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To provide an overview of the I‐CAH Registry. Following the successful roll‐out of the I‐DSD Registry in the 2000s, it was felt that there was a need for a registry for congenital adrenal hyperplasia (CAH) and this was launched in 2014 as a dedicated module within the original registry. In addition to supporting and promoting research, the I‐CAH Registry acts as an international tool for benchmarking of clinical care and it does this through the collection of standardised data for specific projects. Surveillance of novel therapies in the field of CAH can also be achieved via global collaborations. Its robust governance ensures adherence to the international standards for rare disease registries. Rare disease registries such as the I‐CAH Registry are important tools for all stakeholders involved in the care of people with CAH. [ABSTRACT FROM AUTHOR]

Previous studies have reported sex differences in cortical gyrification. Since most cortical folding is principally defined in utero, sex chromosomes as well as gonadal hormones are likely to influence sex‐specific aspects of local gyrification. Classic congenital adrenal hyperplasia (CAH) causes high levels of androgens during gestation in females, whereas levels in males are largely within the typical male range. Therefore, CAH provides an opportunity to study the possible effects of prenatal androgens on cortical gyrification. Here, we examined the vertex‐wise absolute mean curvature—a common estimate for cortical gyrification—in individuals with CAH (33 women and 20 men) and pair‐wise matched controls (33 women and 20 men). There was no significant main effect of CAH and no significant CAH‐by‐sex interaction. However, there was a significant main effect of sex in five cortical regions, where gyrification was increased in women compared to men. These regions were located on the lateral surface of the brain, specifically left middle frontal (rostral and caudal), right inferior frontal, left inferior parietal, and right occipital. There was no cortical region where gyrification was increased in men compared to women. Our findings do not only confirm prior reports of increased cortical gyrification in female brains but also suggest that cortical gyrification is not significantly affected by prenatal androgen exposure. Instead, cortical gyrification might be determined by sex chromosomes either directly or indirectly—the latter potentially by affecting the underlying architecture of the cortex or the size of the intracranial cavity, which is smaller in women. [ABSTRACT FROM AUTHOR]

Background: Congenital adrenal hyperplasia (CAH) due to 21‐hydroxylase (21OH) deficiency is an autosomal recessive inborn error of cortisol biosynthesis, with varying degrees of aldosterone production. There is a continuum of phenotypes which generally correlate with genotype and the expected residual 21OH activity of the less severely impaired allele. CYP21A1P/CYP21A2 chimeric genes caused by recombination between CYP21A2 and its highly homologous CYP21A1P pseudogene are common in CAH and typically associated with salt‐wasting CAH, the most severe form. Nine chimeras have been described (CH‐1 to CH‐9). Aims: The aim of this study was to genetically evaluate two variant alleles carried by a 22‐year‐old female with the non‐salt‐wasting simple virilizing form of CAH and biallelic 30‐kb deletions. Methods: The haplotypes of the CYP21A2 heterozygous variants, as well as the chimeric junction sites, were determined by Sanger sequencing TA clones of an allele‐specific PCR product. Results: Genetic testing revealed two rare CYP21A1P/CYP21A2 chimeras: allele 1 matches the previously described CAH CH‐1 chimera but without the P30L variant, and allele 2, termed here as novel CAH CH‐10, has a junction site between c.293‐37 and c.29314, which is expected to retain partial 21OH activity. Conclusion: These two variant alleles further document the complex nature of RCCX modules and highlight that not all CYP21A1P/CYP21A2 chimera severely impair 21OH activity. [ABSTRACT FROM AUTHOR]

Congenital adrenal hyperplasia (CAH) is a rare condition usually referred to as a group of genetic disorders resulting due to a deficiency of steroid enzymes required by adrenal glands to produce cortisol and mineralocorticoid hormones. It has an autosomal recessive mode of inheritance and is further categorized into two types—Classic and Non‐Classic. Non‐Classic CAH is a more common milder form that presents late after puberty. Classic CAH, although more severe, is rare and detected at birth and is associated with the life‐threatening adrenal crisis in both sexes and virilization of the external genitalia in females (46, XX) patients, whereas in males, no overt abnormality of the external genitalia is present. We present a case of a four‐month‐old male child with the classic form of CAH who was brought with complaints of loose stools, projectile non bilious vomiting, decreased urine output, and failure to feed for 3 days. The child had a clinical presentation of salt wasting with hypoglycemia and hyperpigmentation of his genitalia. The USG findings revealed increased anteroposterior diameter of renal pelvis indicative of a growth in the suprarenal area. 17‐hydroxyprogesterone (17‐OHP) was found to be elevated confirming the diagnosis. He was treated with hydrocortisone with gradual improvement in his glucose and electrolytes. The patient was discharged home on replacement therapy consisting of oral prednisolone and fludrocortisone acetate and followed up as outpatient with significant improvement in the clinical findings. The fact that the child was not screened for CAH at birth led to the critical consequences of the disease in this case. To prevent life‐threatening adrenal crisis and help perform appropriate sex assignments for affected female patients, newborn screening (NBS) programs for the classical form of CAH should be made mandatory even in low‐ and middle‐income countries. [ABSTRACT FROM AUTHOR]

