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Background: C3 Glomerulopathy (C3G) is a heterogenous disease characterized by dysregulation of the complement alternative pathway (AP). Within 10 years of a diagnosis, roughly 50% of patients with C3G will progress to end stage kidney disease (ESKD). Historically, treatment options have been limited to nonspecific immune suppression with suboptimal response rates to recommended therapies. Advances in immunology and the emergence of novel complement targeted therapies have shifted the focus toward identifying the distinct underlying etiologies of C3G. Summary: In this review, we provide a description of the current landscape and challenges faced in tbe classification, evaluation, and treatment of patients with C3G. Key Message: C3G can be broadly separated into four distinct groups: (1) Genetic mutations/variants, (2) Autoimmune/Acquired auto-antibodies, (3) Monoclonal immunoglobulin associated C3G (MIg-C3G), and (4) C3G without an identified cause. Therapy directed towards the underlying pathogenetic cause of disease may improve outcomes in a disease in which current treatment options are largely ineffective.

Diabetic ketoacidosis (DKA) is a complication of diabetes melli tus (DM) that can theoretically occur in people of any age. While DKA can typically be the first pr esentation of type 1 DM in younger people, a first pr esentation is rare in older adults. Pancreatic cancer often manifests with new DM or hyperglycaemia, but very rarely as DKA. We report a case of an 89-year-old woman who was incidentally diagn osed with DKA during workup for an unwitnessed fall. Her DKA was promptly managed, and she was subsequently diagnosed with metasta tic pancreatic cancer. Given the advanced stage of her malignancy, the multidisciplinary team consensus was for a palliative approach. She passed away on day 10 of the admission. T o our knowledge, this is the first report of a first DKA presentation as a manifestation of pancreatic cancer in an adult aged over 70 years. To date, there is no effective screening test for pancreatic cancer in the general population. However, new-onset DM in the appropriate context might indicate the need for further evaluation. While it is possible that unresectable tumours are identified, earlier diagnosis of DM with pancreatic cancer may facilitate more timely management, including earlier advanced care planning.

Delayed arginine vasopressin deficiency (AVP-D) can present in patients following traumatic brain injury (TBI) and may occur years after the trauma, presenting with nonspecific symptoms. The objective of this case is to highlight the importance of considering the delayed onset AVP-D in patients with a history of TBI. We report a case of a patient who had sustained severe traumatic brain injury 8 years before and who presented with polydipsia, behavioural disorder and frequent falls during the last 3 months. The diagnosis of AVP-D was confirmed by water restriction with a positive response to desmopressin, and pituitary MRI showed an absent spontaneous posterior hyperintensity on T1WI. Follow-up confirmed permanent diabetes insipidus as well as a suspected anterior pituitary deficiency. Pituitary dysfunction occurs following TBI and is correlated with severity. As in our case, symptoms are generally non-specific and are difficult to explore given the patient’s neurologic sequelae. MRI 8 years post trauma showed changes in pituitary morphology. Some authors have proposed the need for active screening of post-TBI patients. This case highlights the need for clinicians to be aware that AVP-D can occur years after traumatic brain injury.

We describe and characterise the case of a 26-year-old female undergoing surgery for a right-sided sinonasal alveolar rhabdomyosarcoma who developed profound, transient arginine vasopressin deficiency (AVP-D, formerly central diabetes insipidus (DI)) associated with anaesthesia. In this case report, we characterise the development of AVP-D with serial copeptin and paired urine and serum osmolality measurements. Based on the anaesthetic agent’s profile and the literature, we attribute this presentation to propofol exposure. We present a description of the literature on anaesthesia-associated DI as well as poignant learning points.

Cushing's disease (CD) is characterized by distinct syndromic features, often accompanied by obesity and depression. However, considering its gradual onset of symptoms, it is usually associated with diagnostic delays. In rare instances, CD may lead to severe infections due to the observed immunosuppression in affected individuals. We present a rare case of an undiagnosed CD in a 20-year-old male with a medical history of depression and obesity, complicated by severe COVID-19 infection. He presented to the Emergency Room with respiratory distress, hypertensive crisis, and fever, ultimately receiving the diagnosis of SARS-CoV-2 pneumonia. The patient required mechanical ventilation and intensive care unit (ICU) admission due to severe acute respiratory distress syndrome (ARDS). During ICU care, he received remdesivir and dexamethasone, subsequently developing severe hyperglycemia and worsened hypertension, requiring insulin and multiple antihypertensive agents to manage metabolic disruption. Upon physical examination, classic signs of hypercortisolism were noted. Subsequent laboratory tests and pituitary magnetic resonance imaging confirmed the diagnosis of CD. The patient underwent surgical resection with significant improvements in body composition and metabolic parameters postoperatively. After surgery, remission of hypercortisolism was evident, accompanied by notable improvements in mood and overall health. This case underscores the importance of recognizing hypercortisolism in the context of metabolic, physical, and mood changes. Timely diagnosis of CD is crucial to mitigate complications such as severe opportunistic infections and their outcomes.

Relative energy deficiency in sport occurs in athletes who have limited energy availability. Its typical features include reversible suppression of the hypothalamic–pituitary–gonadal axis. In addition, it may be accompanied by hepatic resistance to growth hormone, leading to a decrease in insulin-like growth factor 1 and dysregulation of the hypothalamic–pituitary–thyroid axis. We present the clinical case of a 33-year-old athlete previously treated effectively for hypothyroidism, who presented with low thyroid-stimulating hormone, low free triiodothyronine, and normal free thyroxine. Based on diet and training interviews and further laboratory tests, dysregulation of the hypothalamic– pituitary–thyroid axis and reversible hypogonadism due to insufficiency of energy available to support energy expenditure were revealed. We also discuss here challenging diagnostic dilemmas that may appear in athletes of normal body weight but result from insufficient energy supply in relation to demand, and review the literature for the clinical course and possible mechanisms underlying the relative energy deficiency.

Background: Bariatric surgery induces significant weight loss, increases insulin sensitivity, and improves dyslipidemia. As one of the most widely performed bariatric surgeries, laparoscopic sleeve gastrectomy (LSG) is thought to improve the metabolic profile along with weight loss. The objective of this study was to evaluate longitudinal changes in the serum metabolite levels after LSG and elucidate the underlying mechanisms of metabolic improvement. Methods: Clinical metabolic parameters and serum samples were collected preoperatively and at 1, 3, and 6 months postoperatively from nine patients with obesity undergoing LSG. Serum metabolites were measured using a non-targeted metabolic liquid chromatography–mass spectrometry method. Results: During the 1, 3, and 6 months postoperative follow-up, the body mass index, HOMA-IR, and liver fat content showed a gradual descending trend. A total of 328 serum metabolites were detected, and 38 were differentially expressed. The up-regulated metabolites were mainly enriched in ketone body metabolism, alpha-linolenic acid and linoleic acid metabolism, pantothenate and CoA biosynthesis, glycerolipid metabolism, and fructose and mannose degradation, while the down-regulated metabolites were closely related to caffeine metabolism, oxidation of branched-chain fatty acids, glutamate metabolism, and homocysteine degradation. Notably, nine metabolites (oxoglutarate, 2-ketobutyric acid, succinic acid semialdehyde, phthalic acid, pantetheine, eicosapentaenoate, 3-hydroxybutanoate, oxamic acid, and dihydroxyfumarate) showed persistent differential expression at 1, 3, and 6 months follow-up. Some were found to be significantly associated with weight loss, insulin resistance improvement, and liver fat content reduction. Conclusions: This finding may provide a new perspective for revealing novel biomarkers and mechanisms of metabolic improvement in obesity and related comorbidities.

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.

Background Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator-activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined. Methods This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months. Conclusion This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D.

