Search Results (284)

A radioiodine-refractory differentiated thyroid cancer patient with rising serum thyroglobulin (Tg) levels underwent ¹⁸F-FDG PET/CT scan, which showed a hypermetabolic region in the proximal segment of esophagus, leading to ambiguity in diagnosis. MRI was immediately added, and PET/MRI fusion image localized an air-containing lesion interlinked with esophagus with enhanced T2 hyperintense mucosal signal, indicating an inflammatory esophageal diverticulum, which was subsequently verified by endoscopy. This case highlights the added value of PET/MRI image fusion in cases with inconclusive ¹⁸F-FDG PET/CT findings, requiring no additional tests and utilizing existing software, thereby minimizing the need for invasive procedures. Full article

Airborne iodine-131 plays a pivotal role in both nuclear medicine and nuclear safety due to its radiotoxicity, volatility, and affinity for the thyroid gland. Although the total exhaled activity after medical I-131 therapy is minimal, over 95% of this activity appears in volatile organic forms, which evade standard filtration and reflect metabolic pathways of iodine turnover. Our experimental work in patients and mice confirms the metabolic origin of these species, modulated by thyroidal function. In nuclear reactor environments, both under routine operation and during accidents, organic iodides such as [¹³¹I]CH₃I have also been identified as major airborne components, often termed “penetrating iodine” due to their low adsorption to conventional filters. This review compares the molecular speciation, environmental persistence, and dosimetric impact of airborne I-131 across clinical, technical, and accidental release scenarios. While routine reactor emissions yield negligible doses (<0.1 µSv/year), severe nuclear incidents like Chernobyl and Fukushima have resulted in significant thyroid exposures. Doses from these events ranged from tens of millisieverts to several Sieverts, particularly in children. We argue that a deeper understanding of chemical forms is essential for effective risk assessment, filtration technology, and emergency preparedness. Iodine-131 exemplifies the dual nature of radioactive substances: in nuclear medicine its radiotoxicity is therapeutically harnessed, whereas in industrial or reactor contexts it represents an unwanted hazard. The same physicochemical properties that enable therapeutic efficacy also determine, in the event of uncontrolled release, the range, persistence, and the potential for unwanted radiotoxic exposure in the general population. In nuclear medicine, exhaled activity after radioiodine therapy is minute but largely organically bound, reflecting enzymatic and metabolic methylation processes. During normal reactor operation, airborne iodine levels are negligible and dominated by inorganic vapors efficiently captured by filtration systems. In contrast, major accidents released large fractions of volatile iodine, primarily as elemental [¹³¹I]I₂ and organically bound iodine species like [¹³¹I]CH₃I. The chemical nature of these compounds defined their atmospheric lifetime, transport distance, and deposition pattern, thereby governing the thyroid dose to exposed populations. Chemical speciation is the key determinant across all scenarios. Exhaled iodine in medicine is predominantly organic; routine reactor releases are negligible; severe accidents predominantly release elemental and organic iodine that drive environmental transport and exposure. Integrating these domains shows how chemical speciation governs volatility, mobility, and bioavailability. The novelty of this review lies not in introducing new iodine chemistry, but in the systematic comparative synthesis of airborne radioiodine speciation across medical therapy, routine nuclear operation, and severe accident scenarios, identifying chemical form as the unifying determinant of volatility, environmental transport, and dose. Full article

