Transgender individuals have a gender identity incongruent with their sex assigned at birth. Social, medical and surgical methods are often affirming. This review focuses on updates from the last 18 months mainly in testosterone use in masculinising gender-affirming hormone therapy (GAHT) in postpubertal adults, and also antiandrogens for suppression or blockade of endogenous testosterone in feminising GAHT. Mental and sexual healthcare are vital for many transgender patients, but are not the focus of this review. There has been a considerable increase in publications regarding testosterone GAHT in recent years, though narrative reviews, opinion pieces and case series continue to dominate. There has also been a notable increase in prospective studies and valuable data particularly from large longitudinal cohorts and studies aiming to refine GAHT prescribing and better understand long-term effects on aspects such as fertility, cardiometabolic and bone health as well as adverse effects. Testosterone GAHT is life changing. Increased research will help GAHT optimisation, and improve understanding of tissue-specific impacts and long-term safety. Longer-term data, prospective studies and utilisation of novel research tools and approaches are needed to enrich our understanding and prescribing of testosterone and its blockers in GAHT.
Obesity during pregnancy is a growing global health concern with implications for maternal, fetal, and intergenerational outcomes. This review highlights pathophysiological mechanisms, clinical risks, and evidence-based management strategies across the preconception, antenatal, and postpartum periods. Maternal obesity amplifies pregnancy-associated insulin resistance, disrupts adipokine balance, and promotes inflammation, placental hormone dysregulation, and aberrant mTOR signaling. These mechanisms increase risks of gestational diabetes, hypertensive disorders, cesarean delivery, and macrosomia. Epigenetic modifications contribute to fetal metabolic programming, raising offspring risk of obesity, type 2 diabetes, and cardiovascular disease. Recent advances emphasize early risk stratification using continuous glucose monitoring, lipid and inflammatory biomarkers, and integration of telehealth-based lifestyle interventions. Precision medicine and microbiome-targeted therapies represent emerging frontiers. Management of obesity in pregnancy requires a continuum of care. Preconception optimization through lifestyle interventions and, in select cases, bariatric surgery improves outcomes. Antenatal care demands individualized metabolic monitoring, adherence to gestational weight gain targets, and pharmacologic interventions such as metformin when indicated. Postpartum priorities include structured weight management, diabetes prevention, and lactation support. Multidisciplinary, culturally tailored strategies are essential to mitigate the global burden of maternal obesity and its intergenerational consequences.
Recent advances in metabolomics, multi-omics integration, and neurogastroenterology have fundamentally reshaped understanding of the human gut microbiome. Rather than microbial composition alone, emerging evidence highlights microbial secretory and signaling activity as a central regulator of brain-gut communication. Understanding how microbiome-derived molecules interact with epithelial, immune, endocrine, and neural pathways is essential for advancing mechanistic insight and precision interventions in disorders of gut-brain interaction (DGBI). Recent studies demonstrate that the gut microbiome functions as a metabolic and endocrine signaling system, producing compounds such as short-chain fatty acids, bile acids, tryptophan-derived metabolites, polyamines, and lipid mediators that act on enteroendocrine cells, immune circuits, mechanosensory pathways, and vagal afferents. These signals are integrated centrally through brainstem and cortical networks, shaping gastrointestinal motility, visceral sensitivity, stress responsiveness, and affective processing. Functional dysbiosis and altered microbial signaling - rather than consistent taxonomic changes - appear to be primary modulators of brain-gut axis dysregulation. Emerging data calls for a reframing of gut-brain disorders as conditions of disrupted microbial signaling. Clinically, they support mechanism-based stratification and targeted dietary, microbiome-directed, and neuromodulatory therapies. The findings identify a need for functional biomarkers and targeted molecular approaches to advance precision medicine in DGBIs.
