Congenital adrenal hyperplasia in pregnancy: approach depends on who is the ‘patient’

Congenital adrenal hyperplasia (CAH) is a group of autosomal-recessive disorders caused by a reduced or absent enzymatic activity at one of the stages of adrenal steroid biosynthesis. Prenatal exposure to androgens leads to external genital masculinization of the affected female child. In pregnancy, the provider may be optimizing care for the woman with CAH or targeting treatment to reduce virilization in the affected unborn child. For the affected adult woman the goals of therapy in pregnancy are to prevent adrenal insufficiency, reduce fetal exposure to androgens and glucocorticoids and to avoid damage to reconstructed genitalia. For prenatal therapy for prevention of virilization of possibly affected female children, dexamethasone is used. However, questions remain about the efficacy and safety of exposing 7/8 unaffected children in the first trimester. Prenatal treatment should only be undertaken after careful discussion with the parents of the risks and benefits in an experienced centre or as part of a research protocol.

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A Case of Salt-Wasting Congenital Adrenal Hyperplasia with Triple Homozygous Mutation: Review of Literature

Journal of Pediatric Genetics ◽

10.1055/s-0040-1705110 ◽

2020 ◽

Author(s):

Maria Laura Iezzi ◽

Gaia Varriale ◽

Luca Zagaroli ◽

Stefania Lasorella ◽

Marco Greco ◽

...

Keyword(s):

Congenital Adrenal Hyperplasia ◽

Autosomal Recessive ◽

Homozygous Mutation ◽

Adrenal Hyperplasia ◽

Phenotype Correlation ◽

Hydroxylase Deficiency ◽

Autosomal Recessive Disorders ◽

Salt Wasting ◽

21 Hydroxylase Deficiency ◽

Recessive Disorders

AbstractCongenital adrenal hyperplasia (CAH) due to steroid 21-hydroxylase deficiency represents a group of autosomal recessive disorders characterized by impaired cortisol production due to altered upstream steroid conversions, subclassified as classic and nonclassic forms. The genotype–phenotype correlation is possible in the most frequent case but not in all. Despite in literature many mutations are known, there is the possibility of finding a new genetic pattern in patients with CAH.

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Congenital Adrenal Hyperplasia with Salt Wasting Crisis: A Case Report

Journal of Nepal Medical Association ◽

10.31729/jnma.4811 ◽

2020 ◽

Vol 58 (221) ◽

Author(s):

Deependra Mandal ◽

Deepa Khanal ◽

Rajan Phuyal ◽

Uttara Adhikari

Keyword(s):

Congenital Adrenal Hyperplasia ◽

Elevated Level ◽

Autosomal Recessive ◽

Oral Prednisolone ◽

Severe Form ◽

Adrenal Hyperplasia ◽

Autosomal Recessive Disorders ◽

Salt Wasting ◽

17 Hydroxyprogesterone ◽

Recessive Disorders

Congenital Adrenal Hyperplasia is a group of autosomal recessive disorders due to deficienciesof enzymes involved in steroidogenesis. The most common form is a 21-hydroxylase deficiencywhich can be classical or non-classical. The severe form also called Classical Congenital AdrenalHyperplasia is usually detected after birth to infant period. If Congenital Adrenal Hyperplasia is notdiagnosed and treated early, neonates are susceptible to sudden death in the early weeks of life. Wereport a case of thirty-five days male with a salt-wasting variant of congenital adrenal hyperplasia.The diagnosis was based on an elevated level of 17-hydroxyprogesterone. He was managed and lifelong oral Prednisolone and Fludrocortisone were prescribed.

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Case Report: Infant With Congenital Adrenal Hyperplasia and 47,XXY

Frontiers in Genetics ◽

10.3389/fgene.2021.808006 ◽

2022 ◽

Vol 12 ◽

Author(s):

Sophia Q. Song ◽

Andrea Gropman ◽

Robert W. Benjamin ◽

Francie Mitchell ◽

Michaela R. Brooks ◽

...

