INTRODUCTION:Opioid-induced adrenal insufficiency (OIAI) is a known, but often overlooked complication associated with chronic opioid use. It is important to recognize OIAI as, if untreated, can lead to increased morbidity and mortality. AREAS COVERED:This narrative review discusses the prevalence, pathophysiology, diagnosis, and management of OIAI, with special emphasis on the current challenges. While investigations and treatment of OIAI is similar to other causes of adrenal insufficiency, it is important to recognize and test for other opioid-induced endocrinopathies. Furthermore, unlike some causes of adrenal insufficiency, OIAI has demonstrated reversibility following the discontinuation of opioids; therefore, cessation of opioids should be considered as a part of a multidisciplinary collaboration. EXPERT OPINION:Identification and appropriate treatment of patients with OIAI is important. Although recognition of this condition is increasing, further investigation is needed to identify additional risk factors to allow close follow-up of those at risk of OIAI or minimize the development OIAI.
INTRODUCTION:Chronic kidney disease (CKD) affects ~30-40% of people living with type-1 diabetes (T1D) and remains a major driver of cardiovascular morbidity, kidney-failure, and premature mortality. Despite advances in diabetes-technologies, kidney-protective pharmacotherapy in T1D has remained largely unchanged since the introduction of renin-angiotensin-system (RAS)-inhibition >30 years ago. In contrast, CKD-treatment in type-2 diabetes (T2D) has been transformed by sodium-glucose co-transporter (SGLT)-inhibitors, glucagon-like peptide (GLP)-1-based therapies, and nonsteroidal mineralocorticoid receptor antagonists. Exclusion of people with T1D from these pivotal trials created a critical evidence-gap. AREAS COVERED:We synthesizes mechanistic-/clinical evidence supporting a paradigm shift in kidney-protection for T1D. Literature searches of PubMed/MEDLINE, Embase, Web of Science, and ClinicalTrials.gov identified relevant English-language publications and ongoing studies through March 2026. We describe how the evolving T1D-phenotype, characterized by rising obesity and cardiometabolic dysfunction, strengthening the rationale for therapeutic translation. We critically evaluate current standards-of-care, unmet needs, and the renoprotective potential and safety of SGLT-inhibitors, GLP-1-based therapies, and finerenone in T1D, highlighting the pivotal FINE-ONE trial and albuminuria as a bridging biomarker for regulatory translation. EXPERT OPINION:CKD-management in T1D is entering a long-overdue phase of therapeutic renewal. Ongoing trials, 'pillar'-strategies, validated surrogate endpoints, precision-medicine, and multidisciplinary care may finally enable meaningful modification of CKD-trajectories.
INTRODUCTION:Resmetirom and semaglutide are the first drugs to be approved for the pharmacological treatment of metabolic-associated steatohepatitis (MASH) and moderate-to-severe liver fibrosis. However, approval was based on histological endpoints obtained during a relatively short trial period, leaving some important questions unanswered. AREAS COVERED:Resmetirom acts directly on the liver by activating thyroid hormone receptor β. Semaglutide acts systemically, reducing weight and improving metabolism. Both drugs induce resolution of MASH and improve liver fibrosis in a significant proportion of patients. The drugs are generally well tolerated, but significant gastrointestinal side effects can occur. Patient selection for treatment and efficacy evaluation should be based on noninvasive tests (NITs), but a substantial unresolved issue remains. Further issues include monitoring and the duration of treatment, as well as the impact of treatment on hepatic and systemic disease outcomes. Ensuring fair access to treatment for all is a challenge facing the global health community. EXPERT OPINION:This review explores the current approach to issues and challenges associated with using resmetirom and semaglutide in patients with MASH, proposing reference points to assist physicians in their clinical practice. Furthermore, we emphasize the importance of implementing interventions within the healthcare system to ensure equitable access to therapies.
