Search Results (47)

Background/Objectives: To evaluate whether a TSH-receptor antibody (TRAb)-first, one-sample diagnostic strategy improves etiologic classification of overt hyperthyroidism compared with conventional pathways, and to assess its implications for imaging use, diagnostic accuracy, and cost efficiency. Methods: In this multicentre retrospective study, 274 adults with newly diagnosed overt hyperthyroidism underwent TRAb measurement, thyroid ultrasound, and scintigraphy during a single clinical encounter. Scintigraphy served as the functional reference standard. We compared the diagnostic performance of TRAb and ultrasound, modeled TRAb-first diagnostic algorithms, and estimated the potential impact of reflex TRAb testing on diagnostic workflow and resource use. Results: Graves’ disease (GD) accounted for 65% of cases. TRAb showed excellent diagnostic accuracy for GD (sensitivity 92.0%, specificity 96.0%; κ = 0.86) and markedly outperformed ultrasound (sensitivity 66.9%, specificity 62.5%; κ = 0.43). A TRAb-first pathway in which TRAb-positive patients are directly classified as GD and TRAb-negative patients undergo scintigraphy achieved 100% sensitivity, 95.8% specificity, and the lowest overall misclassification rate. Replacing scintigraphy with ultrasound in TRAb-negative patients substantially reduced specificity (~60%) and yielded significant overdiagnosis of GD. Ultrasound identified numerous nodules but detected only one low-risk carcinoma (malignancy rate: 1.2%), suggesting limited oncologic yield. A TRAb-first strategy would have avoided two-thirds of scintigraphies and minimized unnecessary imaging. Conclusions: A TRAb-first diagnostic approach offers the most accurate, efficient, and clinically appropriate pathway for etiologic assessment of overt hyperthyroidism. Scintigraphy should be reserved for TRAb-negative patients, while ultrasound should be used selectively for structural evaluation rather than as part of routine etiologic work-up. Reflex TRAb testing may further streamline care by enabling rapid, one-sample etiologic diagnosis and reducing resource use. Full article

Background/objectives: The study aimed to present cases of malignant struma ovarii from seven centers in Türkiye and evaluate them within the context of the existing literature. Methods: We retrospectively analyzed clinical data from 17 patients treated at seven centers, focusing on clinical features, surgical management, pathology, thyroid function, adjuvant treatment, and outcomes. Additionally, a literature review including eight studies with 178 patients was conducted. Results: The mean age of patients was 44.7 years, with a mean tumor size of 9.2 cm. Elevated Ca 125 was found in 33.3% of patients, while thyroid function abnormalities and hyperthyroidism signs were rare. Pelvic pain and menstrual irregularities were common presenting symptoms. A total of 16 patients (94.1%) had unilateral tumors. Total abdominal hysterectomy with bilateral salpingo-oophorectomy and unilateral salpingo-oophorectomy were the most frequent surgical approaches. Histopathology predominantly showed classical papillary thyroid carcinoma (13 patients, 76%). All patients were FIGO stage I, with no metastasis. Thyroidectomy was performed in seven patients, identifying two concurrent thyroid cancers. Four patients received adjuvant radioactive iodine therapy. During a median follow-up of 43 months, no deaths and one recurrence were observed. The literature review showed a diagnosis age ranging 43–53 years and papillary thyroid carcinoma as the most common subtype. Thyroidectomy and RAI treatment were selectively applied. Among the reported studies, recurrence occurred in 7 of 76 patients (9.2%), while 5-year disease-free and overall survival rates exceeded 94% and 100%, respectively. BRAF mutations were uncommon. Conclusions: Malignant struma ovarii is a rare tumor with a favorable prognosis when diagnosed early and managed appropriately. Full article

