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Clinical Endocrinology May 2024Lipoid congenital adrenal hyperplasia (LCAH) is caused by mutations in STAR. A systematic review of phenotype-genotype correlation and data on testicular histology in...
OBJECTIVE
Lipoid congenital adrenal hyperplasia (LCAH) is caused by mutations in STAR. A systematic review of phenotype-genotype correlation and data on testicular histology in LCAH patients is unavailable. We aim to describe our experience and provide phenotype-genotype correlation. DESIGN, PATIENTS AND MEASUREMENTS: Retrospective review of three genetically proven LCAH patients from our centre and per-patient data analysis from a systematic review of 292 probands. The phenotypic subgroups of 46,XY were Group A (typical female genitalia), Group B (atypical genitalia) and Group C (typical male genitalia).
RESULTS
We report three new LCAH probands from India, all diagnosed post-infancy with preserved gonadal function and one novel variant. The systematic review reports 46,XY to 46,XX LCAH ratio of 1.1 (155:140). Patients with 46,XY LCAH in Group A were diagnosed in infancy (116/117) and had higher mineralocorticoid involvement than Group C (96.4% vs. 75%, p = 0.035), whereas Group C had preserved gonadal function. Hyperplastic adrenals are noted in ~60% of LCAH diagnosed with primary adrenal insufficiency in infancy. There was no report of gonadal germ cell cancer and rare reports of germ cell neoplasia in situ in adolescents, especially with intraabdominal gonads. Two-thirds of LCAH probands were East-Asian and 11/16 regional recurrent variants were from East Asia. There was minimal overlap between variants in Groups A (n = 55), B (n = 9) and C (n = 8). All nonsense and frameshift and most of the splice-site variants and deletion/insertions were present in Group A.
CONCLUSIONS
We report three new cases of LCAH from India. We propose a phenotype-derived genotypic classification of reported STAR variants in 46,XY LCAH.
Topics: Adolescent; Humans; Male; Female; Adrenal Hyperplasia, Congenital; Mutation; Phosphoproteins; Phenotype; Genotype; Disorder of Sex Development, 46,XY
PubMed: 38368602
DOI: 10.1111/cen.15032 -
The Journal of Clinical Endocrinology... May 2024To conduct a systematic review (SR) and meta-analysis (MA) on health-related quality-of-life (QoL) and associated factors among children/adolescents with congenital... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To conduct a systematic review (SR) and meta-analysis (MA) on health-related quality-of-life (QoL) and associated factors among children/adolescents with congenital adrenal hyperplasia (CAH).
METHOD
Following registration in the PROSPERO International Prospective Register of Systematic Reviews(reg no: CRD42022313389), Google Scholar, PubMed, LILACS, Cochrane, and Scopus databases were searched up to March 5, 2022, using predefined search strategy/MESH terms to identify original studies describing/assessing self-reported/parent-reported health-related QoL in patients with CAH ≤21 years. Methodological quality was assessed by Newcastle-Ottawa Quality Assessment Scale (NOS), and heterogeneity by I2 statistics. MA assessed mean difference (MD) in QoL between children/adolescents with CAH and healthy children/adolescents.
RESULTS
Among 1308 publications, the 12 studies eligible for the SR (CAH n = 781) showed NOS scales of 3 to 7/9, and the 6 eligible for MA (CAH n = 227) showed moderate-considerable heterogeneity. MA showed that parent-reported psychosocial QoL (MD 9.9 [-12.6,7.3], P ≤ .001) {consisting of school (MD 7.4[-12.2, -2.5], P = .003), emotional (MD 5.6 [-10.2, -0.9], P = .02) and social domains (MD 4.3 [-8.1, -0.5], P = .03), and self-reported school domain QoL (MD 8.5 [-15.9, -1.2], P = .02) was lower in children/adolescents with CAH while parent-reported and self-reported physical QoL were similar to controls.Factors associated with lower QoL among children/ adolescents with CAH included poor disease control, poor medication compliance, and complications including hyperpigmentation, virilization, hypertension, hospital admission, and urinary incontinence.
CONCLUSION
Based on available data, children/adolescents with CAH had preserved physical QoL but impaired psychosocial QoL, especially in the school domain. Factors associated with lower QoL included poor disease control and disease/treatment-related complications. There is a need for further high-quality research that investigates the relationship between disease control, provision of psychosocial support, and improvement in QoL in children/adolescents with CAH.