Background and clinical significance: Idiopathic hypertrophic pachymeningitis (IHPM) is a rare inflammatory disorder characterized by diffuse or focal dural thickening and heterogeneous presentations. We report a corticosteroid-responsive IHPM with elevated anti-thyroglobulin (anti-Tg) antibodies despite oncologic control after thyroidectomy. This case suggests that systematic assessment for autoimmunity should be a standard component of the IHPM work-up. Case presentation: A 77-year-old woman presented with recurrent vertigo, imbalance, and headaches. Brain MRI showed diffuse pachymeningeal thickening with mild heterogeneous enhancement, radiologically stable over >2 years. Extensive evaluation excluded infectious, neoplastic (including paraneoplastic), cerebrospinal fluid hypotension and systemic autoimmune causes; findings did not support IgG4-related disease. Thyroid work-up revealed hypothyroidism with multinodular goiter; total thyroidectomy was performed, and there was no indication for adjuvant radioiodine therapy. Despite oncologic control, anti-Tg antibodies remained markedly elevated, while anti-thyroid peroxidase antibodies (anti-TPO) declined. Symptoms repeatedly improved with oral methylprednisolone and recurred on taper; adverse effects were mild and manageable. The patient remains under clinical and oncologic surveillance with symptom-guided steroid re-challenge. Conclusions: IHPM may exhibit a dissociation between clinical response and radiologic course. Persistently elevated anti-Tg after thyroidectomy can coexist with IHPM and may signal ongoing autoimmunity rather than active cancer. Full article

Over the past several decades, rapid advances in molecular genomics have transformed our understanding of thyroid malignancies and are increasingly integrated into international clinical guidelines. Mutational profiles and epigenetic events are now recognized not only as diagnostic and prognostic tools but also as predictors of therapeutic response. Papillary, follicular, oncocytic, medullary, and anaplastic thyroid carcinomas harbor distinct early driver mutations, such as BRAFV600E, RAS, and fusion events (RET, NTRK, and ALK), that cooperate with secondary alterations (TERT promoter, TP53, PIK3CA, and CDKN2A/B loss) to drive dedifferentiation, metastasis, and therapeutic resistance. Insights from The Cancer Genome Atlas (TCGA) and transcriptomic scoring systems (e.g., BRAF–RAS score) now link genotype to tumor morphology, metastatic tropism, and radioactive iodine refractoriness. These molecular insights have been incorporated into updated risk stratification frameworks, preoperative surgical planning, and treatment algorithms, informing the selection of kinase inhibitors, redifferentiation strategies, and enrollment in genotype-directed clinical trials for radioiodine-refractory disease. This review synthesizes recent evidence connecting genomic alterations to clinical behavior and highlights their translation into evolving approaches for thyroid cancer management. Full article

An 8-year-old castrated male Pomeranian with a non-resectable functional thyroid carcinoma and concurrent myxomatous mitral valve disease was referred for radioactive-iodine therapy. Due to clinical thyrotoxicosis at referral and concurrent cardiac disease, the radioiodine dose was selected conservatively at the lower end of the reported therapeutic range. Despite a conservative radioactive iodine dose, the dog developed acute thyrotoxic decompensation consistent with thyroid storm (manifesting as anxiety, diarrhea, hyperthermia, hypersalivation, and marked tachycardia) within hours of treatment. Propranolol and butorphanol administration led to rapid clinical stabilization. Before the second radioactive iodine therapy, methimazole and propranolol were used for subsequent management, effectively controlling thyrotoxicosis risk and enabling a higher radioiodine dose. Serum thyroxine normalized within 1 month after the second treatment, and the dog maintained complete clinical remission thereafter. Radioactive iodine therapy served as definitive therapy to prevent recurrent life-threatening thyrotoxicosis, resulting in a euthyroid state and long-term survival. This case describes the first documented case of a dog with thyroid carcinoma developing probable thyroid storm associated with radioiodine treatment and subsequently achieving a favorable prognosis. Full article

Follicular-cell-derived thyroid carcinoma, while typically associated with a favorable prognosis, can undergo dedifferentiation into poorly differentiated (PDTC) or anaplastic thyroid carcinoma (ATC), leading to enhanced aggressiveness and radioiodine resistance. This review systematically examines the genetic and molecular mechanisms driving this pathological progression, highlighting the roles of key mutations—such as BRAF, RAS, TERT, and TP53—and the disregulation of signaling pathways, including MAPK and PI3K/AKT. These alterations promote the loss of thyroid-specific functions, including iodide metabolism, and correlate with poor clinical outcomes. In recent years, therapeutic strategies aimed at tumor redifferentiation have emerged as a promising approach for radioiodine-refractory disease. We summarize recent advances in the use of targeted agents, particularly BRAF and MEK inhibitors, to restore radioiodine avidity and improve treatment response. While early clinical studies show encouraging results, including tumor shrinkage and restored RAI uptake in selected patients, challenges such as treatment resistance and patient selection remain. Future efforts should focus on refining molecular stratification, developing rational combination therapies, and integrating novel modalities such as immunotherapy to overcome resistance. A deeper understanding of redifferentiation mechanisms not only provides insights into thyroid cancer progression but also supports the development of personalized treatment strategies for high-risk patients. Full article

