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International Heart Journal 2024
Topics: Humans; Adrenal Hyperplasia, Congenital; Hyperplasia
PubMed: 38296561
DOI: 10.1536/ihj.23-647 -
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 2023The standard treatment for congenital adrenal hyperplasia (CAH) in children is still hydrocortisone. Improved strategies for timing of the dose during the day and the... (Review)
Review
BACKGROUND
The standard treatment for congenital adrenal hyperplasia (CAH) in children is still hydrocortisone. Improved strategies for timing of the dose during the day and the dose per square meter body surface area used in children of different ages and developmental phases have improved the situation and outcome for the patients. Neonatal screening enables an earlier diagnosis and initiation of treatment, prevents from adrenal crisis, and improves growth and development also for children with the less severe forms of CAH.
SUMMARY
This review describes the current treatment strategies for children with CAH and discusses some potential treatment options that have been developed with the primary aim to decrease the adrenal androgen production. Novel modified release glucocorticoid therapies are also discussed.
KEY MESSAGES
The long-term effects of the new adjunct therapies are unknown, and some are not suitable for use in children and adolescents. The effects of the new therapies on bone mineral density, gonadal functions, and long-term cognitive development are yet to be assessed. It is not known what levels of adrenal androgens are optimal for normal growth, puberty, and bone health. The basis of using glucocorticoids and mineralocorticoids in the treatment of CAH remains, and in some individuals, it may be beneficial to add therapies to reduce the androgen load during certain life stages.
Topics: Infant, Newborn; Adolescent; Child; Humans; Adrenal Hyperplasia, Congenital; Androgens; Glucocorticoids; Hydrocortisone; Mineralocorticoids
PubMed: 35086098
DOI: 10.1159/000522260 -
Proceedings of the National Academy of... Feb 2013Over the last two decades, we have extensively studied the genetics of congenital adrenal hyperplasia caused by 21-hydroxylase deficiency (CAH) and have performed 8,290...
Over the last two decades, we have extensively studied the genetics of congenital adrenal hyperplasia caused by 21-hydroxylase deficiency (CAH) and have performed 8,290 DNA analyses of the CYP21A2 gene on members of 4,857 families at risk for CAH--the largest cohort of CAH patients reported to date. Of the families studied, 1,507 had at least one member affected with one of three known forms of CAH, namely salt wasting, simple virilizing, or nonclassical CAH. Here, we report the genotype and phenotype of each affected patient, as well as the ethnic group and country of origin for each patient. We showed that 21 of 45 genotypes yielded a phenotypic correlation in our patient cohort. In particular, contrary to what is generally reported in the literature, we found that certain mutations, for example, the P30L, I2G, and I172N mutations, yielded different CAH phenotypes. In salt wasting and nonclassical CAH, a phenotype can be attributed to a genotype; however, in simple virilizing CAH, we observe wide phenotypic variability, particularly with the exon 4 I172N mutation. Finally, there was a high frequency of homozygous I2G and V281L mutations in Middle Eastern and Ashkenazi Jewish populations, respectively. By identifying the predominant phenotype for a given genotype, these findings should assist physicians in prenatal diagnosis and genetic counseling of parents who are at risk for having a child with CAH.
Topics: Adrenal Hyperplasia, Congenital; Cohort Studies; Ethnicity; Gene Deletion; Gene Frequency; Genotype; Humans; Models, Genetic; Mutation; New York; Phenotype; Steroid 21-Hydroxylase
PubMed: 23359698
DOI: 10.1073/pnas.1300057110 -
Journal of Clinical Research in... Nov 2023Patients with congenital adrenal hyperplasia (CAH) require lifelong therapy with glucocorticoids to suppress androgen excess and substitute for deficient cortisol. An... (Observational Study)
Observational Study
OBJECTIVE
Patients with congenital adrenal hyperplasia (CAH) require lifelong therapy with glucocorticoids to suppress androgen excess and substitute for deficient cortisol. An important aspect of care is the prevention of metabolic sequelae. In infants, potentially lethal nocturnal hypoglycaemia has been described. In adolescence, visceral obesity, hypertension, hyperinsulinism and insulin resistance are reported. To date, systematic studies of glucose profiles in this age group with CAH are lacking.
METHODS
This was a monocentric, prospective, observational study to determine the glucose profiles under different treatment regimens in a cohort of young patients with CAH. The continuous glucose monitoring device used was the latest generation FreeStyle Libre 3 sensor in blinded mode. Therapeutic and auxological data were obtained.
