Phenotypic profiling of parents with cryptic nonclassic congenital adrenal hyperplasia: findings in 145 unrelated families

Abstract

Objective To comprehensively phenotype parents identified with nonclassic congenital adrenal hyperplasia (NCCAH) by family genetic studies, termed here as cryptic NCCAH and to define the incidence of cryptic NCCAH in the parents of a large cohort of patients with 21-hydroxylase deficiency. Design Genotyping was performed on 249 parents of 145 unrelated congenital adrenal hyperplasia CAH) patients. Parents with two CYP21A2 mutations underwent extensive evaluation. Results Of the 249 parents, ten (4%; seven females and three males) were identified as having cryptic NCCAH. The majority was of ethnicities previously reported to have a higher incidence of NCCAH. Cosyntropin stimulation performed in eight parents provided biochemical confirmation (17-hydroxyprogesterone range 56–364 nmol/l) and cortisol response was % 500 nmol/l in three parents (38%). Of the seven women (27–54 years) with cryptic NCCAH, four had prior infertility, two reported irregular menses, two had treatment for hirsutism, one had androgenic alopecia. Men were asymptomatic. All cryptic NCCAH parents reported normal puberty and had normal height. Adrenal hypertrophy and a small adrenal myelolipoma were observed in two parents; testicular adrenal rest tissue was not found. Conclusions Parents diagnosed with NCCAH by genetic testing are mostly asymptomatic. Temporary female infertility and suboptimal cortisol response were commonly observed. Ongoing glucocorticoid therapy is not indicated in adults with CAH identified by family genotype studies unless symptomatic, but glucocorticoid stress coverage should be considered in select cases. Parents of a child with CAH have a 1:25 risk of having NCCAH; if the mother of a child with CAH has infertility, evaluation for NCCAH is indicated.

Relationship of CYP21A2 genotype and serum 17-hydroxyprogesterone and cortisol levels in a large cohort of Italian children with premature pubarche

“…Suboptimal cortisol responses to ACTH stimulation was found in 28% of our NCCAH patient, in agreement with recent studies showing low cortisol responses in a subset of patients with NCCAH (26)(27)(28). No signs or symptoms consistent with adrenal insufficiency were either reported by any of our patients or those included in the previous studies (28).…”

“…No signs or symptoms consistent with adrenal insufficiency were either reported by any of our patients or those included in the previous studies (28). The finding of abnormal biochemical data in the absence of remarkable clinical history is difficult to interpret, and the need in these patients for cortisol during stressful conditions is unknown.…”

Talla final en varones sintomáticos con hiperplasia suprarrenal no clásica tratados con glucocorticoides. Casos clínicos

“…Sin embargo, existe un amplio rango de gravedad en los síntomas clíni-cos, que varía entre formas asintomáticas 5,12 hasta aquellas que se asocian con signos de hiperandrogenismo. [1][2][3] Estos hallazgos sugieren que la sintomatología clínica es la que determina la necesidad de tratamiento.…”

Szteroid-21-hidroxiláz-deficientia, a congenitalis adrenalis hyperplasia leggyakoribb oka

“…A nem-klasszikus 21-OHD-betegeket nemritkán helytelenül polycystás petefészek betegséggel diagnosztizálják [39,40]. Férfiakban a kórkép a legtöbb-ször nem okoz észlelhető tünetet [41]. A klasszikus 21-OHD-re jellemző TART és a melllékvesetumor ritkán nem-klasszikus 21-OHD-ben is megjelenhet.…”