Pseudo-Cushing Syndrome With an Atypically High Cortisol Burden and Clinical Improvement With Adrenal Enzyme Inhibitor.

Distinguishing between Cushing syndrome (CS) and pseudo Cushing syndrome (PCS), also known as physiological hypercortisolism, can be difficult. PCS is caused by nonneoplastic overactivity of the hypothalamic-pituitary-adrenal axis and may be secondary to a range of conditions, including obesity, physical stress, malnutrition, and chronic alcoholism, and typically results in a lesser degree of hypercortisolism and fewer clinical features than CS. Management of PCS includes treatment of the underlying cause and reassessment of hypercortisolemia following improvement in the underlying etiology, as this may result in normalization of cortisol levels. The role of adrenal enzyme inhibitors in lowering cortisol levels in those with PCS is poorly understood. We report a case of a man presenting with weight loss who was found to have severe hypercortisolemia and elevated adrenocorticotropin (ACTH) complicated by infection, neuropsychiatric disturbance, and hypokalemia. Despite high cortisol levels, he was phenotypically not cushingoid, and the circadian rhythm of cortisol was preserved. Extensive investigations did not demonstrate a cause of symptoms or source of ACTH. Medical management with ketoconazole improved neuropsychiatric symptoms, and weight gain with nasogastric feeds resulted in the normalization of cortisol levels and resolution of symptoms following ketoconazole cessation.

Understanding the hidden epidemic of metabolic syndrome in people accessing community rehabilitation: a cross-sectional study of physical activity, dietary intake, and health literacy.

PURPOSE: To determine the prevalence of metabolic syndrome in patients attending outpatient community rehabilitation in Melbourne, Australia and to compare health literacy, physical activity, and dietary intake of people with and without metabolic syndrome. MATERIALS AND METHODS: A cross-sectional, multi-centre, observational study of adults (n = 193) presenting to rehabilitation with various health complaints. Metabolic syndrome was determined according to the International Diabetes Federation joint consensus worldwide definition. Health literacy was assessed using the Rapid Estimate of Adult literacy in Medicine (REALM) and the Short Test of Functional Health Literacy in Adults (S-TOFHLA). Physical activity was assessed using accelerometers and dietary intake was assessed using a food frequency questionnaire. RESULTS: One hundred and twenty three participants (64%) had metabolic syndrome. Of these, only three (2%) knew they had it. People with metabolic syndrome scored lower on health literacy (S-TOFHLA MD -2.10, 95% confidence interval (CI) -3.98 to -0.22) and took 1311 (95%CI 375 to 2246) fewer daily steps than those without metabolic syndrome. There were no differences in dietary intake. CONCLUSIONS: Metabolic syndrome is a prevalent and under-recognised condition in community rehabilitation. Community healthcare professionals and health services may need to consider a broader approach to management including lifestyle assessment and intervention of patients with various conditions. Implications for rehabilitationAlmost two-thirds of adults in community rehabilitation had underlying, undetected metabolic syndrome.Adults with metabolic syndrome completed less objectively measured physical activity and had lower health literacy levels than those without metabolic syndrome.A broader approach to management may need to be considered in community rehabilitation where patients presenting for rehabilitation of various conditions would likely benefit from lifestyle assessment and intervention.

Real-world artificial intelligence-based opportunistic screening for diabetic retinopathy in endocrinology and indigenous healthcare settings in Australia.

This study investigated the diagnostic performance, feasibility, and end-user experiences of an artificial intelligence (AI)-assisted diabetic retinopathy (DR) screening model in real-world Australian healthcare settings. The study consisted of two components: (1) DR screening of patients using an AI-assisted system and (2) in-depth interviews with health professionals involved in implementing screening. Participants with type 1 or type 2 diabetes mellitus attending two endocrinology outpatient and three Aboriginal Medical Services clinics between March 2018 and May 2019 were invited to a prospective observational study. A single 45-degree (macula centred), non-stereoscopic, colour retinal image was taken of each eye from participants and were instantly screened for referable DR using a custom offline automated AI system. A total of 236 participants, including 174 from endocrinology and 62 from Aboriginal Medical Services clinics, provided informed consent and 203 (86.0%) were included in the analysis. A total of 33 consenting participants (14%) were excluded from the primary analysis due to ungradable or missing images from small pupils (n = 21, 63.6%), cataract (n = 7, 21.2%), poor fixation (n = 2, 6.1%), technical issues (n = 2, 6.1%), and corneal scarring (n = 1, 3%). The area under the curve, sensitivity, and specificity of the AI system for referable DR were 0.92, 96.9% and 87.7%, respectively. There were 51 disagreements between the reference standard and index test diagnoses, including 29 which were manually graded as ungradable, 21 false positives, and one false negative. A total of 28 participants (11.9%) were referred for follow-up based on new ocular findings, among whom, 15 (53.6%) were able to be contacted and 9 (60%) adhered to referral. Of 207 participants who completed a satisfaction questionnaire, 93.7% specified they were either satisfied or extremely satisfied, and 93.2% specified they would be likely or extremely likely to use this service again. Clinical staff involved in screening most frequently noted that the AI system was easy to use, and the real-time diagnostic report was useful. Our study indicates that AI-assisted DR screening model is accurate and well-accepted by patients and clinicians in endocrinology and indigenous healthcare settings. Future deployments of AI-assisted screening models would require consideration of downstream referral pathways.

