Dipeptidyl peptidase-4 inhibitors (DPP-4i) have an important place in the management of type 2 diabetes. The DPP-4 enzyme is ubiquitously distributed throughout the human body and has multiple substrates through which it regulates several important physiological functions. DPP-4 regulates several immune functions, including T-cell activation, macrophage function, and secretion of cytokines. Studies have reported an increase in autoimmune diseases like bullous pemphigoid, inflammatory bowel disease, and arthritis with DPP-4i use. The relationship of DPP-4i and autoimmune diseases is a complex one and warrants further research into the effect of DPP-4 inhibition on the immune system to understand the pathogenesis more clearly. Whether a particular cluster of autoimmune diseases is associated with DPP-4i use remains an important contentious issue. Nevertheless, a heightened awareness from the clinicians is required to identify and treat any such diseases. Through this review, we explore the clinical and pathophysiological characteristics of this association in light of recent evidence.

Primary hyperparathyroidism (PHPT) is a common metabolic bone disease affecting 1% of the adult population. Patients with PHPT have reduced BMD, especially at the cortical bone. However, studies evaluating its impact on fracture risk have shown contradictory results. In an effort to further inform fracture risk for this patient population, a meta‐analysis of studies of fracture in patients with PHPT compared with a control population was undertaken. Articles were searched in PubMed/MEDLINE, Excerpta Medica, Cochrane Central Register of Controlled Trials, Latin American and Caribbean Health Sciences Literature, and Web of Science bibliographic databases. The meta‐analysis included 17 studies involving 3807 PHPT cases and 11,908 controls. The primary outcome was to determine the risk of vertebral fracture (VF), nonvertebral fracture, hip fracture, distal radius fracture, and total fracture (TF) among patients with PHPT in comparison with a control population. BMD (lumbar spine, femoral neck, total hip, and distal radius) and serum 25‐hydroxy vitamin D level, as well as possible predictors of VF as secondary outcomes were assessed. From this meta‐analysis, it was found that there was a significantly increased risk of VF (risk ratio [RR], 2.57; 95% CI, 1.3–5.09; p = 0.007) and TF (RR, 1.71; 95% CI, 1.48–1.97; p < 0.00001) in patients with PHPT. There was a significant decrease in BMD in patients with PHPT versus controls at all four sites. Older age, longer duration since menopause, and lower BMD at lumbar spine and distal radius were predictors for VF. To conclude, patients with PHPT had a significantly higher risk for VF and TF in comparison with controls. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Coronavirus disease 2019 (COVID-19) is associated with a high risk of mortality and complications in patients with diabetes mellitus. Achieving good glycemic control is very important in diabetic patients to reduce complications and mortality due to COVID-19. Recent studies have shown the mortality benefit and anti-inflammatory effects of Dipeptidyl-peptidase-4 inhibitors (DPP-4i) in diabetic patients with COVID-19. DPP-4i may have a beneficial role in halting the severity of infection primarily by three routes, namely viral entry inhibition, anti-inflammatory and anti-fibrotic effects and glycemic control. This has raised the pro-mising hypothesis that DPP-4i might be an optimal strategy for treating COVID-19 in patients with diabetes. This review aims to summarise the possible therapeutic non-glycemic effects of DPP-4i in diabetic patients diagnosed with COVID-19 in the light of available evidence.

Premature ovarian insufficiency (POI) is a common cause of infertility in women, characterised by amenorrhea and elevated FSH under the age of 40 years. In some cases, POI is syndromic in association with other features such as sensorineural hearing loss in Perrault syndrome. POI is a heterogeneous disease with over 80 causative genes known so far; however, these explain only a minority of cases. Using whole-exome sequencing (WES), we identified a MRPL50 homozygous missense variant (c.335T > A; p.Val112Asp) shared by twin sisters presenting with POI, bilateral high-frequency sensorineural hearing loss, kidney and heart dysfunction. MRPL50 encodes a component of the large subunit of the mitochondrial ribosome. Using quantitative proteomics and western blot analysis on patient fibroblasts, we demonstrated a loss of MRPL50 protein and an associated destabilisation of the large subunit of the mitochondrial ribosome whilst the small subunit was preserved. The mitochondrial ribosome is responsible for the translation of subunits of the mitochondrial oxidative phosphorylation machinery, and we found patient fibroblasts have a mild but significant decrease in the abundance of mitochondrial complex I. These data support a biochemical phenotype associated with MRPL50 variants. We validated the association of MRPL50 with the clinical phenotype by knockdown/knockout of mRpL50 in Drosophila, which resulted abnormal ovarian development. In conclusion, we have shown that a MRPL50 missense variant destabilises the mitochondrial ribosome, leading to oxidative phosphorylation deficiency and syndromic POI, highlighting the importance of mitochondrial support in ovarian development and function.

Oncocytic adrenocortical tumours (OATs) or oncocytomas are extremely rare and are usually benign and nonfunctional. We report the case of a 4-year-old male with a right-sided, functional oncocytic adrenocortical adenoma, who presented with precocious puberty and Cushing's syndrome. After work-up, the patient underwent laparoscopic adrenalectomy. The excised adrenal mass weighed 21 g and measured 3.5 cm in maximum dimension. Histological examination demonstrated no features suggestive of aggressive biological behaviour. The patient had no features of recurrent or metastatic disease and had prepubertal testosterone levels with suppressed hypothalamic-pituitary-adrenal axis twelve months after the surgery. A discussion of this case and a review of the literature on functional OATs in the pediatric population are presented.