Congenital adrenal hyperplasia due to 21 hydroxylase deficiency

Congenital adrenal hyperplasia that results from a deficiency in one or another of the enzymes of CORTISOL biosynthesis. In most cases, 21-hydroxylation is impaired in the ZONA FASCICULATA of the ADRENAL CORTEX so that 17-HYDROXYPROGESTERONE (17-OHP) is not converted to 11-DEOXYCORTISOL. This causes excessive production of ANDROGENS and VIRILIZATION. Caused by germline mutations in the CYP21A2 gene. OMIM: 201910

Also Known As:

21 alpha hydroxylase deficiency; 21 hydroxylase deficiency; 21-Hydroxylase Deficiency; Adrenal hyperplasia III; Attenuated congenital adrenal hyperplasia; CYP21 deficiency; Congenital adrenal hyperplasia 1; LOCAH; Late-onset congenital adrenal hyperplasia; NCCAH; Non classic congenital adrenal hyperplasia

Networked: 1120 relevant articles (16 outcomes, 82 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Congenital Adrenal Hyperplasia (Hyperplasia, Congenital Adrenal)
2.	Adrenal Insufficiency (Adrenal Gland Hypofunction)
3.	Hyperprolactinemia
4.	Cystic Fibrosis (Mucoviscidosis)
5.	Duchenne Muscular Dystrophy (Muscular Dystrophy, Becker)

Experts

1.	Merke, Deborah P: 20 articles (10/2021 - 02/2002)
2.	Auchus, Richard J: 14 articles (01/2022 - 08/2014)
3.	Hasegawa, Tomonobu: 13 articles (01/2022 - 01/2004)
4.	Falhammar, Henrik: 13 articles (01/2021 - 12/2007)
5.	Reisch, Nicole: 10 articles (03/2022 - 10/2013)
6.	Turcu, Adina F: 10 articles (02/2021 - 06/2015)
7.	Krone, Nils: 10 articles (12/2019 - 01/2005)
8.	Mendonca, Berenice B: 10 articles (08/2019 - 02/2002)
9.	Homma, Keiko: 10 articles (08/2017 - 01/2004)
10.	Nordenström, Anna: 9 articles (01/2021 - 01/2007)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Congenital adrenal hyperplasia due to 21 hydroxylase deficiency:

