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Summary: Objective: Hydrocortisone via nasogastric (NG) tube is used in sick children with adrenal insufficiency; however, there is no licensed formulation for NG administration. Methods: We investigated hydrocortisone recovery after passage through NG tubes in vitro for three formulations: liquid suspension, crushed tablets mixed with water, and hydrocortisone granules designed for oral administration to children. Cortisol was measured by LC‐MS/MS. Results: Hydrocortisone content was variable and recovery low after preparation in syringe and prior to passage through NG tubes. For doses, 0.5 and 2.0 mg mean percentage recovery was as follows: liquid suspension 57% and 58%; crushed tablets 46% and 30%; and hydrocortisone granules 78% and 71%. Flushing the administering syringe increased recovery. Hydrocortisone recovery after passage with flushing through 6‐12Fr gauge NG tubes was variable: liquid suspension 61%‐92%, crushed tablets 40%‐174%, hydrocortisone granules 61%‐92%. Administration of hydrocortisone granules occluded 6 and 8Fr NG tubes; however, administration using a sampling needle to prevent granules being administered gave a recovery of 74%‐98%. Conclusions: The administration of hydrocortisone through NG tubes is possible; however, current methods deliver a variable dose of hydrocortisone, generally less than that prescribed. Attention should be placed on the technique used to optimize drug delivery such as flushing of the administering syringe. Hydrocortisone granules block small NG tubes but behaved as well as the commonly used liquid suspension when prepared with a filtering needle that filters out granules. [ABSTRACT FROM AUTHOR]

Background: Patients with SDHx mutations need long-term radiological surveillance for the development of paragangliomas and phaeochromocytomas, but no longitudinal data exist. The aim of the study was to assess the performance of rapid-sequence non-contrast magnetic resonance imaging (MRI) in the long-term monitoring of patients with SDHx mutations. Methods: Retrospective study between 2005 and 2015 at a University Hospital and regional endocrine genetics referral centre. Clinical and imaging data of 47 patients with SDHx mutations (SDHB (36), SDHC (6) and SDHD (5)) who had surveillance for detection of paragangliomas by rapid-sequence non-contrast MRI (base of skull to pubic symphysis) were collected. Results: Twelve index cases (nine SDHB, one SDHC and two SDHD) and 35 mutation-positive relatives were monitored for a mean of 6.4 years (range 3.1-10.0 years). Mean age at the end of the study: SDHB 46.9 ± 17.6 years; SDHC 42.3 ± 24.4 years; SDHD 54.9 ± 10.6 years. On excluding imaging at initial diagnosis of index cases, 42 patients underwent 116 rapid-sequence MRI scans: 83 scans were negative and 31 scans were positive for sPGL/HNPGL in 13 patients. Most patients had multiple scans (n = number of patients (number of rapid-sequence MRI scans during screening)): n = 9 (2), n = 20 (3), n = 6 (4), n = 1 (6). Nine patients (three index) were diagnosed with new paragangliomas during surveillance and non-operated tumour size was monitored in nine patients. There were two false-positive scans (1.6%). Scans were repeated every 27 ± 9 months. Conclusions: Biannual rapid-sequence non-contrast MRI is effective to monitor patients with SDHx mutations for detection of new tumours and monitoring of known tumours [ABSTRACT FROM AUTHOR]

Steroidogenesis enzyme inhibitors are the mainstay of medical therapy in Cushing's syndrome (CS). Ketoconazole (KTZ) and metyrapone are the most commonly used agents. Although there is considerable experience of their use in individual specialist centres, these drugs have not been rigorously tested in prospective clinical trials. Clinicians face uncertainties and concerns with respect to the safety profile of these agents, and best means to monitor effect. We review steroidogenesis inhibitors in the management of CS, including older agents (KTZ, metyrapone, etomidate and mitotane) and those currently under development (LCI699, non-racemic KTZ), and offer a practical approach for their use in clinical practice. [ABSTRACT FROM AUTHOR]

Objective: Despite published guidelines no unified approach to hormone replacement in congenital adrenal hyperplasia (CAH) exists. We aimed to explore geographical and temporal var iations in the treatment with glucocorticoids and mineralocorticoids in CAH. Design: This retrospective multi-center study, including 31 centers (1 6 countries), analyzed data from the International-CAH Registry. Methods: Data were collected from 461 patients aged 0-18 years with cla ssic 21-hydroxylase deficiency (54.9% females) under follow-up between 1982 and 2018. Type, dose and timing of glucocorticoid and mineralocorticoid replacement were 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-equival ent dose for body surface, with the lowest dose (median with interquartile range) of 12.0 (10.0-14.5) mg/m 2/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 2 010 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 countr ies 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. [ABSTRACT FROM AUTHOR]

