expression and Different HLA Haplotype Associations

“…The response of plasma 17-hydroxyprogesterone to ACTH yields essentially no false negatives and ap pears to be the most sensitive and specific diagnostic test for LOCAH. The elevated 17-hydroxyprogesterone response in LOCAH is approximately 10-fold greater than the mildly elevated responses seen in classic 21-hydroxylase deficiency heterozygotes [24][25][26][27][28][29], idiopathic hirsutism, or the polycystic ovary syndrome [16,30,31], Mild adrenal hyperandrogenism would not be expected to cause symptoms in men and probably explains why there have been few reports of LOCAH in men [32,33], One man with LOCAH. however, developed an apparent adrenal rest tumor [33], an entity frequently associated with the classic form of CAH [34][35][36].…”

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

“…In 1975 Lee and Garesis [3] described an abnormal increase in serum 17-OH progesterone levels in heterozygote parents following an ACTH infusion. Later, Gutai et al [4] and Krenskyei al.…”