This review summarizes recent advances in understanding bone outcomes associated with lifestyle, surgical, and pharmacological weight-loss strategies. Lifestyle-induced weight loss achieved through calorie restriction is consistently associated with reductions in hip areal bone mineral density (aBMD) when weight loss is clinically meaningful. However, recent randomized controlled trials show that structured lifestyle interventions incorporating resistance exercise and adequate nutritional support can mitigate bone loss and preserve bone strength. These studies also emphasize the added value of advanced imaging techniques for evaluating bone quality beyond aBMD alone. In the surgical setting, accumulating evidence clarifies the detrimental skeletal effects of sleeve gastrectomy and other bariatric procedures, with postmenopausal women and adults over 60 years at particularly high risk. Preventive approaches, including targeted physical activity and antiresorptive therapies, are under active investigation. In parallel, emerging data on antiobesity medications are beginning to elucidate their skeletal effects, including changes in bone microarchitecture and fracture risk. Lifestyle interventions can attenuate skeletal impairment and preserve bone quality during calorie-restriction-induced weight loss. In contrast, bariatric surgery, particularly sleeve gastrectomy, adversely affects bone health, especially in postmenopausal women. The skeletal impact of antiobesity medications remains incompletely defined and warrants further study.
Early gestational diabetes mellitus (eGDM) is being increasingly detected on the background of rising obesity rates and widespread early pregnancy screening. However, diagnostic criteria and management strategies remain uncertain. This review summarizes current evidence on diagnostic thresholds, maternal and fetal outcomes, and the impact of early treatment, with an emphasis on balancing benefits and risks. While observational studies link eGDM to adverse maternal and fetal outcomes, evidence from intervention studies remains limited. The Treatment of Booking Gestational Diabetes Mellitus (TOBOGM) is the only large multicenter randomized controlled trial (RCT) published till date. The early intervention arm in the study received education on dietary counseling and capillary blood glucose monitoring, with pharmacotherapy using insulin or metformin introduced when indicated. The trial reported that treatment before 14 weeks reduced neonatal respiratory distress in higher glycemic bands but increased the risk of small-for-gestational-age state at lower glycemic bands. Notably, one-third of the untreated control group reverted to normoglycemia at 24-28 weeks. Given the uncertainties in diagnostic thresholds used in TOBOGM, a composite risk score-based approach integrating clinical and biochemical parameters may provide an alternative for identifying pregnancies in need of intervention. Current diagnostic criteria may not identify eGDM pregnancies that would benefit from intervention. Redefining diagnostic thresholds and integrating them with clinical risk factors could categorize pregnancies in need of intervention. Appropriately designed RCTs are required to generate evidence for accurate identification and optimal treatment of eGDM.
Hypertriglyceridemia (HTG) is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD) and acute pancreatitis (AP). Early detection and treatment are important to prevent such complications. This review briefly outlines the etiology and novel treatments of HTG and recent findings from contemporary HTG registries. HTG is associated with an increased prevalence of cardiometabolic risk factors, including obesity, diabetes, and hepatic steatosis. Novel ribonucleic acid-based treatments for HTG have shown a substantial reduction in plasma triglycerides and a lower incidence of AP. A recent trial confirmed such benefit in patients with triglycerides >500 mg/dl (5.6 mmol/l), albeit with an increase in low-density lipoprotein-cholesterol, a reduction in remnant cholesterol and no change in apolipoprotein B. There is a need to harmonize the definitions of HTG and improve the care of individuals with severe HTG and familial chylomicronemia syndrome. New and evolving international registries are beginning to provide useful real-world data. Patient registries for HTG have provided valuable data for understanding the link between HTG and other cardiometabolic disorders; they can inform the planning of clinical services and the translation of the findings of new and future clinical trials of triglyceride-lowering therapies.
Alongside its impact on cardio-metabolic parameters, obesity has been linked to infertility. This article aimed to provide a comprehensive review of the most current evidence linking male and female obesity and infertility. The risk of infertility affects both sexes: in males, excess adiposity alters the optimal functioning of the hypothalamic-pituitary-gonadal axis, affects function of the testicles and causes disruptions in spermatogenesis and sperm maturation whereas in females, obesity upsets the normal hormonal milieu which negatively impacts ovarian and uterine function leading to anovulation, menstrual irregularities, difficulties in development of embryo and implantation and recurrent miscarriages, especially in women with polycystic ovarian syndrome (PCOS) where hyperinsulinemia, hyperandrogenemia and other metabolic disruptions are involved. Numerous studies have established clear links between male and female obesity with infertility and to its pathophysiology and demographics. Evidence on treatment of obesity and impact on fertility outcomes is variable and needs further exploration.