Context: There is no licensed oral native testosterone (NT) because of challenges in the formulation. Licensed oral formulations of the ester, testosterone undecanoate (TU), require a meal for absorption and generate supraphysiological dihydrotestosterone (DHT) levels. Objective: To develop an oral NT formulation. Design and methods: A lipid-based formulation of native testosterone filled into so ft-gelatin capsules at 40 mg per capsule was designed with 2 years of stability at ambient temperature. Pharmacokinetic comparison studies of this oral lipidic NT formulation to oral TU were conducted in dogs and hypogonadal men. Results: In dogs, 40 mg NT was well absorbed under fasted conditions wh ereas 40 mg TU required a high-fat meal: for NT, the mean fed/fasted AUC ratio was 1.63 and for TU 7.05. In hypogonadal men, fed and fasted NT had similar pharmacokinetics: Cmax mean 26.5 vs 30.4 nmol/L (769 vs 882 ng/dL), AUC0-10 h 87 vs 88.6 h nmol/L. NT (fed state) showed a testosterone AUC increase of 45% between 120 and 200 m g, and NT 200 mg gave a similar mean AUC0-10 h to TU 80 mg: 87 vs 64.8 h nmol/L. Serum TU levels were variable an d on a molar basis were ~ten-fold higher than serum testosterone levels after TU 80 mg fed. The DHT: testosterone A UC0-10 h ratio was more physiological for NT than TU being 0.19 vs 0.36. There were no emerging safety concerns with NT. Conclusion: This novel oral lipidic native testosterone formulation has potential advantages over oral TU of dosing independently of food and a lower risk of supraphysiological DHT levels. Significance statement There is no licensed oral testosterone because of challenges in formulation, and the oral formulations of the ester, testosterone undecanoate, require a fatty meal for absorption and generate supraphysiological dihydrotestosterone levels. We have overcome the design challenges and formulated an oral native testosterone that can be taken with or without food and provides physiological levels of testosterone and dihydrotestosterone in hypogonadal men. This formulation, DITEST, has the potential advantage of being oral for patients who do not tolerate injections and less risk of adverse events that might theoretically be associated with elevated dihydrotestosterone levels. Future studies will need to define the dosing regimen for replacement in hypogonadal men. [ABSTRACT FROM AUTHOR]

Objective Hyperandrogenism in congenital adrenal hyperplasia ( CAH) provides an in vivo model for exploring the effect of androgens on erythropoiesis in women. We investigated the association of androgens with haemoglobin (Hb) and haematocrit (Hct) in women with CAH. Design Cross-validation study. Patients Women with CAH from Sheffield Teaching Hospitals, UK (cohort 1, the training set: n = 23) and National Institutes of Health, USA (cohort 2, the validation set: n = 53). Measurements Androgens, full blood count and basic biochemistry, all measured on the same day. Demographic and anthropometric data. Results Significant age-adjusted correlations ( P < 0·001) were observed for Ln testosterone with Hb and Hct in cohorts 1 and 2 (Hb r = 0·712 & 0·524 and Hct r = 0·705 & 0·466), which remained significant after adjustments for CAH status, glucocorticoid treatment dose and serum creatinine. In the combined cohorts, Hb correlated with androstenedione ( P = 0·002) and 17-hydroxyprogesterone ( P = 0·008). Hb and Hct were significantly higher in cohort 1 than those in cohort 2, while there were no group differences in androgen levels, glucocorticoid treatment dose or body mass index. In both cohorts, women with Hb and Hct in the highest tertile had significantly higher testosterone levels than women with Hb and Hct in the lowest tertile. Conclusions In women with CAH, erythropoiesis may be driven by androgens and could be considered a biomarker for disease control. [ABSTRACT FROM AUTHOR]

The article discusses a study to determine whether succinate is implicated in regulating neutrophil survival responses where peripheral blood neutrophils from patients with heterozgous germ line SDHBx mutations were isolated. The study identifies key metabolic differences between neutrophils and macrophages and raises further important questions regarding the metabolic control of neutrophil function and survival.