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Archives of Disease in Childhood Oct 1951
Topics: Adrenal Gland Diseases; Adrenal Glands; Adrenal Hyperplasia, Congenital; Fetus; Humans; Hyperplasia
PubMed: 14886050
DOI: 10.1136/adc.26.129.423 -
Proceedings of the Royal Society of... Nov 1962
Topics: Adrenal Cortex; Adrenal Hyperplasia, Congenital; Adrenal Insufficiency; Genetic Diseases, X-Linked; Humans; Hypoadrenocorticism, Familial
PubMed: 14023572
DOI: No ID Found -
Frontiers in Endocrinology 2022To raise awareness of Cytochrome P450 Oxidoreductase Deficiency (PORD, a rare form of congenital adrenal hyperplasia (CAH), through a case of pregnant woman with...
OBJECTIVE
To raise awareness of Cytochrome P450 Oxidoreductase Deficiency (PORD, a rare form of congenital adrenal hyperplasia (CAH), through a case of pregnant woman with virilization symptoms.
CASE DESCRIPTION
A 30-year-old Chinese woman was referred to hospital after 7 years of presenting signs of virilization, including voice deepening, acromegaly, hirsutism, clitoromegaly, and acne. These symptoms appeared since her third gestation. Her second birth died 9 hours after birth and had signs of clitoris hypertrophy. Her third born was a son who presented with flat nose, radius and humerus bone malformation, and small penis at birth. Panel of POR-related genetic tests revealed that the patient carried c.1370 G>A (p.R457H), which is a POR heterozygous gene, while her husband carried a POR heterozygous gene as well, c.1379 C>A (p.S460Y). Two heterozygous mutations of the POR were found in her son: c.1370 G>A and c.1379 C>A. In PORD, c.1370 G>A (p.R457H) was reported as a susceptible gene, while c.1379 C>A (p.S460Y) has not been reported as responsible for the disease so far.
DISCUSSION AND LITERATURE REVIEW
PORD is a rare form of CAH and caused by POR gene mutations. Most PORD patients are identified and diagnosed in pediatrics department. Internal medicine and obstetrics physicians are unfamiliar with the disease. As clinical manifestations are diverse, PORD could be easy to miss or to be misdiagnosed. Typical clinical manifestation includes adrenal insufficiency-related symptoms, such as bone malformations and sexual development disorders. PORD is diagnosed through genetic testing. Investigations of steroid metabolic products in urine through gas chromatography-mass spectrometry or liquid chromatography-mass spectrometry are also helpful for the diagnosis, but neither of them are widely available in China. In this case, the patient had a history of infertility, and her third child was born with congenital defect and carried a PORD-related gene. In general clinical practice, if a pregnant woman presents with abnormal virilization symptoms, CAH possibilities should be considered, including rare causes such as PORD.
CONCLUSION
PORD is a rare autosomal recessive genetic disease. We summarised the clinical characteristics and genotypes that were previously reported in the Chinese population and identified a novel mutation.
Topics: Humans; Male; Child; Pregnancy; Infant, Newborn; Female; Adult; Adrenal Hyperplasia, Congenital; Antley-Bixler Syndrome Phenotype; Virilism; Disorders of Sex Development; Oxidoreductases
PubMed: 36518257
DOI: 10.3389/fendo.2022.1020880 -
Experimental and Clinical Endocrinology... Feb 2019The introduction of newborn screening programmes in most Western countries for classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency (CAH) enables... (Review)
Review
The introduction of newborn screening programmes in most Western countries for classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency (CAH) enables timely introduction of life-saving glucocorticoid replacement in affected babies. Early diagnosis and optimised pediatric care not only successfully led to survival but also allow that almost all patients reach adulthood. Cohort studies in adults, however, provided evidence for significant health problems and co-morbidities of adult patients such as life-threatening adrenal crises, cardiovascular and metabolic health problems, fertility problems, benign endocrine tumours, and osteopenia and osteoporosis. This review summarises the current state of knowledge aiming to emphasize the neccessity of primary and secondary prevention of additional long-term health issues as a major task of health professionals in the care of CAH.
Topics: Adrenal Hyperplasia, Congenital; Adult; Child; Humans; Infant, Newborn
PubMed: 30812049
DOI: 10.1055/a-0820-2085 -
Frontiers in Endocrinology 2024Patients with primary adrenal insufficiency due to congenital adrenal hyperplasia (CAH) are at risk for adrenal crisis during infectious illnesses. Increased risk of...
