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Endocrine Oct 2021The association between glucocorticoid replacement therapy for adrenal insufficiency (AI) and osteoporosis is unclear. Fracture is a major cause of morbidity in patients... (Meta-Analysis)
Meta-Analysis
PURPOSE
The association between glucocorticoid replacement therapy for adrenal insufficiency (AI) and osteoporosis is unclear. Fracture is a major cause of morbidity in patients with osteoporosis. This study aims to determine if patients on glucocorticoid replacement therapy for AI have an increased rate of fractures compared to the general population.
METHODS
We included all studies with adult patients receiving glucocorticoid replacement therapy for either congenital adrenal hyperplasia (CAH), primary adrenal insufficiency (PAI), or secondary adrenal insufficiency (SAI). Studies without fracture data were excluded, as well as meeting abstracts. Studies with fractures but without a control group were eligible to be included in the systematic review but not in the meta-analysis. The primary outcome was the number of fractures, which was further differentiated into osteoporotic fractures. In addition, the glucocorticoid dose equivalents used were noted whenever possible.
RESULTS
Seventeen studies were included in the systematic review. Seven were used in the meta-analysis of any fracture and six were used for osteoporotic fracture. The reported fracture rate ranged between no fracture to 60.8% in the patient group and no fracture to 43.8% in the control group. The odds ratio (OR) for any fracture was 2.71 (95%CI: 1.36-5.43, P = 0.005) and for osteoporotic fracture 2.76 (95%CI: 2.39-3.19 P < 0.00001), favoring the control group.
CONCLUSIONS
Patients with AI on glucocorticoid replacement therapy have a higher rate of fractures compared to the control population.
Topics: Addison Disease; Adrenal Hyperplasia, Congenital; Adrenal Insufficiency; Adult; Fractures, Bone; Glucocorticoids; Hormone Replacement Therapy; Humans
PubMed: 33846948
DOI: 10.1007/s12020-021-02723-z -
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 Cochrane Database of Systematic... Mar 2020Congenital adrenal hyperplasia (CAH) is an autosomal recessive condition which leads to glucocorticoid deficiency and is the most common cause of adrenal insufficiency... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Congenital adrenal hyperplasia (CAH) is an autosomal recessive condition which leads to glucocorticoid deficiency and is the most common cause of adrenal insufficiency in children. In over 90% of cases, 21-hydroxylase enzyme deficiency is found which is caused by mutations in the 21-hydroxylase gene. Managing individuals with CAH due to 21-hydroxylase deficiency involves replacing glucocorticoids with oral glucocorticoids (including prednisolone and hydrocortisone), suppressing adrenocorticotrophic hormones and replacing mineralocorticoids to prevent salt wasting. During childhood, the main aims of treatment are to prevent adrenal crises and to achieve normal stature, optimal adult height and to undergo normal puberty. In adults, treatment aims to prevent adrenal crises, ensure normal fertility and to avoid the long-term consequences of glucocorticoid use. Current glucocorticoid treatment regimens can not optimally replicate the normal physiological cortisol level and over-treatment or under-treatment is often reported.
OBJECTIVES
To compare and determine the efficacy and safety of different glucocorticoid replacement regimens in the treatment of CAH due to 21-hydroxylase deficiency in children and adults.
SEARCH METHODS
We searched the Cochrane Inborn Errors of Metabolism Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews, and trial registries (ClinicalTrials.gov and WHO ICTRP). Date of last search of trials register: 24 June 2019.
SELECTION CRITERIA
Randomised controlled trials (RCTs) or quasi-RCTs comparing different glucocorticoid replacement regimens for treating CAH due to 21-hydroxylase deficiency in children and adults.
DATA COLLECTION AND ANALYSIS
The authors independently extracted and analysed the data from different interventions. They undertook the comparisons separately and used GRADE to assess the quality of the evidence.
