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Current Opinion in Endocrinology,... Dec 2012Congenital adrenal hyperplasia (CAH) can present management challenges to the pediatric clinician. Glucocorticoid replacement remains the cornerstone of treatment;... (Review)
Review
PURPOSE OF REVIEW
Congenital adrenal hyperplasia (CAH) can present management challenges to the pediatric clinician. Glucocorticoid replacement remains the cornerstone of treatment; however, there are new formulations and delivery mechanisms being studied. Clinicians continue to discuss the optimal treatment of patients from the prenatal stage, through infancy to adulthood. As well, the role of genetics in the clinical care of patients with CAH, and screening for complications, remain topics of discussion. This review will highlight advances made in the past year, as they pertain to the management of pediatric patients with CAH.
RECENT FINDINGS
This article covers recent studies pertaining to optimal medication regimens, including prenatal dexamethasone treatment; medication delivery; monitoring of hormonal control; and the role of genotyping and genetics in the management of children with CAH.
SUMMARY
Much remains to be learned about the optimal management of children with CAH, including fludrocortisone replacement in simple-virilizing patients, frequency of specific monitoring strategies (e.g., electrolytes, bone age), catecholamine status, stress-dosing in nonclassical adrenal hyperplasia, and early screening for complications or metabolic sequelae. Further randomized and prospective studies are needed to address these issues.
Topics: Adolescent; Adrenal Hyperplasia, Congenital; Child; Child, Preschool; Comorbidity; Dexamethasone; Drug Administration Schedule; Drug Delivery Systems; Female; Genotype; Glucocorticoids; Humans; Infant; Infant, Newborn; Male; Mass Screening; Mothers; Pregnancy; Prenatal Diagnosis
PubMed: 23037928
DOI: 10.1097/MED.0b013e32835a1a1b -
International Braz J Urol : Official... 2022Clitoroplasty constitutes an important step in feminizing surgery for congenital adrenal hyperplasia (CAH) (1). In this video we present a technique that aims to...
INTRODUCTION
Clitoroplasty constitutes an important step in feminizing surgery for congenital adrenal hyperplasia (CAH) (1). In this video we present a technique that aims to preserve clitoral sensitivity and engorgement while minimizing the risk of neurovascular lesion.
MATERIALS AND METHODS
We present a video of a three-year-old girl with history of CAH classical form, PRADER-III, who underwent clitoroplasty. After an initial endoscopic evaluation of the urogenital sinus, the clitoris was degloved and a rectangular incision was made on the ventral corpora cavernosa 15mm above the corpora bifurcation and 0.5 mm below the coronal sulcus. The cavernous tissue was partially resected. The upper and lower borders of the rectangular gap were closed by a 5-0 PDS running suture similar to the Mikulicz technique. Next, the edge of the glans was deepithelialized to reduce its size. For improved clitoral positioning, the clitoris was sutured to the pubic fat. From that point onward the procedure followed that of a standard vaginoplasty using the en-bloc technique (2-4). Thus far we have performed this technique in 33 patients, with 31 of them being girls with CAH and 2 being women with clitoral hypertrophy.
CONCLUSION
Corporoplasty is a simplified technique for clitoroplasty, with the advantage being that is faster and safer than the technique that involves the dissection of the neurovascular bundle. In addition, corporoplasty has the possible benefit of preserving the cavernosal blood flow that permits the engorgement of the clitoris during sexual arousal.
Topics: Adrenal Hyperplasia, Congenital; Child, Preschool; Clitoris; Female; Gynecologic Surgical Procedures; Humans; Hypertrophy; Male; Plastic Surgery Procedures
PubMed: 35263057
DOI: 10.1590/S1677-5538.IBJU.2022.0018 -
Fertility and Sterility Jan 2019Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is caused by mutations in the CYP21A2 gene, located on the short arm of chromosome 6. The two main... (Review)
Review
Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is caused by mutations in the CYP21A2 gene, located on the short arm of chromosome 6. The two main underlying mechanisms of CYP21A2 defects are large gene deletion and conversion. Anticipation of the phenotypes associated with different combinations of CYP21A2 mutations remains the most important determinant in prenatal diagnosis and counseling of the expectant couple who are determined to be at risk for congenital adrenal hyperplasia.
Topics: Adrenal Hyperplasia, Congenital; Female; Gene Deletion; Genotype; Humans; Mutation; Phenotype; Pregnancy; Steroid 21-Hydroxylase
PubMed: 30611409
DOI: 10.1016/j.fertnstert.2018.11.007 -
Journal of the Formosan Medical... Feb 2006Seventeen alpha-hydroxylase deficiency (17OHD) is a rare form of congenital adrenal hyperplasia in which defects in the biosynthesis of cortisol and sex steroid result...
