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Endocrine Reviews Jan 2022Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders affecting cortisol biosynthesis. Reduced activity of an enzyme required for cortisol... (Review)
Review
Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders affecting cortisol biosynthesis. Reduced activity of an enzyme required for cortisol production leads to chronic overstimulation of the adrenal cortex and accumulation of precursors proximal to the blocked enzymatic step. The most common form of CAH is caused by steroid 21-hydroxylase deficiency due to mutations in CYP21A2. Since the last publication summarizing CAH in Endocrine Reviews in 2000, there have been numerous new developments. These include more detailed understanding of steroidogenic pathways, refinements in neonatal screening, improved diagnostic measurements utilizing chromatography and mass spectrometry coupled with steroid profiling, and improved genotyping methods. Clinical trials of alternative medications and modes of delivery have been recently completed or are under way. Genetic and cell-based treatments are being explored. A large body of data concerning long-term outcomes in patients affected by CAH, including psychosexual well-being, has been enhanced by the establishment of disease registries. This review provides the reader with current insights in CAH with special attention to these new developments.
Topics: Adrenal Hyperplasia, Congenital; Humans; Hydrocortisone; Infant, Newborn; Mutation; Neonatal Screening; Steroid 21-Hydroxylase
PubMed: 33961029
DOI: 10.1210/endrev/bnab016 -
Journal of Pediatric and Adolescent... Oct 2017The congenital adrenal hyperplasias comprise a family of autosomal recessive disorders that disrupt adrenal steroidogenesis. The most common form is due to... (Review)
Review
The congenital adrenal hyperplasias comprise a family of autosomal recessive disorders that disrupt adrenal steroidogenesis. The most common form is due to 21-hydroxylase deficiency associated with mutations in the 21-hydroxylase gene, which is located at chromosome 6p21. The clinical features associated with each disorder of adrenal steroidogenesis represent a clinical spectrum that reflect the consequences of the specific mutations. Treatment goals include normal linear growth velocity and "on-time" puberty in affected children. For adolescent and adult women, treatment goals include regularization of menses, prevention of progression of hirsutism, and preservation of fertility. For adolescent and adult men, prevention and early treatment of testicular adrenal rest tumors is beneficial. In this article key aspects regarding pathophysiology, diagnosis, and treatment of congenital adrenal hyperplasia are reviewed.
Topics: Adolescent; Adrenal Hyperplasia, Congenital; Adult; Child; Female; Fertility; Hirsutism; Humans; Male; Mutation; Sexual Maturation; Steroid 21-Hydroxylase
PubMed: 28450075
DOI: 10.1016/j.jpag.2017.04.001 -
The Journal of Clinical Endocrinology... Nov 2018To update the congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency clinical practice guideline published by the Endocrine Society in 2010.
OBJECTIVE
To update the congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency clinical practice guideline published by the Endocrine Society in 2010.
CONCLUSIONS
The writing committee presents updated best practice guidelines for the clinical management of congenital adrenal hyperplasia based on published evidence and expert opinion with added considerations for patient safety, quality of life, cost, and utilization.
Topics: Adrenal Hyperplasia, Congenital; Cost-Benefit Analysis; Endocrinology; Female; Fetal Therapies; Genetic Counseling; Glucocorticoids; Humans; Infant, Newborn; Long-Term Care; Neonatal Screening; Patient Safety; Quality of Life; Societies, Medical; Therapies, Investigational
PubMed: 30272171
DOI: 10.1210/jc.2018-01865 -
The Lancet. Diabetes & Endocrinology Nov 2021Adrenal myelolipomas are benign, lipomatous tumours with elements of myeloid cells, most of which present as adrenal incidentalomas and comprise 3·3-6·5% of all... (Review)
Review
Adrenal myelolipomas are benign, lipomatous tumours with elements of myeloid cells, most of which present as adrenal incidentalomas and comprise 3·3-6·5% of all adrenal masses. Adrenal myelolipomas are usually unilateral (in 95% of cases), variable in size, most often found during midlife, and affect both sexes almost equally. On imaging, adrenal myelolipomas show pathognomonic imaging features consistent with the presence of macroscopic fat. Large adrenal myelolipomas can cause symptoms of mass effect, and can occasionally be complicated by haemorrhage. In the event of a concomitant adrenal cortical adenoma or hyperplasia, adrenal hormone excess might be detected in patients with adrenal myelolipoma. Patients with congenital adrenal hyperplasia exhibit a higher prevalence of adrenal myelolipomas than other patient groups, and are at risk of developing large and bilateral lesions. This Review discusses the pathogenesis, clinical presentation, and management of adrenal myelolipomas.
