COVID-19-related adrenal haemorrhage: Multicentre UK experience and systematic review of the literature.

OBJECTIVE: Adrenal haemorrhage (AH) is an uncommon, usually incidental imaging finding in acutely unwell patients. AH has been reported during coronavirus disease 2019 (COVID-19) infection and following ChAdOx1 nCoV-19 (Oxford-AstraZeneca) vaccination. The Society for Endocrinology (SfE) established a task force to describe the UK experience of COVID-19-related AH. DESIGN: A systematic literature review was undertaken. A survey was conducted through the SfE clinical membership to identify patients with COVID-19-related AH using a standardized data collection tool. RESULTS: The literature search yielded 25 cases of COVID-19-related AH (19 bilateral; 13 infection-related, and 12 vaccine-related). Eight UK centres responded to the survey with at least one case. A total of 18 cases were included in the descriptive study, including 11 from the survey and 7 UK-based patients from the systematic review. Seven patients (4 males; median age 53 (range 26-70) years), had infection-related AH (four bilateral). Median time from positive COVID-19 test to AH detection was 8 (range 1-30) days. Eleven cases of vaccine-related AH (eight bilateral) were captured (3 males; median age 47 (range 23-78) years). Median time between vaccination (nine Oxford-AstraZeneca and two Pfizer-BioNTech) and AH was 9 (range 2-27) days; 9/11 AH occurred after the first vaccine dose. Acute abdominal pain was the commonest presentation (72%) in AH of any cause. All 12 patients with bilateral AH and one patient with unilateral AH required glucocorticoid replacement. CONCLUSION: Adrenal haemorrhage with consequential adrenal insufficiency can be a complication of COVID-19 infection and vaccination. Adrenal function assessment is mandatory to avoid the potentially fatal consequences of unrecognized adrenal insufficiency.

Immune checkpoint inhibitor induced hypophysitis: a specific disease of corticotrophs?

Introduction: The aim of this study was to define functional and anatomical pituitary disease at the time of presentation following immune checkpoint inhibitor (ICI) therapy and to describe any changes in pituitary function over time. Methods: We conducted a retrospective observational audit of patients on ICI therapy at our centre between January 2013 and September 2023. We reviewed all patients on ICI therapy under the care of the oncology department at University Hospital Plymouth, a 1000-bedded hospital serving a population of 500,000 people. From this group, we identified all individuals referred to the endocrinology department with a suspected diagnosis of adrenal insufficiency. Patients were established on adrenal steroid replacement and subsequently underwent formal pituitary testing. People were included if they had pituitary disease, as evidenced by low ACTH, other pituitary dysfunction and/or abnormalities on pituitary imaging. Results: Nine hundred and fifty-four patients received ICI therapy during the study period, and 37 (a prevalence of 3.9%) developed hypothalamic-pituitary-adrenal axis dysfunction. Their mean age was 65 years, and 70% were male. About 86.5% of the total patients affected were treated for metastatic malignancies. Ten of the 37 patients died during follow-up as a direct consequence or complication of their primary cancer diagnosis. The median interval for the onset of symptoms was 4 months. Following repeated testing, there was no recovery in cortisol or ACTH levels for any individual. Other permanent anterior pituitary hormone defects were unusual. Hypophysitis associated with immunotherapy appears to specifically target the corticotrophs, with no evidence of recovery over time. There was a specific abnormality seen in MRI scans of 7 of 27 patients who had scans, which appeared to be a particular feature of immune-mediated hypophysitis. These were confined to the anterior aspect of the pituitary gland, appearing as striations, and were not visible on any of the scans performed more than 3 months after the likely onset of the disease. Conclusion: These data show that immune-related hypophysitis is a common complication of immune checkpoint inhibitor therapy. This may result in an imaging abnormality within the areas of the pituitary that are richest in corticotrophs. The endocrine consequence of this is a permanent defect in ACTH and, therefore, cortisol production.

Pituitary haemorrhage and infarction: the spectrum of disease.

BACKGROUND: Pituitary apoplexy is an acute syndrome of haemorrhage or infarction into the pituitary. The condition is relatively well-described. Less well-described is sub-acute presentation of the same condition. OBJECTIVE: To compare the clinical presentation and natural history of subacute pituitary haemorrhage/infarction with pituitary apoplexy (acute). METHOD: Retrospective analysis of a consecutive cohort of 55 patients (33 with pituitary apoplexy, 22 with subacute disease) presenting to University Hospital Plymouth between 1994 and 2019. Comparison of the clinical, endocrinological and radiological features at presentation. Comparison of clinical treatment and subsequent outcomes for the two groups. RESULTS: There were no significant differences in predisposing factors for the two groups. Acute headache was more frequent in the acute group. Chronic headache was common in both groups prior to presentation. Low sodium was more common at presentation in the acute group (11/26 vs 2/19 P = 0.02) otherwise there were no differences in endocrine deficit at presentation. A significant proportion showed an improvement in endocrine function at follow up (acute 8/31, subacute 5/21 P = 1.0). MRI characteristics were variable at presentation and follow up in both groups. Ring enhancement with contrast was more frequent in acute (14/20 vs 3/11 P = 0.03). This appearance resolved at follow up in the majority. CONCLUSIONS: Pituitary apoplexy has a characteristic and dramatic presentation. Subacute pituitary haemorrhage/infarction shows similar natural history and outcome. These conditions would appear to represent a spectrum of the same condition.

Real-World Clinical Experience of Semaglutide in Secondary Care Diabetes: A Retrospective Observational Study.

INTRODUCTION: The glucagon-like peptide-1 receptor analogue (GLP-1RA) semaglutide is associated with improvements in glycaemia and cardiovascular risk factors in clinical trials. The aim of this study was to examine the real-world impact of semaglutide administered by injection in people with type 2 diabetes (T2D) across three secondary care sites in Wales. METHODS: A retrospective evaluation of 189 patients with T2D initiated on semaglutide between January 2019 and June 2020 with at least one follow-up visit was undertaken. RESULTS: At baseline, participants had a mean age of 61.1 years, mean glycated haemoglobin (HbA1c) of 77.8 mmol/mol (9.3%) and mean body weight of 101.8 kg. At 6 and 12 months of follow-up, mean HbA1c reductions of 13.3 mmol/mol (1.2%) and 16.4 mmol/mol (1.5%), respectively, were observed, and mean weight loss at 6 months was 3.0 kg (all p < 0.001). At 12 months, there were significant reductions in total cholesterol (0.5 mmol/L) and alanine transaminase (4.8 IU/L). Patients naïve to GLP-1RAs or with higher baseline HbA1c at baseline had greater glycaemic reductions, although clinically significant HbA1c reductions were also observed in those who switched from other GLP-1RAs, whose body mass index was < 35.0 and > 35.0 kg/m2 or who had lower baseline HbA1c. Semaglutide was generally well tolerated, although adverse-effects limited use in 18 patients (9.5%). CONCLUSION: Semaglutide provided clinically and statistically significant reductions in HbA1c, body weight, lipids and liver enzymes.