Background We explored the utility of a small multi-gene DNA panel for assessing molecular profiles of thyroid nodules and influencing clinical decisions by comparing outcomes between tested and untested nodules. Methods Between April 2022 and May 2023, we prospectively performed fine-needle aspiration (FNA) with gene testing via DNA panel of 11 genes (BRAF, RAS [NRAS, HRAS, KRAS], EZH1, DICER1, EIF1AX, PTEN, TP53, PIK3CA, TERT promoter) in 278 consecutive nodules (panel group). Propensity score-matching (1:1) was performed with 475 nodules that consecutively underwent FNA without gene testing between January 2021 and December 2021 (control group). Results In the panel group, positive call rate for mutations was 41.7% (BRAF 16.2%, RAS 12.6%, others 11.5%, double mutation 1.4%) for all nodules, and 40.0% (BRAF 4.3%, RAS 19.1%, others 15.7%, double mutation 0.9%) for indeterminate nodules. Benign call rate was 69.8% for all nodules, and 75.7% for indeterminate nodules. In four nodules, additional TP53 (in addition to BRAF or EZH1) or PIK3CA (in addition to BRAF or TERT) mutations were co-detected. Sensitivity, specificity, positive predictive value, and negative predictive value were 80.0%, 53.3%, 88.1%, 38.1% for all nodules, and 78.6%, 45.5%, 64.7%, 62.5% for indeterminate nodules, respectively. Panel group exhibited lower surgical resection rates than the control group for all nodules (27.0% vs. 52.5%, P

Background Adrenocortical carcinomas (ACCs) are rare tumors with aggressive but varied prognosis. Stage, Grade, Resection status, Age, Symptoms (S-GRAS) score, based on clinical and pathological factors, was found to best stratify the prognosis of European ACC patients. This study assessed the prognostic performance of modified S-GRAS (mS-GRAS) scores including modified grade (mG) by integrating mitotic counts into the Ki67 index (original grade), in Korean ACC patients. Methods Patients who underwent surgery for ACC between January 1996 and December 2022 at three medical centers in Korea were retrospectively analyzed. mS-GRAS scores were calculated based on tumor stage, mG (Ki67 index or mitotic counts), resection status, age, and symptoms. Patients were divided into four groups (0–1, 2–3, 4–5, and 6–9 points) based on total mS-GRAS score. The associations of each variable and mS-GRAS score with recurrence and survival were evaluated using Cox regression analysis, Harrell’s concordance index (C-index), and the Kaplan–Meier method. Results Data on mS-GRAS components were available for 114 of the 153 patients who underwent surgery for ACC. These 114 patients had recurrence and death rates of 61.4% and 48.2%, respectively. mS-GRAS score was a significantly better predictor of recurrence (C-index=0.829) and death (C-index=0.747) than each component (P

Background To evaluate whether insulin resistance and impaired insulin secretion are useful predictors of incident diabetes in Koreans using nationwide population-representative data to enhance data privacy. Methods This study analyzed the data of individuals without diabetes aged >40 years from the Korea National Health and Nutrition Examination Survey (KNHANES) 2007–2010 and 2015 and the National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS). Owing to privacy concerns, these databases cannot be linked using direct identifiers. Therefore, we generated 10 synthetic datasets, followed by statistical matching with the NHIS-HEALS. Homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of β-cell function (HOMA-β) were used as indicators of insulin resistance and insulin secretory function, respectively, and diabetes onset was captured in NHIS-HEALS. Results A median of 4,580 (range, 4,463 to 4,761) adults were included in the analyses after statistical matching of 10 synthetic KNHANES and NHIS-HEALS datasets. During a mean follow-up duration of 5.8 years, a median of 4.7% (range, 4.3% to 5.0%) of the participants developed diabetes. Compared to the reference low–HOMA-IR/high–HOMA-β group, the high–HOMA-IR/low– HOMA-β group had the highest risk of diabetes, followed by high–HOMA-IR/high–HOMA-β group and low–HOMA-IR/low– HOMA-β group (median adjusted hazard ratio [ranges]: 3.36 [1.86 to 6.05], 1.81 [1.01 to 3.22], and 1.68 [0.93 to 3.04], respectively). Conclusion Insulin resistance and impaired insulin secretion are robust predictors of diabetes in the Korean population. A retrospective cohort constructed by combining cross-sectional synthetic and longitudinal claims-based cohort data through statistical matching may be a reliable resource for studying the natural history of diabetes.

Background Identifying risk factors for postpartum type 2 diabetes in women with gestational diabetes mellitus (GDM) is crucial for effective interventions. We examined whether changes in insulin sensitivity after delivery affects the risk of type 2 diabetes in women with GDM. Methods This prospective cohort study included 347 women with GDM or gestational impaired glucose tolerance, who attended the follow-up visits at 2 months postpartum and annually thereafter. Changes in insulin sensitivity were calculated using the Matsuda index at GDM diagnosis and at 2 months postpartum (ΔMatsuda index). After excluding women with pregestational diabetes or those followed up only once, we analyzed the risk of postpartum type 2 diabetes based on the ΔMatsuda index tertiles. Results The incidence of type 2 diabetes at the two-month postpartum visit decreased with increasing ΔMatsuda index tertiles (16.4%, 9.5%, and 1.8%, P=0.001). During a 4.1-year follow-up, 26 out of 230 women who attended more than two follow-up visits (11.3%) developed type 2 diabetes. Compared to the lowest tertile, subjects in the highest ΔMatsuda index tertile showed a significantly reduced risk of type 2 diabetes (hazard ratio, 0.33; 95% confidence interval, 0.12 to 0.93; P=0.036) after adjusting for confounders. Conclusion Improvement in insulin sensitivity after delivery is associated with a reduced risk of postpartum type 2 diabetes in women with GDM. Postpartum changes in insulin sensitivity could be a useful prediction for future type 2 diabetes development in women with GDM.

The influence of thyroid hormone (TH) on liver metabolism has attracted the attention of pharmacologists seeking new treatments for metabolic dysfunction-associated steatotic liver disease (MASLD), an increasingly common metabolic disorder. In this context, the selective induction of autophagy by TH in preclinical models has been identified as a promising mechanism. In this process, TH clears intrahepatic fat through lipophagy while protecting against inflammation and mitochondrial damage in hepatocytes via mitophagy. Furthermore, TH-induced aggrephagy may represent a protective mechanism to mitigate the development of MASLD-associated hepatocellular carcinoma. Considering the defects in autophagy observed during the progression of human MASLD, the induction of autophagy by TH, its metabolites, and its analogs represent a novel strategy to combat hepatic damage across the MASLD spectrum.

Background Thyroid-associated ophthalmopathy (TAO) involves tissue expansion and inflammation, potentially causing a hypoxic microenvironment. Hypoxia-inducible factor (HIF)-1α is crucial in fibrosis and adipogenesis, which are observed in TAO progression. We investigated the effects of hypoxia on orbital fibroblasts (OFs) in TAO, focusing on the role of HIF-1α in TAO progression. Methods OFs were isolated from TAO and non-TAO patients (as controls). In addition to HIF-1α, adipogenic differentiation markers including peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer binding protein (CEBP) were measured by Western blot, and phenotype changes were evaluated by Oil Red O staining under both normoxia and hypoxia. To elucidate the effect of HIF-1α inhibition, protein expression changes after HIF-1α inhibitor treatment were evaluated under normoxia and hypoxia. Results TAO OFs exhibited significantly higher HIF-1α expression than non-TAO OFs, and the difference was more distinct under hypoxia than under normoxia. Oil Red O staining showed that adipogenic differentiation of TAO OFs was prominent under hypoxia. Hypoxic conditions increased the expression of adipogenic markers, namely PPARγ and CEBP, as well as HIF-1α in TAO OFs. Interleukin 6 levels also increased in response to hypoxia. The effect of hypoxia on adipogenesis was reduced at the protein level after HIF-1α inhibitor treatment, and this inhibitory effect was sustained even with IGF-1 stimulation in addition to hypoxia. Conclusion Hypoxia induces tissue remodeling in TAO by stimulating adipogenesis through HIF-1α activation. These data could provide insights into new treatment strategies and the mechanisms of adipose tissue remodeling in TAO.