Topics: Adrenal Gland Neoplasms; Adrenal Hyperplasia, Congenital; Adrenocorticotropic Hormone; Aged; Female; Humans; Male; Middle Aged; Mutation; Myelolipoma; Prognosis; Proto-Oncogene Proteins; Tomography, X-Ray Computed
PubMed: 34450092
DOI: 10.1016/S2213-8587(21)00178-9 -
Endocrinology and Metabolism Clinics of... Mar 2021Congenital adrenal hyperplasia encompasses a group of autosomal recessive defects in cortisol biosynthesis, and 21-hydroxylase deficiency accounts for 95% of such cases.... (Review)
Review
Congenital adrenal hyperplasia encompasses a group of autosomal recessive defects in cortisol biosynthesis, and 21-hydroxylase deficiency accounts for 95% of such cases. Non-classic 21-hydroxylase deficiency is due to partial enzymatic defects, which present with normal cortisol synthesis, but excessive production of adrenal androgens, including 11-oxygenated androgens. Non-classic 21-hydroxylase deficiency is relatively common, and its phenotype resembles closely that of polycystic ovary syndrome. This review focuses primarily on non-classic 21-hydroxylase deficiency, its clinical features, diagnosis, and management.
Topics: Adrenal Hyperplasia, Congenital; Androgens; Endocrinologists; Female; Humans; Polycystic Ovary Syndrome
PubMed: 33518183
DOI: 10.1016/j.ecl.2020.10.008 -
Endocrine Reviews Nov 2021Adrenarche is the maturational increase in adrenal androgen production that normally begins in early childhood. It results from changes in the secretory response to... (Review)
Review
Adrenarche is the maturational increase in adrenal androgen production that normally begins in early childhood. It results from changes in the secretory response to adrenocorticotropin (ACTH) that are best indexed by dehydroepiandrosterone sulfate (DHEAS) rise. These changes are related to the development of the zona reticularis (ZR) and its unique gene/enzyme expression pattern of low 3ß-hydroxysteroid dehydrogenase type 2 with high cytochrome b5A, sulfotransferase 2A1, and 17ß-hydroxysteroid dehydrogenase type 5. Recently 11-ketotestosterone was identified as an important bioactive adrenarchal androgen. Birth weight, body growth, obesity, and prolactin are related to ZR development. Adrenarchal androgens normally contribute to the onset of sexual pubic hair (pubarche) and sebaceous and apocrine gland development. Premature adrenarche causes ≥90% of premature pubarche (PP). Its cause is unknown. Affected children have a significantly increased growth rate with proportionate bone age advancement that typically does not compromise growth potential. Serum DHEAS and testosterone levels increase to levels normal for early female puberty. It is associated with mildly increased risks for obesity, insulin resistance, and possibly mood disorder and polycystic ovary syndrome. Between 5% and 10% of PP is due to virilizing disorders, which are usually characterized by more rapid advancement of pubarche and compromise of adult height potential than premature adrenarche. Most cases are due to nonclassic congenital adrenal hyperplasia. Algorithms are presented for the differential diagnosis of PP. This review highlights recent advances in molecular genetic and developmental biologic understanding of ZR development and insights into adrenarche emanating from mass spectrometric steroid assays.