1.	Hydrocortisone (Cortisol)FDA LinkGeneric 03/01/1994 - "In comparison to normal children, the 24-hour quantitative parameters of 17-OHP and D4A secretion were significantly greater in NCCAH patients, but serum cortisol concentrations were similar in the two groups. " 01/01/2022 - "The study group comprised 75 subjects (26 males) with NCCAH (61 hydrocortisone-treated [21 males] and 14 untreated [5 males]) and 134 healthy sex- and age-matched subjects (41 males) with normal puberty served as controls. " 03/28/2023 - "Dosage of hydrocortisone during late infancy is positively associated with changes in body mass index during early childhood in patients with 21-hydroxylase deficiency." 01/01/2022 - "Optimizing the Timing of Highest Hydrocortisone Dose in Children and Adolescents With 21-Hydroxylase Deficiency." 01/01/2021 - "Adrenal suppression and anthropometric data at two years of age was not influenced by the initial hydrocortisone dose in patients with 21-hydroxylase deficiency."
2.	GlucocorticoidsIBA 01/01/2020 - "There are currently limited trials comparing the efficacy and safety of different glucocorticoid replacement regimens for treating 21-hydroxylase deficiency CAH in children and adults and we were unable to draw any firm conclusions based on the evidence that was presented in the included trials. " 01/01/2020 - "Randomised controlled trials (RCTs) or quasi-RCTs comparing different glucocorticoid replacement regimens for treating CAH due to 21-hydroxylase deficiency in children and adults. " 01/01/2011 - "The present study aimed to evaluate the association between polymorphic variants involved inglucocorticoid action and/or metabolism and the mean daily glucocorticoid dose in 21-hydroxylase deficiency patients. " 10/01/2007 - "Our study emphasizes the need for regular laboratory monitoring and lower glucocorticoid dose during infancy in 21-hydroxylase deficiency." 03/01/2003 - "The purpose of this study was to determine BMD, lean mass, and fat mass in young adult male (M, n = 15) and female (F, n = 15) patients with 21-hydroxylase deficiency, who had been treated with currently recommended low doses of glucocorticoids. "
3.	Adrenocorticotropic Hormone (ACTH)FDA Link 11/01/2015 - "The gold standard for diagnosing NCCAH is the ACTH stimulation test. " 01/01/1995 - "Basal 17-OHP levels were helpful in detecting altered steroidogenesis in 3, thus suggesting that in some PP patients, LOCAH due to this enzymatic defect may remain undiagnosed if ACTH stimulation test is not routinely performed." 01/01/2022 - "The first set of patients (year 1, training set, n = 58), including 8 children with NCCAH verified by ACTH test and genetic analysis, was used to train the model. " 07/01/2021 - "Between July 2006 and July 2015 ACTH-tests were conducted in 365 children and adolescents (Age 1-20 y) suspected to have NCCAH. " 01/01/2019 - "A literature review revealed that 17-OHP-secreting SCT-NOS may uncommonly show positive responses to ACTH stimulation similar to 21-hydroxylase deficiency. "
4.	Prednisolone (Predate)FDA LinkGeneric 02/01/2008 - "Oral prednisolone may be an option for patients with CAH due to 21-hydroxylase deficiency." 10/01/2004 - "One-year clinical evaluation of single morning dose prednisolone therapy for 21-hydroxylase deficiency." 02/01/2008 - "The aim of this study was to compare the efficacy of oral prednisolone and oral hydrocortisone in the treatment of CAH due to 21-hydroxylase deficiency. " 07/01/2003 - "Low dose prednisolone is only effective in late-onset congenital adrenal hyperplasia and dopamine agonists only in hyperprolactinemia. " 03/01/2010 - "Low dose prednisolone is to only be administered at late onset congenital adrenal hyperplasia and dopamine agonists at hyperprolactinemia. "
5.	SteroidsIBA 12/01/1980 - "Use of the colonic potential difference as a means of assessing the efficacy of different suppressive steroid regimens was explored in a patient with incomplete 21-hydroxylase deficiency. " 10/16/2023 - "The aim of this study was to determine the comparative utility of 21DF for screening and diagnosis of CAH due to classical 21-hydroxylase deficiency using a second-tier LC-MS/MS method that included the separation of isomeric steroids to 17OHP and 21DF. " 08/01/1999 - "Our study provides the first mass spectrometric reference data on amniotic fluid steroid concentrations and underscores the high accuracy of prenatal hormonal diagnosis of 21-hydroxylase deficiency." 11/17/2023 - "Steroids were compared between genetically confirmed NCCAH, HTZ, and PCOS. " 10/16/2023 - "Steroid profile results were generated for 924 non-CAH baby samples (median gestational age 37 weeks, range 22 to 43 weeks) and 17 babies with 21-hydroxylase deficiency. "