Congenital adrenal hyperplasia includes defects in the synthesis of steroid hormones in the adrenal cortex. The implications of this disorder manifest in other genitourinary organs, including ovaries and uterus. The diagnosis may be suspected based on the clinical and radiologic features. [ABSTRACT FROM AUTHOR]

Background: Congenital adrenal hyperplasia (CAH) due to 21‐hydroxylase deficiency is an autosomal recessive disease of steroidogenesis that affects 1 in 15,000. Approximately, 10% of the CAH population also suffer from CAH‐X, a connective tissue dysplasia consistent with hypermobility type Ehlers–Danlos syndrome (EDS). Most patients with CAH‐X carry a contiguous gene deletion involving CYP21A2 encoding 21‐hydroxylase and TNXB encoding tenascin‐X (TNX), but some are of unknown etiology. Methods: We conducted clinical evaluation and medical history review of EDS‐related manifestations in subjects from two unrelated CAH families who carry a heterozygous TNXB c.12463+2T>C variant that alters the splice donor site of intron 42. A next generation sequencing (NGS) based EDS panel composed of 45 genes was performed for index patients from each family. TNX expression in patient skin biopsy tissues and dermal fibroblasts was assessed by qRT‐PCR and Sanger sequencing. Results: All three evaluated CAH patients carrying the TNXB splice site variant had moderate EDS manifestations. An NGS panel excluded involvement of other known EDS‐related variants. RNA assay on skin biopsies and dermal fibroblasts did not detect splicing errors in TNX mRNA; however, the removal of intron 42 was less efficient in the allele harboring the splice site variant as evidenced by the existence of a premature TNX RNA form, leading to an allele specific decrease in TNX mRNA. Conclusions: Carrying a TNXB c.12463+2T>C variant at the intron 42 splice donor site causes an allele specific decrease in TNX expression, which can be associated with moderate EDS in CAH patients. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Congenital adrenal hyperplasia (CAH) is a group of genetic endocrine disorders, caused by enzyme deficiencies in the conversion of cholesterol to cortisol. More than 90% of the cases have 21-hydroxylase deficiency (21-OHD). The clinical phenotype of the disease is classified as classic, the severe form, and nonclassic, the mild form. In this study, it was planned to characterize the mutations that cause 21-OHD in Turkish CAH patients by direct sequencing and multiplex ligation-dependent probe amplification (MLPA) analysis and to investigate the type of CAH (classic or nonclassic type) that these mutations cause. A total of 124 CAH patients with 21-OHD and 100 healthy volunteers were recruited to the study. Most of the mutations were detected by direct sequencing. Large gene deletions/duplications/conversions were investigated with MLPA analysis. Results were evaluated statistically. At the end of our study, 66 different variations were detected including SNPs and deletions/duplications/conversions. Of these variations, 18 are novel, of which three cause amino acid substitutions. In addition, 15 SNPs which cause amino acid changes were identified among these variations. If similar results are obtained in different populations, these mutations, in particular the novel mutation 711 G>A, may be used as markers for prenatal diagnosis. [ABSTRACT FROM AUTHOR]

The primary treatment for patients with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD) is glucocorticoid replacement therapy, which at supraphysiologic levels can result in diminished bone accrual and lead to osteopenia and osteoporosis. Unlike other diseases treated with chronic glucocorticoid therapy, previous studies of patients with 21OHD have not demonstrated a detrimental effect of glucocorticoid treatment on bone mineral density (BMD). It has been postulated that the elevated androgens typically found in these patients have a protective effect on bone integrity, but the precise mechanism remains unknown. We propose that the inhibitory effect of corticosteroid therapy on bone formation is counteracted by estrogen's effect on bone resorption through the RANK-L/osteoprotegerin (OPG) system. A better understanding of the mechanism by which patients with 21OHD are protected against bone loss may lead to novel therapeutic measures to prevent or treat osteopenia and osteoporosis in other conditions, including postmenopausal women. [ABSTRACT FROM AUTHOR]