INTRODUCTION:Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is a rare genetic endocrine disorder characterized by impaired cortisol synthesis, excessive adrenal androgen production, and elevated adrenocorticotropic hormone (ACTH) concentrations. The current standard of care involves supraphysiologic doses of glucocorticoids to suppress ACTH and manage androgen excess, often leading to long-term complications. AREAS COVERED:A literature search of PubMed was conducted. This review critically examines the pharmacology, clinical efficacy, and potential role of crinecerfont in redefining CAH management. EXPERT OPINION:Crinecerfont, a selective corticotropin-releasing factor type 1 receptor (CRF1) antagonist, offers a novel therapeutic approach by targeting ACTH secretion at its hypothalamic origin. Recent Phase 2 and Phase 3 trials have demonstrated promising efficacy and safety across adult, adolescent, and pediatric populations. Crinecerfont may represent a promising adjunctive therapy in CAH management, addressing both biochemical control as well as quality of life and potentially long-term outcomes.
INTRODUCTION:Metabolic dysfunction-associated fatty liver disease (MAFLD) affects 25-30% of the global population, with the Middle East and North Africa (MENA) region showing some of the highest prevalence rates, reaching up to 40%. MAFLD is a common cause of cirrhosis and hepatocellular carcinoma and is a leading indication for liver transplantation in this region. Hitherto, there have been no specific pharmacotherapies for MAFLD. However, the recent conditional approval of resmetirom and semaglutide by the FDA for the treatment of non-cirrhotic moderate-to-advanced (fibrosis stages 2 or 3) metabolic-associated steatohepatitis (MASH) offers a much-needed therapeutic option for this largely underserved condition. AREAS COVERED:An expert panel from the MENA region conducted a comprehensive literature search via PubMed and Google Scholar, focusing on clinical trials and international guidelines for resmetirom and semaglutide. This review identifies the target treatment population, proposes criteria for cessation of therapy, outlines monitoring protocols, and addresses regional knowledge gaps. EXPERT OPINION:The approval of the first two drugs for MASH is a milestone. Access to and affordability of these therapies will be the crucial determinants of their actual adoption. Future efforts should consider individualized treatment pathways stratified by cost, regulatory status, and healthcare infrastructure, while generating further regional evidence.
BACKGROUND:This study aimed to examine the association between iron deficiency (ID) and thyroid dysfunction among Jordanian adults. RESEARCH DESIGN AND METHODS:A cross-sectional analysis was conducted using data from 3,605 participants in a 2017 nationwide survey covering all 12 Jordanian governorates. Sociodemographic, anthropometric, and biochemical data were collected, including serum ferritin, thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4). Participants were categorized as having iron deficiency (ID), iron deficiency anemia (IDA), or control group (CG). Kruskal-Wallis and chi-square tests were used, with p < 0.05 considered significant. RESULTS:Individuals with ID and IDA had significantly lower FT3 and FT4 levels and higher TSH levels compared to CG. The prevalence of hypothyroidism and combined hypothyroidism plus subclinical hypothyroidism was higher in the IDA group (p = 0.0011 and p = 0.0126, respectively). No significant associations were observed for hyperthyroidism or subclinical hyperthyroidism. CONCLUSION:Iron deficiency, particularly IDA, was associated with an increased prevalence of hypothyroidism among Jordanian adults. These findings highlight the importance of thyroid function screening in individuals with low iron status and underline the need for longitudinal studies to clarify causal pathways.
INTRODUCTION:Prolactinoma, the most common functioning pituitary tumor, poses ongoing challenges due to variable clinical presentation, treatment resistance, and high recurrence rates. While normalization of prolactin (PRL) is a primary therapeutic goal, increasing evidence suggests that both insufficient and excessive PRL suppression may influence long-term outcomes. AREAS COVERED:A narrative literature search of PubMed, Embase, Scopus, Cochrane, and Web of Science was conducted without date restrictions. The review primarily included English-language studies published from 2015 through February 2026, while selected earlier studies were included when they provided essential background context. This review synthesizes current evidence on optimal prolactin levels in prolactinoma management, based on literature from clinical and observational studies. We examine the role of PRL dynamics as a marker of treatment response across pharmacological and surgical approaches. Particular attention is given to predictors of remission, recurrence after dopamine agonist withdrawal, and the clinical implications of both hyper- and hypoprolactinemia. EXPERT OPINION:Lower prolactin levels are associated with improved clinical outcomes; however, excessively low levels do not necessarily indicate optimal therapy and may carry overlooked risks. Early PRL trends reflect tumor response, underscoring the need to define optimal targets for individualized prolactinoma management.