Topics: Humans; Quality of Life; Adrenal Hyperplasia, Congenital; Child; Adolescent
PubMed: 38332657
DOI: 10.1210/clinem/dgae068 -
Frontiers in Endocrinology 2023[This corrects the article DOI: 10.3389/fendo.2022.982953.].
[This corrects the article DOI: 10.3389/fendo.2022.982953.].
PubMed: 37842302
DOI: 10.3389/fendo.2023.1269711 -
Frontiers in Endocrinology 2023[This corrects the article DOI: 10.3389/fendo.2022.982953.].
[This corrects the article DOI: 10.3389/fendo.2022.982953.].
PubMed: 37842296
DOI: 10.3389/fendo.2023.1276185 -
Hormone Research in Paediatrics 2024There are increased calls to address psychosocial needs among individuals with classical congenital adrenal hyperplasia (CAH). However, cross-cultural disparities exist...
INTRODUCTION
There are increased calls to address psychosocial needs among individuals with classical congenital adrenal hyperplasia (CAH). However, cross-cultural disparities exist in treatment practices and psychosocial outcomes that impact the generalizability of evidence-based recommendations. To date, this disparity has not been quantified. The present scoping review uses a dual approach to contrast rates of CAH diagnosis with CAH psychosocial research rates across countries.
METHODS
Six electronic database searches were conducted for: (1) CAH incidence/birth/prevalence rates; and (2) psychosocial research with affected individuals and their families. Two authors reviewed each abstract for inclusion criteria.
RESULTS
Sixty-eight and 93 full-text articles, respectively, were evaluated for incidence and country. The countries/regions with the highest reported CAH rates are Thailand, Ghana, and India. Those with the greatest portion of psychosocial publications are the USA, Germany, and the UK.
CONCLUSION
A discrepancy exists between those countries with the highest CAH rates and those publishing psychosocial research. Specifically, increased rates of CAH are seen in non-Western countries/regions, whereas most psychosocial research arises out of Western Europe and the USA. Due to cultural differences between these regions, increased global collaboration is needed to both inform psychosocial research and translate findings in ways that are representative worldwide.
Topics: Humans; Adrenal Hyperplasia, Congenital; Cross-Cultural Comparison; Germany; Incidence; Europe
PubMed: 37552959
DOI: 10.1159/000531167 -
Archives of Endocrinology and Metabolism Mar 2023Congenital adrenal hyperplasia due to 21-hydroxylase deficiency is an autosomal recessive disorder caused by gene mutations, and its molecular diagnosis is widely used... (Review)
Review
Congenital adrenal hyperplasia due to 21-hydroxylase deficiency is an autosomal recessive disorder caused by gene mutations, and its molecular diagnosis is widely used in clinical practice to confirm the hormonal diagnosis. Hence, considering the miscegenation of the Brazilian population, it is important to determine a mutations panel to optimise the molecular diagnosis. The objective was to review the mutations' distribution among Brazilian regions. Two reviewers screened Brazilian papers up to February 2020 in five databases. The pair-wise comparison test and Holm method were used in the statistical analysis. Nine studies were selected, comprising 769 patients from all regions. Low proportion of males and salt-wasters was identified in the North and Northeast regions, although without significant difference. Large gene rearrangements also had a low frequency, except in the Center-West and South regions (p < 0.05). The most frequent mutations were p.I172N, IVS2-13A/C>G, p.V281L and p.Q318X, and significant differences in their distributions were found: p.V281L was more frequent in the Southeast and p.Q318X in the Center-West and Northeast regions (p < 0.05). Thirteen new mutations were identified in 3.8%-15.2% of alleles, being more prevalent in the North region, and six mutations presented a founder effect gene. Genotype-phenotype correlation varied from 75.9%-97.3% among regions. The low prevalence of the salt-wasting form, affected males and severe mutations in some regions indicated pitfalls in the clinical diagnosis. The good genotype-phenotype correlation confirms the usefulness of molecular diagnosis; however, the Brazilian population also presents significant prevalence of novel mutations, which should be considered for a molecular panel.
Topics: Male; Humans; Adrenal Hyperplasia, Congenital; Steroid 21-Hydroxylase; Brazil; Genotype; Phenotype; Mutation
PubMed: 37011374
DOI: 10.20945/2359-3997000000593 -
The Journal of Clinical Endocrinology... Aug 2023Adrenal medullary hyperplasia (AMH) is a rare, incompletely described disorder of the adrenal medulla that is associated with catecholamine excess. (Meta-Analysis)
Meta-Analysis
CONTEXT
Adrenal medullary hyperplasia (AMH) is a rare, incompletely described disorder of the adrenal medulla that is associated with catecholamine excess.