Hyperthyroidism is a common endocrine disorder in elderly cats, often leading to concurrent cardiac abnormalities. Understanding the development of these cardiac abnormalities and the effect of treatment is crucial for optimizing monitoring strategies and long-term management. Hyperthyroid cats frequently develop cardiomegaly, with left ventricular concentric and/or eccentric hypertrophy, and left atrial dilation. Cardiac abnormalities described in humans with multinodular toxic goiter may differ from those in cats, but, as in humans, these abnormalities are often reversible once thyroid hormone levels are normalized. Definitive treatment options for hyperthyroidism, such as radioiodine therapy and thyroidectomy, are the most successful at restoring the normal thyroid hormone levels. Medical therapy and iodine-restricted diets can also help normalize thyroid hormone levels, thereby aiding the reversal of cardiac abnormalities. However, cats with pre-existing cardiac diseases, like hypertrophic cardiomyopathy, may not show reversible cardiac changes due to these concurrent primary cardiac diseases. Cats with hyperthyroidism should routinely undergo echocardiographic evaluations to monitor for concurrent cardiac abnormalities, both before and after treatment. More importantly, every cat older than 6 years of age with echocardiographic or clinical signs of heart disease should be screened for hyperthyroidism. With appropriate treatment of hyperthyroidism, heart failure can be prevented. Full article

Background: Subclinical hyperthyroidism grade 1 (SCH G1, TSH > 0.1 mU/L) is common in patients with thyroid unifocal autonomy (UFA) and associated with cardiovascular risks and increased mortality. While ¹³¹I radioiodine therapy (¹³¹I-RIT) effectively treats UFA, it frequently induces hypothyroidism, partly due to extra-nodular absorbed dose (AD) enhanced by residual TSH stimulation. Objective: We hypothesized that short-term LT3-induced TSH suppression at the time of RIT would promote long-term euthyroidism. Patients and Methods: A retrospective study was conducted on 95 UFA patients with SCH G1 (2001–2024). Patients underwent baseline and post-LT3 thyroid scintigraphy, and then received ¹³¹I-RIT with individualized dosimetry. Long-term bioclinical follow-up was achieved. Results: Short-term low-dose LT3 suppression caused no adverse events and significantly reduced TSH (0.45 to 0.047 mU/L). Whole-gland ¹²³I uptake decreased moderately (11.0 to 8.4%), while extra-nodular lobe uptake dropped markedly (1.77 to 0.73%) (all p < 0.0001). This focused activity on the UFA (2.5-fold increase), maintaining mean UFA AD (about 260 Gy) but reducing extra-nodular AD (61 to 37 Gy, p < 0.0001). Despite low ¹³¹I doses (mean 181 MBq), a dose–response relationship was observed: higher AD correlated with greater nodular lobe volume reduction (p < 0.033). At the 88-month follow-up, 93% of patients achieved normal thyroid function; one had persistent SCH G1, two were borderline hypothyroid, and two required LT4. Conclusions: ¹³¹I-RIT under brief LT3-induced TSH suppression induces sustained euthyroidism in SCH G1 with UFA. This simple, low-risk strategy reduces radioprotection concerns and is under evaluation to determine cardiovascular benefits. Full article