Seventeen alpha-hydroxylase deficiency (17OHD) is a rare form of congenital adrenal hyperplasia in which defects in the biosynthesis of cortisol and sex steroid result in mineralocorticoid excess, hypokalemic hypertension and sexual abnormalities such as pseudohermaphroditism in males, and sexual infantilism in females. The disease is inherited in an autosomal recessive pattern, and is caused by mutations in the gene encoding cytochrome P450c17 (CYP17), which is the single polypeptide that mediates both 17alpha-hydroxylase and 17,20-lyase activities. We report the case of a 15-year-old patient with 17OHD who had a female phenotype but male karyotype (46,XY). The diagnosis was made based on classical clinical features, biochemical data and molecular genetic study. Two mutations were identified by polymerase chain reaction amplification and sequencing, including a S106P point mutation in exon 2 and a 9-bp (GACTCTTTC) deletion from nucleotide position 1519 in exon 8 of CYP17. The first of these mutations was found in the father and the second in the mother, and both have been previously reported in Asia. The patient's hypertension and hypokalemia resolved after glucocorticoid replacement and treatment with potassium-sparing diuretics. Sex hormone replacement was prescribed for induction of sexual development and reduction of the final height. Prophylactic gonadectomy was scheduled. In summary, 17OHD should be suspected in patients with hypokalemic hypertension and lack of secondary sexual development so that appropriate therapy can be implemented.
Topics: Adolescent; Adrenal Hyperplasia, Congenital; Base Sequence; Female; Humans; Hypertension; Hypokalemia; Mutation; Sequence Deletion; Steroid 17-alpha-Hydroxylase
PubMed: 16477341
DOI: 10.1016/S0929-6646(09)60342-9 -
Steroids Mar 2012Congenital adrenal hyperplasia (CAH) is a family of autosomal recessive disorders. 21-Hydroxylase deficiency, in which there are mutations in CYP21A2 (the gene encoding... (Review)
Review
Congenital adrenal hyperplasia (CAH) is a family of autosomal recessive disorders. 21-Hydroxylase deficiency, in which there are mutations in CYP21A2 (the gene encoding the adrenal 21-hydroxylase enzyme), is the most common form (90%) of CAH. In classic CAH there is impaired cortisol production with diagnostic increased levels of 17-OH progesterone. Excess androgen production results in virilization and in the newborn female may cause development of ambiguous external genitalia. Three-fourths of patients with classic CAH also have aldosterone insufficiency, which can result in salt-wasting; in infancy this manifests as shock, hyponatremia and hyperkalemia. CAH has a reported incidence of 1:10,000-1:20,000 births although there is an increased prevalence in certain ethnic groups. Nonclassic CAH (NCCAH) is a less severe form of the disorder, in which there is 20-50% of 21-hydroxylase enzyme activity (vs. 0-5% in classic CAH) and no salt wasting. The degree of symptoms related to androgen excess is variable and may be progressive with age, although some individuals are asymptomatic. NCCAH has an incidence of 1:1000-1:2000 births (0.1-0.2% prevalence) in the White population; an even higher prevalence is noted in certain ethnic groups such as Ashkenazi Jews (1-2%). As many as two-thirds of persons with NCCAH are compound heterozygotes and carry a severe and mild mutation on different alleles. This paper discusses the genetics of NCCAH, along with its variable phenotypic expression, and reviews the clinical course in untreated patients, which includes rapid early childhood growth, advanced skeletal age, premature adrenarche, acne, impaired reproductive function in both sexes and hirsutism as well as menstrual disorders in females. Finally, it addresses treatment with glucocorticoids vs. non treatment and other therapies, particularly with respect to long term issues such as adult metabolic disease including insulin resistance, cardiovascular disease, metabolic syndrome, and bone mineral density.
Topics: Adrenal Hyperplasia, Congenital; Bone Density; Humans; Metabolic Syndrome; Obesity; Reproductive Physiological Phenomena; Skin Diseases
PubMed: 22186144
DOI: 10.1016/j.steroids.2011.12.009 -
Fertility and Sterility Feb 2014Congenital adrenal hyperplasia (CAH) is the most frequently encountered genetic steroid disorder affecting fertility. Steroid hormones play a crucial role in sexual... (Review)
Review
Congenital adrenal hyperplasia (CAH) is the most frequently encountered genetic steroid disorder affecting fertility. Steroid hormones play a crucial role in sexual development and reproductive function; patients with either 21- hydroxylase or 11β-hydroxylase deficiency thus face immense challenges to their fertility. Given the relevance of CAH in reproductive medicine as well as the diagnostic challenges posed by the phenotypic overlap with polycystic ovary syndrome, we review the reproductive pahophysiology of both classic and nonclassic CAH and present contemporary treatment options.