INTRODUCTION:Graves' disease (GD) is a systemic autoimmune disorder, ultimately caused by autoantibodies stimulating the TSH receptor (TSHR-Ab) on thyroid follicular cells. Novel targeted therapies are under investigation, but treatment of GD still relies on antithyroid drugs (ATDs), radioactive iodine, or thyroidectomy. AREAS COVERED:Narrative review of original articles, randomized clinical trials, systematic reviews and meta-analyses, guidelines on PubMed from inception to March 2026, using the following terms: GD, management of GD, thyroidectomy, hypoparathyroidism, hypocalcemia, recurrent laryngeal nerve injury, hematoma, near-infrared autofluorescence, indocyanine green angiography, Graves' orbitopathy, thyroid eye disease. EXPERT OPINION:Thyroidectomy is the least common treatment for GD. However, it effectively eradicates hyperthyroidism, if all thyroid tissue is removed. Preoperative preparation includes ATD treatment to restore euthyroidism whenever possible, iodine solution (controversial in patients rendered euthyroid prior to surgery), and vitamin D (with or without calcium), if deficient. In patients with risk factors for cardiovascular (CV) complications, thyroidectomy may prevent the CV risk associated with unstable/severe hyperthyroidism. Thyroidectomy is safe in the hands of skilled, high-volume surgeons, with a low incidence of the main complications, i.e. hypoparathyroidism, recurrent laryngeal nerve injury, and hematoma.
BACKGROUND:The Hellenic study on Insulin Technique and Administration (HELITA) is a national questionnaire survey in Greece aiming to assess insulin administration practices among people with diabetes. RESEARCH DESIGN AND METHODS:The study enrolled 701 insulin-treated adults with type 1 and type 2 diabetes recruited from 40 diabetes care settings. Participants completed a structured questionnaire on insulin administration practices and underwent physical assessment of all injection sites by diabetes educators. RESULTS:Most participants (57.6%) reused insulin pen needles, while 38.9% did not rotate injection sites. Incorrect insulin dose titration was reported by 17.3%, 39.1% used long needles (8 mm), and 30.1% stored insulin incorrectly after first use. Notably, 41.1% had never had their injection sites inspected by healthcare professionals, and lipohypertrophy was diagnosed in 55.1%. Multivariate analysis showed that missed insulin doses (Odds Ratio: 1.73, 95% Confidence Interval: 1.14-2.62, p = 0.01) and lipohypertrophy were associated with poorer glycemic control. Increased risk of lipohypertrophy was observed among participants who did not rotate injection sites, reused needles, or lacked systematic education on insulin administration. CONCLUSIONS:Continuous education on insulin injection practices may contribute to improving glycemic control and reducing the risk of lipohypertrophy.
INTRODUCTION:Tirzepatide, a glucagon-like peptide-1 receptor agonist (GLP1RA) and glucose-dependent insulinotropic-peptide (GIP), has shown efficacy regarding weight-loss. METHODS:Systematic review and network meta-analysis of randomized controlled trials. MEDLINE, EMBASE, and Cochrane CENTRAL databases were searched between 2014 and 2024 for trials comparing sleeve gastrectomy (SG), Tirzepatide and other pharmacotherapies to control or each other. Eligible studies: adults with obesity and weight loss outcomes ≥24 weeks. Primary outcome: percentage change total body weight. Secondary outcomes included adverse events. Pairwise and network meta-analyses were performed. Interventions ranked by: P-score, mean difference (MD), 95% confidence intervals (CI). RESULTS:Data from 23 trials (14,293 participants) were analyzed. SG (MD 21.1% TWL, 95% CI 14.2% to 28.0%) and Tirzepatide 10 or 15 mg (MD 21.3% TWL, 95% CI 17.3% to 25.2%) demonstrated statistically equivalent weight-loss efficacy (P-score: 0.84) and had the most favorable effectiveness profiles. Semaglutide 2.4 mg (MD 12.7% TWL) and Liraglutide 3.0 mg (MD 5.1% TWL) showed moderate efficacy, whilst Orlistat showed minimal effect (MD 2.7% TWL, 95% CI -4.2% to 9.6%). Network meta-analysis of adverse events demonstrated that Semaglutide 2.4 mg and Orlistat had the most favorable safety profiles amongst pharmacotherapies. CONCLUSIONS:Tirzepatide 10 mg and 15 mg is equivalent to SG regarding weight-loss efficacy. REGISTRATION:This paper was registered with PROSPERO (ID: CRD420251016726). Due to institutional academic requirements and checks, registration was completed after the review began, however the review protocol (supplement material S1) was developed prior to the review, provided by the authors, and thoroughly adhered to by the authors.