Radionuclide molecular imaging of epidermal growth factor receptor (EGFR) expression might permit the selection of patients for EGFR-targeting therapies. Designed ankyrin repeat protein (DARPin) E01 with a high affinity to the ectodomain III of the EGFR is a possible EGFR imaging probe. The goal of this study was to evaluate the potential of radiolabeled DARPin E01 for in vivo imaging of EGFR. DARPin E01 containing the (HE)₃-tag was site-specifically labeled with a residualizing ^99mTc (using ^99mTc]Tc(CO)₃). Two methods providing non-residualizing ¹²³I labels, direct electrophilic radioiodination and indirect radioiodination using [¹²³I]I-para-iodobenzoate (PIB), were tested. [^99mTc]Tc-(HE)₃-E01 and [¹²³I]I-(HE)₃-E01-PIB preserved specific binding to EGFR-expressing cells and affinity in the single-digit nanomolar range. Direct labeling with ¹²³I resulted in a substantial loss of binding. In vitro cellular processing studies showed that both [^99mTc]Tc-(HE)₃-E01 and [¹²³I]I-(HE)₃-E01-PIB had rapid binding and relatively slow internalization. Evaluation of [^99mTc]Tc-(HE)₃-E01 biodistribution in normal CD1 mice showed that its hepatic uptake was non-saturable, suggesting that this tracer does not bind to murine EGFR. A side-by-side comparison of biodistribution and tumor targeting of [^99mTc]Tc-(HE)₃-E01 and [¹²³I]I-(HE)₃-E01-PIB was performed in Nu/j mice bearing EGFR-positive A-431 and EGFR-negative Ramos human cancer xenografts. Both radiolabeled DARPins demonstrated EGFR-specific tumor uptake. However, [¹²³I]I-(HE)₃-E01-PIB had appreciably lower uptake in normal organs compared to [^99mTc]Tc-(HE)₃-E01, which provided significantly (p < 0.05) higher tumor-to-organ ratios. Gamma-camera imaging confirmed that [¹²³I]I-(HE)₃-E01-PIB demonstrated a higher imaging contrast in preclinical models than [^99mTc]Tc-(HE)₃-E01. In conclusion, DARPin (HE)₃-E01 labeled using a non-residualizing [¹²³I]I-para-iodobenzoate (PIB) label is the preferred radiotracer for in vivo imaging of EGFR expression in cancer. Full article

Background: Sodium/iodide symporter (NIS) is a membrane protein involved in iodide transport into cells, making it a key component of thyroid physiology and radioiodine therapy for thyroid cancer. Although NIS is expressed in many extrathyroidal tissues, including breast tumors, its functional role and prognostic significance in these contexts remain a subject of active investigation. Understanding the mechanisms regulating NIS, its influence on cellular processes such as migration and metastasis, and its connection with transcription factors like FOXA1 could contribute to the development of new therapeutic strategies for breast cancer treatment. This study aims to investigate the correlation between sodium/iodide symporter (NIS) expression and response to neoadjuvant chemotherapy in patients with triple-negative breast cancer (TNBC). Methods: The current retrospective study included 161 TNBC patients who received neoadjuvant chemotherapy followed by mastectomy. NIS expression was assessed via immunohistochemistry, graded semi-quantitatively from 0 to 3+. The Residual Cancer Burden (RCB) scale was used to evaluate the response to chemotherapy. Statistical analysis included Lilliefors tests and Kendall’s tau correlation coefficient. Publicly available Cancer Genome Atlas datasets were analyzed to assess the relationship between NIS and FOXA1 expression. Results: NIS immunopositivity was observed in 69.5% of TNBC samples compared to 63.3% GATA-3-positive and 31.0% of Mammaglobin-positive samples. While no significant correlation was found between NIS expression and age, TNM stage, or Ki-67, a statistically significant moderate positive correlation (τ = 0.481, p < 0.01) was identified between NIS expression and RCB index, indicating that higher NIS expression was associated with a poorer response to neoadjuvant chemotherapy. TCGA data analysis revealed a statistically significant increase in NIS mRNA expression in FOXA1-mutated TNBC samples compared to FOXA1-wild-type samples (p < 0.05). Younger patients exhibited higher Ki-67 levels (τ = −0.416, p < 0.05). Conclusions: Higher NIS expression correlates with chemoresistance to neoadjuvant chemotherapy in TNBC patients. This phenomenon may be linked to FOXA1 activity, suggesting that NIS may represent a potential biomarker for chemoresistance in TNBC. The inverse correlation between patient age and Ki-67 levels may be associated with a different mutational landscape in younger patients. Full article

