Heritable thyroid tumors represent a clinically important subset of endocrine neoplasms, accounting for approximately 3-9% of well-differentiated thyroid cancers and 25% of medullary thyroid cancers. In patients presenting with a new thyroid malignancy, recognition of an underlying hereditary cancer predisposition syndrome has important implications for management, surveillance for associated malignancies, and testing of at-risk relatives. This review summarizes the epidemiology, clinical presentation, histopathologic features, management, and surveillance recommendations for hereditary thyroid tumors in the setting of familial non-medullary thyroid cancer, multiple endocrine neoplasia type 2, familial adenomatous polyposis, Cowden syndrome, Li-Fraumeni syndrome, DICER1 syndrome, CHEK2-related cancer predisposition, and Carney complex. In the future, continued research is needed to better understand genotype-phenotype correlations, optimize surveillance strategies, and improve risk stratification to enable more personalized care for patients and families affected by these conditions.
Wolfram syndrome (WS) is a rare, progressive monogenic neurodegenerative disorder in which childhood-onset, insulin-deficient diabetes mellitus usually precedes optic atrophy and other multisystemic manifestations such as hearing loss, diabetes insipidus, urological and neuro-psychiatric abnormalities. This review summarises the underlying genetic basis and pathophysiology of Wolfram syndrome type 1 (WS1) and Wolfram syndrome type 2 (WS2), their neuro-ophthalmologic manifestations and phenotypic spectrum, as well as the multimodal biomarkers that are being used to objectively measure disease severity. Although classically known as a recessive condition with complex, severe, multiorgan involvement, WS1 caused by dominant WFS1 variants and a more limited form of the disease are increasingly being recognized. Biomarkers based on optical coherence tomography (OCT) parameters show promise for early diagnosis and disease monitoring. Lastly, emerging therapeutic options and future directions for treatment trials are discussed.
Thyroid eye disease is an immune-mediated orbital disorder most commonly associated with Graves' disease. Inflammatory expansion of orbital tissues causes proptosis, exposure symptoms, diplopia, and, in severe cases, dysthyroid optic neuropathy, with significant physical and psychological impact. Maintaining euthyroidism and promoting smoking cessation are central in its management; requiring close coordination between Ophthalmology and Endocrinology teams. Management of thyroid eye disease is guided by disease activity, severity, and phenotype, with the greatest response to immunomodulatory therapy occurring during the active inflammatory phase. Established therapies include glucocorticoids, orbital radiotherapy, steroid staring agents, whilst newer options such as biologics have expanded the therapeutic landscape. Surgical treatments are important in treating sight threatening disease refractory to medical therapy and in staged rehabilitation once disease inactivity and thyroid stability are achieved. This review outlines established as well as emerging therapies.
Orbital metastases (OM) are uncommon but clinically significant manifestations of systemic malignancy. Endocrine tumours represent a rare source of OM, often posing diagnostic and therapeutic challenges due to their variable presentation and indolent course. OM from endocrine tumours most commonly originate from differentiated thyroid carcinoma and neuroendocrine neoplasms. Presenting symptoms include proptosis, diplopia, pain and visual impairment, frequently mimicking inflammatory or primary orbital disorders. Imaging typically demonstrates mass-like orbital lesions, while in some cases definitive diagnosis based on histopathology may be required. Management is individualized and may include radiotherapy and/or surgical excision combined with systemic therapy in case of disseminated disease. Prognosis largely depends on the extent of systemic disease and tumour biology rather than orbital involvement alone. Although rare, OM should be considered in patients with endocrine malignancies presenting with orbital symptoms. Early recognition and multidisciplinary approach are essential to optimize visual outcomes, alleviate symptoms and guide systemic disease management.
Pituitary and hypothalamic tumours and disorders cause visual impairment due to proximity to structures critical for vision: intracranial optic nerves, chiasm and optic tracts. Visual dysfunction arising from compression of these structures typically has a profound impact upon quality of life. Visual fields should not be interpreted in isolation but in the context of a complete neuro-ophthalmic evaluation. Optical coherence tomography (OCT), specifically peripapillary retinal nerve fibre layer (pRNFL) and macular ganglion cell layer (mGCL), quantifies the degree of structural damage of the anterior visual pathway and optic chiasm. OCT changes may precede the onset of visual field changes in asymptomatic patients with chronic compression of the optic nerve or chiasm, and also have a prognostic role for predicting the recovery in visual function following surgery. This review focuses on an overview of the impact of pituitary and hypothalamic disorders, namely pituitary adenomas, macroprolactinomas, pituitary apoplexy, craniopharyngiomas, rathke cleft cysts, optic pathway gliomas, suprasellar meningiomas, hypophysitis and inflammatory disease on visual fields and function. The impact of interventions such as medical therapy, surgery and radiotherapy, as well as the adverse outcomes upon the visual function are also discussed. We highlight the key role of the neuro-ophthalmologist, within the multidisciplinary team, in the diagnosis and monitoring of these patients.