Background Previous studies of fixed-dose radioiodine therapy (RIT) for Graves’ disease (GD) have utilized a variety of techniques and reported differing success rates. This study sought to compare the efficacy of RIT using two fixed-dose protocols and to estimate the optimal radioiodine (RAI) activity for the treatment of GD. Methods This retrospective trial enrolled 658 patients with GD who received RIT between January 2014 and December 2021. Participants were divided into two groups: protocol 1, which utilized a thyroid size-specific RAI dose, and protocol 2, which employed a modified dose calculation approach. The primary outcome assessed was the presence of euthyroidism or hypothyroidism at the 6-month follow-up. The success rates of RIT were compared between the two protocols. Results The RIT success rate was marginally lower for protocol 2 than for protocol 1 (63.6% vs. 67.2%); however, the risk of treatment failure did not differ considerably between the groups (relative risk, 1.1089; 95% confidence interval, 0.8937 to 1.3758; P=0.3477). The median RAI activity associated with protocol 2 was lower than that for protocol 1 (10.7 mCi vs. 15.0 mCi, P=0.0079), and the frequency of hypothyroidism was significantly lower in the protocol 2 group (39.0% vs. 48.9%, P=0.0117). Conclusion The success rate of the modified dose calculation protocol was comparable to that of the thyroid size-specific RAI dose protocol. The former approach reduced RAI activity and the incidence of hypothyroidism following RIT without compromising the success rate.

The prevalence of obesity in Korea has steadily increased over the past decade, reaching 38.4% in 2021. Notably, the rate of class II–III obesity, defined as a body mass index (BMI) of 30 kg/m2 or higher, exceeded 7% in the same year. Since January 2019, the National Health Insurance Service (NHIS) has provided coverage for bariatric surgery (BS) for eligible patients. Coverage is available for individuals with a BMI of 35 kg/m2 or higher, or those with a BMI of 30 kg/m2 or higher who also have obesity-related comorbidities. Additionally, partial reimbursement is offered for BS in patients with type 2 diabetes mellitus who have BMI values between 27.5 and 30 kg/m2. From 2019 to 2022, the NHIS recorded 9,080 BS procedures, with sleeve gastrectomy being the most commonly performed. The average percentage of weight loss 198±99.7 days post-surgery was 17.9%, with 80.0% of patients losing more than 10% of their body weight. This article presents the trends in obesity and BS in Korea.

Background We examined the impact of gout on the end-stage renal disease (ESRD) risk in patients with type 2 diabetes mellitus (T2DM) and determined whether this association differs according to chronic kidney disease (CKD) status. Methods Using the Korean National Health Insurance Service, this nationwide cohort study enrolled 847,884 patients with T2DM who underwent health checkups in 2009. Based on the presence of CKD (estimated glomerular filtration rate

Diabetes is a serious public health concern that significantly contributes to the global burden of disease. In Korea, the prevalence of diabetes is 12.5% among individuals aged 19 and older, and 14.8% among individuals aged 30 and older as of 2022. The total number of people with diabetes among those aged 19 and older is estimated to be 5.4 million. The incidence of diabetes decreased from 8.1 per 1,000 persons in 2006 to 6.3 per 1,000 persons in 2014, before rising again to 7.5 per 1,000 persons in 2019. Meanwhile, the incidence of type 1 diabetes increased significantly, from 1.1 per 100,000 persons in 1995 to 4.8 per 100,000 persons in 2016, with the prevalence reaching 41.0 per 100,000 persons in 2017. Additionally, the prevalence of gestational diabetes saw a substantial rise from 4.1% in 2007 to 22.3% in 2023. These changes have resulted in increases in the total medical costs for diabetes, covering both outpatient and inpatient services. Therefore, effective diabetes prevention strategies are urgently needed.

Background This study investigated the prognostic importance of the hemoglobin glycation index (HGI) for macrovascular and microvascular outcomes, mortality, and hypoglycemia occurrence in a type 2 diabetes cohort and compared it to glycated hemoglobin (HbA1c). Methods Baseline and mean first-year HGI and HbA1c, and the variability thereof, were assessed in 687 individuals with type 2 diabetes (median follow-up, 10.6 years). Multivariable Cox regression was conducted to evaluate the associations of HGI and HbA1c parameters with macrovascular (total and major cardiovascular events) and microvascular outcomes (microalbuminuria, advanced renal failure, retinopathy, and peripheral neuropathy), mortality (all-cause and cardiovascular), and moderate/severe hypoglycemia occurrence. Results During follow-up, there were 215 total cardiovascular events (176 major) and 269 all-cause deaths (131 cardiovascular). Microalbuminuria developed in 126 patients, renal failure in 104, retinopathy in 161, and neuropathy in 177. There were 90 hypoglycemia episodes. Both HGI and HbA1c predicted all adverse outcomes, except microalbuminuria and hypoglycemia. Their adjusted risks were roughly equivalent for all outcomes. For example, the adjusted hazard ratios (HRs) with 95% confidence intervals (CIs), estimated for 1 standard deviation increments, of mean first-year HGI were 1.23 (1.05 to 1.44), 1.20 (1.03 to 1.38), 1.36 (1.11 to 1.67), 1.28 (1.09 to 1.67), and 1.29 (1.09 to 1.54), respectively, for cardiovascular events, all-cause mortality, renal failure, retinopathy, and neuropathy; whereas the respective HRs (95% CIs) of mean HbA1c were 1.31 (1.12 to 1.53), 1.28 (1.11 to 1.48), 1.36 (1.11 to 1.67), 1.33 (1.14 to 1.55), and 1.29 (1.09 to 1.53). Conclusion HGI was no better than HbA1c as a predictor of adverse outcomes in individuals with type 2 diabetes, and its clinical use cannot be currently advised.

Background Phosphatidylinositol 3-kinase (PI3K) regulates cellular development and energy homeostasis. However, the roles of its subunits in organ development remain largely unknown. Methods We explored the roles of PI3K catalytic subunits in steroidogenic factor 1 (SF1)-expressing cells through knockout (KO) of the p110α and p110β subunits. Results We examined mice with a double KO of p110α and p110β in SF1-expressing cells (p110αβ KOSF1). Although these animals exhibited no significant changes in the development of the ventromedial hypothalamus, we noted pronounced hypotrophy in the adrenal cortex, testis, and ovary. Additionally, corticosterone and aldosterone levels were significantly reduced. The absence of these subunits also resulted in decreased body weight and survival rate, along with impaired glucose homeostasis, in p110αβ KOSF1 mice. Conclusion The data demonstrate the specific roles of PI3K catalytic subunits in the development and function of SF1-expressing organs.