6.	Dexamethasone (Maxidex)FDA LinkGeneric 12/10/1997 - "Although in our experience prenatal treatment with dexamethasone is effective in preventing virilisation of girls with 21-hydroxylase deficiency, some adverse events have been noted in treated infants. " 10/01/2010 - "To conduct a systematic review and meta-analyses of studies that evaluated the effects of dexamethasone administration during pregnancies at risk for classical CAH because of 21-hydroxylase deficiency (CYP21A2). " 03/23/2022 - "Prenatal dexamethasone treatment for classic 21-hydroxylase deficiency in Europe." 01/01/2011 - "Long-term outcome of prenatal dexamethasone treatment of 21-hydroxylase deficiency." 02/09/2002 - "In an 18-year-old woman non-classic 21-hydroxylase deficiency was diagnosed and dexamethasone treatment was instituted. "
7.	Cosyntropin (Cortrosyn)FDA LinkGeneric 01/15/1992 - "A second woman with high salivary 17-OPH had a Cosyntropin-stimulation response consistent with heterozygosity for 21-hydroxylase deficiency. " 01/15/1992 - "One of the women with high basal salivary 17-OHP had a 60-minute Cosyntropin response, which was diagnostic of NCCAH. " 01/01/2018 - "The cosyntropin test is used to diagnose adrenal insufficiency (AI) and nonclassical congenital adrenal hyperplasia (NCCAH). " 11/01/1988 - "Two of 44 patients tested with cosyntropin (Cortrosyn) had 21-hydroxylase deficiency, whereas two other patients had hyperprolactinemia caused by pituitary tumors. " 08/01/2019 - "Twenty-three hydrocortisone-treated children and adolescents (7 males) diagnosed with NCCAH by cosyntropin stimulation test and CYP21A2 gene mutation analysis were recruited to this study; 6 healthy siblings were also recruited. "
8.	Gonadotropin-Releasing Hormone (GnRH)FDA Link 10/01/1994 - "Suppression of the ovary with GnRH-a treatment was beneficial in these patients with late-onset congenital adrenal hyperplasia. " 06/01/2005 - "This study examines the impact of GH and LHRH analog (LHRHa) on final adult height in patients with CAH due to 21-hydroxylase deficiency. " 10/01/1994 - "To determine the effectiveness of GnRH-agonist (GnRH-a) treatment in women with late onset congenital adrenal hyperplasia. " 10/01/1981 - "The pituitary gonadotropic responsiveness to acute and prolonged administration of LH/FSH-releasing hormone (LHRH) were assessed in 6 patients with untreated congenital virilizing adrenal hyperplasia (partial 21-hydroxylase deficiency). " 01/01/2019 - "From 2008 to 2017, 147 girls who had undergone stimulation tests with gonadotropin-releasing hormone and ACTH were diagnosed with CPP; of these, seven (4.8%) were eventually diagnosed with NCCAH. "
9.	PregnanetriolIBA 01/01/2008 - "Auxological data are the gold standard indexes of the therapeutic conditions in patients with CYP21 deficiency over long-term periods, whereas urinary pregnanetriol (PT) for 24 h has been used as an index for short-term periods. " 01/01/2008 - "The Range of 2.2-3.3 mg/gCr of Pregnanetriol in the First Morning Urine Sample as an Index of Optimal Control in CYP21 Deficiency." 03/01/1976 - "The diagnosis of 21-hydroxylase deficiency was substantiated by the findings of 17-ketosteroid and pregnanetriol excretions of 18.1 and 8.1 mg/24 hours, respectively. " 01/01/2021 - "First Morning Pregnanetriol and 17-Hydroxyprogesterone Correlated Significantly in 21-Hydroxylase Deficiency." 04/01/1999 - "A patient with 21-hydroxylase deficiency, for whom elevated pregnanetriol (P3) levels in urine were not suppressed during treatment with cortisone acetate (65 mg/m2 x day), was examined. "
10.	Cortisone FDA Link 01/01/2011 - "We evaluated 53 patients with classical forms of 21-hydroxylase deficiency who were receiving cortisone acetate. " 03/01/2001 - "During the past 50 years since the discovery of cortisone therapy as an effective treatment for CAH, many advances have been made in the management of 21-hydroxylase deficiency. " 10/01/2001 - "Failure of cortisone acetate therapy in 21-hydroxylase deficiency in early infancy." 04/01/1999 - "A patient with 21-hydroxylase deficiency, for whom elevated pregnanetriol (P3) levels in urine were not suppressed during treatment with cortisone acetate (65 mg/m2 x day), was examined. " 05/02/1978 - "Analysis of glucocorticoid metabolites in the neonatal period: catabolism of cortisone acetate by an infant with 21-hydroxylase deficiency."