Systemic therapy for refractory thyroid carcinoma has moved from chemotherapy and broad multikinase inhibitors towards molecularly targeted treatment. This review summarizes recent practice-changing developments in radioiodine-refractory differentiated thyroid carcinoma, with brief updates on medullary and anaplastic thyroid carcinoma. Recent guidelines and clinical studies emphasize early molecular testing, and careful selection of patients for personalized systemic therapy. Lenvatinib remains the preferred first-line multikinase inhibitor for most progressive radioiodine-refractory differentiated thyroid cancers without actionable alterations, while cabozantinib is the best-supported option after lenvatinib. Selective Rearranged during transfection (RET), Neurotrophic Tropomyosin Receptor Kinase (NTRK), and Anaplastic Lymphoma Kinase (ALK) inhibitors have reshaped treatment for fusion-positive disease, and MAPK inhibition can restore radioiodine avidity in selected tumours. In anaplastic thyroid carcinoma, BRAF/MEK-directed treatment and emerging immunotherapy-targeted therapy combinations have prolonged survival and in select instances also enabled resection. Contemporary management of refractory thyroid carcinoma relies heavily on early molecular testing and utilizing genotype-directed targeted therapy options.
Type 1 diabetes is increasingly complicated by obesity and broader metabolic dysfunction, yet there are barriers to the use of adjunctive pharmacotherapies in this population. This review evaluates the evidence for metformin, glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs), and sodium-glucose cotransporter-2 (SGLT2) inhibitors (SGLT2i) in type 1 diabetes, with a focus on weight loss, glycaemic control, insulin dose requirements and safety. Despite advances, metformin remains the only adjunct widely endorsed in national guidelines for adults with type 1 diabetes. In clinical trials, GLP-1RAs used alongside automated insulin delivery systems demonstrate significant improvements in weight, glucose sensor time-in-range, and total daily insulin dose, without increased risk of diabetic ketoacidosis (DKA). SGLT2i produce more modest weight and HbA1c improvements, and may be associated with an increased risk of DKA, although they have a clear evidence base for independent cardiovascular benefits. There is an increasing demand by patients and desire by physicians to utilize adjunctive medications in type 1 diabetes. Many patients with type 1 diabetes who are highly likely to benefit from the weight loss and cardiorenal risk reduction effects of these drugs are denied access to them because of putative safety concerns and a dearth of clinical trial evidence in type 1 diabetes. Identifying patients with type 1 diabetes most likely to tolerate and benefit from these agents is a research priority. Real world datasets accounting for the increased off license use of these drugs offers an opportunity to rapidly develop evidence-based guidance.
Diabetes foot ulcers (DFUs) affect millions globally, and are a global health challenge, contributing significantly to morbidity, mortality, and healthcare costs. This review article critically evaluates advances in artificial intelligence and new technologies and their potential to transform diabetes foot complications. Artificial intelligence-based thermal and clinical image analysis offer the potential for early detection, remote diagnosis and monitoring and to mitigate disparities in specialist access. Incorporating novel pressure and temperature sensing, wearable technologies could enhance foot monitoring and enable personalized care and intervention. However, ethical challenges with artificial intelligence, including accountability, limited explainability, data security and equitable access will have to be addressed. Artificial intelligence and wearable technologies could herald a paradigm shift in diabetes foot health and research. However, these exciting tools are not yet ready for adoption in clinical practice. Larger, well funded clinical intervention studies and greater collaboration between clinicians, artificial intelligence scientists and product engineers, working in partnership with people with diabetes, is needed if these approaches are to fulfil their potential.