Prior research has highlighted poor clinical outcomes in coronavirus disease 2019 (COVID-19)-infected patients with diabetes; however, susceptibility to COVID-19 infection in patients with diabetes has not been extensively studied. Participants aged ≥30 years who underwent COVID-19 testing from December 2019 to April 2020 were analyzed using the National Health Insurance Service data in South Korea. In a cohort comprising 29,433 1:1 propensity score-matched participants, COVID-19 positivity was significantly higher in participants with diabetes than in those without diabetes (512 [3.5%] vs. 395 [2.7%], P

Abstract Background Research on the relationship between dietary phytochemical intake and the anthropometric indices as well as the diabetic foot ulcers (DFUs) remains inconsistent. We aimed to investigate the associations of dietary phytochemical index (DPI) with the novel anthropometric indices and the severity of DFUs. Methods This cross-sectional study was conducted on 339 adults with type 2 diabetes. Dietary intake was assessed using three 24-hour dietary recalls. To quantify the phytochemical content of the diet, the DPI estimation was done through an equation proposed by McCarty. The International Working Group on the Diabetic Foot (IWGDF) criteria and Wagner classification system were applied to assess DFUs. New anthropometric indices including a body shape index (ABSI), body roundness index (BRI) and abdominal volume index (AVI) were calculated based on formulas. We employed analysis of variance (ANOVA), analysis of covariance (ANCOVA) and logistic regression to explore associations between DPI and the anthropometric indices and DFU variables. Results Our results revealed no significant association between DPI and the foot ulcer indices, following adjusting for the possible covariates. Furthermore, we also examined the relationship between diabetic neuropathy, as measured by monofilament score, and the DPI. Similarly, we did not find any substantial relationship between the DPI and monofilament score (OR: 1.18; 95% CI: 0.66–2.09; Ptrend = 0.56), as well as biochemical indices. Our analysis did not reveal any significant associations between the DPI and ABSI (OR: 0.70; 95% CI: 0.35–1.38; Ptrend = 0.30), BRI (OR: 0.80; 95% CI: 0.33–1.95; Ptrend = 0.59), and AVI (OR: 1.99; 95% CI: 0.92–4.33; Ptrend = 0.08). Conclusions Our study revealed no significant links between the DPI and foot ulcer indices, neuropathy measures, and anthropometric indices. These findings imply that factors beyond dietary phytochemical intake may exert greater influence on the development of foot ulcers in diabetes.

Abstract Objective This study aims to explore the association between the triglyceride-glucose (TyG) index and vitamin D status to enhance our understanding of how vitamin D status relates to metabolic health and to provide evidence for the early diagnosis of vitamin D deficiency (VDD) using the TyG index. Methods We conducted a comprehensive search in various databases, including PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), China Biology Medicine disc, China Science and Technology Journal Database, and Wanfang Data to gather articles published from the inception of these databases until February 19, 2024. We assessed the quality of included studies using the Newcastle-Ottawa Scale (NOS) for case-control studies and the Agency for Healthcare Research and Quality (AHRQ) methodology checklist for cross-sectional studies. Statistical analyses in this study were conducted using conversion methods for non-standard data formats and consolidation techniques for combining multiple groups. The Fisher transformation method was used for correlation coefficients. We used a random-effects model considering the inherent clinical heterogeneity among the studies, and assessed statistical heterogeneity with the Cochrane Q test and I2 statistic, complemented by subgroup analyses and sensitivity analysis. Results Our meta-analysis selected a total of nine studies. The analysis revealed that patients with vitamin D deficiency (VDD group) exhibited a significantly higher TyG index than those without deficiency (no-VDD group), with a mean difference (MD) of 0.16 (95% CI: 0.10 to 0.23, I2 = 93%). This association was particularly pronounced among patients with type 2 diabetes (T2DM), showing an MD of 0.15 (95% CI: 0.05 to 0.26, I2 = 55%). Additionally, a negative correlation was observed between the TyG index and vitamin D levels, with a correlation coefficient (r) of -0.236 (95% CI: -0.310 to -0.159, I2 = 91%). Excluding each study sequentially in the sensitivity analyses did not significantly alter the outcomes. Conclusions Our findings demonstrate a significant association between the TyG index and vitamin D status across diverse populations, including those with T2DM, subclinical hypothyroidism (SCH), and metabolic associated fatty liver disease (NAFLD). Our results reveal a notable disparity in the TyG index between vitamin D deficient and non-deficient groups, suggesting that vitamin D may play a critical role in metabolic health. These findings highlight the need for further research to explore the underlying mechanisms and clinical implications of vitamin D in the context of various metabolic disorders.

Abstract Background Type 2 diabetes mellitus (T2DM) was one of the most prevalent comorbidities among patients with coronavirus disease 2019 (COVID-19). Interactions between different metabolic parameters contribute to the susceptibility to the virus; thereby, this study aimed to rank the importance of clinical and laboratory variables as risk factors for COVID-19 or as protective factors against it by applying machine learning methods. Method This study is a retrospective cohort conducted at a single center, focusing on a population with T2DM. The patients attended the Yazd Diabetes Research Center in Yazd, Iran, from February 20, 2020, to October 21, 2020. Clinical and laboratory data were collected within three months before the onset of the COVID-19 pandemic in Iran. 59 patients were infected with COVID-19, while 59 were not. The dataset was split into 70% training and 30% test sets. Principal Component Analysis (PCA) was applied to the data. The most important components were selected using a ‘sequential feature selector’ and scored by a Linear Discriminant Analysis model. PCA loadings were then multiplied by the PCs’ scores to determine the importance of the original variables in contracting COVID-19. Results HDL-C, followed by eGFR, showed a strong negative correlation with the risk of contracting the virus. Higher levels of HDL-C and eGFR offer protection against COVID-19 in the T2DM population. But, the ratio of BUN to creatinine did not show any correlation. Conversely, the AIP, TyG index and TG showed the most positive correlation with susceptibility to COVID-19 in such a way that higher levels of these factors increase the risk of contracting the virus. The positive correlation of diastolic BP, TyG-BMI index, MAP, BMI, weight, TC, FPG, HbA1C, Cr, systolic BP, BUN, and LDL-C with the risk of COVID-19 decreased, respectively. Conclusion The atherogenic index of plasma, triglyceride glucose index, and triglyceride levels are the most significant risk factors for COVID-19 contracting in individuals with T2DM. Meanwhile, high-density lipoprotein cholesterol is the most protective factor.

Abstract Background This study aimed to compare the diagnostic accuracy of four indicators, including waist-to-height ratio (WHTR), vascular adiposity index (VAI), TG/HDL-C, and BMI/HDL-C for metabolic syndrome (MS) in Chinese adults aged 40 years and above. Additionally, the study aimed to develop an efficient diagnostic model displayed by a nomogram based on individual’s BMI and circulating HDL-C level. Methods A cross-sectional study was conducted on 699 participants aged 40 years and above. Quartiles of BMI/HDL-C, TG/HDL-C, VAI, and WHTR were used as independent variables, and metabolic syndrome was used as the dependent variable. Logistic regression was conducted to explore the impact of each parameter on the risk of MS. The areas under the receiver operating characteristics were compared to determine the accuracy of the indicators in diagnosing MS in the participants. Logistic regression was run to construct the nomograms, and the performance of the nomogram was assessed by a calibration curve. Results MS subjects had higher levels of BMI, BFM, PBF, VFA, AMC, WC, SCR, TG, and insulin, but lower LDH and HDL-C levels than the subjects without MS. The BMI/HDL-C ratio was positively correlated with the prevalence of MS and its components. The final diagnostic model included five variables: gender, BFM, WC, TG, and BMI/HDL-C. The model showed good calibration and discrimination power with an AUC of 0.780. The cut-off value for the nomogram was 0.623 for diagnosing MS. Conclusions BMI/HDL-C ratio was an independent risk factor for MS in Chinese adults. BMI/HDL-C was significantly correlated with MS and its components. BMI/HDL-C was the most powerful diagnostic indicator compared to other indicators, including TG/HDL-C, VAI and WHTR for diagnosing MS. The nomogram drawn based on the diagnostic model provided a practical tool for diagnosing MS in Chinese adults.