OBJECTIVE
To increase knowledge about AMH by reviewing the reported cases of this disorder.
DESIGN
Systematic review and meta-analysis of the genotype/phenotype relationship in all reported cases of AMH.
SETTING
Literature review and analysis.
PATIENTS OR OTHER PARTICIPANTS
All cases of AMH published to date.
MAIN OUTCOME MEASURE(S)
Characteristics of AMH cases and genotype-phenotype relationships.
RESULTS
A total of 66 patients, median age of 48 years, were identified from 29 reports. More than one-half were male (n = 39, 59%). The majority had unilateral (73%, n = 48) disease; 71% (n = 47) were sporadic and 23% (n = 15) were associated with the MEN2. Most (91%, n = 60) displayed signs and symptoms of excess catecholamine secretion, particularly hypertension. Elevated catecholamine concentrations (86%, n = 57) and adrenal abnormalities on imaging were common (80%, n = 53). More than one-half (58%, n = 38) had concurrent tumors: pheochromocytoma (42%, n = 16/38); medullary thyroid cancer (24%, n = 9/38); and adrenocortical adenoma (29%, n = 11/38). Most (88%, n = 58) underwent adrenalectomy with 45/58 achieving symptom resolution. Adrenalectomy was less common in patients under 40 years and those with bilateral disease (both P < .05).
CONCLUSION
AMH may be sporadic or associated with MEN2, most have catecholamine excess and imaging abnormalities. Unilateral involvement is more common. Most reported patients have been treated with adrenalectomy, which is usually curative with regard to catecholamine hypersecretion.
Topics: Male; Humans; Female; Hyperplasia; Adrenal Gland Neoplasms; Pheochromocytoma; Adrenal Medulla; Adrenalectomy; Catecholamines
PubMed: 36896586
DOI: 10.1210/clinem/dgad121 -
Frontiers in Endocrinology 2022Many patients with congenital adrenal hyperplasia (CAH) refrain from seeking pregnancy, suffer from infertility or worry about pregnancy complications, mainly due to... (Meta-Analysis)
Meta-Analysis
UNLABELLED
Many patients with congenital adrenal hyperplasia (CAH) refrain from seeking pregnancy, suffer from infertility or worry about pregnancy complications, mainly due to genitalia abnormalities, anovulation, unreceptive endometrium and metabolic disturbances. Despite those challenges, many live births have been reported. In this systematic review, we focused on the key to successful assisted reproduction strategies and the potential pregnancy complications. We did a systematic literature search of Pubmed, Medline and Scopus for articles reporting successful pregnancies in CAH other than 21-hydroxylase deficiency, and found 25 studies reporting 39 pregnancies covering deficiency in steroidogenic acute regulatory protein, 17α-hydroxylase/17,20-lyase, 11β-hydroxylase, P450 oxidoreductase, cytochrome b5 and 3β-hydroxysteroid dehydrogenase. We summarized various clinical manifestations and tailored reproduction strategy for each subtype. Furthermore, a meta-analysis was performed to evaluate the pregnancy complications of CAH patients. A total of 19 cross-sectional or cohort studies involving 1311 pregnancies of classic and non-classic CAH patients were included. Surprisingly, as high as 5.5% (95% CI 2.3%-9.7%) of pregnancies were electively aborted, and the risk was significantly higher in those studies with a larger proportion of classic CAH than those with only non-classical patients (8.43% (4.1%-13.81%) VS 3.75%(1.2%-7.49%)), which called for better family planning. Pooled incidence of miscarriage was 18.2% (13.4%-23.4%) with a relative risk (RR) of 1.86 (1.27-2.72) compared to control. Glucocorticoid treatment in non-classical CAH patients significantly lowered the miscarriage rate when compared to the untreated group (RR 0.25 (0.13-0.47)). CAH patients were also more susceptible to gestational diabetes mellitus, with a prevalence of 7.3% (2.4%-14.1%) and a RR 2.57 (1.29-5.12). However, risks of preeclampsia, preterm birth and small for gestational age were not significantly different. 67.8% (50.8%-86.9%) CAH patients underwent Cesarean delivery, 3.86 (1.66-8.97) times the risk of the control group. These results showed that fertility is possible for CAH patients but special care was necessary when planning, seeking and during pregnancy.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=342642, CRD42022342642.