CONTEXT
Patients with primary adrenal insufficiency due to congenital adrenal hyperplasia (CAH) are at risk for adrenal crisis during infectious illnesses. Increased risk of infection including COVID-19 has been variably reported.
OBJECTIVE
To evaluate COVID-19 illness outcomes and stress dose practices in a large cohort of patients with CAH during the first two years of the pandemic and compare observations of COVID-19 infection in patients with CAH to the general USA population.
METHODS
Between March 2020 and November 2022, patients with CAH followed at the National Institutes of Health Clinical Center were queried about COVID-19 infection during their routine visits. Cases of COVID-19 were compared to controls. COVID-19 infection rates and symptoms were compared to general USA population data from the Centers for Disease Control and Prevention.
RESULTS
Of 168 patient visits, there were 54 (32%) cases of COVID-19 infection, and 15 (28%) were pediatric. Overall an association was found between acquiring COVID-19 and obesity (p=0.018), and adults acquiring COVID-19 were on lower doses of fludrocortisone (p=0.008). Fewer cases of COVID-19 infection were reported in those receiving hydrocortisone or modified-release hydrocortisone compared to longer acting glucocorticoids (p=0.0018). In our CAH population, the pattern of COVID-19 infection rates and COVID-related symptomatology were similar to those observed in the general USA population. Most patients with the presumed alpha variant reported anosmia and ageusia, while gastrointestinal symptoms were commonly reported during the delta and omicron waves. Stress dosing occurred in 30/54 cases, and 7 received parenteral hydrocortisone. Two hospitalizations occurred; one pediatric and one adult, both with co-morbidities. There were 5 emergency room visits and no reported deaths.
CONCLUSION
Patients with CAH with close follow-up do not appear to be at increased risk of acquiring COVID-19 or to have a more severe course of COVID-19 compared to the general USA population. Obesity may increase risk of acquiring COVID-19 in patients with CAH, and overall infection risk may be lower in those receiving short-acting and circadian glucocorticoid replacement therapy. Established age-appropriate guidelines for stress dosing during infectious illnesses should be used for patients with CAH and COVID-19. COVID-19 specific guidelines are not indicated. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT00250159.
Topics: Adult; Child; Humans; Adrenal Hyperplasia, Congenital; COVID-19; Glucocorticoids; Hydrocortisone; Obesity; SARS-CoV-2; United States; Case-Control Studies
PubMed: 38405151
DOI: 10.3389/fendo.2024.1348130 -
American Family Physician Mar 1999Congenital adrenal hyperplasia was once considered a rare inherited disorder with severe manifestations. Mild congenital adrenal hyperplasia, however, is common,... (Review)
Review
Congenital adrenal hyperplasia was once considered a rare inherited disorder with severe manifestations. Mild congenital adrenal hyperplasia, however, is common, affecting one in 100 to 1,000 persons in the United States and frequently eluding diagnosis. Both classic and nonclassic forms of the disease are caused by deficiencies in the adrenal enzymes that are used to synthesize glucocorticoids. The net result is increased production from the adrenal gland of cortisol precursors and androgens. Even mild congenital adrenal hyperplasia can result in life-threatening sinus or pulmonary infections, orthostatic syncope, shortened stature and severe acne. Women with mild congenital adrenal hyperplasia often present with hirsutism, oligomenorrhea or infertility. Congenital adrenal hyperplasia is diagnosed by demonstration of excess cortisol precursors in the serum during an adrenal corticotropic hormone challenge. Diagnosis of congenital adrenal hyerplasia in fetuses that are at risk for congenital adrenal hyperplasia can be determined using human leukocyte antigen haplotype or by demonstration of excess cortisol precursors in amniotic fluid. Treatment includes carefully monitored hormone replacement therapy. Recognition of the problem and timely replacement therapy can reduce morbidity and enhance quality of life in patients that are affected by congenital adrenal hyperplasia.