Fertility and pregnancy in women with functioning pituitary adenomas are often compromised. Advances in surgical, medical and multidisciplinary care have improved outcomes, although important uncertainties remain regarding management before, during, and after pregnancy. Recent systematic reviews and meta-analyses have provided updated evidence on pregnancy outcomes in women with prolactinomas, acromegaly, and Cushing's disease. Although medical therapy is used selectively during pregnancy, studies of cabergoline and bromocriptine have consistently demonstrated overall maternal and fetal safety. Favorable surgical prolactinoma outcomes in specialized centers have led to evolving recommendations, with surgery increasingly considered an alternative to traditional dopamine agonist therapy for selected patients. Owing to the relative rarity of functioning pituitary adenomas in pregnancy, current clinical practice and guidelines rely largely on limited retrospective evidence regarding the disease course and outcomes. Although new medical therapies for acromegaly and Cushing's disease are now available, data to support their use in pregnancy are lacking. Management therefore remains individualized and emphasizes shared decision-making.
Given the global rise of MASLD, which impacts approximately one-third of the population, there is a need for earlier diagnosis and effective treatment strategies to avoid long-term hepatic cardiovascular and renal complications. This review summarizes the recent advances in noninvasive diagnosis and new pharmacological agents approved for MASLD. The main step forward in diagnostics is a step away from invasive biopsy and emphasis on noninvasive methods including serum biomarkers (e.g. CK-18 and FGF21), imaging (e.g. MRI-PDFF and US-FLI), combination of the two and use of artificial intelligence and machine learning models, for early detection and risk stratification of MASLD and MASH. Multiomics approaches, such as metabolomics and lipidomics, reveal disease-specific signatures, and may help with phenotypic classification of MASLD. Personalized management for MASLD include gut microbiota modulation and point-of-care devices for rapid diagnosis. Novel therapies include THR β agonists, GLP-1/dual GLP-1/GIP agonists, FXR agonists and FGF analogues, which show promise in reducing hepatic fat and fibrosis. These findings enable earlier MASLD diagnosis and tailored interventions, improving clinical outcomes in primary care and resource-limited settings. Future research should focus on validating cost-effective tools, and developing combination therapies to address the multifaceted nature of MASLD.
This review outlines the indications for medical management of hypercortisolism and summarizes available and emerging pharmacologic agents. Endogenous Cushing syndrome is a complex endocrine disorder resulting from chronic cortisol excess. The underlying etiology of Cushing syndrome is due to either adrenocorticotropic hormone (ACTH)-dependent causes, such as pituitary tumors (Cushing disease) or ectopic ACTH syndrome from nonpituitary neuroendocrine tumors, or ACTH-independent causes, such as autonomous cortisol production by adrenal adenomas, hyperplasia, or carcinomas. Cushing syndrome is associated with increased cardiometabolic morbidity and mortality, infections, thromboembolic events, cognitive and psychiatric disorders, and reduced quality of life. Successful treatment significantly reduces mortality and improves associated clinical and metabolic consequences of chronic hypercortisolism. Management of Cushing syndrome varies depending on the underlying etiology. While surgical resection of the causal lesion remains the first-line treatment for all etiologies of Cushing syndrome, second-line treatments, such as medical management, radiation therapy, and bilateral adrenalectomy, may be needed when surgery is not feasible or has failed. We discuss the efficacy of medical therapies for hypercortisolism, combination therapy strategies, special considerations in unique populations, and monitoring protocols. Finally, we explore emerging treatments and potential future directions in the management of this complex condition.