MAIN RESULTS
Searches identified 1729 records with 43 records subject to further examination. After screening, we included five RCTs (six references) with a total of 101 participants and identified a further six ongoing RCTs. The number of participants in each trial varied from six to 44, with participants' ages ranging from 3.6 months to 21 years. Four trials were of cross-over design and one was of parallel design. Duration of treatment ranged from two weeks to six months per treatment arm with an overall follow-up between six and 12 months for all trials. Overall, we judged the quality of the trials to be at moderate to high risk of bias; with lack of methodological detail leading to unclear or high risk of bias judgements across many of the domains. All trials employed an oral glucocorticoid replacement therapy, but with different daily schedules and dose levels. Three trials compared different dose schedules of hydrocortisone (HC), one three-arm trial compared HC to prednisolone (PD) and dexamethasone (DXA) and one trial compared HC with fludrocortisone to PD with fludrocortisone. Due to the heterogeneity of the trials and the limited amount of evidence, we were unable to perform any meta-analyses. No trials reported on quality of life, prevention of adrenal crisis, presence of osteopenia, presence of testicular or ovarian adrenal rest tumours, subfertility or final adult height. Five trials (101 participants) reported androgen normalisation but using different measurements (very low-quality evidence for all measurements). Five trials reported 17 hydroxyprogesterone (17 OHP) levels, four trials reported androstenedione, three trials reported testosterone and one trial reported dehydroepiandrosterone sulphate (DHEAS). After four weeks, results from one trial (15 participants) showed a high morning dose of HC or a high evening dose made little or no difference in 17 OHP, testosterone, androstenedione and DHEAS. One trial (27 participants) found that HC and DXA treatment suppressed 17 OHP and androstenedione more than PD treatment after six weeks and a further trial (eight participants) reported no difference in 17 OHP between the five different dosing schedules of HC at between four and six weeks. One trial (44 participants) comparing HC and PD found no differences in the values of 17 OHP, androstenedione and testosterone at one year. One trial (26 participants) of HC versus HC plus fludrocortisone found that at six months 17 OHP and androstenedione levels were more suppressed on HC alone, but there were no differences noted in testosterone levels. While no trials reported on absolute final adult height, we reported some surrogate markers. Three trials reported on growth and bone maturation and two trials reported on height velocity. One trial found height velocity was reduced at six months in 26 participants given once daily HC 25 mg/m²/day compared to once daily HC 15 mg/m²/day (both groups also received fludrocortisone 0.1 mg/day), but as the quality of the evidence was very low we are unsure whether the variation in HC dose caused the difference. There were no differences noted in growth hormone or IGF1 levels. The results from another trial (44 participants) indicate no difference in growth velocity between HC and PD at one year (very low-quality evidence), but this trial did report that once daily PD treatment may lead to better control of bone maturation compared to HC in prepubertal children and that the absolute change in bone age/chronological age ratio was higher in the HC group compared to the PD group.
AUTHORS' CONCLUSIONS
There are currently limited trials comparing the efficacy and safety of different glucocorticoid replacement regimens for treating 21-hydroxylase deficiency CAH in children and adults and we were unable to draw any firm conclusions based on the evidence that was presented in the included trials. No trials included long-term outcomes such as quality of life, prevention of adrenal crisis, presence of osteopenia, presence of testicular or ovarian adrenal rest tumours, subfertility and final adult height. There were no trials examining a modified-release formulation of HC or use of 24-hour circadian continuous subcutaneous infusion of hydrocortisone. As a consequence, uncertainty remains about the most effective form of glucocorticoid replacement therapy in CAH for children and adults. Future trials should include both children and adults with CAH. A longer duration of follow-up is required to monitor biochemical and clinical outcomes.
Topics: Adolescent; Adrenal Hyperplasia, Congenital; Child; Child, Preschool; Dexamethasone; Glucocorticoids; Humans; Infant; Prednisolone; Quality of Life; Randomized Controlled Trials as Topic; Young Adult
PubMed: 32190901
DOI: 10.1002/14651858.CD012517.pub2 -
Revista Da Associacao Medica Brasileira... Dec 2020There is no pooled information about pelvic floor parameters (muscle assessment, disorders) of women with gynecologicaL endocrinopathies (eg. polycystic ovary syndrome,...
There is no pooled information about pelvic floor parameters (muscle assessment, disorders) of women with gynecologicaL endocrinopathies (eg. polycystic ovary syndrome, congenital adrenal hyperplasia, premature ovarian insufficiency). Given that, a systematic review was performed on the Pubmed, Scopus, Google Scholar, Scielo and PEDro databases regarding the main gynecological endocrinopathies [polycystic ovary syndrome (PCOS), premature ovarian insufficiency (POI), congenital adrenal hyperplasia (CAH) and hyperprolactinemia (HPL)] since their inception to April 2020. Data quality assessment was made by the Newcastle-Ottawa Scale (NOS) adapted for cross-sectional studies. A total of 4,272 results were retrieved from all databases. After excluding duplicate results and screening by title and abstract, nine studies were selected for quantitative analysis. Seven studies were performed with women with PCOS and two studies with POI. Women with PCOS presented a higher prevalence of urinary incontinence (UI) among obese women, a higher thickness of the levator ani muscle, and higher levels of muscle activity measured by surface electromyograph when compared to the control women. Regarding POI, there was no association with UI, FI, and POP. NOS found that the quality assessment for these selected studies ranged from 5 to 8. We concluded that higher pelvic muscle activity and volume were found in women with PCOS, with further studies needed to confirm this data. Literature was scant about POI, CAH, and HPL.
Topics: Cross-Sectional Studies; Female; Humans; Pelvic Floor; Polycystic Ovary Syndrome; Prevalence; Urinary Incontinence
PubMed: 33331587
DOI: 10.1590/1806-9282.66.12.1742 -
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