Autoimmune thyroid disease (AITD) exemplifies an organ-specific autoimmune disorder, including Hashimoto’s thyroiditis (HT) and Graves’ disease (GD). HT is characterized by hypothyroidism, whereas GD primarily presents as hyperthyroidism. Immunological evidence indicates that AITD pathogenesis requires both a permissive genetic background and environmental triggers to initiate and sustain disease progression. However, the exact molecular and cellular pathways through which these elements synergize to trigger and sustain autoimmune responses remain unclear. Emerging evidence suggests that epigenetic regulation serves as the key interface decoding genetic predisposition through environmental stimuli in AITD etiology. Studies show that environmental epigenetic reprogramming initiates AITD development in genetically susceptible individuals. Epigenetic regulators, including DNA methylation, histone modifications, and non-coding RNA activity, finely tune transcriptional outputs to influence disease trajectories. Beyond elucidating AITD pathogenesis, these epigenetic alterations offer clinical value as diagnostic biomarkers and modifiable therapeutic targets, facilitating precision medicine approaches from early detection to customized interventions. These epigenetic modifications not only elucidate AITD pathophysiology but also provide measurable markers for early diagnosis and molecular targets for personalized treatment strategies. Full article

Objectives: Graves’ disease (GD) is the most common cause of hyperthyroidism and is associated with marked changes in body weight and body composition. Although weight loss is frequently reported, the extent and clinical relevance of body composition alterations, as well as their relationship with thyroid function, remain unclear. This study aimed to evaluate body composition and eating habits in patients with newly diagnosed hyperthyroid GD according to pre-morbid weight variation, and to compare these findings with those of matched euthyroid controls. Methods: Forty-four consecutive GD patients were enrolled and stratified based on the presence or absence of pre-morbid weight loss. Anthropometric measurements, thyroid function tests, thyroid volume, dietary habits (PREDIMED score, macronutrient intake and total daily caloric intake) and body composition assessed by bioelectrical impedance analysis (BIA) were collected. Standardized phase angle (SPA) and body cell mass index (BCMI) were calculated as nutritional indices. Body composition parameters and dietary adherence were compared with those of 44 age-, sex- and BMI-matched euthyroid controls. Results: Most GD patients (70.3%) reported weight loss before diagnosis; however, the magnitude of weight change did not correlate with the biochemical severity of thyrotoxicosis. Patients without weight loss showed higher fat mass percentage and higher caloric intake than those who lost weight. SPA was significantly associated with FT3, FT4 and TRAb levels, independently of age, sex, BMI and fat mass. Compared with controls, GD patients exhibited lower phase angle and SPA, higher extracellular water percentage and reduced BCMI, whereas fat mass and adherence to the Mediterranean diet were similar. Conclusions: Hyperthyroid GD patients display increased extracellular water and reduced body cell mass. SPA is inversely associated with GD severity and represents a valuable clinical tool for assessing nutritional status in thyrotoxic patients. Pre-morbid weight changes are not proportional to disease severity and may instead reflect increased caloric intake. Full article

Background: Monocarboxylate-transporter-8-(MCT8) deficiency, or Allan–Herndon–Dudley syndrome (AHDS), is a rare X-linked disorder caused by pathogenic variants in the SLC16A2 gene, leading to impaired transport of thyroid hormones, primarily T3 and T4, across cell membranes. The resulting central hypothyroidism and peripheral hyperthyroidism cause neurodevelopmental impairment and thyrotoxicosis. Despite the availability of therapy options, e.g., with triiodothyroacetic acid (TRIAC), diagnosis is often delayed, partly due to normal TSH levels or incomplete genetic panels. MCT8 deficiency is not yet included in newborn-screening programs worldwide. Case Description: We present a case of an infant genetically diagnosed with MCT8 deficiency at 5 months of age after presenting with muscular hypotonia, lack of head control, and developmental delay. Thyroid function testing revealed a normal TSH, low free T4, and significantly elevated free T3 and free T3/T4 ratio. Treatment with TRIAC (Emcitate^®) was initiated promptly, with close drug monitoring. Despite persistent motor deficits and dystonia, some developmental progress was observed, as well as reduction in hyperthyroidism. Discussion/Conclusions: This case underscores the importance of early free T3 and fT3/fT4 ratio testing in infants with unexplained developmental delay. Broader inclusion of SLC16A2 in genetic panels and consideration of newborn screening could improve early diagnosis and outcomes in this rare but treatable condition. Full article