Circadian biology influences the gastrointestinal system as exemplified by hormonal patterns that modulate appetite. Indeed, people tend to get hungrier towards the later parts of the day. How misalignment of our circadian biology with behavioral factors (i.e. diet, exercise, sleep, etc.) influences obesity related disease has been an area of intense recent investigation. The gastrointestinal hormones (e.g. ghrelin, glucagon-like polypeptide-1, glucose dependent insulinotrophic peptide, peptide tyrosine-tyrosine, and insulin) play unique roles across the 24-h cycle in fostering anticipatory responses that promote desires to eat while concurrently responding to environmental stimuli. A persons chronotype has emerged as a target area since it provides a metric of circadian biology interacting with environmental factors and affects all people. In fact, later chronotypes tend to be at higher risk for obesity, due to in part, alterations in gastrointestinal hormones (e.g. GIP, insulin) that align with behavioral observations of greater food intake and desires to eat fatty/sweet foods later in the day. Changes in gastrointestinal hormones across the 24-h cycle impact obesity risk when misalignment of our circadian biology occurs with behavioral cycles. Better understanding how chronotype modulates appetite may enable personalized prescription of exercise, diet and/or medication to foster reduced chronic disease risk.
This review aims to discuss the cardiometabolic-renal-glycaemic effects of adjunctive diabetes agents in the management of type 1 diabetes. Recent studies have investigated the effectiveness and safety of adjunctive diabetes agents such as metformin, SGLT2 inhibitors and GLP-1 receptor agonists in individuals with type 1 diabetes. A rising trend of use of diabetes technology, notably continuous glucose monitoring (CGM) and continuous subcutaneous insulin infusion (CSII) devices, with improvement of glycaemic control, is observed. Questions arise whether these adjunctive diabetes agents and technologies confer cardiometabolic protective effects in patients with type 1 diabetes. The most widely studied adjunctive diabetes agent for type 1 diabetes is metformin. Meta-analyses suggest that metformin modestly improves glucose control, weight, lipid profile, and carotid intima-media thickness in patients with type 1 diabetes and mild obesity. SGLT2 inhibitors have been shown to modestly improve glycaemic control, weight, and blood pressure but are associated with increased risk of diabetic ketoacidosis in individuals with type 1 diabetes. The use of GLP-1 RA in type 1 diabetes with mild obesity provided modest HbA1c and weight reduction, but gastrointestinal side effects were common. The results of the ongoing phase 3 clinical trial of finerenone study in type 1 diabetes on chronic kidney disease progression are awaited. Observational studies suggest that CSII and CGM may also reduce cardiovascular events and hospitalizations in patients with type 1 diabetes.
Accurate measurement of parathyroid hormone (PTH) remains essential for the diagnosis and management of disorders of mineral metabolism, particularly in parathyroid disorders including in chronic kidney disease-mineral and bone disorder. Persistent inter-assay variability limits the comparability of clinical results across platforms and impedes guideline harmonization. This review focuses on recent advances in methodology, highlighting recent developments that move the field toward harmonization or even standardization of PTH assays. Recent landmark studies have applied liquid chromatography-tandem mass spectrometry (LC-MS/MS) as a candidate reference measurement procedure, enabling direct quantification of intact 1-84PTH with improved specificity. Novel immunocapture LC-MS/MS workflows demonstrate enhanced analytical precision and reveal substantive biases among commercial immunoassays. Recent progress in feasibility of harmonizing calibration was shown in a multicenter study where immunoassays were calibrated against LC-MS/MS reference methods, yielding reduced inter-assay bias, facilitating shared reference intervals. High-accuracy isotope-dilution mass spectrometry has been deployed to characterize reference materials, supporting future standard formulation. Emerging LC-MS/MS methods and harmonization strategies represent significant progress toward future standardization of assays for PTH. While technical complexity and cost still remain barriers, recent developments point towards improved analytical comparability and enhanced clinical interpretation.
Diabetes mellitus affects one in nine adults worldwide, with timely diagnosis and accurate classification being essential for patient management. C-peptide is an important biomarker in the diagnostic workup. As diabetes sub-typing and treatment options continue to evolve, this review will highlight the important aspects of C-peptide analysis and interpretation and additionally, evaluate its current and emerging clinical role. Several sample types and testing strategies such as fasting, random and stimulated C-peptide are available which are reviewed here. Random nonfasting C-peptide is convenient to perform in clinic and performs well compared to gold standard testing for classification of severe insulin deficiency and insulin dependence. C-peptide measurement may also be useful for classifying type 2 diabetes subtypes and in predicting response to treatment. Despite ongoing efforts towards standardization of C-peptide, variation still exists between analytical methods. This review summarizes recent literature relating to preanalytical, analytical and clinical aspects of C-peptide testing. Future research in this area may build on the role of C-peptide in predicting glycaemic control, clinical complications and response to pharmacotherapy.