Congenital adrenal hyperplasia (CAH) is a family of autosomal recessive disorders caused by mutations that encode for enzymes involved in one of the various steps of adrenal steroid synthesis. These defects result in the absence or the decreased synthesis of cortisol from its cholesterol precursor. The anterior pituitary secretes excess adrenocorticotrophic hormone (ACTH) via feedback regulation by cortisol, which results in overstimulation of the adrenals and causes hyperplasia. Symptoms due to CAH can vary from mild to severe depending on the degree of ensymatic defect. In the classical form of CAH, there is a severe enzymatic defect owing to mutations in the CYP21 gene. Classically affected female fetuses undergo virilization of the genitalia prenatally and present with genital ambiguity at birth; however, prenatal treatment of CAH with dexamethasone to prevent ambiguity has been successfully utilized for over a decade. In the less severe, late-onset form of CAH, prenatal virilization does not occur. The milder enzyme deficiency was termed nonclassical 21- hydroxylase deficiency (NC21OHD) in 1979 and was later found to be the most common autosomal recessive disorder in humans. Disease frequency of NC21OHD varies between ethnic groups with the highest ethnic-specific disease frequency in Ashkenazi Jews at 1/27. NC21OHD is diagnosed by serum elevations of 17-OHP that plot on a nomogram between the range for unaffected individuals and levels observed for classical CAH and is typically confirmed with molecular genetic analysis. Similar to classical CAH, nonclassical 21-hydroxylase deficiency may cause premature development of pubic hair, advanced bone age, acelerated linear growth velocity and diminished final height in both males and females. Severe cystic acne has also been attributed to nonclassical CAH. Women may present with symptoms of androgen excess, including hirsutism, temporal baldness, and infertility. Menarche in females may be normal or delayed and secondary amenorrhea is a frequent occurence. Polycystic ovary syndrome may also be seen in these patients. In males, early beard growth, acne, and growth spurt may prompt the diagnosis of NC21OHD. Although many males appear to be asymptomatic, they may present with oligozoospermia or diminished fertility. Individuals presenting to dermatology and infertility clinics with symptoms of hyperandrogenemia are rarely screened for NC21OHD. However, with hormonal and molecular genetic screening, previously undiagnosed patients may be identified and can therefore receive glucocorticoid treatment, which has been shown to reverse symptoms within 3 months. [ABSTRACT FROM AUTHOR]

In order to understand the impact of viral hepatitis on anti-oxidant defence system of the body, blood levels of superoxide dismutase (SOD), an enzymatic anti-oxidant, and total anti-oxidant (TAO) were evaluated and co-related to etiological viral hepatitis in various forms of liver diseases. A total number of 110 patients including 50 patients with acute viral hepatitis (AVH), 30 patients with chronic active hepatitis (CAH) and 30 patients with cirrhosis of liver were analysed for different hepatitis viral markers and the anti-oxidant levels in their blood. For comparison, blood from 100 healthy persons were also simultaneously tested for anti-oxidant levels. Analysis of results indicated that none of the patients belonging to these three liver diseases had hepatitis A viral (HAV) and hepatitis D viral (HDV) infections. AVH group had mainly hepatitis B viral (HBV), hepatitis C viral (HCV) and hepatitis E viral (HEV) infections, CAH group had B and C infections and cirrhosis group had B, C and E infections. A sizeable number of patients in each group had no markers and were labelled as non-BCE group. On co-relating anti-oxidant levels to viral etiology in these patients, it was observed that in comparison to healthy control group, SOD level was significantly reduced in all the patients irrespective of the viral etiology (P<0.05–0.001). The impact of different viruses on reduction in SOD level was recorded to be the same with no significant difference in SOD level between any two viral infections. On the contrary, TAO level in the majority of patients was found to be comparable with that observed in healthy persons. An appreciable change in SOD level but little impact on TAO level during viral hepatitis may be explained by the possible adaptive rise of some other anti-oxidant level in the blood of these patients. [Copyright &y& Elsevier]