Objectives: To evaluate the loss of quality of life (QoL) in patients with chronic obstructive sialadenitis (COS) using the Chronic Obstructive Sialadenitis Questionnaire (COSQ). Methods: The COSQ was administered to patients diagnosed with COS, with the diagnosis confirmed by sialendoscopy. Epidemiological data, obstructive causes and potentially obstructive entities were collected. QoL was assessed using the COSQ. Results: A total of 344 glands in 278 patients with COS were analyzed. Most patients were women (71.94%), and the main obstructive cause was stenosis (47.96%), followed by lithiasis, lack of papilla distensibility (LPD), and mucus plug. Stenosis was significantly more frequent in the parotid gland and in women, whereas lithiasis predominated in the submandibular gland and in men. The mean COSQ score was 30.55 and it was significantly higher in women (p < 0.005), parotid gland (p < 0.005), and in long-standing cases (p < 0.05). Stenosis and LPD were the obstructive causes with the greatest impact on QoL (p < 0.005), while lithiasis had the least impact. Potentially Obstructive Entities (POEs), such as eosinophilic sialodochitis, Sjögren’s syndrome, or radioiodine-induced sialadenitis, were associated with a notable loss of QoL. Likewise, patients without associated POEs presented significantly lower COSQ values (p < 0.05). Conclusions: COS significantly affects QoL, particularly in women and in cases of parotid gland, stenosis, and LPD. Lithiasis has the least impact on QoL. It is important to standardize a thorough evaluation of COS using validated tools such as the COSQ, which are fundamental for understanding the disease and predicting the outcomes of therapeutic interventions. Full article

Radioiodine-refractory differentiated thyroid cancer (RAIR-DTC) is associated with poor prognosis and limited systemic options. This narrative review focuses on lenvatinib (LEN), a multitarget tyrosine kinase inhibitor that significantly prolongs progression-free survival. Evidence from the SELECT trial and real-world data indicates that its benefits can be enhanced through early initiation, maintenance of a high relative dose intensity, and proactive toxicity management. Planned drug holidays help sustain treatment while avoiding prolonged unplanned interruptions. In selected patients with locally advanced, initially unresectable disease, neoadjuvant LEN may enable conversion surgery, facilitating subsequent treatments. However, the current data are mainly from case series and early-phase studies. After dose reduction, re-escalation can restore disease control, and LEN rechallenge after a drug-free interval may restore sensitivity in later lines. Thus, LEN should be integrated into personalized multidisciplinary care to optimize outcomes across treatment courses. Nevertheless, key limitations remain, as much of the supporting evidence is derived from post hoc or retrospective analyses. Prospective studies are required to validate the optimization strategies, define stage-specific benefits, and determine their impact on overall survival. Full article

Thyroid cancer (TC), the most prevalent endocrine neoplasia, has shown a progressive incidence, highlighting the need for new therapeutic approaches—especially for radioiodine-refractory cases, often associated with mutations in genes such as BRAF, RAS, and TP53. This review proposes a mechanistic model that highlights two interrelated characteristics of the tumor microenvironment (TME): redox imbalance and chronic inflammation, key elements in tumor progression and treatment resistance. Thus, natural phenolic compounds, such as curcumin, quercetin, resveratrol, and epigallocatechin gallate (EGCG), function not as simple antioxidants but as pleiotropic agents that reprogram the TME. A central mechanism of action for these compounds is the modulation of the purinergic axis (CD39/CD73/adenosine), a critical immune-metabolic checkpoint. By selectively inducing lethal oxidative stress in tumor cells, suppressing pro-survival inflammatory pathways—such as that mediated by nuclear factor kappa B (NF-κB)—and destabilizing the immunosuppressive shield conferred by adenosine, certain phytochemicals demonstrate the potential to restore immune surveillance and promote tumor apoptosis. In this context, a critical analysis of the evidence related to targeting purinergic signals becomes essential, since pharmacological reinforcement of this pathway, especially when combined with immunotherapies based on immune checkpoint blockade, emerges as a promising strategy for overcoming therapeutic resistance. Full article