Adrenal insufficiency is a potentially life-threatening condition requiring timely diagnosis. Baseline morning cortisol remains the initial diagnostic test; however, indeterminate values (3-15 μg/dl) necessitate dynamic testing, which is costly and labor-intensive. This review summarizes recent advances in diagnostic approaches for patients with indeterminate baseline cortisol levels. Studies support lowering morning cortisol cutoff values to reduce unnecessary cosyntropin testing. Dehydroepiandrosterone sulfate (DHEAS), when age-adjusted and sex-adjusted, may help rule out primary adrenal insufficiency in indeterminate cases. Salivary cortisone has emerged as a practical, home-based screening alternative that circumvents cortisol-binding globulin variability. The insulin tolerance test and overnight metyrapone test remain valuable for central adrenal insufficiency diagnosis, with recent data supporting revised cortisol thresholds. Emerging evidence supports a multimodal diagnostic approach combining baseline cortisol with adjunctive markers such as DHEAS and salivary cortisone. These strategies may reduce reliance on dynamic testing while maintaining diagnostic accuracy, ultimately improving patient convenience and healthcare efficiency.
This review aims to compare the different methods of achieving adequate thyroid-stimulating hormone (TSH) stimulation prior to radioiodine (RAI) therapy in patients with differentiated thyroid carcinoma (DTC). It focuses on thyroid hormone withdrawal strategies and recombinant human TSH, examining their relative efficacy, safety, and impact on patient quality of life. Additionally, the review highlights recent guideline updates, and how these approaches influence postoperative risk stratification, treatment decision-making, and follow-up. Emerging evidence is challenging traditional assumptions regarding optimal TSH stimulation thresholds and the necessity of prolonged thyroid hormone withdrawal, reflecting a broader shift toward individualized, risk-adapted management strategies in DTC. THW (Thyroid hormone withdrawal) delivers higher lesion doses; rhTSH (Recombinant human TSH) reduces whole-body radiation, with similar outcomes in low/intermediate-risk patients. Both achieve comparable ablation success, but rhTSH is safer and better tolerated. Both are suitable for dynamic risk stratification while rhTSH allows continued TSH suppression, aiding follow-up. Both THW and rhTSH are effective, but modern practice is shifting toward individualized, patient-centered use of rhTSH. However, THW still remains relevant in high disease burden and resource-limited settings. Future research is focused on optimizing thresholds, clarifying its role in molecular profiling, re-differentiation, and dosimetry-guided therapies.
The aim of radioactive iodine (RAI) in differentiated thyroid cancer (DTC) is ablation of thyroid remnant and/or treatment of residual disease. This review compares guidelines recommending the use of RAI (or not) in DTC, with a focus on randomized trials in low-risk DTC. Molecular genotyping offers therapeutic options in advanced RAI-refractory DTC. The ESTIMABL2 and IoN trials suggest that thyroidectomy (with or without central compartment lymph node dissection) followed by surveillance is sufficient in low-risk DTC, despite key differences in inclusion criteria, recurrence-definition, and monitoring protocols. RAI practice is tailored in many aspects: selection of intermediate-risk DTC for RAI and activity based on individual factors, including early dynamic risk assessment; lesional dosimetry in advanced DTC; restrictions following RAI; and choice of systemic therapy in the RAI-refractory setting. RAI in DTC is evolving towards a risk-adapted model. Escalating evidence indicates that RAI may be safely withheld in a large proportion of low-risk DTC. Optimal management of intermediate-risk DTC remains controversial, due to heterogeneity in clinical and pathological characteristics and conflicting data over survival advantage. Well designed studies incorporating molecular genotype may be key in identifying those most likely to benefit from RAI and in elucidating mechanisms of RAI-resistance.