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Current Opinion in Endocrinology,... Jun 2016In recent years, important steps have been taken to improve the treatment of congenital adrenal hyperplasia (CAH), a relatively stagnant area for decades. In this... (Review)
Review
PURPOSE OF REVIEW
In recent years, important steps have been taken to improve the treatment of congenital adrenal hyperplasia (CAH), a relatively stagnant area for decades. In this review, we summarize these advances and propose future lines of investigation.
RECENT FINDINGS
The two main goals of CAH treatment are to replace the deficient hormones when necessary and to dampen the adrenocorticotropin activation and the ensuing adrenal androgen excess. Glucocorticoids have been the mainstay of CAH treatment, but available preparations only partially meet the clinical needs. Recent efforts have focused on improving the delivery of glucocorticoid replacement agents, to closer mimic the physiologic secretion pattern. Examples include modified release oral glucocorticoids and continuous subcutaneous hydrocortisone pumps. Furthermore, nonglucocorticoid approaches to address the androgen excess have emerged, such as inhibition of key androgenic enzymes and adrenocorticotropin secretion blockade by corticotropin-releasing hormone receptor antagonists.
SUMMARY
The promising recent progress made in CAH treatment brings new perspectives for individualized care in this complex disease.
Topics: Adrenal Hyperplasia, Congenital; Humans
PubMed: 27032061
DOI: 10.1097/MED.0000000000000256 -
Frontiers in Endocrinology 20223β-hydroxysteroid dehydrogenase 2 (3βHSD2) deficiency is a rare form of congenital adrenal hyperplasia (CAH), with fewer than 200 cases reported in the world...
BACKGROUND
3β-hydroxysteroid dehydrogenase 2 (3βHSD2) deficiency is a rare form of congenital adrenal hyperplasia (CAH), with fewer than 200 cases reported in the world literature and few data on outcomes.
PATIENTS AND METHODS
We report a mixed longitudinal and cross-sectional study from a single Algerian center between 2007 and 2021. Virilization and under-masculinization were assessed using Prader staging and the external masculinization score (EMS), pubertal development staged according to the system of Tanner. Adrenal steroids were measured using mass spectrophotometry (LC-MS/MS). A genetic analysis of was performed using Sanger sequencing.
RESULTS
A 3βHSD2 defect was confirmed in 6 males and 8 females from 10 families (8 consanguineous), with p.Pro222Gln mutation in all but two siblings with a novel deletion: c.453_464del or p.(Thr152_Pro155del). Probable 3βHSD2 deficiency was diagnosed retrospectively in a further 6 siblings who died, and in two patients from two other centers. In the genetically confirmed patients, the median (range) age at presentation was 20 (0-390) days, with salt-wasting (n = 14) and genital anomaly (n = 10). The Prader stage for female patients was 2 (1-2) with no posterior fusion of the labia. The EMS for males was 6 (3-9). Median (range) values at diagnosis for 17-hydroxyprogesterone (17-OHP), dehydroepiandrosterone sulfate (DHEA-S), and 17-hydroxypregnenolone (17OHPreg) were elevated: 73.7 (0.37-164.3) nmol/L; 501.2(9.4-5441.3) nmol/L, and 139.7 (10.9-1500) nmol/l (NB >90 nmol/L diagnostic of 3βHSD2 defect). Premature pubarche was observed in four patients (3F:1M). Six patients (5F:1M) entered puberty spontaneously, aged 11 (5-13) years in 5 girls and 11.5 years in one boy. Testicular adrenal rest tumors were found in three boys. Four girls reached menarche at 14.3 (11-14.5) years, with three developing adrenal masses (surgically excised in two) and polycystic ovary syndrome (PCOS), with radiological evidence of ovarian adrenal rest tumor in one. The median IQ was 90 (43-105), >100 in only two patients and <70 in three.
CONCLUSIONS
The prevalence of 3βHSD2 deficiency in Algeria appears high, with p.Pro222Gln being the most frequent mutation. Mortality is also high, with significant morbidity from adrenal tumors and PCOS in adolescence and an increased risk of learning disability. The finding of adrenal tumors in older patients with 3βHSD2 indicates under-replacement, requiring effective hydrocortisone and fludrocortisone treatment rather than surgical removal.