Topics: 17-alpha-Hydroxyprogesterone; Adrenal Hyperplasia, Congenital; Adult; Child; Diagnosis, Differential; Humans; Patient Education as Topic; Severity of Illness Index; Steroid 11-beta-Hydroxylase; Steroid 21-Hydroxylase; Teaching Materials
PubMed: 10088875
DOI: No ID Found -
Frontiers in Endocrinology 2024Prenatal-onset androgen excess leads to abnormal sexual development in 46,XX individuals. This androgen excess can be caused endogenously by the adrenals or gonads or by... (Review)
Review
Prenatal-onset androgen excess leads to abnormal sexual development in 46,XX individuals. This androgen excess can be caused endogenously by the adrenals or gonads or by exposure to exogenous androgens. The most common cause of 46,XX disorders/differences in sex development (DSD) is congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, comprising >90% of 46,XX DSD cases. Deficiencies of 11β-hydroxylase, 3β-hydroxysteroid dehydrogenase, and P450-oxidoreductase (POR) are rare types of CAH, resulting in 46,XX DSD. In all CAH forms, patients have normal ovarian development. The molecular genetic causes of 46,XX DSD, besides CAH, are uncommon. These etiologies include primary glucocorticoid resistance (PGCR) and aromatase deficiency with normal ovarian development. Additionally, 46,XX gonads can differentiate into testes, causing 46,XX testicular (T) DSD or a coexistence of ovarian and testicular tissue, defined as 46,XX ovotesticular (OT)-DSD. PGCR is caused by inactivating variants in , resulting in glucocorticoid insensitivity and the signs of mineralocorticoid and androgen excess. Pathogenic variants in the gene lead to aromatase deficiency, causing androgen excess. Many genes are involved in the mechanisms of gonadal development, and genes associated with 46,XX T/OT-DSD include translocations of the ; copy number variants in , , , , , and , and sequence variants in , , , , , , and . Progress in cytogenetic and molecular genetic techniques has significantly improved our understanding of the etiology of non-CAH 46,XX DSD. Nonetheless, uncertainties about gonadal function and gender outcomes may make the management of these conditions challenging. This review explores the intricate landscape of diagnosing and managing these conditions, shedding light on the unique aspects that distinguish them from other types of DSD.
Topics: Humans; Adrenal Hyperplasia, Congenital; 46, XX Disorders of Sex Development; Female; Male; Disorders of Sex Development
PubMed: 38812815
DOI: 10.3389/fendo.2024.1354759 -
BMJ Open Sep 2022The 'DSD Pathways' study was initiated to assess health status and patterns of care among people enrolled in large integrated healthcare systems and diagnosed with...
PURPOSE
The 'DSD Pathways' study was initiated to assess health status and patterns of care among people enrolled in large integrated healthcare systems and diagnosed with conditions comprising the broad category of disorders (differences) of sex development (DSD). The objectives of this communication are to describe methods of cohort ascertainment for two specific DSD conditions-classic congenital adrenal hyperplasia with 46,XX karyotype (46,XX CAH) and complete androgen insensitivity syndrome (CAIS).
PARTICIPANTS
Using electronic health records we developed an algorithm that combined diagnostic codes, clinical notes, laboratory data and pharmacy records to assign each cohort candidate a 'strength-of-evidence' score supporting the diagnosis of interest. A sample of cohort candidates underwent a review of the full medical record to determine the score cutoffs for final cohort validation.
FINDINGS TO DATE
Among 5404 classic 46,XX CAH cohort candidates the strength-of-evidence scores ranged between 0 and 10. Based on sample validation, the eligibility cut-off for full review was set at the strength-of-evidence score of ≥7 among children under the age of 8 years and ≥8 among older cohort candidates. The final validation of all cohort candidates who met the cut-off criteria identified 115 persons with classic 46,XX CAH. The strength-of-evidence scores among 648 CAIS cohort candidates ranged from 2 to 10. There were no confirmed CAIS cases among cohort candidates with scores <6. The in-depth medical record review for candidates with scores ≥6 identified 61 confirmed cases of CAIS.
FUTURE PLANS
As the first cohort of this type, the DSD Pathways study is well-positioned to fill existing knowledge gaps related to management and outcomes in this heterogeneous population. Analyses will examine diagnostic and referral patterns, adherence to care recommendations and physical and mental health morbidities examined through comparisons of DSD and reference populations and analyses of health status across DSD categories.
