Update on adrenal steroid hormone biosynthesis and clinical implications

Steroid biosynthesis is a complex process in which cholesterol is converted to steroid hormones with the involvement of multiple enzymes and cofactors. Inborn conditions affecting adrenal steroidogenesis are relatively common in paediatric practice and have serious implications on patient mortality and morbidity. This paper provides an overview of novel insights into human adrenal steroid biosynthesis. Inborn errors of steroidogenesis associated with congenital adrenal hyperplasia are discussed, with a particular focus on the pathophysiology and clinical features of 21-hydroxylase deficiency. The final section of the review presents more recent findings and clinical implications of adrenal-specific androgen biosynthesis

Efeito da aplicação de diferentes tratamentos térmicos no conteúdo de resíduo de anticoccidiano em carne de frango.

Resumo: Anticoccidianos são compostos utilizados na prevenção de uma doença parasitária muito comum na criação de frangos de corte. A nicarbazina é um complexo constituído por 4,4´-dinitrocarbanilida (DNC) e 2-hidroxi-4,6- dimetil-pirimidina (HDP) amplamente utilizado como anticoccidiano. Contudo, a deposição de DNC em carne de frango é uma preocupação recorrente. O objetivo deste estudo foi avaliar o efeito de tratamentos térmicos convencionais sobre o conteúdo de DNC em carne de frango. A carne contaminada com DNC foi obtida de frangos alimentados com ração contendo nicarbazina (180 mg.kg-1 ). Foram realizados 2 experimentos com carne de frango submetida ao aquecimento por cozimento, grelha, micro-ondas, fritura e forneamento. No primeiro, realizou-se avaliação cinética da degradação de DNC na carne, enquanto que no segundo comparou-se a eficiência dos tratamentos. As concentrações de DNC na carne foram determinadas por LC-MS/MS. Os resultados indicaram que os tratamentos induziram a degradação de DNC na faixa de 52 a 69%. O cozimento foi o procedimento mais eficiente dentre os tratamentos avaliados. A degradação nos procedimentos com grelha, micro-ondas e fritura não diferiu (p?0,05) do valor para o cozimento. A redução dos níveis de DNC foi associada à hidrólise desta molécula. Considerando a legislação atual, que regulamenta o monitoramento de DNC, confirmou-se que os tratamentos podem tornar a carne mais segura ao consumidor

Health status of children and young persons with congenital adrenal hyperplasia in the UK (CAH-UK): a cross-sectional multi-centre study

Objective There is limited knowledge on the onset of comorbidities in congenital adrenal hyperplasia (CAH) during childhood. We aimed to establish the health status of children with CAH in the UK. Design and methods This cross-sectional multicentre study involved 14 tertiary endocrine UK units, recruiting 101 patients aged 8–18 years with classic 21-hydroxylase deficiency and 83 controls. We analysed demographic, clinical and metabolic data, as well as psychological questionnaires (Strengths and Difficulties (SDQ), Paediatric Quality of Life (PedsQL)). Results Patient height SDS in relation to mid-parental height decreased with age, indicating the discrepancy between height achieved and genetic potential height. Bone age was advanced in 40.5% patients, with a mean difference from the chronological age of 1.8 (±2.3) years. Patients were more frequently overweight (27%) or obese (22%) compared to controls (10.8% and 10.8%, respectively, P < 0.001). No consistent relationship between glucocorticoid dose and anthropometric measurements or hormonal biomarkers was detected. A small number of patients had raised total cholesterol (3.0%), low HDL (3.0%), raised LDL (7.0%) and triglycerides (5.0%). SDQ scores were within the ‘high’ and ‘very high’ categories of concern for 16.3% of patients. ‘School functioning’ was the lowest PedsQL scoring dimension with a median (interquartile range) of 70 (55–80), followed by ‘emotional functioning’ with a median of 75 (65–85). Conclusions Our results show an increased prevalence of problems with growth and weight gain in CAH children and suggest reduced quality of life. This highlights the urgent need to optimise management and monitoring strategies to improve long-term health outcomes

International practice of corticosteroid replacement therapy in congenital adrenal hyperplasia - data from the I-CAH registry.

