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The Journal of Clinical Endocrinology... Sep 2010We developed clinical practice guidelines for congenital adrenal hyperplasia (CAH).
OBJECTIVE
We developed clinical practice guidelines for congenital adrenal hyperplasia (CAH).
PARTICIPANTS
The Task Force included a chair, selected by The Endocrine Society Clinical Guidelines Subcommittee (CGS), ten additional clinicians experienced in treating CAH, a methodologist, and a medical writer. Additional experts were also consulted. The authors received no corporate funding or remuneration.
CONSENSUS PROCESS
Consensus was guided by systematic reviews of evidence and discussions. The guidelines were reviewed and approved sequentially by The Endocrine Society's CGS and Clinical Affairs Core Committee, members responding to a web posting, and The Endocrine Society Council. At each stage, the Task Force incorporated changes in response to written comments.
CONCLUSIONS
We recommend universal newborn screening for severe steroid 21-hydroxylase deficiency followed by confirmatory tests. We recommend that prenatal treatment of CAH continue to be regarded as experimental. The diagnosis rests on clinical and hormonal data; genotyping is reserved for equivocal cases and genetic counseling. Glucocorticoid dosage should be minimized to avoid iatrogenic Cushing's syndrome. Mineralocorticoids and, in infants, supplemental sodium are recommended in classic CAH patients. We recommend against the routine use of experimental therapies to promote growth and delay puberty; we suggest patients avoid adrenalectomy. Surgical guidelines emphasize early single-stage genital repair for severely virilized girls, performed by experienced surgeons. Clinicians should consider patients' quality of life, consulting mental health professionals as appropriate. At the transition to adulthood, we recommend monitoring for potential complications of CAH. Finally, we recommend judicious use of medication during pregnancy and in symptomatic patients with nonclassic CAH.
Topics: Adrenal Hyperplasia, Congenital; Algorithms; Comorbidity; Evidence-Based Practice; Female; Humans; Infant, Newborn; Models, Biological; Neonatal Screening; Practice Guidelines as Topic; Pregnancy; Steroid 21-Hydroxylase
PubMed: 20823466
DOI: 10.1210/jc.2009-2631 -
Tidsskrift For Den Norske Laegeforening... Apr 2017Congenital adrenal hyperplasia is attributed to inherited enzyme defects in the adrenal cortex. The classical form results in reduced production of cortisol and... (Review)
Review
Congenital adrenal hyperplasia is attributed to inherited enzyme defects in the adrenal cortex. The classical form results in reduced production of cortisol and aldosterone, accompanied by an increase in production of adrenal cortical androgens. This causes virilisation in girls, adrenocortical failure and early puberty in both sexes. This article describes the genetics, clinical picture, diagnostics and treatment.
Topics: Adrenal Hyperplasia, Congenital; Female; Glucocorticoids; Humans; Male; Puberty, Precocious; Steroid 21-Hydroxylase; Virilism
PubMed: 28383228
DOI: 10.4045/tidsskr.16.0376 -
The Journal of Clinical Endocrinology... Jan 2022
Topics: 17-alpha-Hydroxyprogesterone; Adrenal Hyperplasia, Congenital; Androstenedione; Humans
PubMed: 34331764
DOI: 10.1210/clinem/dgab555 -
Hormone Research in Paediatrics 2022The adrenal has played a major role in the history of pediatric endocrinology. Cases of congenital adrenal hyperplasia (CAH) were reported in the 19th century, leading... (Review)
Review
The adrenal has played a major role in the history of pediatric endocrinology. Cases of congenital adrenal hyperplasia (CAH) were reported in the 19th century, leading to the understanding that the adrenal influenced sexual phenotypes as well as being mysteriously required for survival. Numerous adrenal steroids were isolated in the early 20th century, and bioassays eventually distinguished glucocorticoids, mineralocorticoids, and androgens. Treatment of CAH with cortisone in 1950 by Wilkins and by Bartter and Albright revolutionized clinical endocrinology and launched a productive era of pediatric adrenal research. Through careful clinical studies, Wilkins established the contemporary approach to treating CAH. Alfred Bongiovanni identified defective 21-hydroxylation in CAH in 1957, followed by deficiencies of 3β-hydroxysteroid dehydrogenase and 11β-hydroxylase. P450 enzymes were described in 1962-1964, and 21-hydroxylation was the first activity ascribed to a P450. Accurate assays for 17OH-progesterone in newborns and in response to ACTH permitted the diagnosis of CAH in children and families. Application of the techniques of molecular genetics elucidated genetic and biochemical bases of these disorders from 1984 to 2004. Pediatric endocrinologists played central roles in identifying the genes responsible for both common and rare forms of congenital adrenal hyperplasia and determining their most appropriate treatments.