Background: Coronavirus Disease 2019 has been associated with dysfunction in multiple endocrine organs, including the thyroid gland. While evidence suggests SARS-CoV-2 may influence thyroid function and promote oncogenesis through inflammation and cytokine storms, its role in thyroid cancer remains unclear. This study investigates whether COVID-19 is associated with an increased risk of thyroid cancer development. Methods: We conducted a retrospective cohort study using the TriNetX global federated health research database, encompassing data from 151 healthcare organizations. Adult patients with confirmed COVID-19 between 1 December 2019 and 31 December 2023, were included and compared to a matched cohort without COVID-19. Patients with prior thyroid cancer history or who had received COVID-19 vaccination were excluded in both groups. Propensity score matching (1:1) was performed for age, gender, and overweight/obesity status. The primary outcome was that new-onset thyroid cancer was diagnosed at least one year after COVID-19 diagnosis. Hazard ratios were calculated using Cox proportional hazards models, and subgroup analyses were performed based on age, gender, thyroid function status and treatment modalities. Results: After matching, a significantly higher thyroid cancer incidence was observed between the post-COVID and non-COVID groups. Subgroup analysis revealed a significantly higher risk of thyroid cancer development following COVID-19 diagnosis in patients who developed hyperthyroidism (HR 2.14, 95% CI: 1.04–4.46) or hypothyroid-ism (HR 1.83, 95% CI: 1.12–2.97) compared with the non-COVID population. Male patients also exhibited a higher risk of thyroid cancer after COVID-19 (HR 1.22, 95% CI 1.02–1.46). For patients with hyperthyroidism or hypothyroidism, those who had prior COVID-19 exhibited a relatively higher risk of developing thyroid cancer than those without a history of COVID-19 (HR 4.387, 95% CI: 2.08–9.24 for hyperthyroidism; HR 2.58, 95% CI: 1.58–4.22 for hypothyroidism). Conclusions: Patients with COVID-19 exhibited an increase in thyroid cancer risk, with specific subgroups—male adults and those with post-infectious thyroid dysfunction—also exhibiting increased risk. These findings suggest a potential relationship between SARS-CoV-2 and thyroid oncogenesis, warranting further prospective research. Full article

Background and Clinical Significance: The concurrent presence of a thyrotropin-secreting hypophyseal adenoma (TSHoma) with a thyroid malignancy, such as papillary thyroid carcinoma (PTC), is exceptionally rare and significantly complicates clinical diagnosis and management. This rare combination raises difficult decisions regarding the treatment sequence and carries the risk of exacerbating either or both conditions. Case report: We present the case of a 59-year-old female patient exhibiting persistent hyperthyroid symptoms with unusually normal TSH levels despite elevated thyroid hormone concentrations. Initial diagnostic imaging revealed a hypophyseal macroadenoma and a diffuse nodular goiter. After the macroadenoma diagnosis, the patient initially refused surgical intervention, and subsequent dopamine agonist therapy proved ineffective. Eight years later, during a routine follow-up, a thyroid ultrasound revealed a diffuse nodular goiter classified as EU-TIRADS 5, and papillary thyroid carcinoma was confirmed through fine needle aspiration biopsy. A total thyroidectomy and subsequent radioactive iodine therapy were performed. However, persistently elevated postoperative TSH levels remained despite high-dose levothyroxine therapy. Due to the increased risk of malignancy recurrence associated with elevated TSH levels, the patient consented to macroadenoma surgery. A successful transsphenoidal macroadenomectomy stabilized the patient’s condition, allowing for the normalization of TSH levels. Conclusions: This case underscores the importance of accurate differential diagnosis and highlights the challenges in managing TSH levels in patients with coexisting thyroid malignancies. With there being no clear guidelines for managing the combination of these conditions, decisions regarding treatment priority should consider the patient’s preferences, the risk of malignancy recurrence or progression, neurological symptoms, and the aggressiveness of the thyroid tumor. Full article