OBJECTIVE: Despite published guidelines no unified approach to hormone replacement in congenital adrenal hyperplasia (CAH) exists. We aimed to explore geographical and temporal variations in the treatment with glucocorticoids and mineralocorticoids in CAH. DESIGN: This retrospective multi-center study, including 31 centers (16 countries), analyzed data from the International-CAH Registry. METHODS: Data was collected from 461 patients aged 0-18 years with classic 21-hydroxylase deficiency (54.9% females) under follow-up between 1982 - 2018. Type, dose and timing of glucocorticoid and mineralocorticoid replacement was analyzed from 4174 patient visits. RESULTS: The most frequently used glucocorticoid was hydrocortisone (87.6%). Overall, there were significant differences between age groups with regards to daily hydrocortisone-equivalent dose for body surface, with the lowest dose (median with interquartile range) of 12.0 (10.0 - 14.5) mg/ m2/ day at age 1 - 8 years and the highest dose of 14.0 (11.6 - 17.4) mg/ m2/ day at age 12-18 years. Glucocorticoid doses decreased after 2010 in patients 0-8 years (p<0.001) and remained unchanged in patients aged 8-18 years. Fludrocortisone was used in 92% of patients, with relative doses decreasing with age. A wide variation was observed among countries with regards to all aspects of steroid hormone replacement. CONCLUSIONS: Data from the I-CAH Registry suggests international variations in hormone replacement therapy, with a tendency to treatment with high doses in children

Detection of p-nitroaniline by lc-ms/ms in raw and cooked broiler breast.

Abstract ? Coccidiosis is a common disease in commercial broiler production. To control this disease, anticoccidials are commonly used. However, there are concerns about the deposition of residues on the tissues of broilers fed with anticoccidials in their diet. The Ministry of Agriculture monitors nicarbazin residues and has detected one of its molecules, dinitrocarbanilide (DNC). However, in thermal processing, p-nitroaniline (p-NA) can be formed, and if chicken meat is ingested excessively by people, p-NA is likely to cause liver damage in humans. Therefore, the objective of this research was to develop a method to detect p-NA by LC-MS/MS in thermally processed chicken breasts. The LOD and LOQ were 10 and 30 &#956;g kg-1 respectively. Up to 640 &#956;g kg-1 p-NA was detected in frying procedure. The results warn to monitor p-NA for the benefit of consumer health and maintenance of exports. Resumo ? A coccidiose é uma doença comum na produção comercial de frangos de corte. Para controlar esta doença, são comumente usados anticoccidianos. No entanto, existem preocupações sobre a deposição de resíduos nos tecidos dos frangos alimentados com anticoccidianos na ração. O Ministério da Agricultura monitora resíduos de nicarbazina e tem detectado uma de suas moléculas, a dinitrocarbanilida (DNC). Porém, no processamento térmico, a p-nitroanilina (p-NA) pode se formar e, caso a carne de frango seja ingerida em excesso pelas pessoas, existe a probabilidade da p-NA ocasionar danos ao fígado de humanos. Portanto, o objetivo desta pesquisa foi desenvolver um método para detectar p-NA por LC-MS/MS em peito de frango submetido a processamentos térmicos. Os LOD e LOQ foram 10 e 30 &#956;g kg-1 respectivamente. Até 640 &#956;g kg-1 de p-NA foi detectada na fritura. Os resultados alertam para se monitorar a p-NA em benefício à saúde do consumidor e manutenção das exportações

Intravoxel incoherent motion as a tool to detect early microstructural changes in meningiomas treated with proton therapy

Purpose: To assess early microstructural changes of meningiomas treated with proton therapy through quantitative analysis of intravoxel incoherent motion (IVIM) and diffusion-weighted imaging (DWI) parameters. Methods: Seventeen subjects with meningiomas that were eligible for proton therapy treatment were retrospectively enrolled. Each subject underwent a magnetic resonance imaging (MRI) including DWI sequences and IVIM assessments at baseline, immediately before the 1st (t0), 10th (t10), 20th (t20), and 30th (t30) treatment fraction and at follow-up. Manual tumor contours were drawn on T2-weighted images by two expert neuroradiologists and then rigidly registered to DWI images. Median values of the apparent diffusion coefficient (ADC), true diffusion (D), pseudo-diffusion (D*), and perfusion fraction (f) were extracted at all timepoints. Statistical analysis was performed using the pairwise Wilcoxon test. Results: Statistically significant differences from baseline to follow-up were found for ADC, D, and D* values, with a progressive increase in ADC and D in conjunction with a progressive decrease in D*. MRI during treatment showed statistically significant differences in D values between t0 and t20 (p&nbsp;= 0.03) and t0 and t30 (p&nbsp;= 0.02), and for ADC values between t0 and t20 (p&nbsp;= 0.04), t10 and t20 (p = 0.02), and t10 and t30 (p&nbsp;= 0.035). Subjects that showed a volume reduction greater than 15% of the baseline tumor size at follow-up showed early D changes, whereas ADC changes were not statistically significant. Conclusion: IVIM appears to be a useful tool for detecting early microstructural changes within meningiomas treated with proton therapy and may potentially be able to predict tumor response