Abstract Background Metabolic syndrome (MetS) imposes a significant health burden on patients globally. Chronic low-grade inflammation is pivotal in the onset and progression of this condition. However, the role of the novel inflammatory marker, red cell distribution width to albumin ratio (RAR), in the development of MetS remains unclear. Methods This population-based cross-sectional study utilized data from the 2011–2020 National Health and Nutrition Examination Survey (NHANES). Participants included individuals over 18 years old with complete data on serum albumin concentration, red cell distribution, and MetS and its components. MetS was defined using the criteria established by the National Cholesterol Education Program Adult Treatment Panel III. The calculation formula for RAR is: RAR = Red cell distribution width (%)/serum albumin (g/dL). Study participants were stratified into four quartiles based on RAR levels. Logistic regression analysis and subgroup analysis were employed to explore the independent interaction between RAR and MetS, as well as investigate the relationship between RAR levels and the specific components of MetS. Finally, the receiver operating characteristic (ROC) curve was used to assess the predictive efficacy of RAR for MetS. Results A total of 4899 participants were included in this study, comprising 2450 males and 2449 females; 1715 individuals (35.01%) were diagnosed with MetS. As the quartile of RAR increased, the proportion of individuals with MetS also increased. Spearman correlation analysis indicated a positive correlation between RAR and the insulin resistance index HOMA-IR. Logistic regression analysis, adjusting for multiple confounding factors, showed that each standard deviation increase in RAR was associated with a significant 1.665-fold increase (95% CI, 1.404–1.975; P

Abstract Background Subclinical hypothyroidism (SCH) is characterized by elevated levels of thyroid hormone (TSH) and normal levels of free thyroxine (FT4). The outcomes of SCH patients are crucial for determining treatment plans; therefore, our aim is to summarize the existing prospective studies to understand the changes in thyroid function over time in SCH patients and the factors influencing these changes, providing references for clinical diagnosis and treatment. Methods We searched PubMed, Embase, Cochrane Library, and Web of Science for prospective follow-up studies on natural outcomes of SCH published until September 2024. Results are presented as the overall risk ratio (RR) and 95% confidence intervals (CI). Results We reviewed 8 prospective follow-up studies involving 1,859 individuals and extracted data from them for a meta-analysis. We found that when TSH levels are ≥ 10 mU/L, patients with SCH are more likely to progress to overt hypothyroidism (OH) (RR11.38, 95%CI 4.98–26.03, P

Abstract Background To explore the association of long non-coding RNA (lncRNA) SNHG1/ miR-195 axis with type 2 diabetes mellitus (T2DM) and islet function. Methods The expression of SNHG1 and miR-195 was measured in T2DM patients and in healthy subjects. Correlation between indciators was evaluated using Pearson correlation analysis. INS-1 cells were used to perform the cell function assays. Insulin secretion by INS-1 was detected using ELISA. Cell counting kit-8 (CCK-8) and flow cytometry was used to detect cell proliferation and apoptosis. Luciferase report assay was to used to verify the target of SNHG1. Results The expression of SNHG1 was increased and miR-195 level was decreased in the serum of T2DM patients. Both SNHG1 and miR-195 could be biomarkers for T2DM diagnosis. The fasting plasma glucose (FPG) and HbA1c were positively related to SNHG1 and negatively related to miR-195. SNHG1 inhibited insulin secretion, and cell proliferation and promoted apoptosis of INS-1 cells via binding to miR-195. Conclusions Detection of SNHG1 and miR-195 might predict T2DM. SNHG1 could suppress proliferation and insulin secretion, but promote apoptosis of INS-1 cells via sponging miR-195.

Abstract Introduction Sarcopenia is defined by low measures of muscle quantity, quality and reduced physical performance. It is associated with higher levels of frailty. Individuals with diabetes mellitus (DM) undergo sarcopenia at an accelerated rate resulting in structural changes potentially culminating in limb loss. Aims To review the evidence on methods of detecting and measuring sarcopenic changes on magnetic resonance imaging (MRI) in the foot in patients with diabetes. Methods A literature review was conducted in accordance with PRISMA guidelines. We searched Embase and Medline (via Ovid), CINAHL (via Ebsco Host), Web of Science and Scopus as well as the grey literature. The MeSH terms “sarcopenia” AND “diabetes mellitus” AND “magnetic resonance imaging” were employed in the primary search string. Results 874 studies were identified. 404 articles were excluded in the title and abstract screening. 33 studies were assessed for eligibility after abstract and title screening was completed by two reviewers. 7 studies evaluating sarcopenia in the foot were included in the final review. Conclusion Sarcopenic changes are evident on MRI of the foot in patients with diabetes and is profound in patients with diabetic neuropathy. The general extent and severity of sarcopenia seems to correlate with clinical scores to assess neuropathy and is implicated in the development of diabetic foot disease.

Delayed puberty in girls is often related to late maturation but is occasionally the first sign of premature ovarian insufficiency (POI). POI is a condition that affects ovarian function and fertility, and its etiology is unknown in most cases. Genetic factors have recently been identified in 20–25% of women with POI, involving genes that regulate various aspects of ovarian development and maintenance. We report a case of delayed puberty due to POI in an adolescent from a non-consanguineous family who carried two variants in the MCM9 gene. MCM9 is essential for DNA replication and repair, and its dysfunction can lead to chromosomal instability and ovarian failure. Our case highlights the importance of targeted gene panel analysis, particularly in POI patients with negative autoimmunity screening, and evidence of ovarian or uterine dysgenesis on pelvic imaging.

We present the case of a 50-year-old Japanese woman who was transferred to our hospital with a 2-day history of fever, sore throat, and malaise. She was diagnosed with acromegaly 9 months ago while being treated for diabetic ketoacidosis, for which she underwent pituitary surgery. She was diagnosed with hypopituitarism postoperatively and was prescribed hydrocortisone and levothyroxine. Her glycemic control was good on metformin. Tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza were positive in the emergency room. Other laboratory findings included thyrotoxicosis (free T3: 9.13 pg/mL; free T4: 3.64 ng/dL; and thyroid-stimulating hormone (TSH):

Objective: Hyperthyroidism increases cardiovascular morbidity and mortality, but the underlying mechanisms are not fully understood. In this study, we compared non-invasive haemodynamics between 20 hyperthyroid patients and 60 euthyroid subjects. Methods: The measurements were performed median 6 days after the initiation of antithyroid medication when the patients were still hyperthyroid. Three controls matched for age, sex, body mass index, and smoking status were selected for each patient. Recordings were performed during rest and passive head-up tilt using whole-body impedance cardiography, radial pulse wave analysis, and finger blood pressure measurements. Results: Systolic and diastolic blood pressures in the aorta and radial artery were similar in hyperthyroid and euthyroid subjects, while finger blood pressure was 16/12 mm Hg lower in hyperthyroidism (P < 0.001). Pulse wave velocity and aortic pulse pressure were similar, but radial pulse pressure was ~5 mm Hg higher in hyperthyroidism (P = 0.040) due to augmented amplification (P = 0.045). Systemic vascular resistance was reduced (−18%), whereas heart rate (+19 beats/min), cardiac index (+28%), and left cardiac work (+31%) were increased in hyperthyroidism (P < 0.001). Subendocardial viability ratio, reflecting the balance between coronary perfusion and pressure load, was reduced by 19% in hyperthyroidism (P < 0.001). Compared with euthyroid subjects, hyperthyroid patients presented with reductions in systolic and diastolic finger blood pressures (P < 0.001), and a higher increase in heart rate (P = 0.014) during upright posture. Conclusions: Hyperthyroid patients exhibited hyperdynamic circulation, reduced vascular resistance, reduced peripheral but not central blood pressure, and higher pulse pressure amplification. Furthermore, the left cardiac workload was increased in parallel with unfavourable changes in coronary perfusion conditions.