Topics: Adrenal Hyperplasia, Congenital; Adrenarche; Androgens; Child; Child, Preschool; Female; Humans; Polycystic Ovary Syndrome; Puberty, Precocious
PubMed: 33788946
DOI: 10.1210/endrev/bnab009 -
Acta Biochimica Polonica 2018The aim of this paper is a straightforward presentation of the steroidogenesis process and the most common type of congenital adrenal hyperplasia (CAH) - 21-hydroxylase... (Review)
Review
The aim of this paper is a straightforward presentation of the steroidogenesis process and the most common type of congenital adrenal hyperplasia (CAH) - 21-hydroxylase deficiency - as well as the analytical diagnostic methods that are used to recognize this disease. CAH is a family of common autosomal recessive disorders characterized by impaired adrenal cortisol biosynthesis with associated androgen excess due to a deficiency of one or more enzymes in the steroidogenesis process within the adrenal cortex. The most common and prototypical example of the CAH disorders group (90-95%) is caused by 21-hydroxylase deficiency. Less frequent types of CAH are 11β-hydroxylase deficiency (up to 8% of cases), 17α-hydroxylase deficiency, 3β-hydroxysteroid dehydrogenase deficiency, P450 oxidoreductase deficiency and StAR deficiencies. In the 21-hydroxylase and 11β-hydroxylase deficiency, only adrenal steroidogenesis is affected, whereas a defect in 3β-hydroxysteroid dehydrogenase or 17α-hydroxylase also involves gonadal steroid biosynthesis. Many countries have introduced newborn screening programs based on immunoassays measuring 17-hydroxyprogesterone from blood spots used for other neonatal screening tests which enable faster diagnosis and treatment of CAH. Currently, chromatographic techniques coupled with mass spectrometry are gaining popularity due to an increase in the reliability of the test results.
Topics: Adrenal Hyperplasia, Congenital; Humans; Infant, Newborn; Neonatal Screening; Steroids
PubMed: 29543924
DOI: 10.18388/abp.2017_2343 -
Nature Reviews. Endocrinology Jun 2022Treatment for congenital adrenal hyperplasia (CAH) was introduced in the 1950s following the discovery of the structure and function of adrenocortical hormones. Although... (Review)
Review
Treatment for congenital adrenal hyperplasia (CAH) was introduced in the 1950s following the discovery of the structure and function of adrenocortical hormones. Although major advances in molecular biology have delineated steroidogenic mechanisms and the genetics of CAH, management and treatment of this condition continue to present challenges. Management is complicated by a combination of comorbidities that arise from disease-related hormonal derangements and treatment-related adverse effects. The clinical outcomes of CAH can include life-threatening adrenal crises, altered growth and early puberty, and adverse effects on metabolic, cardiovascular, bone and reproductive health. Standard-of-care glucocorticoid formulations fall short of replicating the circadian rhythm of cortisol and controlling efficient adrenocorticotrophic hormone-driven adrenal androgen production. Adrenal-derived 11-oxygenated androgens have emerged as potential new biomarkers for CAH, as traditional biomarkers are subject to variability and are not adrenal-specific, contributing to management challenges. Multiple alternative treatment approaches are being developed with the aim of tailoring therapy for improved patient outcomes. This Review focuses on challenges and advances in the management and treatment of CAH due to 21-hydroxylase deficiency, the most common type of CAH. Furthermore, we examine new therapeutic developments, including treatments designed to replace cortisol in a physiological manner and adjunct agents intended to control excess androgens and thereby enable reductions in glucocorticoid doses.