Topics: Humans; Adrenal Hyperplasia, Congenital; Mineralocorticoids; Endocrinology; Glucocorticoids; Androgens
PubMed: 36446323
DOI: 10.1159/000526468 -
Reviews in Endocrine & Metabolic... Jun 2022Patients with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21OHD) need life-long medical treatment to replace the lacking glucocorticoids and... (Review)
Review
Patients with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21OHD) need life-long medical treatment to replace the lacking glucocorticoids and potentially lacking mineralocorticoids and to lower elevated adrenal androgens. Long-term complications are common, including gonadal dysfunction, infertility, and cardiovascular and metabolic co-morbidity with reduced quality of life. These complications can be attributed to the exposure of supraphysiological dosages of glucocorticoids and the longstanding exposure to elevated adrenal androgens. Development of novel therapies is necessary to address the chronic glucocorticoid overexposure, lack of circadian rhythm in glucocorticoid replacement, and inefficient glucocorticoid delivery with concomitant periods of hyperandrogenism. In this review we aim to give an overview about the current treatment regimens and its limitations and describe novel therapies especially evaluated for 21OHD patients.
Topics: Adrenal Hyperplasia, Congenital; Androgens; Glucocorticoids; Hormone Replacement Therapy; Humans; Quality of Life
PubMed: 35199280
DOI: 10.1007/s11154-022-09717-w -
Endocrinology and Metabolism (Seoul,... Aug 2022A plethora of negative long-term outcomes have been associated with congenital adrenal hyperplasia (CAH). The causes are multiple and involve supra-physiological gluco-... (Review)
Review
A plethora of negative long-term outcomes have been associated with congenital adrenal hyperplasia (CAH). The causes are multiple and involve supra-physiological gluco- and mineralocorticoid replacement, excess adrenal androgens both intrauterine and postnatal, elevated steroid precursor and adrenocorticotropic hormone levels, living with a congenital condition as well as the proximity of the cytochrome P450 family 21 subfamily A member 2 (CYP21A2) gene to other genes. This review aims to discuss the different long-term outcomes of CAH.
Topics: Adrenal Hyperplasia, Congenital; Humans; Steroid 21-Hydroxylase
PubMed: 35799332
DOI: 10.3803/EnM.2022.1528 -
Endocrinology and Metabolism Clinics of... Jun 2015Adrenal steroidogenesis is a dynamic process, reliant on de novo synthesis from cholesterol, under the stimulation of ACTH and other regulators. The syntheses of... (Review)
Review
Adrenal steroidogenesis is a dynamic process, reliant on de novo synthesis from cholesterol, under the stimulation of ACTH and other regulators. The syntheses of mineralocorticoids (primarily aldosterone), glucocorticoids (primarily cortisol), and adrenal androgens (primarily dehydroepiandrosterone and its sulfate) occur in separate adrenal cortical zones, each expressing specific enzymes. Congenital adrenal hyperplasia (CAH) encompasses a group of autosomal-recessive enzymatic defects in cortisol biosynthesis. 21-Hydroxylase (21OHD) deficiency accounts for more than 90% of CAH cases and, when milder or nonclassic forms are included, 21OHD is one of the most common genetic diseases.