Background: To explore whether IgG4 is involved in the pathogenesis of IgG4 HT. Methods: Serum TgAb IgG4 and TPOAb IgG4 were measured in IgG4 HT and non-IgG4 HT. C1q, mannose-binding lectin (MBL), Bb, C3d, C4d, and membrane attack complex (MAC) in thyroid tissues from IgG4 HT, non-IgG4 HT, and controls were examined by immunohistochemistry. We assessed IgG4 and MAC deposition in mouse thyroid by immunohistochemistry after injecting purified IgG4 into mice. The glycosylation patterns of TgAb IgG4 from IgG4 HT were identified by MALDI-TOF-MS. The ability of IgG4 to bind to MBL before and after deglycosylation was assessed by ELISA. MBL and MAC fluorescence were detected in thyrocytes after the addition of IgG4 or deglycosylated IgG4. Results: Serum TgAb IgG4 and TPOAb IgG4 levels were significantly higher in the IgG4 HT group. MBL, Bb, C3d, C4d, and MAC levels were significantly higher in the thyroid tissues of IgG4 HT than in non-IgG4 HT (all P < 0.001). IgG4 colocalized with MBL by immunofluorescence. In mice, follicular cell structure disruption was observed after the injection of IgG4 from IgG4 HT, as well as the colocalization of IgG4 with MAC. High levels of TgAb IgG4 glycosylation patterns, including monogalactose glycan (G1F), galactose-deficient glycan (G0F), and high-mannose glycan (M5), were detected in IgG4 HT. After deglycosylation, IgG4 reduced its ability to bind to MBL, and there was low MBL and MAC activation in thyrocytes. Conclusion: High levels of IgG4 glycosylation patterns, including G1F, G0F, and M5, may activate the complement lectin pathway, thereby participating in the pathogenesis of IgG4 HT.

The aim of this study was to identify pitfalls in ovarian tissue cryopreservation protocol from referral to surgical procedures and to analyze factors associated with chemotherapy exposure of the cryopreserved tissue and decreased ovarian function in a cohort of young girls at high risk of infertility. The study population comprised 200 girls eligible for ovarian tissue cryopreservation between 2002 and 2020 at the Children's Hospital of the University Central Hospital of Helsinki (Finland). Analyses included the evaluation of the proportion of patients who underwent ovarian tissue cryopreservation, factors associated with patient selection and timing of ovarian tissue cryopreservation, and ovarian function during long-term follow-up in relation to oncological treatments. Lack of counseling was identified as the major reason for not receiving ovarian tissue cryopreservation. A longer interval from scheduling gonadotoxic therapy to cryopreservation correlated with a higher exposure to alkylating agents of the ovarian tissue. The long-term ovarian function was mainly influenced by age at the time of gonadotoxic treatment. Current selection criteria for ovarian tissue cryopreservation should be implemented in order to stratify patients at risk of infertility and timely identify those at higher risk, especially in relation to age and pubertal stage. Efforts to increase healthcare providers’ awareness and facilitate guided timing in relation to the treatment protocols are needed to guarantee early access to ovarian tissue cryopreservation for all patients at high risk of infertility. Lay summary Girls affected by cancer may undergo aggressive treatments to cure the disease, such as chemotherapy and radiotherapy, which can harm the ovaries. These treatments often result in the destruction of the ovaries and infertility. Nowadays, an option exists to help these girls recover their fertility after the cancer has been successfully treated. A fragment or an entire ovary can be removed by surgery and frozen before the treatments begin. When the girls are well and wish as adults to start a family, this fragment can be reimplanted back into the remaining ovary to restore fertility. This technique is called ovarian tissue cryopreservation. In this article, we report on the experience of ovarian tissue cryopreservation at the Children’s Hospital in Finland for 200 girls undergoing cancer treatment with a high risk of subsequent infertility. We analyzed the proportion of girls who had ovarian tissue cryopreservation performed among those exposed to aggressive treatments and investigated the reasons why some of them did not undergo the procedure. We also examined the time passing before the procedure was done to identify potential avoidable sources of delay. Finally, we explored how the ovaries of all the girls functioned during the time after the cancer diagnosis and looked at this in relation to their cancer treatments and ovarian tissue freezing.

Phosphatidylinositol-3 kinase (PI3K) is a critical intracellular pathway that regulates cell growth, metabolism, and survival and has been implicated in most human cancers. Targeting this pathway has been approved as a therapeutic option for breast cancer and lymphoma (e.g. alpelisib, idelalisib), and there are several clinical trials underway in additional types of cancer. However, PI3K is an important mediator of the action of insulin, and the use of PI3K inhibitors has been associated with hyperglycemia. We report the case of a 53-year-old female with metastatic breast cancer who developed acute grade 3 hyperglycemia from a novel PI3K inhibitor, inavolisib. We review the treatment options for PI3K inhibitor-associated hyperglycemia. Treatment strategies that minimize hyperinsulinemia may be preferable considering animal models have demonstrated that hyperinsulinemia may result in partial reactivation of the PI3K pathway and counter the anti-cancer effectiveness of PI3K inhibitors.

Assessment of hormone concentrations can be subjected to laboratory pitfalls. Macro-hormones are hormone– autoantibody complexes which are cleared slowly from circulation and cause a false elevation in hormones’ concentrations. Macro-prolactin and macro-thyroid-stimulating hormone (TSH) are most frequently encountered while macro-follicle-stimulating hormone (FSH) has been rarely reported. We describe the case of a 30-year-old woman who had a gynaecological consultation due to failure in achieving pregnancy after 8 months of unprotected intercourse. She had regular menses, did not complain of climacteric symptoms and her medical history was unremarkable. Antral follicle count and anti-mullerian hormone concentrations were normal, and regular ovulation was documented. Unexpectedly, high early follicular phase FSH concentrations were confirmed on two occasions (57 and 51 IU/L), raising the suspicion of primary ovarian insufficiency. After excluding Turner’s syndrome and autoimmune oophoritis, a laboratory artifact was hypothesized. Following polyethylene glycol precipitation, FSH levels dropped from 41.1 IU/L to 6.54 IU/L (recovery 16%) and the presence of macro-FSH was concluded. Laboratory interference can lead to misdiagnosis and unnecessary treatments. A laboratory artifact should be suspected when inconsistency exists between clinical presentation and laboratory results. Only five other cases of macro-FSH have been reported to date. Although macro-hormones generally have low biological activity and do not require treatment, the role of anti-FSH antibodies has been hypothesized in primary ovarian insufficiency and in vitro fertilization failure.

Objective: There are few reports of subacute thyroiditis (SAT) during pregnancy. This study aimed to clarify the clinical characteristics of SAT in pregnant patients. Methods and results: Seven patients diagnosed with SAT during pregnancy at our institution from January 2004 to December 2021 were identified, and their clinical findings were retrospectively examined. At SAT diagnosis, the median age was 34 (range: 31–42) years, the median duration of pregnancy was 5 (4–24) weeks, and all patients had neck pain but no fever. On laboratory examination, median (range) free thyroxine, free triiodothyronine, and C-reactive protein levels were 2.66 (1.14–7.77) ng/dL, 7.1 (3.3–16.1) pg/mL, and 2.22 (0.42–5.79) mg/dL, respectively, and all patients had a hypoechoic lesion of the thyroid gland. Three patients (43%) were treated with steroids, and three patients (43%) received replacement therapy with levothyroxine for hypothyroidism following destructive thyroiditis. There were no pregnancy complications in any of the cases. These seven patients (pregnancy group) were compared with 217 non-pregnant female patients (non-pregnancy group) aged 31 to 42 years who were diagnosed with SAT at our institution from 2016 to 2019. The frequency of body temperatures above 37°C was lower in the pregnancy group than in the non-pregnancy group (0% vs 65%). Conclusion: Patients who develop SAT during pregnancy may have less fever than non-pregnant patients with SAT. There were no pregnancy complications in the pregnancy group in this study. This suggests that adverse pregnancy outcomes may be avoided by the appropriate management of SAT, including hypothyroidism after destructive thyroiditis.