Therapies and Procedures

1.	Therapeutics 01/01/2015 - "Female patients with 21-hydroxylase deficiency CAH were evaluated using a questionnaire with items relating to knowledge of their condition and its therapy; consistency of medical, surgical, and psychological care; childhood friends and play behavior; and genital, pubertal, and sexual development. " 02/01/2001 - "The introduction of laparoscopic techniques may give an impulse to the application of surgical therapy at a larger scale in patients with 21-hydroxylase deficiency who are difficult to treat with adrenal suppression therapy." 02/01/1997 - "Non-classical 21-hydroxylase deficiency in infancy and childhood: the effect of time of initiation of therapy on puberty and final height." 12/01/1992 - "This future specialty of "gestational endocrinology" is already being used for embryonic therapy of 21-hydroxylase deficiency." 01/22/1987 - "Our experience indicates that improved surgical correction of the external genitalia and better compliance with therapy will be necessary to improve fertility rates among women with congenital adrenal hyperplasia due to 21-hydroxylase deficiency."
2.	Oral Administration 03/01/2002 - "We have analyzed the kinetics of salivary cortisol (F) and 17-hydoxyprogesterone (17OHP) after a single oral administration of hydrocortisone (HC; 10 mg; 0700 h) in healthy male volunteers (n = 10; 18-29 yr) and in patients with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (males, n = 7; females, n = 3; 8.5-20.4 yr). " 03/01/2002 - "Cortisol and 17-hydroxyprogesterone kinetics in saliva after oral administration of hydrocortisone in children and young adolescents with congenital adrenal hyperplasia due to 21-hydroxylase deficiency." 01/01/2020 - "In this prospective case-control non-inferiority study we investigated 20 women with non-classic 21-hydroxylase deficiency carrying biallelic CYP21A2 mutations and with serum 17-hydroxyprogesterone (17OHP) >10 ng/mL after stimulation with Synacthen® (tetracosactrin) and 20 age- and body mass index-matched healthy women with 17OHP after Synacthen® <2 ng/mL. Each participant underwent sequentially an insulin tolerance test to evaluate cortisol secretion and a sodium depletion test, obtained by oral administration of 40 mg of furosemide under low sodium diet (<20 mmol during 24 hours), to evaluate renin and aldosterone secretion. "
3.	Sodium-Restricted Diet (Diet, Sodium Restricted) 01/01/2020 - "In this prospective case-control non-inferiority study we investigated 20 women with non-classic 21-hydroxylase deficiency carrying biallelic CYP21A2 mutations and with serum 17-hydroxyprogesterone (17OHP) >10 ng/mL after stimulation with Synacthen® (tetracosactrin) and 20 age- and body mass index-matched healthy women with 17OHP after Synacthen® <2 ng/mL. Each participant underwent sequentially an insulin tolerance test to evaluate cortisol secretion and a sodium depletion test, obtained by oral administration of 40 mg of furosemide under low sodium diet (<20 mmol during 24 hours), to evaluate renin and aldosterone secretion. "
4.	Adrenalectomy 02/01/2002 - "Surgical adrenalectomy should be considered in females with classic CAH attributable to 21-hydroxylase deficiency and a history of poor hormonal control. " 11/09/2000 - "Adrenal specimens obtained from three other patients with 21-hydroxylase deficiency who had undergone bilateral adrenalectomy and specimens obtained at autopsy from eight other patients were examined histologically. " 11/01/2000 - "Three Caucasian female patients with 21-hydroxylase deficiency were treated with bilateral adrenalectomy. " 08/01/2018 - "Late onset adrenal insufficiency after adrenalectomy due to latent nonclassical 21-hydroxylase deficiency: A case report." 05/01/2015 - "A 14-year-old female with classical congenital adrenal hyperplasia because of 21-hydroxylase deficiency underwent bilateral adrenalectomy at 6 years of age as a result of poor hormonal control. "
5.	Ligation 06/01/2021 - "Subjects were diagnosed with 21-hydroxylase deficiency by direct Sanger sequencing or multiple ligation-dependent probe amplification analysis and followed up in Pusan National University Children's Hospital from July 2008 to April 2019. " 04/01/2020 - "21-Hydroxylase deficiency: Mutational spectrum and Genotype-Phenotype relations analyses by next-generation sequencing and multiplex ligation-dependent probe amplification." 02/12/2019 - "[Diagnostic value of multiplex ligation dependent probe amplification combined with Sanger sequencing in 21-hydroxylase deficiency]." 06/01/2023 - "Cost-effective genotyping for classical congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD) in resource-poor settings: multiplex ligation probe amplification (MLPA) with/without sequential next-generation sequencing (NGS)." 09/01/1995 - "We describe a methodology for genetic diagnosis of 21-hydroxylase deficiency that utilizes gene-specific PCR amplification in conjunction with thermostable DNA ligase to discriminate single nucleotide variations in a multiplexed ligation detection assay. "