Associations between age-related diseases and behavioral alterations have been highlighted in previous studies. This study investigates the prevalence of diseases and behavioral changes in non-diseased and diseased senior cats before and after diagnosis, concentrating on four prevalent diseases: 1. osteoarthritis, 2. chronic kidney disease, 3. hyperthyroidism, and 4. cognitive dysfunction syndrome. An online survey was performed by 594 German cat-owners with a cat older than nine years; prevalent diseases, related medications, and scaled behavioral questions before and after diagnosis were queried. Chi-Quadrat-Test and Spearman’s rank correlation were used to detect correlations between behavioral changes and diseases. Multiple linear regression was used to determine dependencies between behavioral changes and each disease pre- and post-diagnosis. Half of the cats had at least one disease diagnosed (54.6%). The most prevalent diseases were osteoarthritis (18.9%), chronic kidney disease (12.3%), and hyperthyroidism (8.9%). Cognitive dysfunction syndrome was diagnosed in 2.9% of the cats. With increasing age, the likelihood of developing at least one disease rose (r_s = 0.204, p < 0.001). Disease-associated behavioral changes were found in the four mentioned diseases, with some behavioral changes occurring before diagnosis. These findings underscore the relevance of early detection of underlying diseases to decelerate ongoing behavioral changes in treatable diseases. Full article

Background/Objectives: Molecular imaging, especially PET, has advanced significantly, shifting from metabolic radiotracers like 2-deoxy-2-[¹⁸F]fluoro-D-glucose [¹⁸F]FDG to target-specific probes. Among these, αvβ6-integrin has emerged as a promising target in cancer and non-cancer diseases. This review focuses on the radiochemical properties and initial clinical applications of the [⁶⁸Ga]Ga-Trivehexin PET probe. Methods: The literature review on [⁶⁸Ga]Ga-Trivehexin systematically evaluated both preclinical and clinical studies, with particular emphasis on its radiochemical characteristics and preliminary clinical applications, while highlighting advancements, associated challenges, and the potential for future developments in the field. Results: This study highlights the significant advancements achieved with [⁶⁸Ga]Ga-Trivehexin in the field of molecular imaging. The optimized multimeric system has substantially enhanced the radiotracer’s pharmacokinetic properties, binding affinity, and selectivity for αvβ6 integrin, demonstrating up to an 18-fold improvement compared to previous monomeric tracers. The synthesis protocol has been refined to achieve high radiochemical purity (>95%), essential for safe clinical use. Preliminary clinical applications, particularly in head and neck cancer (HNC) and pancreatic ductal adenocarcinoma (PDAC), have shown promising results, with high detection rates and improved differential diagnosis compared to [¹⁸F]FDG. Furthermore, [⁶⁸Ga]Ga-Trivehexin PET/CT has shown potential in non-oncological conditions, such as idiopathic pulmonary fibrosis (IPF) and primary hyperthyroidism, suggesting broader clinical applicability. Conclusions: [⁶⁸Ga]Ga-Trivehexin is a promising PET probe for imaging αvβ6-integrin in cancers and non-oncological diseases like idiopathic pulmonary fibrosis (IPF) and primary hyperparathyroidism (PHP). Full article

Background/Objectives: Gestational trophoblastic disease (GTD) is a group of disorders including complete, partial, and invasive/metastatic hydatidiform moles, as well as gestational trophoblastic neoplasia (GTN) (choriocarcinoma; placental site trophoblastic tumor, PSTT; epithelioid trophoblastic tumor, ETT; or mixed forms). These entities are characterized by increased trophoblast proliferation, rarely complicated by hyperthyroidism. Methods: Our systematic literature review (PRISMA guidelines; PubMed, Web of Science, and Scopus databases) searched for histologically confirmed cases of GTN associated with clinical or subclinical hyperthyroidism. We described the clinical–pathologic features and the pathways of hyperthyroidism in GTD. Results: We identified just 32 choriocarcinomas and one PSTT; other non-histologically confirmed cases could have been identified, as some patients received a clinical diagnosis based on serum human chorionic gonadotropin (hCG) levels and imagining data and were treated accordingly. As regards choriocarcinomas, patients’ age range was 15–45 (mean 27) years. Metastases involved the lungs (53%), brain (25%), and liver (19%) (less frequently, the kidneys, spleen, ovaries, vagina, pelvis/abdomen, or thyroid). The time to recurrence range was 1–36 (mean 12) months. On follow-up, 10 patients (32%) were alive with disease and 6 (19%) showed no evidence of disease, while most of the women (15 cases, 48%) died of disease. The hCG level range was 10,000–3,058,000,000 (mean 128,957,613) IU/L. At least some symptoms and/or signs of hyperthyroidism were evident with variable intensity in most cases and significantly improved within 2–3 weeks after treatment. Conclusions: Increased trophoblast proliferation could stimulate thyroid function via increasing the half-life of thyroxine-binding globulin. Secondly, increased hCG demonstrates cross-reactivity with the thyroid-stimulating hormone due to similar α-subunits. Moreover, basic isoforms of hCG may facilitate thyrotropic activity. Full article