Topics: Adrenal Hyperplasia, Congenital; Animals; Female; Fertility; Humans; Infertility; Male; Steroid 21-Hydroxylase
PubMed: 24355046
DOI: 10.1016/j.fertnstert.2013.11.002 -
The Journal of Steroid Biochemistry and... Sep 2015Congenital adrenal hyperplasias (CAH) are a group of autosomal recessive defects in cortisol biosynthesis. Substantial progress has been made since the description of... (Review)
Review
Congenital adrenal hyperplasias (CAH) are a group of autosomal recessive defects in cortisol biosynthesis. Substantial progress has been made since the description of the first report, 150 years ago. This article reviews some of the recent advances in the genetics, diagnosis and treatment of CAH. In addition, we underline the aspects where further progress is required, including, among others, better diagnostic modalities for the mild phenotype and for some of the rare forms of disease, elucidation of epigenetic factors that lead to different phenotypes in patients with identical genotype and expending on treatment options for controlling the adrenal androgen excess.
Topics: Adrenal Cortex Hormones; Adrenal Hyperplasia, Congenital; Animals; Epigenesis, Genetic; Genotype; History, 19th Century; History, 20th Century; History, 21st Century; Humans
PubMed: 26047556
DOI: 10.1016/j.jsbmb.2015.05.013 -
The Lancet. Diabetes & Endocrinology Dec 2013The management of congenital adrenal hyperplasia involves suppression of adrenal androgen production, in addition to treatment of adrenal insufficiency. Management of... (Review)
Review
The management of congenital adrenal hyperplasia involves suppression of adrenal androgen production, in addition to treatment of adrenal insufficiency. Management of adolescents with congenital adrenal hyperplasia is especially challenging because changes in the hormonal milieu during puberty can lead to inadequate suppression of adrenal androgens, psychosocial issues often affect adherence to medical therapy, and sexual function plays a major part in adolescence and young adulthood. For these reasons, treatment regimen reassessment is indicated during adolescence. Patients with non-classic congenital adrenal hyperplasia require reassessment regarding the need for glucocorticoid drug treatment. No clinical trials have compared various regimens for classic congenital adrenal hyperplasia in adults, thus therapy is individualised and based on the prevention of adverse outcomes. Extensive patient education is key during transition from paediatric care to adult care and should include education of females with classic congenital adrenal hyperplasia regarding their genital anatomy and surgical history. Common issues for these patients include urinary incontinence, vaginal stenosis, clitoral pain, and cosmetic concerns; for males with classic congenital adrenal hyperplasia, common issues include testicular adrenal rest tumours. Transition from paediatric to adult care is most successful when phased over many years. Education of health-care providers on how to successfully transition patients is greatly needed.
Topics: Adolescent; Adrenal Hyperplasia, Congenital; Disease Management; Glucocorticoids; Humans
PubMed: 24622419
DOI: 10.1016/S2213-8587(13)70138-4 -
BioMed Research International 201321-Hydroxylase deficiency (21-OHD) is the most common cause of congenital adrenal hyperplasia (CAH), resulting from deletions or mutations of the P450 21-hydroxylase... (Review)
Review
21-Hydroxylase deficiency (21-OHD) is the most common cause of congenital adrenal hyperplasia (CAH), resulting from deletions or mutations of the P450 21-hydroxylase gene (CYP21A2). Children with 21-OHD need chronic glucocorticoid (cGC) therapy, both to replace congenital deficit in cortisol synthesis and to reduce androgen secretion by adrenal cortex. GC-induced osteoporosis (GIO) is the most common form of secondary osteoporosis that results in an early, transient increase in bone resorption accompanied by a decrease in bone formation, maintained for the duration of GC therapy. Despite the conflicting results in the literature about the bone status on GC-treated patients with 21-OHD, many reports consider these subjects to be at risk for osteoporosis and fractures. In bone cells, at the molecular level, GCs regulate various functions including osteoblastogenesis, osteoclastogenesis, and the apoptosis of osteoblasts and osteocytes. In this paper, we focus on the physiology and biosynthesis of endogenous steroid hormones as well as on the effects of GCs on bone cells, highlighting the pathogenetic mechanism of GIO in children with 21-OHD.
Topics: Adolescent; Adrenal Cortex; Adrenal Hyperplasia, Congenital; Apoptosis; Child; Child, Preschool; Female; Glucocorticoids; Humans; Infant; Male; Mutation; Osteocytes; Osteoporosis; Steroid 21-Hydroxylase
PubMed: 23484098
DOI: 10.1155/2013/250462 -
Polish Archives of Internal Medicine Jan 2023
Topics: Humans; Myelolipoma; Adrenal Gland Neoplasms; Adrenal Hyperplasia, Congenital; Mixed Function Oxygenases
PubMed: 36382926
DOI: 10.20452/pamw.16369