Poorly differentiated thyroid malignancy, a rare histological type of aggressive thyroid malignancy with associated difficulties and gaps in its histological and molecular characterization, might lead to challenging clinical presentations that require a prompt multimodal approach. This case study involved a 56-year-old, non-smoking male with a rapidly developing goiter (within 2–3 months) in association with mild, non-specific neck compressive symptoms. His medical history was irrelevant. A voluminous goiter with substernal and posterior extension up to the vertebral bodies was detected using an ultrasound and computed tomography (CT) scan and required emergency thyroidectomy. He had normal thyroid function, as well as negative thyroid autoimmunity and serum calcitonin. The surgery was successful upon “Y” incision, which was used to give better access to the retrosternal component in order to avoid a sternotomy. Post-operatively, the subject developed hypoparathyroidism-related hypocalcemia and showed a very high serum thyroglobulin level (>550 ng/mL). The pathological report confirmed poorly differentiated, multifocal thyroid carcinoma (with an insular, solid, and trabecular pattern) against a background of papillary carcinoma (pT3b, pN0, and pM1; L1; V2; Pn0; R1; and stage IVB). The subject received 200 mCi of radioiodine therapy for 6 weeks following the thoracic surgery. Whole-body scintigraphy was performed before radioiodine therapy and showed increased radiotracer uptake at the thyroid remnants and pre-tracheal levels. Additionally, single-photon emission computed tomography combined with CT (SPECT/CT) was performed, and confirmed the areas of intense uptake, in addition to a moderate uptake in the right and left pulmonary parenchyma, suggesting lung metastasis. To conclude, an overall low level of statistical evidence exists regarding poorly differentiated malignancy in substernal goiters, and the data also remains scarce regarding the impact of genetic and molecular configurations, such as the BRAF-positive profile, in this specific instance. Furthermore, multimodal management includes additional diagnosis methods such as SPECT/CT, while long-term multilayered therapy includes tyrosine kinase inhibitors if the outcome shows an iodine-resistant profile with a poor prognosis. Awareness remains a key factor in cases of a poorly differentiated carcinoma presenting as a rapidly growing goiter with substernal extension in an apparently healthy adult. A surgical approach, while varying with the surgeon’s skills, represents a mandatory step to ensure a better prognosis. In addition to a meticulous histological characterization, genetic/molecular features provide valuable information regarding the outcome and can further help with the decision to use new anti-cancer drugs if tumor response upon radioiodine therapy is no longer achieved; such a development is expected in this disease stage in association with a BRAF-positive configuration. Full article

Background: Risk assessment in hyperthyroidism remains challenging. The aim of the present study is to determine the influence of hyperthyroid metabolic status on blood clotting and an increased risk of thrombosis. Methods: This prospective study included 50 patients after radical thyroidectomy and ablative radioiodine therapy because of thyroid carcinoma who were compared with 50 control subjects in a euthyroid metabolic state. Latent hyperthyroid patients with basal thyroid-stimulating hormone (TSH) ≤ 0.15 mU/L on levothyroxine hormone therapy were included. The control group was selected to match the patient group based on age and sex. The evaluation data were collected using laboratory coagulation tests and patient questionnaires. A bleeding and a thrombosis score were determined. Results: The coagulation parameters between the patient and control groups showed statistically significant differences. In particular, the patients’ group showed a significantly shortened activated partial thromboplastin time (aPTT/p = 0.009) and a significantly higher plasminogen activator inhibitor 1 (PAI-1/p < 0.001) compared to the control group. Age, sex, and medication use were not found to influence the patients’ laboratory results. Only body mass index was higher in the patient group than in the control group. Conclusions: Our results support a shift in the coagulation system in latent hyperthyroid metabolism towards increased coagulability and reduced fibrinolysis. A latent hyperthyroid metabolic state appears to be associated with an increased risk of thrombosis. Further prospective cohort studies with large patient populations are needed to verify the association between (latent) hyperthyroidism and thromboembolic events as well as to determine therapeutic anticoagulation or to adjust the indication for exogenous administration of thyroid hormone. Full article