Multiple endocrine neoplasia type 2 is an autosomal dominant hereditary syndrome characterized by a predisposition to medullary thyroid carcinoma and pheochromocytoma. The discovery of the RET proto-oncogene as the molecular driver of this syndrome has revolutionized the management of this disease, enabling presymptomatic diagnosis of medullary thyroid carcinoma, which leads to prophylactic thyroidectomy, screening for pheochromocytomas, and the discovery of systemic therapies that control advanced disease. This article reviews genotype-phenotype correlations, clinical manifestations, and current therapeutic strategies, including the use of selective tyrosine kinase inhibitors. In addition, we propose an algorithm for the treatment of advanced medullary thyroid carcinoma and metastatic pheochromocytoma.
South Asians are more prone to obesity and prediabetes due to a combination of non-modifiable and modifiable risk factors. While non-modifiable factors are largely unchangeable, addressing modifiable factors particularly dietary patterns is crucial for intervention. As South Asian dietary practices differ substantially from other populations, international dietary recommendations may not always be appropriate. Therefore, this review synthesizes South Asian-specific nutrition advice. Evidence was drawn from interventional studies involving South Asians identified through a systematic search, and from country-specific guidelines, recommendations, and consensus statements from South Asian countries. In total, 10 interventional studies and 14 guidelines were included. The main recommendations included a reduction of total energy intake by approximately 15% or 500 kcal/day, carbohydrate intake ranging from 49% to 65% of total energy, fat intake of, 19-32%, protein intake of 15-19%, incorporation of pre-meal nut consumption and achieving a target weight loss of .5-7%.
Skeletal muscle mass (SMM) is a key determinant of physical performance, metabolic health, and functional capacity across the lifespan. This paper provides an evidence-based overview of the effects of exercise on SMM accrual across different age groups and associated practical applications for exercise training. Evidence suggests that hypertrophic responses may vary across the lifespan, with differences observed between children and youth, middle-aged, and older populations. In younger and middle-aged populations, the primary training objective should be directed toward increasing SMM, while in older individuals, resistance training is particularly relevant for mitigating age-related declines in muscle mass. Despite these age-related differences, resistance exercise has consistently been shown to be a highly effective stimulus for increasing skeletal muscle mass across all age groups. Furthermore, in certain populations, particularly less trained individuals, endurance training modalities may also contribute to skeletal muscle adaptations. However, endurance training alone is generally associated with less pronounced effects on SMM and may primarily be implemented to support overall health-related outcomes.
Polyendocrine metabolic ovarian syndrome (PMOS) or polycystic ovary syndrome (PCOS) is highly prevalent in South Asian women and is frequently associated with early insulin resistance and elevated cardiometabolic risk at comparatively low body mass index (BMI), predisposing them to type 2 diabetes (T2D) and obesity. Conventional clinical markers (BMI, fasting glucose, and androgens) incompletely capture the metabolic heterogeneity of PCOS, particularly in lean or centrally adipose phenotypes common in this population. Metabolomics provides an integrated, pathway-level view of systemic metabolism and has identified perturbations in amino-acid networks, mitochondrial fatty-acid oxidation, complex lipids, bile acids, and steroid metabolism. Emerging evidence supports distinct metabolic endotypes that may refine early risk stratification for dysglycaemia and weight gain. We provide an overview of metabolomics research in PCOS, with a translational focus on early risk stratification for T2D and obesity in South Asian women, and outline priorities for the development of clinically actionable biomarkers.