Topics: Adrenal Hyperplasia, Congenital; Androgen-Insensitivity Syndrome; Child; Cohort Studies; Health Status; Humans; Male; Sexual Development
PubMed: 36130763
DOI: 10.1136/bmjopen-2022-063409 -
Annals of Internal Medicine Feb 2002Congenital adrenal hyperplasia describes a group of inherited autosomal recessive disorders characterized by an enzymatic defect in cortisol biosynthesis, compensatory... (Review)
Review
Congenital adrenal hyperplasia describes a group of inherited autosomal recessive disorders characterized by an enzymatic defect in cortisol biosynthesis, compensatory increases in corticotropin secretion, and adrenocortical hyperplasia. 21-Hydroxylase deficiency is responsible for more than 95% of cases and is one of the most common known autosomal recessive disorders. The classic or severe type presents in the newborn period or early childhood with virilization and adrenal insufficiency, with or without salt loss; the mild or nonclassic form presents in late childhood or early adulthood with mild hyperandrogenism and is an important cause of masculinization and infertility in women. This wide range of phenotypic expression is mostly explained by genetic variation, although genotype-phenotype discrepancies have been described. Reproductive, metabolic, and other comorbid conditions, including risk for tumors, are currently under investigation in both forms of the disease. A high proportion of patients with adrenal incidentalomas may be homozygous or heterozygous for 21-hydroxylase deficiency. Women with congenital adrenal hyperplasia often develop the polycystic ovary syndrome. Ectopic adrenal rest tissue is often found in the testes of men with congenital adrenal hyperplasia; characteristic clinical and radiologic findings help differentiate this tissue from other tumors. Levels of corticotropin-releasing hormone are elevated in patients with depression and anxiety and are expected to be elevated in patients with congenital adrenal hyperplasia; it is unknown whether patients with 21-hydroxylase deficiency have an increased incidence of these psychiatric disorders. Abnormalities in both the structure and function of the adrenal medulla have been shown in patients with classic congenital adrenal hyperplasia, and the degree of adrenomedullary impairment may be a biomarker of disease severity. The 21-hydroxylase-deficient mouse has provided a useful model with which to examine disease mechanisms and test new therapeutic interventions in classic disease, including gene therapy. Treatment of this condition is intended to reduce excessive corticotropin secretion and replace both glucocorticoids and mineralocorticoids. However, clinical management is often complicated by inadequately treated hyperandrogenism, iatrogenic hypercortisolism, or both. New treatment approaches currently under investigation include combination therapy to block androgen action and inhibit estrogen production, and bilateral adrenalectomy in the most severely affected patients. Other approaches, which are in a preclinical stage of investigation, include treatment with a corticotropin-releasing hormone antagonist and gene therapy.
Topics: Adrenal Hyperplasia, Congenital; Animals; Female; Humans; Male; Models, Animal; Steroid 21-Hydroxylase
PubMed: 11848730
DOI: 10.7326/0003-4819-136-4-200202190-00012 -
Archives of Endocrinology and Metabolism Jan 2023Herein, we compared ambulatory blood pressure (ABP) between young adults with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase enzyme (21OHase) deficiency and...
OBJECTIVE
Herein, we compared ambulatory blood pressure (ABP) between young adults with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase enzyme (21OHase) deficiency and a control group. Additionally, we analyzed correlations between the glucocorticoid dose and androgen levels and ABP parameters.
SUBJECTS AND METHODS
This case-control study included 18 patients (6 males and 12 females) and 19 controls (8 males and 11 females) matched by age (18-31 years). ABP monitoring was used to estimate blood pressure (BP) over a 24-h period.
RESULTS
No difference was noted between patients and controls in terms of systolic BP (males, 115.5 ± 5.6 117.0 ± 9.3, = 0.733; and females, 106.4 ± 7.9 108.4 ± 7.6, = 0.556, respectively) and diastolic BP during 24 h (males, 62.8 ± 7.5 66.2 ± 5.6, = 0.349; and females, 62.7 ± 4.9 62.3 ± 4.9, = 0.818, respectively). Systolic and diastolic BP and pulse pressure during daytime and nocturnal periods were similar between patients and controls. Furthermore, no differences were detected in the percentage of load and impaired nocturnal dipping of systolic and diastolic BP between patients and controls during the 24-h period. Additionally, the glucocorticoid dose (varying between = -0.24 to 0.13, > 0.05) and androgens levels (varying between = 0.01 to 0.14, > 0.05) were not associated with ABP parameters.
CONCLUSION
No signs of an elevated risk for hypertension were observed based on ABP monitoring in young adults with CAH attributed to 21OHase deficiency undergoing glucocorticoid replacement therapy.
Topics: Adolescent; Adult; Female; Humans; Male; Young Adult; Adrenal Hyperplasia, Congenital; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Case-Control Studies; Glucocorticoids; Hypertension; Steroid 21-Hydroxylase
PubMed: 35929901
DOI: 10.20945/2359-3997000000504