RESULTS
The cohort consisted of 10 children/adolescents with a mean age of 11 years. Three patients exhibited morning fasting hyperglycaemia. Overall, 6 out of 10 patients had unacceptably few total values in the desired range of 70-120 mg/dL. Tissue glucose values above 140-180 mg/dL were found in 5 of 10 patients. The mean value for glycosylated haemoglobin for the cohort was of 5.8%. All pubertal adolescents with reverse circadian regimens had significantly higher glucose levels at night. Two adolescents showed asymptomatic nocturnal hypoglycaemia.
CONCLUSION
Most of the patients exhibited abnormalities in glucose metabolism. Two-thirds had elevated total 24h glucose values outside the age-appropriate reference values. Thus, this aspect may need to be addressed early in life by adjusting the doses, treatment regimen or dietary measures. Consequently, reverse circadian therapy regimens should be critically indicated and closely monitored due to the potential metabolic risk.
Topics: Infant; Humans; Child; Adolescent; Adrenal Hyperplasia, Congenital; Blood Glucose; Prospective Studies; Blood Glucose Self-Monitoring; Hydrocortisone; Hypoglycemia; Glucose
PubMed: 37218136
DOI: 10.4274/jcrpe.galenos.2023.2023-3-5 -
Fertility and Sterility Jan 2019Couples at risk for autosomal recessive congenital adrenal hyperplasia often request anticipatory guidance and genetic counseling. Initially, hormones in amniotic fluid... (Review)
Review
Couples at risk for autosomal recessive congenital adrenal hyperplasia often request anticipatory guidance and genetic counseling. Initially, hormones in amniotic fluid were measured to distinguish affected female fetuses from unaffected fetuses. With the molecular era, more-targeted approaches became possible. Prenatal genetic diagnosis via amniocentesis or chorionic villus sampling was used to determine the need for continuing fetal therapy (dexamethasone), allowing cessation if the fetus was unaffected. Newer methods now allow diagnosis earlier in gestation, further shortening the treatment time for unaffected female fetuses who will not develop genital ambiguity. Preimplantation genetic testing permits transfer only of an unaffected female or male fetus. Analysis of maternal cell-free DNA based on quantitative differences in the amount of allele parental DNA permits affected pregnancies to be differentiated from unaffected pregnancies.
Topics: Adrenal Hyperplasia, Congenital; Embryo Transfer; Female; Genetic Counseling; Genetic Testing; Humans; Male; Pregnancy; Preimplantation Diagnosis; Prenatal Diagnosis
PubMed: 30611408
DOI: 10.1016/j.fertnstert.2018.11.041 -
Frontiers in Endocrinology 2022Since the introduction of glucocorticoid (GC) replacement therapy, congenital adrenal hyperplasia (CAH) is no longer a fatal disease. The development of neonatal... (Review)
Review
Since the introduction of glucocorticoid (GC) replacement therapy, congenital adrenal hyperplasia (CAH) is no longer a fatal disease. The development of neonatal screening programs and the amelioration of GC treatment strategies have improved significantly life expectancy in CAH patients. Thanks to these achievements, CAH patients are now in their adulthood, but an increased incidence of cardiovascular risk factors has been reported compared to general population in this stage of life. The aim of CAH treatment is to both prevent adrenal insufficiency and suppress androgen excess; in this delicate balance, under- as well as overtreatment might be equally harmful to long-term cardiovascular health. This work examines the prevalence of metabolic features and cardiovascular events, their correlation with hormone levels and GC replacement regimen in CAH patients and focuses on precocious markers to early detect patients at higher risk and new potential treatment approaches.
Topics: Adrenal Hyperplasia, Congenital; Adult; Cardiovascular Diseases; Glucocorticoids; Hormone Replacement Therapy; Humans; Infant, Newborn; Metabolic Syndrome
PubMed: 35979433
DOI: 10.3389/fendo.2022.934675 -
Clinical Endocrinology Aug 2019Adrenonodular hyperplasia and tumour formation are potential long-term complications of congenital adrenal hyperplasia (CAH) with little known regarding the clinical... (Clinical Trial)
Clinical Trial Observational Study
OBJECTIVE
Adrenonodular hyperplasia and tumour formation are potential long-term complications of congenital adrenal hyperplasia (CAH) with little known regarding the clinical implications. Our aim was to describe volumetric adrenal morphology and determine the association between radiological findings and comorbidities in adults with classic CAH.
DESIGN
This was a cross-sectional study of 88 patients (mean age 29.2 ± 13 years, 47 females) with classic CAH seen in a tertiary referral centre.