Topics: Adrenal Cortex Neoplasms; Adrenal Hyperplasia, Congenital; Adrenocortical Adenoma; Aldosterone; Androgens; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Glucocorticoids; Hormone Replacement Therapy; Humans; Hydrocortisone; Mineralocorticoids; Myelolipoma; Risk Factors
PubMed: 26038201
DOI: 10.1016/j.ecl.2015.02.002 -
International Heart Journal 2024
Topics: Humans; Adrenal Hyperplasia, Congenital; Hyperplasia
PubMed: 38296561
DOI: 10.1536/ihj.23-647 -
Proceedings of the National Academy of... Feb 2013Over the last two decades, we have extensively studied the genetics of congenital adrenal hyperplasia caused by 21-hydroxylase deficiency (CAH) and have performed 8,290...
Over the last two decades, we have extensively studied the genetics of congenital adrenal hyperplasia caused by 21-hydroxylase deficiency (CAH) and have performed 8,290 DNA analyses of the CYP21A2 gene on members of 4,857 families at risk for CAH--the largest cohort of CAH patients reported to date. Of the families studied, 1,507 had at least one member affected with one of three known forms of CAH, namely salt wasting, simple virilizing, or nonclassical CAH. Here, we report the genotype and phenotype of each affected patient, as well as the ethnic group and country of origin for each patient. We showed that 21 of 45 genotypes yielded a phenotypic correlation in our patient cohort. In particular, contrary to what is generally reported in the literature, we found that certain mutations, for example, the P30L, I2G, and I172N mutations, yielded different CAH phenotypes. In salt wasting and nonclassical CAH, a phenotype can be attributed to a genotype; however, in simple virilizing CAH, we observe wide phenotypic variability, particularly with the exon 4 I172N mutation. Finally, there was a high frequency of homozygous I2G and V281L mutations in Middle Eastern and Ashkenazi Jewish populations, respectively. By identifying the predominant phenotype for a given genotype, these findings should assist physicians in prenatal diagnosis and genetic counseling of parents who are at risk for having a child with CAH.
Topics: Adrenal Hyperplasia, Congenital; Cohort Studies; Ethnicity; Gene Deletion; Gene Frequency; Genotype; Humans; Models, Genetic; Mutation; New York; Phenotype; Steroid 21-Hydroxylase
PubMed: 23359698
DOI: 10.1073/pnas.1300057110 -
The British Journal of Radiology Nov 2017Adrenal cortical hyperplasia manifests radiologically as a non-malignant growth, or enlargement, of the adrenal glands, specifically the cortex, although the cortex... (Review)
Review
Adrenal cortical hyperplasia manifests radiologically as a non-malignant growth, or enlargement, of the adrenal glands, specifically the cortex, although the cortex cannot be definitively identified by conventional imaging. Controlled by the pituitary gland, the adrenal cortex drives critical processes, such as the production of cortisol, mineralocorticoid and sex hormones. Any disruption in the multiple enzymes and hormones involved in these pathways may cause serious or life-threatening symptoms, often associated with anatomical changes in the adrenal glands. Diagnosis and treatment of adrenal cortical hyperplasia requires a thorough clinical evaluation. As imaging has become more robust so has its role in the diagnosis and treatment of adrenal conditions. CT has been the primary modality for adrenal imaging owing to reproducibility, temporal and spatial resolution and broad access. MRI serves a complimentary role in adrenal imaging and can be used to further evaluate indeterminate CT findings or serve as an adjunct tool without the use of ionizing radiation. Ultrasound and fluoroscopy (genitography) are most commonly used in children and foetuses to evaluate congenital adrenal hyperplasia. This article will discuss the clinical presentation, laboratory workup and imaging features of adrenal cortical hyperplasia, both congenital and acquired.
Topics: Adolescent; Adrenal Glands; Adrenal Hyperplasia, Congenital; Adrenocorticotropic Hormone; Adult; Cushing Syndrome; Diagnosis, Differential; Female; Humans; Hyperplasia; Infant, Newborn; Magnetic Resonance Imaging; Male; Middle Aged; Organ Size; Pituitary ACTH Hypersecretion; Steroid 21-Hydroxylase; Tomography, X-Ray Computed
PubMed: 28707538
DOI: 10.1259/bjr.20170330