Thyroid eye disease (TED) is a complex autoimmune orbital disease where clinical assessment tools, such as the Clinical Activity Score, often fail to capture the underlying molecular transitions between active inflammation and permanent fibrosis. As the field moves toward precision medicine, tear film metabolomics has emerged as a powerful, noninvasive source of biomarkers that can decode the orbital microenvironment. This review synthesizes current evidence on the metabolic signatures of TED, highlighting the shift from traditional protein biomarkers to small-molecule metabolites, including lipids, amino acids, and oxidative stress products. The current literature provides evidence that alterations in amino acid metabolism, polyamine synthesis, acylcarnitine profiles, and other markers of oxidative stress indicate disease activity in TED. We explore how liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) have identified key dysregulated pathways-most notably in the ornithine-polyamine axis, with an increased putrescine-to-ornithine ratio correlating best with inflammatory activity. By bridging the gap between systemic thyroid dysfunction and localized ocular manifestations, tear metabolomics offers a promising noninvasive approach for biomarker development, disease stratification, and therapeutic decision-making in thyroid eye disease.

Thyroid eye disease (TED) is the most common extrathyroidal manifestation of Graves' disease, causing proptosis, diplopia, and, in severe cases, vision loss. The 2020 approval of the first insulin-like growth factor 1 receptor (IGF-1R) inhibitor for TED introduced disease-specific pharmacotherapy and prompted accelerated development of additional biological agents across multiple mechanistic classes. This review summarizes the clinical trial evidence for biological agents currently approved or in late-stage development for TED, drawing on peer-reviewed publications, conference presentations, and sponsor disclosures through early 2026. Among the mechanistic classes evaluated, IGF-1R inhibition has accumulated the largest randomized trial evidence base. Multiple IGF-1R-directed agents, delivered by intravenous, subcutaneous, and oral routes, have demonstrated statistically significant reductions in proptosis in placebo-controlled trials, with responder rates that vary by agent, route, and disease activity. Interleukin-6 receptor (IL-6R) antagonism produced discordant Phase 3 primary endpoint outcomes across 2 parallel pivotal trials. Neonatal Fc receptor (FcRn) inhibition and selective interleukin-17A blockade each failed to meet primary endpoints in Phase 2 or Phase 3 studies. B-cell directed therapies and other off-label agents have produced inconsistent results in smaller, generally nonrandomized studies. In parallel, the use of orbital decompression has declined in the era following IGF-1R inhibitor approval, reflecting the changing role of surgery in pathways that initially lead with medical therapy. As comparative trial data emerge and the field moves toward treatment selection based on phenotype, clinicians will be better equipped to individualize biological therapy by disease stage, severity, safety profile, and patient preference.

High-iodine groundwater is a widespread hydrogeochemical anomaly and an important environmental and health concern worldwide. It is commonly distributed in arid and semi-arid inland basins, alluvial plains, and coastal zones influenced by seawater intrusion. Its formation is governed by coupled hydrogeochemical and biogeochemical processes. Long-term exposure to high-iodine groundwater is associated with adverse health outcomes, particularly thyroid dysfunction and increased risks of goiter and thyroid cancer. Because in situ remediation alone is often insufficient to ensure sustained reduction of iodine to levels suitable for safe drinking water, engineered water treatment remains the most direct and reliable option. Among them adsorption is widely studied and practically relevant treatment approach. This review critically evaluates the adsorbent materials relevant to high-iodine groundwater remediation, including metal-based materials, carbonaceous adsorbents and functionalized organic materials. These materials target the dominant groundwater iodine species through distinct mechanisms such as ion exchange, strong metal-iodine interactions, moderate oxidation-adsorption coupling, and multi-site binding enabled by tailored functional groups or pore environments. Current evidence shows that adsorbent performance depends not only on adsorption capacity, but also on species selectivity, matrix tolerance, and practical applicability under trace-level and chemically complex groundwater conditions. However, most existing adsorbents remain limited by narrow iodine-species selectivity, interference from competing anions and natural organic matter, and insufficient evidence for regeneration and field applicability. This review highlights the key material classes, mechanistic foundations, critical limitations, and design principles that should guide the development of selective, robust, and practically usable adsorbents for high-iodine groundwater remediation.