In this manuscript, the relation of the hypothalamic-pituitary-adrenal axis to energy handling, thyroid function, gonadal and growth hormones are discussed against the background of stress. Clinical data from the SHIP-PAGE (steroid hormones in patients with pituitary, adrenal and gonadal endocrinopathies) study are provided to show that the HPA axis is sensitive to glucose and interferes with the activities of other pituitary axes. While chronic stress leads to central hypogonadism and a loss in muscle mass, high glucose loads hamper the plasticities of the HPA, the hypothalamic-pituitary-gonadal as well as the hypothalamic-pituitary-growth hormone axes but elevate insulin concentrations. Therefore, prevention programs ideally include strategies to reduce stress and promote muscle activity.
The growing burden and heterogeneity of type 2 diabetes mellitus (T2DM) require management strategies that extend beyond episodic clinic visits. Digital health technologies mHealth platforms, wearables, telemedicine, continuous glucose monitoring (CGM), and connected insulin delivery now generate high-frequency, real-world data that can support continuous care. Evidence suggests that the use of mHealth platforms among individuals with T2DM is associated with an approximate 0.5% reduction in HbA1c, highlighting their potential clinical benefit(1). When coupled with artificial intelligence (AI), these systems shift diabetes management toward prediction, personalization, and proactive intervention. This review appraises the clinical evidence for technology-enabled T2DM care and examines how AI improves risk stratification, detection of dysglycemia patterns, treatment optimization, and behavioural support. We discuss implementation challenges related to data quality, interoperability, governance, explainability, bias, regulatory oversight, and equity, with attention to low- and middle-income contexts. We propose a roadmap for translating AI-enabled diabetes ecosystems into routine care while maximizing effectiveness, safety, and accessibility.
Diabetes distress (DD) is a phenomenon that highlights the emotional strain of having diabetes and the unrelenting demands of this illness; DD is very high and known in a poorly studied area of South Asia. This review is based on evidence published since 2023 and provides an enhancement of the 2023 South Asian Federation of Endocrine Societies (SAFES) recommendations. A 2025 systematic review and meta-analysis found pooled prevalence of type 2 diabetes distress of 85% in Pakistan, 42% in India and Bangladesh and 25% in Sri Lanka with emotional burden turning out to be the prevailing domain. The predictors of increased distress are always female gender, low socioeconomic status, prolonged period of the disease, comorbidities and poor glycemic control. Qualitative research indicates that South Asian patients are distressed due to family strain, out-of-pocket expenditure compelling them to decide whether to purchase the drug or not and fragmented health systems that isolate mental and physical health care. Cultural factors such as gendered roles in care giving, limited resources in the household budget and lack of social support increase emotional load and limit self-management. Clinicians can deal with diabetes distress by screening with validated measures and including short-term psychosocial counseling with diabetes visits, simplifying regimens to minimize hypoglycemia, addressing social support shortfalls and promoting care that is gender-sensitive and affordable. The review can guide South Asian clinicians to identify, evaluate and act on diabetes distress in resource limited, culturally diverse environments which will in turn enhance the glycemic and quality of life outcomes.
Thyroid hormones (THs) are fundamental regulators of skeletal muscle energy metabolism and protein turnover. Instead of directly stimulating muscle growth, they create the intracellular environment required for effective adaptation to exercise. Adequate TH availability supports mitochondrial integrity, ribosome biogenesis, and coordinated protein turnover, thereby enabling the translation of anabolic signaling into structural adaptation and remodeling. Accordingly, reduced translational efficiency during hypothyroidism may blunt hypertrophic responses. In contrast, hyperthyroidism accelerates proteolytic pathways and compromises net protein gain despite elevated turnover. Training modalities determine the physiological outcome within this endocrine context, with endurance exercise primarily enhancing oxidative remodeling, while resistance training, when sufficient biosynthetic capacity is present, can stimulate myofibrillar accretion. Reduced energy availability lowers T3 concentrations and may attenuate adaptive efficiency across both modalities. Overall, thyroid status emerges as a critical determinant of muscle remodeling capacity, underscoring the clinical relevance of thyroid assessment in exercise-based interventions.
