Skoukinney3444

0038) and 60% (AUC0-270 min, P = 0.003), respectively) compared with the control meal. No significant hemodynamic effects were noted (blood pressure, AUC0-270 min, P = 0.86, heart rate, AUC0-270 min, P = 0.96). CONCLUSION Our study demonstrates that sacubitril/valsartan increases the postprandial plasma concentrations of gastrin and cholecystokinin in healthy individuals. The results thus suggest that neprilysin-mediated degradation of gastrin and cholecystokinin is physiologically relevant and may have a role in heart failure patients treated with sacubitril/valsartan.Biochemical characterization of primary bilateral macronodular adrenocortical hyperplasia (PBMAH) by distinct plasma steroid profiles has not been previously studied. Our objective was to assess plasma steroid profiles in the diagnosis of PBMAH. Thirty six subjects (22 females, 14 males) with PBMAH matched in age and gender to 336 control subjects. Comparisons included an additional 39 subjects (26 females, 13 males) with other adrenal tumors. LC-MS/MS-based steroid profiling of 15 plasma steroids was used with classification by discriminant analysis. Germline ARMC5 sequencing was performed in all PBMAH cases. Compared to controls, PBMAH showed increased plasma 11-deoxycortisol, corticosterone, 11-deoxycorticosterone, 18-hydroxycortisol and aldosterone, but lower progesterone, DHEA and DHEA-S with distinct differences in subjects with and without disease-causing variants in ARMC5 . Larger differences in PBMAH vs. CPA were most obvious for corticosterone, but there were also similar trends for 18-hydroxycortisol and aldosterone. Similar patterns for aldosterone and 18-hydroxycortisol were present in PBMAH and PA but not SCS disease groups, whereas 18-oxocortisol was clearly highest in PA. Discriminant analyses, restricted to panels of 9 selected steroids, indicated correct classification of PBMAH compared to control and CPA groups in 96% of cases and similarly correct classification of PBMAH and other bilateral disease groups; correct classification of subjects with and without disease-causing germline variants in ARMC5 was achieved in 92% of subjects with PBMAH. Subjects with PBMAH show distinctive plasma steroid profiles that may even point to their genetics and offer a supplementary single-test alternative for screening purposes.BACKGROUND The burden and management of primary adrenal insufficiency (PAI) in Africa have not been well documented. We aimed to identify specific disease characteristics, patient demographics and patterns of clinical management in established PAI in Africa. METHODS An online survey of physicians' experience relating to PAI. RESULTS There were 1334 responses received, 589 were complete, and 332 respondents reported managing patients with hypoadrenalism. The described responses were related to a calculated pool of 5787 patients with hypoadrenalism (2746 females, 3041 males), of whom 2302 had PAI. RBPJ Inhibitor-1 nmr The likely causes of PAI in Sub-Saharan Africa (SSA) versus the Middle East and North Africa (MENA) regions included autoimmune disease (20% versus 60.3%; p less then 0.001), tuberculosis (34% versus 4.1%; p less then 0.001), AIDS (29.8% versus 1%; p less then 0.001), malignancy, and genetic conditions. Sixteen percent of AD patients (376/2302) presented in an adrenal crisis. Medical emergency identification was not used by 1233 (83.6%) SSA versus 330 (40.4%) MENA patients (p less then 0.001), respectively. Relative non-availability of diagnostic tests across both regions included adrenal antibodies 63% versus 69.6% (p=0.328), s-cortisol 49.4% versus 26.7% (p=0.004), s-ACTH 55.7% versus 53.3% (p=0.217), adrenal CT scans 52.4% versus 31.8% (p=0.017) in the SSA and MENA region, respectively. Across the entire cohort, the overall hydrocortisone use and extrapolated proportion of synacthen use were 59.4% and 50.7%, respectively. CONCLUSIONS Through the perception and practice of health care professionals, we identified significant challenges in the diagnosis and management of PAI which may herald high mortality. Differences between regions may reflect the allocation of health-care resources.Multiple endocrine neoplasia type 1 (MEN1), an autosomal dominant disorder caused by MEN1 germline mutations, is characterised by parathyroid, pancreatic and pituitary tumours. MEN1 mutations also cause familial isolated primary hyperparathyroidism (FIHP), a milder condition causing hyperparathyroidism only. Identical mutations can cause either MEN1 or FIHP in different families, thereby implicating a role for genetic modifiers in altering phenotypic expression of tumours. We therefore investigated the effects of genetic background and potential for genetic modifiers on tumour development in adult Men1+/- mice, which develop tumours of the parathyroids, pancreatic islets, anterior pituitary, adrenal cortex, and gonads, that had been backcrossed to generate C57BL/6 and 129S6/SvEv congenic strains. A total of 275 Men1+/- mice, aged 5-26 months were macroscopically studied, and this revealed that genetic background significantly influenced the development of pituitary, adrenal and ovarian tumours, which occurred in mice over 12 months of age and more frequently in C57BL/6 females, 129S6/SvEv males, and 129S6/SvEv females, respectively. Moreover, pituitary and adrenal tumours developed earlier, in C57BL/6 males and 129S6/SvEv females, respectively, and pancreatic and testicular tumours developed earlier in 129S6/SvEv males. Furthermore, glucagon-positive staining pancreatic tumours occurred more frequently in 129S6/SvEv Men1+/- mice. Whole genome sequence analysis of 129S6/SvEv and C57BL/6 Men1+/- mice revealed >54,000 different variants in >300 genes. These included, Coq7, Dmpk, Ccne2, Kras, Wnt2b, Il3ra, and Tnfrsf10a, and qRT-PCR analysis revealed that Kras was significantly higher in pituitaries of male 129S6/SvEv mice. Thus, our results demonstrate that Kras and other genes could represent possible genetic modifiers of Men1.OBJECTIVE The neurophysiological mechanisms underlying cognitive dysfunction in primary hyperparathyroidism (PHPT) and brain regions affected are not clear. We assessed neural activation during cognitive testing (matrix reasoning, paired associates, and logical memory) using functional magnetic resonance imaging (fMRI) in 23 patients with PHPT and 23 healthy controls. A subset with PHPT was re-assessed 6 months post- parathyroidectomy (PTX). DESIGN This is an observational study comparing neural activation by fMRI in patients with PHPT to normative controls. Postmenopausal women were studied at a tertiary referral center. RESULTS There were no between-group differences in cognitive task performance. Patients with PHPT had lower neural activation versus controls (max Z = 4.02, all p less then 0.01) during matrix reasoning in brain regions involved in executive function [left frontal lobe (k=57) and right medial frontal gyrus (k=72)] and motor function [right precentral gyrus (k=51)]. During paired associates (verbal memory), those with PHPT had greater activation in the right inferior parietal lobule (language/mathematical operations; k=65, p less then 0.