Hypercalcaemia is a recognised complication of thyrotoxicosis usually related to increased bone resorption. However, coexistent hyperphosphataemia is uncommon and may create diagnostic uncertainty. It is postulated that serum calcium and phosphate levels rise due to high bone turnover and increased renal reabsorption of phosphate in response to excess thyroxine. Hypercalcaemia may also alter the clinical presentation of thyrotoxicosis, making both diagnosis and management challenging. We report two patients with this unusual biochemical presentation. The first patient was a 69-year-old woman who presented with body aches, lethargy, low mood, constipation, polyuria, and proximal muscle weakness for 2 months. The second was a 56-year-old woman who presented with palpitations, anxiety, tremulousness, dyspnoea, dysphagia, and headache for 4 months. Both had multinodular goitres (MNGs) without eye disease. Their TSH levels were undetectably low with extremely high free T4 levels. Serum calcium and phosphate levels were high in both patients. ALP levels were mildly elevated, vitamin D levels were deficient or insufficient, and parathyroid hormone (PTH) levels were low-normal. DXA scans revealed severe osteoporosis. Both patients improved clinically and biochemically with adequate intravenous hydration, frusemide, carbimazole, propranolol, and bisphosphonates. The second patient underwent a successful left thyroid lobectomy, while the first patient remained well on medical treatment. Unexplained hypercalcaemia and hyperphosphataemia should alert the clinicians to the possibility of underlying thyrotoxicosis. Prompt recognition and management is essential to prevent bone loss, correct metabolic abnormalities, and avoid complications. Clinicians should also consider the possibility of hypercalcaemia associated with thyroid dysfunction in patients presenting with nonspecific symptoms such as fatigue, constipation, proximal weakness, polyuria, or mood changes.

BACKGROUND Thyroid eye disease (TED) and IgG4-related orbital disease are distinct inflammatory conditions that rarely occur simultaneously. Their coexistence can pose diagnostic and therapeutic challenges, particularly in patients with systemic comorbidities. This report describes a rare case of concurrent TED and IgG4-related orbital disease in a patient with diabetes mellitus and details the surgical approach and postoperative results. CASE REPORT A 72-year-old man with a history of TED and diabetes had been experiencing progressive proptosis and orbital swelling for approximately 17 years. Despite consulting several doctors, he was refused surgery due to the associated high risks. He had facial changes, exophthalmos, and dry eyes, which led him to visit our clinic. Clinical evaluation and orbital imaging revealed changes consistent with TED, along with a localized orbital tumor extending into the deep orbital region. To alleviate the proptosis, we first performed an orbital tumor resection, along with orbital fat and bone decompression surgery. Five months later, we conducted an additional surgical resection of the residual right superior orbital tumor. Histopathological examination and immunohistochemical staining of the resected tissue, together with serological findings, confirmed the diagnosis of IgG4-related orbital disease. CONCLUSIONS This case highlights the importance of considering multiple etiologies in patients with atypical or long-standing TED. While orbital decompression is commonly performed for TED-associated proptosis, the presence of a localized IgG4-related orbital lesion can require surgical excision. This report suggests that combined surgical management can be considered in selected cases.

Significant extension of thyroid masses into the mediastinum has historically necessitated high-morbidity sternotomy or thoracotomy incisions during substernal thyroidectomy. This preliminary experience from a single-center, tertiary-care academic institution illustrates a combined minimally invasive robotic-assisted thoracic surgery (RATS) and transcervical approach for substernal thyroidectomy. Patients are considered for the minimally invasive approach for substantial goiter extension into the anterior and posterior mediastinum, in addition to risk factors for wound healing complications associated with sternotomy. Relative exclusion criteria include prior thoracic surgery or radiographic extrathyroidal invasion into mediastinal structures. Using the Intuitive Surgical da Vinci Xi platform, right-sided RATS mobilization of the mediastinal component is immediately followed by transcervical excision. The robotic approach enables precise identification and dissection of critical neurovascular and aerodigestive structures, thereby facilitating safe transcervical delivery. Two procedures utilizing this approach were completed without complications. By avoiding sternotomy, both patients were discharged home following abbreviated inpatient stays of just 2 days. Robotic-assisted thoracic surgery represents a promising alternative to traditional invasive approaches for substernal thyroidectomy, preliminarily showing safety and feasibility, and the potential to reduce morbidity and improve recovery times.