Topics: Abortion, Spontaneous; Adrenal Hyperplasia, Congenital; Cross-Sectional Studies; Cytochromes b5; Female; Glucocorticoids; Humans; Hydroxysteroid Dehydrogenases; Infant, Newborn; Pregnancy; Pregnancy Complications; Premature Birth; Reproduction; Steroid 17-alpha-Hydroxylase
PubMed: 36120452
DOI: 10.3389/fendo.2022.982953 -
Hormone Research in Paediatrics 2023Congenital adrenal hyperplasia (CAH) is an autosomal recessive genetic disorder that causes defects in the adrenal cortex enzymes that impair the biosynthesis of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Congenital adrenal hyperplasia (CAH) is an autosomal recessive genetic disorder that causes defects in the adrenal cortex enzymes that impair the biosynthesis of cortisol, aldosterone, or both. The most common type is the 21-hydroxylase enzyme deficiency in approximately 95% of cases resulting from CYP21A2 gene mutations or deletions.
OBJECTIVES
This study aimed to systematically review the national differences in CAH incidence and analyze the pooled results to determine disparities and whether ethnicity can predispose people to develop CAH.
METHODS
PubMed, Scopus, and LILACS were used to achieve results until June 22, 2018. Study eligibility criteria included availability of full-text; English, Spanish, or Portuguese languages; incidence or number of new cases; and number of live births or sample population. Only the classic CAH type (salt-wasting and simple-virilizing) was considered, and no distinction was made between the enzyme deficiency types.
RESULTS
This study summarizes the findings of 58 studies and 31 countries (from 1969 to 2017), in which the overall CAH incidence was 1:9,498 (95% confidence interval: 1:9,089, 1:9,945). Countries from the Eastern Mediterranean and Southeast Asia revealed the highest CAH incidence. The lowest incidence was reported in countries of the Western Pacific of Asia. No remarkable difference was observed in the Hispanics/Latino and White groups. However, they manifested a higher incidence of CAH than people identified as Black or of African descent. Published studies on CAH incidence in the sub-Saharan African region and parts of Europe were insufficient.
CONCLUSIONS
This study highlights the at-risk population for CAH and regions that need monitoring for CAH. The highest CAH incidence could be attributed to higher consanguinity, less genetic diversity, or other genetic causes since CAH is an inherited genetic disorder. Cultural practices in some places regarding consanguineous unions or geographic isolation may directly affect the incidence. Newborn screening for CAH may be unavailable in many developing countries, thereby affecting the actual CAH incidence. Therefore, healthcare workers should be trained to recognize CAH at an early stage to reduce its complications and mortality.
Topics: Infant, Newborn; Humans; Adrenal Hyperplasia, Congenital; Neonatal Screening; Adrenal Cortex; Mutation; Steroid 21-Hydroxylase
PubMed: 35973409
DOI: 10.1159/000526401 -
Egyptian Journal of Forensic Sciences 2022Little is known how COVID-19 is affecting children. Autopsies help gain an understanding of the pathophysiology of new and developing diseases. Numerous post-mortem...
BACKGROUND
Little is known how COVID-19 is affecting children. Autopsies help gain an understanding of the pathophysiology of new and developing diseases. Numerous post-mortem studies had been conducted in adults with COVID-19, but few in children. Thereby, this systematic review aims to investigate the autopsy findings from pediatric COVID-19 patients.
RESULTS
There were a total of 15 patients from eight studies. COVID-19 mainly affects the heart and lungs. Pathology findings from the heart of COVID-19 pediatric patients include diffuse inflammatory infiltrate, myocarditis, cardiomyocyte necrosis, pericarditis, and interstitial edema. Histopathology abnormalities observed in the lungs are diffuse alveolar damage, cytopathic changes, thrombi in arterioles and septal capillaries, lung congestion, focal acute hemorrhage and edema, focal exudative changes, and mild pneumocyte hyperplasia. In addition, pathological findings from other organs, such as the liver, kidney, brain, bone marrow, lymph node, skin, spleen, muscle, colon, parotid gland, and adrenal of COVID-19 pediatric patients are also included in this review.
CONCLUSION
Cardiomyocyte necrosis, interstitial edema, lung congestion, and diffuse alveolar damage are the most significant pathologic findings of the heart and lung in pediatric COVID-19 patients. More studies are needed to elucidate the pathophysiology of SARS-CoV-2 in autopsy findings and to determine the exact cause of death since it could be related to COVID-19 or other comorbidities.
PubMed: 35855892
DOI: 10.1186/s41935-022-00288-0