PURPOSE OF REVIEW:Single-cell technologies have transformed our understanding of common cancers, though remain limited in scope for rare disease. The purpose of this review is to describe the impact of these studies on adrenocortical carcinoma. RECENT FINDINGS:Pangenomic studies in adrenocortical carcinoma have revealed that this disease is comprised of distinct molecular subtypes with prognostic import. Recent, though limited, single cell studies in adrenocortical carcinoma have characterized a unique interplay between steroidogenic cancer cell populations and the immune system. SUMMARY:Studies to date suggest that adrenocortical carcinoma is comprised of heterogeneous populations that coexist in specific ecotypes, with distinct features that may contribute to intrinsic therapeutic resistance. To leverage translational potential of these findings, large-scale multiinstitutional studies, including spatial information, are needed.
PURPOSE OF REVIEW:Functional gonadotroph tumors (FGTs) are rare tumors of the anterior pituitary gland which produce and secrete gonadotropins leading to symptoms. Given that these tumors are not common, there is limited information available regarding optimal management. RECENT FINDINGS:Symptoms attributable to gonadotropin secretion are often nonspecific in men and is often underrecognized in women. Consequently, many patients present with symptoms related to tumor mass effect, including visual changes and/or headaches, and are subsequently - or retrospectively - recognized to have an FGT. SUMMARY:A high level of clinical suspicion and thorough investigations will allow for detection of FGT. Like other pituitary tumors, surgery is the primary form of treatment. Although long-term follow-up data are limited given the rarity of this tumor, recurrence is reported and therefore long-term follow-up is necessary.
PURPOSE OF REVIEW:Thyroid dysfunction often delays surgery during preoperative evaluation, though evidence on perioperative risk and biochemical optimization is limited. This review explores recent literature on perioperative outcomes in hypothyroidism and hyperthyroidism, focusing on surgery delays, rapid optimization strategies, and areas of uncertainty. RECENT FINDINGS:Observational studies and meta-analyses link subclinical hypothyroidism with adverse cardiovascular outcomes in cardiac surgeries, but evidence for non-cardiac surgeries is limited. Overt hypothyroidism is associated with complications like impaired wound healing, prolonged ventilation, and cardiovascular issues, making euthyroid state preferable before surgery, despite retrospective, heterogeneous data. For hyperthyroid patients undergoing total thyroidectomy, recent literature questions the need for biochemical euthyroid state; evidence for non-thyroid surgeries is sparse and extrapolated from thyroid surgeries. Selective use of liothyronine and therapeutic plasma exchange in severe or urgent cases shows promise, but evidence is limited and low quality. SUMMARY:Current management of thyroid dysfunction is largely consensus-driven and based on limited evidence. Routine elective surgery optimization is advised for overt thyroid disease; however, in urgent cases, surgery after starting appropriate therapy and multidisciplinary planning is often reasonable. Future research should focus on prospective outcome data, rapid correction strategies, and the role of modern care pathways in reducing endocrine-related surgical risks.
PURPOSE OF REVIEW:Thyroid eye disease (TED) is a debilitating autoimmune disorder that can cause facial disfigurement, impair vision and reduce the quality of life. Novel insights into the pathogenesis of TED in the recent years have stimulated efforts to develop newer targeted medical therapies. This review summarizes latest advances in the medical management of TED, with a particular focus on novel targeted therapies. RECENT FINDINGS:Intravenous methylprednisolone is the conventional first line treatment for active moderate-to-severe TED. Although it is effective in reducing soft tissue inflammation associated with TED, it has limited efficacy in resolving proptosis and diplopia. Teprotumumab, a monoclonal antibody against insulin-like growth factor-1 receptor (IGF-1R), has emerged as an important disease modifying drug for TED. It is highly effective in reducing activity and improving manifestations of TED, including proptosis and diplopia. However, concerns remain related to its limited availability, high cost, potential adverse effects such as hearing loss, and durability of its treatment effects. More recently, Veligrotug (a full antagonist monoclonal antibody to IGF-1R) hasalso been shown to be effective in the treatment of active moderate-to-severe TED. Furthermore, there is some evidence to support the use of rituximab (monoclonal antibody against CD20) and tocilizumab (monoclonal antibody against interleukin-6) in early-onset and steroid-resistant active TED, respectively. Multiple other new forms of targeted therapies are currently being studied. SUMMARY:The development of novel targeted medications with expanding therapeutic options may facilitate personalized management of TED in the future.