INTRODUCTION:Fracture risk is substantially increased in chronic kidney disease (CKD) and rises with declining kidney function. Skeletal fragility in CKD results from reduced bone mass, altered bone microarchitecture, and disturbances in mineral and endocrine regulation of bone turnover, leading to high morbidity and mortality. AREAS COVERED:This review summarizes recent data on fracture incidence across CKD stages and discusses current diagnostic challenges, including the role and limitations of fracture risk prediction tools, dual-energy X-ray absorptiometry, and biochemical markers of mineral metabolism and bone turnover. The contribution of advanced imaging techniques to microarchitectural assessment is also addressed. Current guideline-based approaches are reviewed, alongside therapeutic considerations and the limited evidence supporting osteoporosis treatments in advanced CKD. A literature search was performed in Pubmed restricted to clinical studies published from 2015 through 2025 for a contemporary update on the topic. Osteoporosis after kidney transplantation was not included. EXPERT OPINION:In the absence of evidence-based treatment protocols for CKD-associated osteoporosis, fracture prevention should rely on pragmatic individualized risk assessment. Optimization of mineral metabolism and cautious use of bone-targeting therapies in high-risk patients are key components of management strategy. Future studies should prioritize CKD-specific fracture outcomes and validated diagnostic strategies to guide treatment decisions.
INTRODUCTION:The traditional school environment places emphasis on educational outcomes. There is great potential to build on existing work to re-design a school of the future that conflates both educational and healthcare provision for our children. This includes provision for the burgeoning global problem of childhood obesity and its sequelae. Through addressing the health, wellbeing and educational needs of our children, the future school should optimize health, happiness and success in adulthood. AREAS COVERED:We provide a template for a re-designed future school that optimizes the educational, health and wellbeing needs of our children (including the prevention of excessive weight gain) through changes to the physical environment, routine, food, cultural, and learning environments. Pubmed searches: published data on childhood obesity and its association with adulthood obesity, and existing innovations within schools, including those to improve physical activity and healthy eating. EXPERT OPINION:Children experience the world (and school) holistically. We need to align our re-design of schools accordingly. Given the links between health, wellbeing and educational attainment in children, we argue that the future school should ultimately contribute meaningfully toward a healthier, happier and more productive society.
INTRODUCTION:Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive disorder marked by severe hypertriglyceridemia and characteristic clinical manifestations, particularly acute pancreatitis. Conventional triglyceride-lowering therapy is largely ineffective. Apolipoprotein (apo) C-III has emerged as a key therapeutic target to lower triglycerides in FCS. AREAS COVERED:This review compares FCS with more common multifactorial chylomicronemia. We searched PubMed for all English language literature focusing on the search terms 'chylomicronemia,' 'hypertriglyceridemia,' 'APOC3 inhibition,' 'plozasiran,' 'olezarsen,' and 'volanesorsen.' We outline traditional management strategies and their limited role in FCS and explore non-traditional therapies including orlistat, lomitapide, inhibitors of angiopoietin like protein 3 (ANGPTL3), and analogues of fibroblast growth factor 21 (FGF21). The primary focus is on RNA-based gene silencing therapeutics that target apo C-III, particularly the small interfering RNA plozasiran and the allele specific oligonucleotides volanesorsen and olezarsen, highlighting key differences in efficacy and tolerability. EXPERT OPINION:In a phase 3 trial of plozasiran, at 10 months, median placebo-adjusted reductions in apo C-III were approximately -90%, while TG levels were reduced up to -59%. Thus, plozasiran and alternative RNA-based therapeutics directed against APOC3 represent transformational therapies for patients with FCS and related phenotypes characterized by severe recalcitrant hypertriglyceridemia.