Topics: Adolescent; Adrenal Gland Neoplasms; Adrenal Hyperplasia, Congenital; Aged; Algeria; Chromatography, Liquid; Cross-Sectional Studies; Female; Genotype; Humans; Male; Morbidity; Polycystic Ovary Syndrome; Retrospective Studies; Tandem Mass Spectrometry
PubMed: 35757411
DOI: 10.3389/fendo.2022.867073 -
Journal of Pediatric Health Care :... 2017Congenital adrenal hyperplasia (CAH) is an endocrine condition that requires parents to administer steroids up to three times daily, supplementing maintenance doses with... (Review)
Review
Congenital adrenal hyperplasia (CAH) is an endocrine condition that requires parents to administer steroids up to three times daily, supplementing maintenance doses with oral or injectable doses during times of illness. The purpose of this integrative review was to explore the management, care, and associated health issues for children with CAH and the family response to the condition. Four literature indexes were searched, with 39 articles included. Four themes emerged: (a) Health- and Development-Related Issues, (a) Effects of Excess Androgens, (c) Life Experience of CAH, and (d) Managing and Averting Adrenal Crisis. Families having a child with CAH face complex concerns related their child's growth, the fear of adrenal crisis events, and the consequences of atypical genitalia for affected girls. Future studies should focus on interventions that provide guidelines to increase parental preparedness in managing adrenal crises and creating support systems for affected girls.
Topics: Adrenal Hyperplasia, Congenital; Child; Child Health; Female; Health Knowledge, Attitudes, Practice; Humans; Male; Parents; Patient Care Management; Patient Education as Topic; Practice Guidelines as Topic; Quality of Life; Steroids
PubMed: 28416079
DOI: 10.1016/j.pedhc.2017.02.004 -
Frontiers in Endocrinology 202321-hydroxylase deficiency (21-OHD) is the most common form of congenital adrenal hyperplasia. In most developed countries, newborn screening enables diagnosis of 21-OHD... (Review)
Review
21-hydroxylase deficiency (21-OHD) is the most common form of congenital adrenal hyperplasia. In most developed countries, newborn screening enables diagnosis of 21-OHD in asymptomatic patients during the neonatal period. In addition, recent advances in genetic testing have facilitated diagnosing 21-OHD, particularly in patients with equivocal clinical information. On the other hand, many challenges related to treatment remain. The goals of glucocorticoid therapy for childhood 21-OHD are to maintain growth and maturation as in healthy children by compensating for cortisol deficiency and suppressing excess adrenal androgen production. It is not easy to calibrate the glucocorticoid dosage accurately for patients with 21-OHD. Auxological data, such as height, body weight, and bone age, are considered the gold standard for monitoring of 21-OHD, particularly in prepuberty. However, these data require months to a year to evaluate. Theoretically, biochemical monitoring using steroid metabolites allows a much shorter monitoring period (hours to days). However, there are many unsolved problems in the clinical setting. For example, many steroid metabolites are affected by the circadian rhythm and timing of medication. There is still a paucity of evidence for the utility of biochemical monitoring. In the present review, we have attempted to clarify the knowns and unknowns about treatment parameters in 21-OHD during childhood.
Topics: Infant, Newborn; Humans; Child; Adrenal Hyperplasia, Congenital; Glucocorticoids; Neonatal Screening; Steroids
PubMed: 36843618
DOI: 10.3389/fendo.2023.1102741 -
Indian Pediatrics Feb 2020Treatment of congenital adrenal hyperplasia (CAH) requires lifelong replacement of glucocorticoids with regular follow up to manage associated morbidities. The current... (Review)
Review
Treatment of congenital adrenal hyperplasia (CAH) requires lifelong replacement of glucocorticoids with regular follow up to manage associated morbidities. The current review focuses on follow-up and management of infants diagnosed with classical CAH pertinent to Indian context. Early initiation of oral hydrocortisone in divided doses is recommended after diagnosis in newborn period, infancy and childhood. Fludrocortisone is recommended for all infants with classical CAH. All infants should be monitored as per protocol for disease and treatment related complications. The role of prenatal steroids to pregnant women with previous history of CAH affected infant for prevention of virilization of female fetus is controversial.
Topics: Administration, Oral; Adrenal Hyperplasia, Congenital; Female; Glucocorticoids; Humans; India; Infant; Male; Mineralocorticoids; Pregnancy; Prenatal Exposure Delayed Effects; Steroids
PubMed: 32060243
DOI: No ID Found -
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 -
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 -
Frontiers in Endocrinology 2023Dysfunction in the hypothalamic-pituitary-adrenal axis has been associated with depressive and anxiety disorders. Little is known about the risk for these disorders...