PURPOSE OF REVIEW: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. RECENT FINDINGS: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. SUMMARY: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.
PURPOSE OF REVIEW:Advances in understanding of autoimmune hyperthyroidism and neonatal Fc receptor (FcRn) biology have created an opportunity for a novel immunomodulatory treatment approach. This review is timely in evaluating newly emerged literature for FcRn blockers Batoclimab (IMVT-1401), Imeroprubart (IMVT-1402) and Efgartigimod (ARGX-113) in Graves' disease and thyroid eye disease. RECENT FINDINGS:Preliminary phase 2 clinical trial data of Batoclimab therapy in Graves' disease demonstrated rapid normalisation of thyroid hormone levels with the majority maintaining this after the treatment course. Rapid declines in anti-TSH receptor antibodies were observed with a subset of patients achieving sustained seroconversion. A case report described maintained remission of Graves' disease 23 months following short-course Batoclimab therapy. Batoclimab was well tolerated with no treatment-related adverse events. Phase 3 clinical trials of Efgartigimod therapy in thyroid eye disease were terminated early due to it unlikely achieving the intended clinical efficacy following interim analysis. Mid- and late-phase clinical trials for Imeroprubart and Batoclimab therapy in Graves' disease and thyroid eye disease are ongoing. SUMMARY:FcRn blockade is a promising new therapeutic approach for the management of autoimmune hyperthyroidism. Durability, cost-effectiveness and patient selection remain to be defined.
PURPOSE OF REVIEW: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 FINDINGS: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. SUMMARY:Contemporary management of refractory thyroid carcinoma relies heavily on early molecular testing and utilizing genotype-directed targeted therapy options.
PURPOSE OF REVIEW: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. RECENT FINDINGS: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. SUMMARY: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.
PURPOSE OF REVIEW:Sarcopenia is a progressive, multifactorial geriatric syndrome linked to increased risk of falls, fractures, disability, frailty, and all-cause mortality. The pathophysiology of this complex syndrome remains unclear. Emerging evidence suggests that chronically elevated parathyroid hormone (PTH) concentration may contribute to muscle decline, increasing the risk of sarcopenia. This review evaluates the most recent evidence on the role of PTH in sarcopenia. RECENT FINDINGS:A recent meta-analysis of eleven observational studies involving 4759 participants supports an association between elevated PTH and a higher risk of sarcopenia. Proposed mechanisms include PTH-mediated alterations in serum calcium levels and modulation of muscle protein metabolism by PTH and its N-terminal fragment. The metabolic effects of elevated PTH may also indirectly affect muscle mass by altering skeletal muscle energy metabolism. SUMMARY:Elevated PTH concentration is increasingly linked to a higher risk of sarcopenia in older adults, although the biological mechanisms behind this remain only partially understood. Most current evidence comes from observational studies and cannot establish causation. Future research should focus on mechanistic studies in humans and interventional trials to determine whether higher PTH concentrations directly cause muscle decline and whether correcting PTH concentrations can lead to significant improvements in muscle mass and function.