METHODS
CT imaging, performed at study entry or when reaching adulthood, was used to create 3-dimensional volumetric models. Clinical, genetic and hormonal evaluations were collected and correlated with adrenal morphology and tumour formation.
RESULTS
Over one-third of the cohort was obese. 53% had elevated 17-OH-progesterone or androstenedione; and 60% had adrenal hyperplasia. Tumours included 11 myelolipomas, 8 benign adrenocortical adenomas, 1 pheochromocytoma and 50% of men had testicular adrenal rest tissue. CAH patients with adrenal hyperplasia had significantly higher number of comorbidities than those with morphologically normal adrenals (P = 0.03). Variables that positively correlated with adrenal volume included hypogonadal/oligomenorrhoeic status, hypertension, androstenedione, aldosterone, and triglyceride levels, and in women, low HDL and insulin resistance. Elevated aldosterone was observed in a subset of patients with simple virilizing CAH.
CONCLUSIONS
Adrenocortical hyperplasia is associated with a number of comorbidities, especially hypogonadism. Aldosterone production associated with adrenal enlargement may play a role in the development of metabolic risk factors. Further studies are needed to assess the long-term impact of the excess adrenal steroid milieu associated with adrenal enlargement to develop improved management strategies for CAH.
Topics: 17-alpha-Hydroxyprogesterone; Adolescent; Adrenal Glands; Adrenal Hyperplasia, Congenital; Adult; Androstenedione; Cohort Studies; Comorbidity; Cross-Sectional Studies; Female; Humans; Insulin Resistance; Male; Maryland; Obesity; Tertiary Care Centers; Tomography, X-Ray Computed; Young Adult
PubMed: 31001843
DOI: 10.1111/cen.13996 -
Ugeskrift For Laeger Mar 2024Congenital adrenal hyperplasia (CAH) arises from genetic enzyme defects, often in CYP21A2, causing primary adrenal insufficiency. In this case report, a man in his late...
Congenital adrenal hyperplasia (CAH) arises from genetic enzyme defects, often in CYP21A2, causing primary adrenal insufficiency. In this case report, a man in his late 20s with lifelong CAH faced challenges in adhering to medication. Suboptimal treatment led to the development of testicular adrenal rest tumours, diagnosed by ultrasound, and hypogonadism. Enhanced adherence restored hormone levels, promoting eugonadism. Adherence plays a crucial role in diminishing tumour size and preventing complications, potentially necessitating orchiectomy in severe cases.
Topics: Humans; Male; Adrenal Hyperplasia, Congenital; Adrenal Rest Tumor; Hypogonadism; Steroid 21-Hydroxylase; Testicular Neoplasms; Adult
PubMed: 38533865
DOI: 10.61409/V12230794 -
Hormone Research in Paediatrics 2022The adrenal has played a major role in the history of pediatric endocrinology. Cases of congenital adrenal hyperplasia (CAH) were reported in the 19th century, leading... (Review)
Review
The adrenal has played a major role in the history of pediatric endocrinology. Cases of congenital adrenal hyperplasia (CAH) were reported in the 19th century, leading to the understanding that the adrenal influenced sexual phenotypes as well as being mysteriously required for survival. Numerous adrenal steroids were isolated in the early 20th century, and bioassays eventually distinguished glucocorticoids, mineralocorticoids, and androgens. Treatment of CAH with cortisone in 1950 by Wilkins and by Bartter and Albright revolutionized clinical endocrinology and launched a productive era of pediatric adrenal research. Through careful clinical studies, Wilkins established the contemporary approach to treating CAH. Alfred Bongiovanni identified defective 21-hydroxylation in CAH in 1957, followed by deficiencies of 3β-hydroxysteroid dehydrogenase and 11β-hydroxylase. P450 enzymes were described in 1962-1964, and 21-hydroxylation was the first activity ascribed to a P450. Accurate assays for 17OH-progesterone in newborns and in response to ACTH permitted the diagnosis of CAH in children and families. Application of the techniques of molecular genetics elucidated genetic and biochemical bases of these disorders from 1984 to 2004. Pediatric endocrinologists played central roles in identifying the genes responsible for both common and rare forms of congenital adrenal hyperplasia and determining their most appropriate treatments.
Topics: Humans; Adrenal Hyperplasia, Congenital; Mineralocorticoids; Endocrinology; Glucocorticoids; Androgens
PubMed: 36446323
DOI: 10.1159/000526468