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Lancet (London, England) Jan 2023Congenital adrenal hyperplasia is a group of autosomal recessive disorders leading to multiple complex hormonal imbalances caused by various enzyme deficiencies in the... (Review)
Review
Congenital adrenal hyperplasia is a group of autosomal recessive disorders leading to multiple complex hormonal imbalances caused by various enzyme deficiencies in the adrenal steroidogenic pathway. The most common type of congenital adrenal hyperplasia is due to steroid 21-hydroxylase (21-OHase, henceforth 21OH) deficiency. The rare, classic (severe) form caused by 21OH deficiency is characterised by life-threatening adrenal crises and is the most common cause of atypical genitalia in neonates with 46,XX karyotype. After the introduction of life-saving hormone replacement therapy in the 1950s and neonatal screening programmes in many countries, nowadays neonatal survival rates in patients with congenital adrenal hyperplasia are high. However, disease-related mortality is increased and therapeutic management remains challenging, with multiple long-term complications related to treatment and disease affecting growth and development, metabolic and cardiovascular health, and fertility. Non-classic (mild) forms of congenital adrenal hyperplasia caused by 21OH deficiency are more common than the classic ones; they are detected clinically and primarily identified in female patients with hirsutism or impaired fertility. Novel treatment approaches are emerging with the aim of mimicking physiological circadian cortisol rhythm or to reduce adrenal hyperandrogenism independent of the suppressive effect of glucocorticoids.
Topics: Infant, Newborn; Humans; Female; Adrenal Hyperplasia, Congenital; Glucocorticoids; Hydrocortisone; Hormone Replacement Therapy; Neonatal Screening
PubMed: 36502822
DOI: 10.1016/S0140-6736(22)01330-7 -
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 -
Lancet (London, England) Nov 2017Congenital adrenal hyperplasia is a group of autosomal recessive disorders encompassing enzyme deficiencies in the adrenal steroidogenesis pathway that lead to impaired... (Review)
Review
Congenital adrenal hyperplasia is a group of autosomal recessive disorders encompassing enzyme deficiencies in the adrenal steroidogenesis pathway that lead to impaired cortisol biosynthesis. Depending on the type and severity of steroid block, patients can have various alterations in glucocorticoid, mineralocorticoid, and sex steroid production that require hormone replacement therapy. Presentations vary from neonatal salt wasting and atypical genitalia, to adult presentation of hirsutism and irregular menses. Screening of neonates with elevated 17-hydroxyprogesterone concentrations for classic (severe) 21-hydroxylase deficiency, the most common type of congenital adrenal hyperplasia, is in place in many countries, however cosyntropin stimulation testing might be needed to confirm the diagnosis or establish non-classic (milder) subtypes. Challenges in the treatment of congenital adrenal hyperplasia include avoidance of glucocorticoid overtreatment and control of sex hormone imbalances. Long-term complications include abnormal growth and development, adverse effects on bone and the cardiovascular system, and infertility. Novel treatments aim to reduce glucocorticoid exposure, improve excess hormone control, and mimic physiological hormone patterns.
Topics: Adrenal Hyperplasia, Congenital; Combined Modality Therapy; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Genetic Predisposition to Disease; Glucocorticoids; Hormone Replacement Therapy; Humans; Infant, Newborn; Male; Neonatal Screening; Rare Diseases; Risk Assessment; Severity of Illness Index; Treatment Outcome
PubMed: 28576284
DOI: 10.1016/S0140-6736(17)31431-9 -
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 -
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 -
Pediatrics in Review Feb 2024We describe congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, which is the most common primary adrenal insufficiency in children and adolescents. In... (Review)
Review
We describe congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, which is the most common primary adrenal insufficiency in children and adolescents. In this comprehensive review of CAH, we describe presentations at different life stages depending on disease severity. CAH is characterized by androgen excess secondary to impaired steroidogenesis in the adrenal glands. Diagnosis of CAH is most common during infancy with elevated 17-hydroxyprogesterone levels on the newborn screen in the United States. However, CAH can also present in childhood, with late-onset symptoms such as premature adrenarche, growth acceleration, hirsutism, and irregular menses. The growing child with CAH is treated with hydrocortisone for glucocorticoid replacement, along with increased stress doses for acute illness, trauma, and procedures. Mineralocorticoid and salt replacement may also be necessary. Although 21-hydroxylase deficiency is the most common type of CAH, there are other rare types, such as 11β-hydroxylase and 3β-hydroxysteroid dehydrogenase deficiency. In addition, classic CAH is associated with long-term comorbidities, including cardiometabolic risk factors, impaired cognitive function, adrenal rest tumors, and bone health effects. Overall, early identification and treatment of CAH is important for the pediatric patient.