PURPOSE OF REVIEW:Normocalcemic primary hyperparathyroidism (NPHPT) is defined by persistently elevated parathyroid hormone (PTH) levels in the presence of normal total and ionized serum calcium after excluding secondary causes of PTH elevation. Increasing use of biochemical screening has led to growing recognition of this phenotype, yet uncertainties remain regarding its natural history, diagnostic criteria, and optimal management. RECENT FINDINGS:NPHPT shares several clinical features with hypercalcemic primary hyperparathyroidism (HPHPT). Substantial rates of osteoporosis, fragility fractures, and nephrolithiasis are reported. Diagnosis requires repeated biochemical measurements, confirmation of normal ionized calcium, and rigorous exclusion of secondary causes such as vitamin D insufficiency, chronic kidney disease, malabsorption, and medication effects. Preoperative localization may also be more difficult than in HPHPT due to smaller adenomas and higher prevalence of multigland disease. SUMMARY:Parathyroidectomy appears safe and effective in selected individuals. However, NPHPT may carry a greater risk of recurrence than HPHPT. Improvements in bone mineral density (BMD) and quality of life (QOL) have been reported after surgery, although renal outcomes remain less certain.This review summarizes current evidence on the epidemiology, diagnosis, clinical manifestations, and management of NPHPT and highlights key areas requiring further study.
PURPOSE OF REVIEW:This review evaluates whether pregestational prediabetes identifies women at risk of subsequent gestational diabetes mellitus (GDM) and examines its association with maternal and offspring outcomes. RECENT FINDINGS:Prediabetes is common in women of reproductive age and often precedes GDM. The risk factors for prediabetes and GDM are similar, such as higher BMI, polycystic ovary syndrome, advancing age, and genetic susceptibility. Both conditions denote underlying insulin resistance with limited beta-cell reserve. Preliminary evidence indicates that women with pregestational prediabetes have a higher likelihood of developing GDM. Risk rises progressively with increasing glycemia. Prediabetes is also associated with modestly increased risks of hypertensive disorders of pregnancy and preterm birth, though associations with cesarean delivery, macrosomia, and neonatal outcomes are inconsistent. Glycated hemoglobin in the prediabetes range early in pregnancy is associated with a higher risk of progression to type 2 diabetes than GDM diagnosed at 24-28 weeks. These observations support the view that pregestational prediabetes may emerge as an early marker of metabolic risk with implications extending beyond pregnancy. SUMMARY:Prediabetes represents a state of increased metabolic risk in women planning pregnancy. It lies along a dysglycemic continuum linking preconception glycemic status to GDM and future diabetes. Incorporating glycemic assessment into preconception care may aid GDM risk stratification. However, the evidence is still evolving, and prospective studies are needed to define the role of pregestational prediabetes in predicting maternal, fetal, and long-term outcomes.
PURPOSE OF REVIEW: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 FINDINGS: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. SUMMARY: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.
Purpose of reviewType 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.Recent findingsDespite 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.SummaryThere 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.
PURPOSE OF REVIEW: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 FINDINGS: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. SUMMARY: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.
PURPOSE OF REVIEW: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. RECENT FINDINGS: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. SUMMARY: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.
PURPOSE OF REVIEW:Familial hypercholesterolemia (FH) in pregnancy poses several challenges, requiring a delicate balance between maternal atherosclerotic cardiovascular disease (ASCVD) risk and foetal safety. The review synthesizes current evidence, research gaps, evaluates emerging data on existing lipid-lowering strategies and highlights evolving guideline recommendations. RECENT FINDINGS:Pregnancy in women with FH has unique considerations for both the mother and the foetus. Data from registries and observational studies indicate that heterozygous FH (HeFH) does not significantly increase foetal adverse outcomes such as congenital malformation, prematurity, low birth weight although there may be a predisposition to early atherogenesis. Maternal risks include preeclampsia, endothelial dysfunction and prothrombotic tendency. Pregnant women with homozygous FH (HoFH) carry a substantially higher morbidity. Management strategies emphasize the need for timely, multidisciplinary care, dietary optimization, selective use of low-dose statins in high-risk HoFH and LDL apheresis for severe cases. Despite emerging evidence of lack of a major teratogenic risk, statins remain contraindicated in most guidelines, during pregnancy and lactation. Time off statins represent a critical gap in ASCVD prevention. SUMMARY:Pregnancy in FH requires a nuanced, stage-specific, individualized approach. Expansion of FH pregnancy registries and prospective studies is essential to guide evidence based care and refine recommendations for the future.