BACKGROUND
Dysfunction in the hypothalamic-pituitary-adrenal axis has been associated with depressive and anxiety disorders. Little is known about the risk for these disorders among individuals with congenital adrenal hyperplasia (CAH), a form of primary adrenal insufficiency.
OBJECTIVE
We investigated the prevalence of depressive and anxiety disorders and antidepressant prescriptions in two large healthcare databases of insured children, adolescents, and young adults with CAH in the United States.
METHODS
We conducted a retrospective cohort study using administrative data from October 2015 through December 2019 for individuals aged 4-25 years enrolled in employer-sponsored or Medicaid health plans.
RESULTS
Adjusting for age, the prevalence of depressive disorders [adjusted prevalence ratio (aPR) = 1.7, 95% confidence interval (CI): 1.4-2.0, p<0.001], anxiety disorders [aPR = 1.7, 95% CI: 1.4-1.9, p<0.001], and filled antidepressant prescriptions [aPR = 1.7, 95% CI: 1.4-2.0, p<0.001] was higher among privately insured youth with CAH as compared to their non-CAH peers. Prevalence estimates were also higher among publicly insured youth with CAH for depressive disorders [aPR = 2.3, 95% CI: 1.9-2.9, p<0.001], anxiety disorders [aPR = 2.0, 95% CI: 1.6-2.5, p<0.001], and filled antidepressant prescriptions [aPR = 2.5, 95% CI: 1.9-3.1, p<0.001] as compared to their non-CAH peers.
CONCLUSIONS
The elevated prevalence of depressive and anxiety disorders and antidepressant prescriptions among youth with CAH suggests that screening for symptoms of depression and anxiety among this population might be warranted.
Topics: United States; Adolescent; Humans; Child; Young Adult; Adrenal Hyperplasia, Congenital; Hypothalamo-Hypophyseal System; Retrospective Studies; Pituitary-Adrenal System; Anxiety Disorders; Antidepressive Agents; Prescriptions
PubMed: 37664854
DOI: 10.3389/fendo.2023.1129584 -
Fertility and Sterility Jan 2019Nonclassical congenital adrenal hyperplasia (NC-CAH) is by far a subtler and milder enzymatic defect to the classical form of the disease. A nuanced understanding of... (Review)
Review
Nonclassical congenital adrenal hyperplasia (NC-CAH) is by far a subtler and milder enzymatic defect to the classical form of the disease. A nuanced understanding of NC-CAH will lead to increased detection of the disorder in those initially misdiagnosed as having polycystic ovary syndrome, will assist in the detection of pregnancies at risk for severe genetic steroid disorders, and will facilitate appropriate ovulation induction and reduction in the hyperandrogenic symptoms which are a cornerstone of the disease. We describe the history of the disease as well as elucidate the pathophysiology, diagnosis, and treatment of the disorder.
Topics: Adrenal Hyperplasia, Congenital; Female; Fertility; Humans; Male; Steroid 21-Hydroxylase
PubMed: 30611403
DOI: 10.1016/j.fertnstert.2018.11.023 -
Archives of Disease in Childhood Dec 2019Steroid biosynthesis is a complex process in which cholesterol is converted to steroid hormones with the involvement of multiple enzymes and cofactors. Inborn conditions... (Review)
Review
Steroid biosynthesis is a complex process in which cholesterol is converted to steroid hormones with the involvement of multiple enzymes and cofactors. Inborn conditions affecting adrenal steroidogenesis are relatively common in paediatric practice and have serious implications on patient mortality and morbidity. This paper provides an overview of novel insights into human adrenal steroid biosynthesis. Inborn errors of steroidogenesis associated with congenital adrenal hyperplasia are discussed, with a particular focus on the pathophysiology and clinical features of 21-hydroxylase deficiency. The final section of the review presents more recent findings and clinical implications of adrenal-specific androgen biosynthesis.
Topics: Adrenal Hyperplasia, Congenital; Glucocorticoids; Hormone Replacement Therapy; Humans; Infant, Newborn; Practice Guidelines as Topic; Steroid 21-Hydroxylase; Steroids
PubMed: 31175123
DOI: 10.1136/archdischild-2017-313873