Keyword(s):

Congenital Adrenal Hyperplasia ◽

Genetic Disorders ◽

Gene Mutations ◽

Tall Stature ◽

Clinical Report ◽

Adrenal Hyperplasia ◽

Hydroxylase Deficiency ◽

Autosomal Recessive Disorders ◽

21 Hydroxylase Deficiency ◽

Recessive Disorders

Congenital adrenal hyperplasia is a group of autosomal recessive disorders in which enzymes in the cortisol biosynthesis pathways are disrupted by gene mutations. The most common form of congenital adrenal hyperplasia, caused by 21-hydroxylase deficiency, is characterized by decreased cortisol and aldosterone synthesis and excessive androgen production. Adult height is often compromised in affected patients. Intellectual capability remains intact in patients with congenital adrenal hyperplasia caused by 21-hydroxylase deficiency, based on previous studies. 47,XXY (KS) is a sex chromosomal aneuploidy that manifests with hypergonadotropic hypogonadism, tall stature, and variable intellectual and behavioral dysfunction. This clinical report describes an infant with 21-hydroxylase deficiency congenital adrenal hyperplasia and 47,XXY. The results of his neurodevelopmental, endocrine, neurological, and physical therapy evaluations during his first 22 months are included and were normal. This is the first published case investigating the neurodevelopmental profile of a patient with the combination of these two genetic disorders.

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Reproductive outcome of a patient with congenital adrenal hyperplasia: case report

International Journal of Reproduction Contraception Obstetrics and Gynecology ◽

10.18203/2320-1770.ijrcog20184171 ◽

2018 ◽

Vol 7 (10) ◽

pp. 4297

Author(s):

Bhagyashree A. ◽

Shylaja A. S. ◽

Yashaswini Srikonda

Keyword(s):

Congenital Adrenal Hyperplasia ◽

Autosomal Recessive ◽

Prenatal Testing ◽

Perioperative Period ◽

Adrenal Hyperplasia ◽

Androgen Excess ◽

Adrenal Steroid ◽

History Of ◽

Stress Dose

Congenital Adrenal Hyperplasia are a group of inherited autosomal recessive enzymatic defects of adrenal steroid biosynthesis. Low pregnancy rate has been reported in women with CAH. Several factors have been suggested to contribute to this subfertility such as androgen excess, adrenal progesterone hyper secretion, consequences of genital reconstructive surgery, secondary PCOS and psychosexual factors. In contrast to this subfertility, pregnancies are normal and uneventful. During pregnancy, maternal & fetal problems are confined to these deficiencies. Adequate glucocorticoid therapy and improvement of surgical and psychological management could contribute to optimize fertility in CAH. The interposition of the placenta on the HPA axis & other endocrine changes during pregnancy impact considerably on the clinical evaluation of CAH. A 21 years old Primigravida presented to us at 13 weeks of gestation with history of CAH on treatment and vaginoplasty done in the childhood. Endocrinologist opinion was taken, and steroids continued. Advised to meet genetist and follow up for prenatal testing. But patient denied. Antenatal period was uneventful. Patient underwent Emergency LSCS in view of CPD in labour at 36+6 weeks of gestation. Pre-op stress dose of steroid given. A girl baby of birth weight 2.13 kg was born with good Apgar scores. Perioperative period uneventful. Preconception health, including hormonal, psychosexual and anatomical barriers to fertility should be addressed early in women with CAH. This review provides fertility outcome and pregnancy issues of a woman with CAH.