Follicular thyroid carcinoma (FTC) is the second most common histological type of thyroid carcinoma. This review aims to summarize the available evidence and guidelines and provide an updated consensus regarding the management of FTC. The cytoarchitectural features of FTC are similar to those of follicular adenoma (FA), and it is difficult to preoperatively distinguish between FA and FTC. For nodules with Bethesda class III–V cytology, molecular test results (if available) should be considered before the operation. However, it should be noted that molecular tests are not available in all countries. The goals of initial surgical therapy for patients with FTC are to improve overall and disease-specific survival, reduce the risk of persistent/recurrent disease and associated morbidity, and permit accurate disease staging and risk stratification while minimizing treatment-related morbidity and unnecessary therapy. Previous studies have reported some prognostic factors such as distant metastasis, age, tumor size, vascular invasion, TERT promoter mutation, and histological subtype. In particular, the degree of vascular invasion is becoming increasingly important. Evaluating these prognostic factors is essential for prognostic prediction and precise management of patients with FTC. Recurrence and distant metastasis of FTC are treated with radioactive iodine (RAI). However, some FTCs become refractory to RAI. Multi-tyrosine kinase inhibitors such as sorafenib and lenvatinib are utilized for treating RAI-refractory FTCs. In addition, given that renin–angiotensin system (RAS) is the most common driver gene for FTC, it is also important to develop RAS inhibitors.

The androgen receptor signaling inhibitor apalutamide is used successfully for the treatment of prostate cancer. An increased risk of hypothyroidism, mostly subclinical, has been reported in the SPARTAN and TITAN trials. We present three cases of subacute deterioration of previously known but well-controlled hypothyroidism treated with levothyroxine, occurring shortly after the initiation of treatment with apalutamide, resulting in severe hypothyroidism. These cases highlight the importance of awareness of thyroid dysfunction during treatment with apalutamide, particularly in patients with pre-existing thyroid disease, common in the general population. We provide practice recommendations for thyroid management prior to and during apalutamide treatment as well as after the interruption of this therapy.

Abstract Background Differentiated thyroid cancer (DTC) requires long-term follow-up due to the risk of delayed recurrence. Follow-up surveillance involves serial neck ultrasound (US) and thyroglobulin (Tg); however, the optimal frequency and diagnostic performance of neck US outside of specialized thyroid cancer centres in higher risk patients is not well defined. We sought to evaluate the diagnostic performance of US and serial Tg in advanced stage DTC. Methods We retrospectively reviewed our thyroid cancer database for patients with stage III and IV DTC from 2006 to 2018, total thyroidectomy, and at least 2 years follow-up to assess recurrence rates. Those with hemi-thyroidectomy or anti-Tg antibodies were excluded. Diagnostic performance of US and Tg were assessed using a composite reference standard of follow-up imaging and pathology. All relevant US were reviewed by a blinded expert radiologist for uniformity. Results Of 136 included patients (91 females, mean age 58.9), 26 (19%) had recurrence of DTC over median follow-up of 6.6 years (IQR 5.3–9.3). The sensitivity and specificity of US in diagnosing cervical recurrence were 73.3% (95% CI 0.51–0.96) and 68.3% (95% CI 0.60–0.77) based on historical reports, respectively, and 80% (95% CI 0.60-1.00) and 87.8% (95% CI 0.82–0.93) based on blinded expert review, respectively. Tg had a sensitivity of 95.5% (95% CI 0.89-1.0) and specificity of 96.2% (95% CI 0.92–0.99) in detecting cervical recurrence or distant metastases. False positive US findings on historical US and subsequent review occurred in 38 (28%) and 15 (11%) patients, respectively, while 5 (3.6%) had false positive Tg results. Conclusion Serial Tg has better sensitivity and specificity than US for detecting recurrence of advanced stage DTC. Furthermore, re-interpretation of abnormal findings using structured US reporting with a subspecialized reader may improve diagnostic performance of US and improve its utility in clinical care.

Abstract Background The presence of hypertension significantly increases the risk of diabetes, particularly type 2 diabetes. Recently, Visceral Adiposity Index (VAI) has been introduced as a straightforward and robust alternative indicator for early detection of metabolic syndrome, cardiovascular disease, and T2DM. Visceral adiposity, more dangerous than subcutaneous fat, is associated with metabolic syndrome and cardiovascular diseases. The VAI and Lipid Accumulation Product (LAP) are indices that quantify visceral fat and lipid overaccumulation, respectively. This study aims to explore the association between VAI, LAP, and type 2 diabetes mellitus (T2DM) in US adults with hypertension using NHANES data from 2005 to 2018. Methods We analyzed data from 5,620 participants with hypertension in The National Health and Nutrition Examination Survey (NHANES). VAI and LAP were calculated using established formulas. The VAI is calculated based on a combination of waist circumference, body mass index (BMI), triglycerides, and high-density lipoprotein (HDL) cholesterol levels. Logistic regression models were applied to evaluate the association between these indices and T2DM, adjusting for potential confounders. Subgroup analyses by age and gender were also conducted to assess variations in risk. Results In all, 5,620 participants were enrolled in our analysis, with 2,754 (49%) being female, and a mean (standard deviation, SD) age of 57 (15) years. The mean (SD) cumulative average VAI and LAP among all participants was 241 (2.71) and 75 (67), respectively. Totally, higher VAI and LAP indices were significantly associated with an increased risk of T2DM in individuals with hypertension. For VAI, the odds ratios (OR) for T2DM were higher in older adults (≥ 60 years) [95% confidence interval (CI): 1.37, 1.22–1.53, per 1 SD increase] and females [95% confidence interval (CI): 1.39, 1.27–1.52, per 1 SD increase], indicating age and gender differences in risk. Non-linear relationships were observed, suggesting thresholds beyond which the risk of T2DM escalates dramatically. Conclusions Both VAI and LAP are reliable markers for assessing T2DM risk in individuals with hypertension. Incorporating these indices into clinical practice could enhance the identification of high-risk individuals and facilitate early intervention strategies. Future longitudinal studies are needed to confirm these associations and explore targeted interventions.

Abstract Background 11β-hydroxylase deficiency (11β-OHD), caused by homozygosity or compound heterozygosity CYP11B1 variants, is the second most common cause of congenital adrenal hyperplasia (CAH). Due to the high degree of sequence identity between CYP11B1 and CYP11B2, chimeric genes, and complex structural variants (SVs), the conventional approach to gene testing for 11β-OHD is facing challenges. The study aimed to clarify the underlying genetic causes of two siblings of a Chinese family with 11β-OHD. Methods Peripheral blood samples and clinical information were collected from subjects and their family members. Sex steroid concentrations were measured using LC-MS/MS. Long-range PCR-based next-generation sequencing (NGS), PCR assay and target long-read sequencing were used to detect the pathogenic variants. Results Early onset hypertension, increased serum levels of adrenocorticotropin (ACTH), progesterone, testosterone, and decreased cortisol and potassium were detected in both affected siblings. Long-range PCR-based NGS identified a heterozygous missense variant (NM_000497.4:c.281 C > T, p.P94> L) in CYP11B1 gene in the two siblings. PCR detected no chimeric CYP11B2/CYP11B1 gene. We finally identified a second pathogenic variant in CYP11B1 gene via target long-read sequencing (T-LRS). This novel variant was a deletion-insertion variant and located chr8:143957269–143,957,579 (hg19) with the insertion of ‘ACAG’ (NM_000497.4:c.954 + 78_980delinsACAG), which was in trans with CYP11B1: c.281 C > T. Conclusions Our study suggests that the integrated long-range PCR-based NGS and T-LRS seem to be the most reliable and accurate method for 11β-OHD genetic diagnosis and carrier sequencing.