A safety and pharmacodynamics study of temelimab, an antipathogenic human endogenous retrovirus type W envelope monoclonal antibody, in patients with type 1 diabetes.

AIM: To report the first study of temelimab, a monoclonal antibody neutralizing the pathogenic human endogenous retrovirus type W envelope, in patients with type 1 diabetes (T1D). MATERIALS AND METHODS: This double-blind, placebo-controlled, randomized clinical trial recruited adult patients with T1D within 4 years postdiagnosis and remaining C-peptide secretion. Sixty-four patients were randomized (2:1) to monthly temelimab 6 mg/kg or placebo during 24 weeks followed by a 24-week, open-label extension, during which all patients received temelimab. The primary objective was the safety and tolerability of temelimab. The secondary objective was to assess the pharmacodynamics response such as C-peptide levels, insulin use, HbA1c, hypoglycaemia and autoantibodies. RESULTS: Temelimab was well tolerated without any group difference in the frequency or severity of adverse events. Concerning exploratory endpoints, there was no difference in the levels of C-peptide, insulin use or HbA1c between treatment groups at weeks 24 and 48. The frequency of hypoglycaemia events was reduced with temelimab (P = 0.0004) at week 24 and the level of anti-insulin antibodies was lower with temelimab (P < 0.01); the other autoantibodies did not differ between groups. CONCLUSIONS: Temelimab appeared safe in patients with T1D. Pharmacodynamics signals (hypoglycaemia and anti-insulin antibodies) under temelimab were observed. Markers of ß-cell functions were not modified by treatment. These results need to be further explored in younger patients with T1D with earlier disease onset.

The high burden of inpatient diabetes mellitus: the Melbourne Public Hospitals Diabetes Inpatient Audit.

OBJECTIVE: To determine the prevalence of diabetes in inpatients in Melbourne hospitals. DESIGN: Point prevalence survey of all inpatients in each hospital on a single day between 30 November 2010 and 22 November 2012. SETTING: 11 hospitals in metropolitan Melbourne including community, secondary and tertiary hospitals and one aged care and rehabilitation centre. PARTICIPANTS: 2308 adult inpatients in all wards apart from intensive care, emergency, obstetrics and psychiatry. MAIN OUTCOME MEASURES: Point prevalence of self-reported diabetes, details of current medication, self-reported frequency of complications. RESULTS: Diabetes status was obtained in 2273 of 2308 inpatients (98.5%). Of these, 562 (24.7%) had diabetes (95% CI, 22.9%-26.5%). Diabetes prevalence ranged from 15.7% to 35.1% in different hospitals (P < 0.001). Patients with diabetes were older, heavier and more likely to be taking lipid-lowering, antihypertensive and blood-thinning medications. Of 388 patients with complete medication information, 270 (69.6%) were taking oral hypoglycaemic agents alone or in combination with insulin, 158 (40.7%) were treated with insulin (67 [17.3%] with insulin alone) and 51 (13.1%) were not taking medication for diabetes. The frequency of diabetes complications was very high: 207/290 (71.4%) for any microvascular complication, 275/527 (52.2%) for any macrovascular complication and 227/276 (82.2%) for any complication. CONCLUSION: The high burden of diabetes in Melbourne hospital inpatients has major implications for patient health and health care expenditure. Optimising care of these high-risk patients has the potential to decrease inpatient morbidity and length of stay as well as preventing or delaying future complications. A formal Australian national audit of inpatient diabetes would determine its true prevalence and consequences, allowing rational planning to deal with shortcomings in its management.