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Congenital adrenal hyperplasia

Oxford Textbook of Endocrinology and Diabetes ◽

10.1093/med/9780199235292.003.0616 ◽

2011 ◽

pp. 865-878

Author(s):

Nils Krone

Keyword(s):

Congenital Adrenal Hyperplasia ◽

Regulatory Protein ◽

Signs And Symptoms ◽

Adrenal Hyperplasia ◽

Steroidogenic Enzymes ◽

Autosomal Recessive Disorders ◽

Chain Cleavage ◽

Adrenal Steroidogenesis ◽

Steroidogenic Acute Regulatory ◽

Recessive Disorders

Congenital adrenal hyperplasia (CAH) represents a group of autosomal recessive disorders of steroidogenesis caused by defects in steroidogenic enzymes involved in glucocorticoid synthesis or in enzymes providing cofactors to steroidogenic enzymes (1, 2). Congenital lipoid adrenal hyperplasia (CLAH) caused by steroidogenic acute regulatory protein (StAR) deficiency is distinct in origin and presentation from the conventional variants of CAH, with the unique feature of lipid accumulation subsequently leading to destruction of adrenal function. This chapter will also mention aldosterone synthase deficiency, which is the only defect in adrenal steroidogenesis causing deficient mineralocorticoid biosynthesis without affecting glucocorticoid biosynthesis. The disorder cannot strictly be considered a CAH variant as it does not result in increased ACTH drive and thus not in adrenal hyperplasia. Novel forms of CAH have emerged during recent years. These include P450 oxidoreductase deficiency (ORD), P450 side-chain cleavage (CYP11A1) deficiency, the nonclassic form of CLAH (StAR deficiency), and apparent cortisone reductase deficiency. All forms of congenital adrenal hyperplasia resemble a disease continuum spanning from mild nonclassic presentations to classic onset with severe signs and symptoms.

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Congenital adrenal hyperplasia – current insights in pathophysiology, diagnostics and management

Endocrine Reviews ◽

10.1210/endrev/bnab016 ◽

2021 ◽

Author(s):

Hedi L Claahsen – van der Grinten ◽

Phyllis W Speiser ◽

S Faisal Ahmed ◽

Wiebke Arlt ◽

Richard J Auchus ◽

...

Keyword(s):

Congenital Adrenal Hyperplasia ◽

Large Body ◽

Well Being ◽

Adrenal Hyperplasia ◽

Hydroxylase Deficiency ◽

New Developments ◽

Autosomal Recessive Disorders ◽

Alternative Medications ◽

21 Hydroxylase Deficiency ◽

Recessive Disorders

Abstract 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 congenital adrenal hyperplasia with special attention to these new developments.

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A Novel Intronic Pathogenic Variant in STAR With a Dominant Negative Mechanism Causes Attenuated Lipoid Congenital Adrenal Hyperplasia

Journal of Investigative Medicine High Impact Case Reports ◽

10.1177/23247096211014685 ◽

2021 ◽

Vol 9 ◽

pp. 232470962110146

Author(s):

Erin Finn ◽

Kimberly Kripps ◽

Christina Chambers ◽

Michele Rapp ◽

Naomi J. L. Meeks ◽

...

Keyword(s):

Congenital Adrenal Hyperplasia ◽

Autosomal Recessive ◽

De Novo ◽

Dominant Negative ◽

Adrenal Hyperplasia ◽

Primary Adrenal Insufficiency ◽

Heterozygous Variant ◽

Novel Variant ◽

Autosomal Recessive Condition ◽

Clinically Significant

Lipoid congenital adrenal hyperplasia (LCAH) is typically inherited as an autosomal recessive condition. There are 3 reports of individuals with a dominantly acting heterozygous variant leading to a clinically significant phenotype. We report a 46,XY child with a novel heterozygous intronic variant in STAR resulting in LCAH with an attenuated genital phenotype. The patient presented with neonatal hypoglycemia and had descended testes with a fused scrotum and small phallus. Evaluation revealed primary adrenal insufficiency with deficiencies of cortisol, aldosterone, and androgens. He was found to have a de novo heterozygous novel variant in STAR: c.65-2A>C. We report a case of a novel variant and review of other dominant mutations at the same position in the literature. Clinicians should be aware of the possibility of attenuated genital phenotypes of LCAH and the contribution of de novo variants in STAR at c.65-2 to the pathogenesis of that phenotype.

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