Topics: Infant, Newborn; Adolescent; Child; Humans; Adrenal Hyperplasia, Congenital; Glucocorticoids; Hydrocortisone; Puberty, Precocious
PubMed: 38296783
DOI: 10.1542/pir.2022-005617 -
Experientia Supplementum (2012) 2019Congenital adrenal hyperplasia (CAH) is a group of seven autosomal recessively inherited disorders of various enzymes participating in adrenal steroid hormone synthesis.... (Review)
Review
Congenital adrenal hyperplasia (CAH) is a group of seven autosomal recessively inherited disorders of various enzymes participating in adrenal steroid hormone synthesis. Patients present with various symptoms depending on the nature and severity of the enzymatic block. More than 95% of all CAH patients suffer from 21-hydroxylase deficiency. The genetic background is well characterized for all CAH subtypes. Characterization of their genetic background has provided important pathophysiologic understanding of steroid biosynthesis disorders. Genotyping is important for confirming diagnosis, determining prognostic factors, and for genetic counseling for family planning and may reveal new therapeutic approaches.
Topics: Adrenal Hyperplasia, Congenital; Genetic Background; Genetic Counseling; Humans
PubMed: 31588535
DOI: 10.1007/978-3-030-25905-1_12 -
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 -
Endocrinology and Metabolism Clinics of... Sep 2019Fertility rates in classic congenital adrenal hyperplasia caused by 21-hydroxylase deficiency are substantially decreased for various reasons, including hormonal,... (Review)
Review
Fertility rates in classic congenital adrenal hyperplasia caused by 21-hydroxylase deficiency are substantially decreased for various reasons, including hormonal, anatomic, psychosocial, and psychosexual causes. However, fecundity is comparable with the general population. Under optimal hormone replacement, the course and outcome of pregnancies is also good. This article summarizes successful gestational management, including preconceptional considerations, adjustment of hormone replacement during pregnancy, delivery and lactation, as well as the prevention of adrenal crises. In nonclassic 21-hydroxylase deficiency, preconceptional low-dose hydrocortisone replacement normalizes the otherwise increased miscarriage rate. Pregnancy reports in rarer forms of congenital adrenal hyperplasia are summarized as well.
Topics: Adrenal Hyperplasia, Congenital; Female; Fertility; Hormone Replacement Therapy; Humans; Hydrocortisone; Preconception Care; Pregnancy; Pregnancy Complications
PubMed: 31345527
DOI: 10.1016/j.ecl.2019.05.011 -
Reviews in Endocrine & Metabolic... Mar 2009Nonclassic adrenal hyperplasia is most commonly attributable to mutations in CYP21A2 (also termed CYP21) encoding steroid 21-hydroxylase. Partial deficiency of this... (Review)
Review
Nonclassic adrenal hyperplasia is most commonly attributable to mutations in CYP21A2 (also termed CYP21) encoding steroid 21-hydroxylase. Partial deficiency of this enzyme causes an imbalance in cortisol synthesis with consequent adrenal androgen excess. Unlike more severe forms of congenital adrenal hyperplasia, this condition is rarely recognized in infants, but rather is a potential cause of premature adrenarche and pubarche in children, virilization in young women, and variable symptoms in young men. This article will review relevant clinical, hormonal and genetic aspects of nonclassic adrenal hyperplasia.
Topics: Adrenal Hyperplasia, Congenital; Female; Humans; Male; Steroid 21-Hydroxylase
PubMed: 18690539
DOI: 10.1007/s11154-008-9097-x