21-Hydroxylase deficiency in Brazil

We determined the frequency of large rearrangements and point mutations in 130 Brazilian patients with 21-hydroxylase deficiency and correlated genotype with phenotype. The frequency of CYP21 deletions was lower (4.4%) than in most of the previous series described, whereas the frequency of large gene conversions was similar to the frequency reported in the literature (6.6%). The most frequent point mutations were I2 splice (41.8% in salt wasting - SW), I172N (32.6% in simple virilizing - SV) and V281L (40.2% in the late onset form - LO). The frequency of the nine most common point mutations was similar to that reported for other countries. The 93 fully genotyped patients were classified into 3 mutation groups based on the degree of enzymatic activity (A<2%, B <FONT FACE="Symbol">@</FONT> 2%, C>20%). In group A, 62% of cases presented the SW form; in group B, 96% the SV form, and in group C, 88% the LO form. We diagnosed 80% of the affected alleles after screening for large rearrangements and 15 point mutations. To diagnose these remaining alleles we sequenced the CYP21 gene of one patient with the SV form and identified a heterozygous G->A transition in codon 424. This mutation leads to a substitution of glycine by serine in a conserved region and was also found in a compound heterozygous state in 4 other patients. The mutation G424S presented a linkage disequilibrium with CYP21P and C4A gene deletions and HLA DR17, suggesting a probable founder effect. Search for the G424S mutation in other populations will reveal if it is restricted to the Brazilian patients or if it has a wider ethnic distribution

Plasma Renin Measurements are Unrelated to Mineralocorticoid Replacement Dose in Patients With Primary Adrenal Insufficiency

This is a pre-copyedited, author-produced version of an article accepted for publication in The Journal of Clinical Endocrinology & Metabolism, following peer review. The version of record Riccardo Pofi, Alessandro Prete, Vivien Thornton-Jones, Jillian Bryce, Salma R Ali, S Faisal Ahmed, Antonio Balsamo, Federico Baronio, Amalia Cannuccia, Ayla Guven, Tulay Guran, Feyza Darendeliler, Claire Higham, Walter Bonfig, Liat de Vries, Tania A S S Bachega, Mirela C Miranda, Berenice B Mendonca, Violeta Iotova, Màrta Korbonits, Nils P Krone, Ruth Krone, Andrea Lenzi, Wiebke Arlt, Richard J Ross, Andrea M Isidori, Jeremy W Tomlinson, Plasma Renin Measurements are Unrelated to Mineralocorticoid Replacement Dose in Patients With Primary Adrenal Insufficiency, The Journal of Clinical Endocrinology & Metabolism, Volume 105, Issue 1, January 2020, Pages 314–326, https://doi.org/10.1210/clinem/dgz055 is available online at:  https://doi.org/10.1210/clinem/dgz05

Plasma Renin Measurements are Unrelated to Mineralocorticoid Replacement Dose in Patients With Primary Adrenal Insufficiency

This is a pre-copyedited, author-produced version of an article accepted for publication in The Journal of Clinical Endocrinology & Metabolism, following peer review. The version of record Riccardo Pofi, Alessandro Prete, Vivien Thornton-Jones, Jillian Bryce, Salma R Ali, S Faisal Ahmed, Antonio Balsamo, Federico Baronio, Amalia Cannuccia, Ayla Guven, Tulay Guran, Feyza Darendeliler, Claire Higham, Walter Bonfig, Liat de Vries, Tania A S S Bachega, Mirela C Miranda, Berenice B Mendonca, Violeta Iotova, Màrta Korbonits, Nils P Krone, Ruth Krone, Andrea Lenzi, Wiebke Arlt, Richard J Ross, Andrea M Isidori, Jeremy W Tomlinson, Plasma Renin Measurements are Unrelated to Mineralocorticoid Replacement Dose in Patients With Primary Adrenal Insufficiency, The Journal of Clinical Endocrinology & Metabolism, Volume 105, Issue 1, January 2020, Pages 314–326, https://doi.org/10.1210/clinem/dgz055 is available online at:  https://doi.org/10.1210/clinem/dgz05

Treatment of congenital adrenal hyperplasia in children aged 0-3 years: a retrospective multicenter analysis of salt supplementation, glucocorticoid and mineralocorticoid medication, growth and blood pressure.

Objectives: International guidelines recommend additional salt supplementation during infancy in classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. The influence of corticoid medication and growth has not been assessed. Aim: To investigate the current use of salt supplementation, fludrocortisone (FC) and hydrocortisone (HC) dosage as well as weight, height, BMI and blood pressure (BP) in CAH children aged 0-3 years. Methods: Retrospective multicentre analysis using data from the I-CAH registry. Salt-treated (ST) and non-salt-treated (NST) children were compared regarding FC and HC dosage, weight, height and BP at 0, 3, 6, 9, 12, 18, 24, 30, and 36 months. Results: We analysed 2483 visits of 331 patients born after year 2000 in 13 countries (male, n = 145) with 203 ST patients (61%). NST children had significantly higher FC dosages at 1.5-4.5 months and higher HC dosages until 1.5 months of age. No differences in weight, length and BP between subgroups were observed. Children of the whole cohort showed increased BMI-SDS during the study period and about half of the reported BP readings were >P95. Conclusion: In children treated with additional salt supplementation, FC and HC dosages are lower during the first months of life but without differences in weight, length and BP until 3 years of age compared to NST children. All children showed an increase in BMI-SDS and a high rate of BP readings >P95 until 3 years, indicating the start of weight gain and negative effects on blood pressure already in very early life