INTRODUCTION:Subclinical atherosclerosis measured by coronary artery calcium (CAC) and osteoporosis often co-exist as indolent 'silent' conditions, remain underdiagnosed and undertreated, and are associated with significant morbidity and mortality. Bone density can be obtained accurately from non-contrast CAC scans, allowing for 'opportunistic' screening of OP without the need for additional tests or radiation, and thereby enhancing the yield of CAC scans and improving patient care globally. AREAS COVERED:This review will seek to highlight the significant relationship between osteoporosis and sub- clinical atherosclerosis. We also highlight the role of opportunistic measurements of bone mineral density (BMD) to accurately detect osteoporosis and osteopenia in CAC scans, without the need for additional radiation, tests, or financial burden. EXPERT OPINION:Osteoporosis is a major health problem, associated with significant morbidity and mortality, yet the condition remains under recognized, under diagnosed and undertreated. CT measurement of bone density is likely superior to BMD measures by DEXA, for fracture prediction. A link between CAC and osteoporosis beyond aging alone highlights the potential role of 'opportunistic screening' by non-enhanced CAC scans for early detection of osteoporosis and subclinical atherosclerosis simultaneously.
INTRODUCTION:Cushing syndrome (CS) is a complex endocrine disorder with multifactorial pathophysiology and diverse comorbidities. Long-term biochemical and clinical control of CS remains challenging. Osilodrostat, a potent oral 11β-hydroxylase inhibitor, has become as a valuable treatment option. AREAS COVERED:This review summarizes current clinical and real-world evidence on the efficacy and safety of osilodrostat in CS, and outlines practical considerations such as dose titration, monitoring, and management of adverse events, along with future directions for optimizing its use. EXPERT OPINION:Osilodrostat is an effective and well-tolerated therapy that leads to significant reductions in cortisol secretion and improves metabolic, cardiovascular, and psychological outcomes in patients with CS. Real-world studies support its efficacy across different forms and severities of endogenous hypercortisolism.
INTRODUCTION:Polycystic ovary syndrome (PCOS) is a lifelong endocrine-metabolic condition with prominent dermatologic manifestations such as hirsutism, acne/seborrhea, and female pattern hair loss (FPHL), which are frequently the initial complaint for seeking medical attention. AREAS COVERED:This review explores the pathogenesis and dermatologic presentation of PCOS across the lifespan, emphasizing evidence-based diagnostic strategies, based on a PubMed literature search through August 2025. It also highlights the impact on quality of life, the need for psychosocial support, and the importance of cultural sensitivity in care. Management approaches are reviewed including pharmacologic therapies, procedures, and considerations across reproductive stages including pregnancy, postpartum, and menopause. Future directions in management are also discussed. EXPERT OPINION:Current care remains largely symptom-driven. A shift toward mechanism-based, personalized therapy is essential. Key priorities include biomarker-guided treatment, standardized assessment tools, cautious antibiotic use with microbiome-sparing approaches, and clinical trials targeting treatment-resistant/recurrent cases and FPHL. In the future, routine care should incorporate phenotype- and biomarker-based algorithms, artificial intelligence (AI)-assisted assessment, and integrated mental health support.
INTRODUCTION:Interlinkage between lipid and carbohydrate metabolism remains a key focus of research into the pathogenesis and novel management of obesity-related conditions like Type 2 Diabetes (T2DM), dyslipidaemia, and Metabolic-Associated Fatty Liver Disease (MAFLD). The activity of Brown Adipose Tissue (BAT) unifies these two facets of metabolism and holds great therapeutic potential. AREAS COVERED:Through a brief narrative review of the current literature using Pubmed, with the search terms 'batokines,' 'metabolism' and 'obesity,' we outline the diverse effects of batokines on metabolism, BAT functioning, and metabolic signaling pathways. We explore a future role of batokines in the management of obesity and T2DM, as a biomarker for BAT activity and predictor and monitor of therapeutic response to future novel mitochondrial uncoupling therapies. EXPERT OPINION:Through its key role in the metabolism of lipids and carbohydrates, the mechanisms of BAT activation shed light on the complex mechanisms that interlink obesity with T2DM and other dysmetabolic conditions. Signaling biomolecules derived from BAT ('batokines') regulate the metabolic functioning of white adipose tissue and skeletal muscle, including glucose, lipid and protein metabolism, insulin sensitivity, and energy expenditure. Insights into batokine physiology will guide the next generation of therapies for obesity and its related dysmetabolic conditions.