PURPOSE OF REVIEW:This review summarizes emerging evidence on the use of the dual glucose-dependent insulinotropic polypeptide (GIP)/glucagon-like peptide-1 (GLP-1) receptor agonist (RA) tirzepatide in improving obstructive sleep apnea (OSA) outcomes in individuals with obesity. RECENT FINDINGS:Tirzepatide has demonstrated significant reductions in apnea-hypopnea index (AHI) among patients with OSA and coexisting obesity. It has recently become the first medication approved by the U.S. Food and Drug Administration (FDA) specifically for moderate-to-severe OSA in adults with obesity. In addition to weight loss, tirzepatide has been associated with reduced cardiovascular, hepatic, and renal events, suggesting broader systemic benefits. SUMMARY:As a dual GIP/GLP-1 RA, tirzepatide represents a promising therapy for OSA in individuals with obesity, offering benefits of both weight reduction and symptom improvement. Given the high burden and underdiagnosis of OSA, particularly in populations with obesity, it should be considered earlier in the treatment algorithm, either in combination with or as an alternative to traditional therapies.
PURPOSE OF REVIEW:To summarize recent advances in therapeutic strategies targeting angiopoietin-like protein 3 (ANGPTL3), a central regulator of triglyceride and remnant lipoprotein metabolism, and to discuss the potential of emerging pharmacologic approaches. RECENT FINDINGS:Several pharmacologic approaches have demonstrated robust lipid-lowering efficacy through ANGPTL3 inhibition. Monoclonal antibodies (evinacumab, SHR-1918) and RNA-based therapies (vupanorsen, zodasiran, solbinsiran) effectively reduce triglycerides, apoprotein B (apoB)-containing lipoproteins, and nonhigh-density lipoprotein cholesterol. The newest and most promising innovation is CRISPR-mediated disruption of ANGPTL3 (CTX310). SUMMARY:ANGPTL3 inhibition represents one of the most powerful current strategies for lowering triglyceride-rich lipoproteins and residual cardiovascular risk. While monoclonal antibodies and RNA-based drugs offer effective, repeat-dose therapies, in vivo CRISPR editing could enable a one-time, lifelong correction of hypertriglyceridemia and mixed dyslipidemia. The main challenge ahead lies in ensuring safety, scalability, and equitable access if long-term efficacy and tolerability are confirmed in phase 3 trials.
PURPOSE OF REVIEW:To highlight the recent advancements in understanding the influence of psychological factors on the causation and management of obesity, which holds significance for clinical practice. RECENT FINDINGS:This review explores developments in understanding psychological risk factors, sequelae, and treatments for obesity. Despite good evidence for psychological therapies in weight management, there are no standardized protocols for assessing patients requiring metabolic and bariatric surgery. Psychological therapies are synergistic with obesity medications. SUMMARY:Obesity is a complex health issue with psychological dimensions. Stress, emotional dysregulation, and cognitive factors contribute to obesity. Stress's physiological impact on adipose tissue distribution and metabolic function, mediated by cortisol, demonstrates this interaction. Obesity leads to psychological consequences, including depression, low self-esteem, and reduced quality of life. The relationship between depression and obesity is modulated by demographic factors and biological mechanisms. Body composition reflects interactions between habits and cultural ideals, and medical models may increase stigma. Psychological interventions like cognitive-behavioral therapy and motivational interviewing effectively maintain weight loss. Psychological assessments before bariatric surgery are crucial for identifying mental health issues. This review highlights psychological dimensions in obesity prevention and treatment strategies.
Purpose of review 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. Recent findings 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. Summary 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.
