title: 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.
  
  
  METHODS
  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.
authors: Program in Developmental Endocrinology and Genetics, Division of Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland 20892, USA. rnandago@childrensnational.org
authors: Radha
authors: R
authors: Nandagopal
authors: Ninet
authors: N
authors: Sinaii
authors: Nilo A
authors: NA
authors: Avila
authors: Carol
authors: C
authors: Van Ryzin
authors: Wuyan
authors: W
authors: Chen
authors: Gabriela P
authors: GP
authors: Finkielstain
authors: Sneha P
authors: SP
authors: Mehta
authors: Nazli B
authors: NB
authors: McDonnell
authors: Deborah P
authors: DP
authors: Merke
mesh_terms: D000311:Adrenal Glands / Q000000981:diagnostic imaging / Q000473:pathology; D000312:Adrenal Hyperplasia, Congenital / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology; D000328:Adult; D000368:Aged; D000886:Anthropometry; D001499:Bayes Theorem; D001827:Body Height / Q000502:physiology; D003366:Cosyntropin; D004247:DNA / Q000235:genetics; D005260:Female; D006728:Hormones / Q000097:blood; D006801:Humans; D017588:Hyperandrogenism / Q000097:blood / Q000150:complications; D007246:Infertility / Q000209:etiology; D008297:Male; D008875:Middle Aged; D010290:Parents; D010641:Phenotype; D011627:Puberty / Q000502:physiology; D013255:Steroid 21-Hydroxylase / Q000235:genetics / Q000502:physiology; D013737:Testis / Q000473:pathology; D014057:Tomography, X-Ray Computed
chemical_list: D006728:Hormones; D003366:Cosyntropin; D004247:DNA; D013255:Steroid 21-Hydroxylase