Abstract Background The cardiometabolic index (CMI) is a novel metric for assessing cardiometabolic health and type 2 diabetes mellitus (DM), yet its relationship with insulin resistance (IR) and prediabetes (preDM) is not well-studied. There is also a gap in understanding the nonlinear associations between CMI and these conditions. Our study aimed to elucidate these associations. Methods We included 13,142 adults from the National Health and Nutrition Examination Survey (NHANES) 2007–2020. CMI was calculated by multiplying the triglyceride-to-high density lipoprotein cholesterol (TG/HDL-C) by waist-to-height ratio (WHtR). Using weighted multivariable linear and logistic regression explored the relationships of CMI with glucose metabolism markers, IR, preDM, and DM. Nonlinear associations were assessed using generalized additive models (GAM), smooth curve fittings, and two-piecewise logistic regression. Results Multivariate regression revealed positive correlations between CMI and glucose metabolic biomarkers, including FBG (β = 0.08, 95% CI: 0.06–0.10), HbA1c (β = 0.26, 95% CI: 0.22–0.31), FSI (β = 4.88, 95% CI: 4.23–5.54), and HOMA-IR (β = 1.85, 95% CI: 1.56–2.14). There were also significant correlations between CMI and increased risk of IR (OR = 3.51, 95% CI: 2.94–4.20), preDM (OR = 1.49, 95% CI: 1.29–1.71), and DM (OR = 2.22, 95% CI: 2.00-2.47). Inverse nonlinear L-shaped associations were found between CMI and IR, preDM, and DM, with saturation inflection points at 1.1, 1.45, and 1.6, respectively. Below these thresholds, increments in CMI significantly correlated with heightened risks of IR, preDM, and DM. Conclusions CMI exhibited inverse L-shaped nonlinear relationships with IR, preDM, and DM, suggesting that reducing CMI to a certain level might significantly prevent these conditions.

Abstract Objective The current systematic review and meta-analysis assessed the prevalence of central precocious puberty (CPP) throughout the novel coronavirus disease 2019 (COVID-19) pandemic. Design A systematic review and meta-analysis were carried out following the principles outlined by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA, 2020). Data sources PubMed, Embase, Web of Science, and WANFANG databases were searched from January 1, 2019, to March 30, 2023. Eligibility criteria for selecting studies (1) children and adolescents ≤ 15 years; (2) studies with the outcome of frequency of central precocious puberty, measured prior to and throughout the COVID-19 pandemic; (3) a novel CPP diagnosis was created depending on all of the following criteria: girls with a chronological age 0.3 UI/L, and/or GnRH-stimulated peak LH levels > 5 IU/L. Data extraction and synthesis The process of extracting data and evaluating the likelihood of bias was carried out by two independent reviewers. The data were pooled employing the generic inverse-variance method and presented as mean differences (MDs) with 95% CIs. The evaluation of heterogeneity was conducted employing the Cochran Q statistic, and the degree of heterogeneity was measured employing the I2 statistic. Results This meta-analysis included 17 studies. In contrast to the same period prior to the COVID-19 pandemic, the occurrence of CPP elevated (OR = 2.57; 95% CI, 1.85–3.56). Moreover, body mass index standard deviation score (BMI SDS) differences between CPP patients prior to COVID-19 and throughout the pandemic follow-up was 0.12 (95% CI − 0.01 to 0.25 P = 0.06). Conclusion Overall, CPP frequency significantly elevated throughout the COVID-19 pandemic. Given the restricted number of cohort investigations in this meta-analysis, additional research may be conducted on larger groups of children in order to establish a correlation between the observed rise in precocious puberty and specific pathogenic factors.

Abstract Background The triglyceride glucose (TyG) index, defined as Ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2], provides insights into overall metabolic status. However, the association between the TyG index and gout has not been investigated. Therefore, this study explored the correlation between the TyG index and gout. Methods Using data from the National Health and Nutrition Examination Survey, which was conducted from 2007 to 2018, this study investigated the relationship between the TyG index and gout. Demographic data and potential risk factors were analyzed and compared using t tests for continuous data and chi-square tests for categorical data. Logistic regression and subgroup analysis were performed to examine the association between the TyG index and gout. Results A total of 14,924 participants were enrolled, among whom 726 (4.86%) were diagnosed with gout. Without controlling for any covariates, a significant positive correlation was observed between an elevated TyG index and increased risk of gout, with an odds ratio (OR) of 2.07 and a 95% confidence interval (CI) ranging from 1.76 to 2.43. After full adjustment, this association remained statistically significant, with an adjusted OR of 1.43 and a 95% CI from 1.14 to 1.80. Subgroup analyses revealed significant interactions, particularly for females (OR = 2.55; 95% CI: 2.00-3.26), individuals with no military service history (OR = 2.15; 95% CI: 1.66–2.43), and those without diabetes (OR = 2.00; 95% CI: 1.64–2.43). Conclusion A positive correlation was observed between the TyG index and gout. Consequently, further large-scale prospective studies are warranted for a comprehensive analysis of the role of the TyG index in gout.

Abstract Background Hyperuricaemia is common among obese children and adolescents, and is closely related to insulin resistance. The aim of this study was to explore the relationships between youth insulin resistance and hyperuricaemia, as well as their relationships with lifestyle factors in youths, to provide early guidance on the risk factors for hyperuricaemia in adolescents. Methods This study included 233 adolescents aged 10 to 20 years. Insulin resistance was evaluated via the homeostasis model assessment-insulin resistance (HOMA-IR) method. Binary logistic regression analysis was used to assess the associations of HOMA-IR with hyperuricaemia status and serum uric acid (UA) levels. The participants were subsequently divided into two groups, the noninsulin resistant group (HOMA-IR ≤ 3.2) and the insulin resistant group (HOMA-IR > 3.2), to further explore the factors that may affect the serum UA level. Finally, the predictive ability of different indicators of hyperuricaemia was evaluated via the ROC curve. Results Binary logistic regression analysis revealed a significant increase in the risk of developing hyperuricaemia for individuals with elevated HOMA-IR (p

Abstract Background Constipation, which affects 16% of adults worldwide, is a chronic health problem characterized by unsatisfactory frequency of bowel movements, causing pain, bloating or incomplete bowel movements. The study aims to assess the magnitude of chronic constipation and associated factors among T2DM patients attending the endocrinology outpatient clinic at Hiwot Fana Comprehensive Specialized University Hospital from January 1 to May 30, 2023. Methods Hospital-based cross-sectional study design was carried out to assess the magnitude and associated factors of chronic constipation among T2DM patients at Hiwot Fana Comprehensive Specialized University Hospital. Using a single population formula 300 T2DM patients were enrolled in this study. The data was analyzed by using the Epi-Data 4.6 and SPSS version 25. Descriptive, bivariate, multivariate, and logistic regression were used. P

Background: Pauci-immune glomerulonephritis (PIGN) is typically secondary to antineutrophil cytoplasmic antibodies (ANCA) small-vessel vasculitis. However, some cases lack detectable circulating ANCA and are called ANCA-negative PIGN (seronegative PIGN). The reported incidence of this varies greatly. Its relationship to ANCA-associated vasculitis (AAV) is unclear. Summary: This review explores the pathophysiology of seronegative PIGN and summarizes findings from twelve studies focusing on this disease. The role of neutrophils appears to be central, with activation through cellular and humoral mechanisms. Most studies have noted less extrarenal involvement and more chronic changes in the kidney biopsy in seronegative PIGN compared to ANCA-positive cases. Studies have mostly reported using corticosteroids with cyclophosphamide for induction therapy and azathioprine for maintenance. The renal survival was noted to be lower compared to ANCA-positive PIGN. Key messages: Whether ANCA-negative PIGN represents a distinct disease or is part of the AAV spectrum remains unclear. Prospective large-scale studies are needed to understand this disease for optimal diagnosis and management.