Sexual dysfunction (SD) is a prevalent but frequently overlooked complication of Type 2 Diabetes Mellitus, with a particularly high burden in South Asia, a region experiencing a rapid rise in diabetes prevalence. Despite its significant effects on quality of life, interpersonal relationships, and psychological well-being, SD is often insufficiently addressed in routine clinical care. This gap is largely influenced by sociocultural barriers, limited openness in patient-physician communication, and inadequate access to specialized services. In men, erectile dysfunction (ED) represents the most common clinical manifestation and may occur before overt cardiovascular disease, reflecting underlying endothelial and vascular abnormalities. In contrast, sexual dysfunction in women is more heterogeneous, encompassing reduced sexual desire, impaired lubrication, difficulty achieving orgasm, and pain during intercourse. These issues often carry profound personal and relational implications within South Asian sociocultural settings. The underlying mechanisms are complex and multifaceted, involving vascular compromise, autonomic neuropathy, hormonal imbalance, as well as psychological and sociocultural influences. Comprehensive evaluation includes the use of validated assessment instruments, focused clinical examination, and appropriate laboratory investigations. Management requires a holistic and culturally appropriate strategy, integrating optimal glycaemic control, management of cardiovascular risk factors, psychosocial support, and involvement of partners when appropriate. In addition, condition-specific pharmacological and non-pharmacological interventions should be tailored to individual needs. This review consolidates current evidence with an emphasis on the South Asian context, identifies significant gaps in regional and gender-specific data, and explores the potential implications of emerging glucose-lowering therapies on sexual health outcomes.
Type 2 diabetes disproportionately affects South Asian populations, who typically develop earlier onset disease associated with a high lifetime burden of complications. Conventional tools to predict diabetes complications, largely derived from European-ancestry cohorts and traditional clinical variables, perform suboptimally in South Asians and leave substantial residual risk unexplained. This review synthesises evidence on non-conventional predictors of microvascular and macrovascular complications in South Asian adults with type 2 diabetes. We examine life-course and early developmental determinants, ectopic fat, socioeconomic and environmental exposures, psychological and behavioural factors, non-conventional glycaemic metrics, novel organ-specific biomarkers, genetics, and artificial intelligence approaches. Although many predictors show promise, most lack validation in longitudinal South Asian cohorts and meaningful predictive value beyond existing clinical risk scores. Integrating diverse data types may enable more precise risk stratification, but robust external validation and evidence of improved patient outcomes are required before implementation in routine diabetes care.
In this review, we discuss the concept of Malnutrition Modulated Diabetes Mellitus, currently labelled as Type 5 diabetes mellitus, a distinct form of diabetes seen in lean, undernourished individuals, particularly in low- and lower middle-income countries. This review highlights the role of early-life and chronic undernutrition in impairing pancreatic β-cell development and diminished insulin secretion with preserved insulin sensitivity. Furthermore, we present epidemiological, experimental, and clinical evidence of undernutrition and its effects on glucose tolerance and discuss the differential diagnoses of this disorder and its differentiating features from other forms of diabetes, and emphasize the need for specific diagnostic criteria and tailored management strategies for this neglected form of diabetes.
Muscle mass is a strong indicator of overall health in older adults. In healthy individuals, an adequate muscle mass is maintained through a balance between anabolic pathways, such as the mTOR pathway (mammalian target of rapamycin), and catabolic pathways, including the myostatin signaling. With aging, hormonal decline, insulin resistance, mitochondrial dysfunction, and lifestyle factors contribute to the development of anabolic resistance. Thus, the regulation of muscle protein synthesis becomes less efficient in older adults. Diagnostic parameters for sarcopenia are highly useful in this population as they enable proper assessment of muscle mass, muscle strength and physical performance. Appropriate management of sarcopenia relies on a multimodal approach that combines physical exercise, tailored nutritional strategies, and potential pharmacological intervention, representing a key strategy for preserving muscle mass, functional capacity, and quality of life in older adults.
Prolactinomas are the most common functioning pituitary adenomas and can present with a broad spectrum of manifestations. As pituitary adenomas grow insidiously and often result in nonspecific symptoms, diagnostic delay is common. The duration of symptoms first reported by the patient to diagnosis can vary greatly, from patients being diagnosed within one year to over 40 years after symptom onset. Early detection of pituitary adenomas is essential to avoid the accumulation of both hyperprolactinemia and mass effect manifestations, such as visual field loss, infertility, and fatigue among others. Worsening of such manifestations in prolactinomas specifically has an inevitable impact on physical and mental health, comorbid conditions, and quality of life (QOL). Here, we review the literature regarding the prevalence, pathophysiology, and clinical evaluation of presenting manifestations of prolactinomas, discuss contributory factors to diagnostic delay and methods to facilitate earlier identification.