Topics: Adrenal Hyperplasia, Congenital; Androgens; Biomarkers; Glucocorticoids; Humans; Hydrocortisone
PubMed: 35411073
DOI: 10.1038/s41574-022-00655-w -
American Family Physician Aug 2019Hirsutism is the excessive growth of terminal hair in a typical male pattern in a female. It is often a sign of excessive androgen levels. Although many conditions can... (Review)
Review
Hirsutism is the excessive growth of terminal hair in a typical male pattern in a female. It is often a sign of excessive androgen levels. Although many conditions can lead to hirsutism, polycystic ovary syndrome and idiopathic hyperandrogenism account for more than 85% of cases. Less common causes include idiopathic hirsutism, nonclassic congenital adrenal hyperplasia, androgen-secreting tumors, medications, hyperprolactinemia, thyroid disorders, and Cushing syndrome. Women with an abnormal hirsutism score based on the Ferriman-Gallwey scoring system should be evaluated for elevated androgen levels. Women with rapid onset of hirsutism over a few months or signs of virilization are at high risk of having an androgen-secreting tumor. Hirsutism may be treated with pharmacologic agents and/or hair removal. Recommended pharmacologic therapies include combined oral contraceptives, finasteride, spironolactone, and topical eflornithine. Because of the length of the hair growth cycle, therapies should be tried for at least six months before switching treatments. Hair removal methods such as shaving, waxing, and plucking may be effective, but their effects are temporary. Photoepilation and electrolysis are somewhat effective for long-term hair removal but are expensive.
Topics: Adrenal Hyperplasia, Congenital; Androgen Antagonists; Antineoplastic Agents, Hormonal; Contraceptives, Oral, Hormonal; Cushing Syndrome; Drug-Related Side Effects and Adverse Reactions; Eflornithine; Female; Glucocorticoids; Gonadotropin-Releasing Hormone; Hair Removal; Hirsutism; Humans; Hyperandrogenism; Hyperprolactinemia; Leuprolide; Mineralocorticoid Receptor Antagonists; Neoplasms; Ornithine Decarboxylase Inhibitors; Polycystic Ovary Syndrome; Spironolactone; Thyroid Diseases
PubMed: 31361105
DOI: No ID Found -
Reviews in Endocrine & Metabolic... Feb 2023Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders of steroidogenesis of the adrenal cortex, most commonly due to 21-hydroxylase deficiency... (Review)
Review
Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders of steroidogenesis of the adrenal cortex, most commonly due to 21-hydroxylase deficiency caused by mutations in the CYP21A2 gene. Although women with CAH have decreased fecundity, they are able to conceive; thus, if pregnancy is not desired, contraception options should be offered. If fertility is desired, women with classic CAH should first optimize glucocorticoid treatment, followed by ovulation induction medications and gonadotropins if needed. Due to the possible pregnancy complications and implications on the offspring, preconception genetic testing and counseling with a high-risk obstetrics specialist is recommended. For couples trying to avoid having a child with CAH, care with a reproductive endocrinology and infertility specialist to utilize in vitro fertilization can be offered, with or without preimplantation genetic testing for monogenic disorders. Prenatal screening and diagnosis options during pregnancy include maternal serum cell free-DNA for sex of the baby, and chorionic villus sampling and amniocentesis for diagnosis of CAH. Pregnant women with classic CAH need glucocorticoids to be adjusted during the pregnancy, at the time of delivery, and postpartum, and should be monitored for adrenal crisis. Maternal and fetal risks may include chorioamnionitis, maternal hypertension, gestational diabetes, cesarean section, and small for gestational age infants. This review on CAH due to 21-hydroxylase deficiency highlights reproductive health including genetic transmission, contraception options, glucocorticoid management, fertility treatments, as well as testing, antenatal monitoring, and management during pregnancy, delivery, and postpartum.
Topics: Child; Pregnancy; Female; Humans; Adrenal Hyperplasia, Congenital; Glucocorticoids; Cesarean Section; Postpartum Period; Steroid 21-Hydroxylase
PubMed: 36399318
DOI: 10.1007/s11154-022-09770-5