Background and Objectives: Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy, but their use is associated with a spectrum of immune-related adverse events (irAEs), including endocrine disorders. This study aims to investigate the incidence, timing, treatment modalities, and impact of ICI-related endocrine side effects in cancer patients. Materials and Methods: This retrospective study analyzed 139 cancer patients treated with ICIs between 2016 and 2022. Data regarding endocrine irAEs, including hypothyroidism, hyperthyroidism, hypophysitis, and diabetes mellitus, were collected. The study examined the timing of irAE onset, management approaches, and the association between irAEs and treatment outcomes. Results: The most common endocrine irAE was hypothyroidism (65.5%), followed by hyperthyroidism (2.3%), hypophysitis (8.6%), and diabetes mellitus (0.7%). These disorders typically emerged within the first six months of ICI therapy. Most cases were managed conservatively or with hormone replacement therapy. Patients who developed endocrine irAEs exhibited a higher objective response rate (ORR) and clinical benefit rate (CBR) compared to those without irAEs. Conclusions: Endocrine dysfunction is a significant toxicity of ICI therapy. Early recognition, prompt diagnosis, and appropriate management are crucial to minimize their impact on patient health and quality of life. This study highlights the potential association between irAEs and improved clinical outcomes. Further research is needed to elucidate the underlying mechanisms and identify predictive biomarkers for irAE development. Full article

Background: Hyperthyroidism, characterized by excessive thyroid hormone production, presents in diverse clinical forms, including overt and subclinical disease. Accurate and timely diagnosis is critical to prevent complications such as cardiac dysfunction, osteoporosis, and thyroid storm. Objective: To provide a comprehensive review of the clinical presentation, diagnostic methods, and management strategies for hyperthyroidism, focusing on current practices, advancements, and challenges in treatment. Methods: This review synthesizes findings from peer-reviewed literature on the diagnosis and management of hyperthyroidism. Results: Thyroid function tests (TFTs) are the cornerstone of hyperthyroidism diagnosis, with suppressed TSH levels and elevated T3 and/or T4 levels confirming overt disease. Thyroid receptor antibodies (TRAb) are critical for diagnosing autoimmune hyperthyroidism and predicting relapse risk. Iodine scintigraphy is utilized in specific cases, such as suspected toxic adenoma or multinodular goiter. Management strategies include beta-blockers for symptomatic relief, though side effects such as bradycardia and fatigue may occur. Antithyroid medications, including methimazole and propylthiouracil, inhibit hormone synthesis, with remission more likely in patients with low TRAb levels and small goiters. Definitive treatments include radioactive iodine therapy (RAI), which effectively reduces thyroid activity but often results in hypothyroidism, and thyroidectomy, a surgical option for large goiters or malignancy, with potential complications like hypocalcemia and recurrent laryngeal nerve injury. Conclusions: The management of hyperthyroidism necessitates a personalized approach integrating diagnostic precision, emerging innovations, and patient-centered care. Full article

It is documented that maternal diseases or treatments influence a newborn’s clinical status at birth. If a prenatal medical history is not available, or if signs or symptoms of a mother’s disease are revealed for the first time during pregnancy or postpartum, their effects on the newborn may be misattributed. Objective: The objective of this study is to emphasize the paramount importance of prenatal care, for both mothers and newborns, as a lack of maternal signs and symptoms during pregnancy does not exclude a potential severe neonatal condition. Materials and methods: We present a series of three cases of pregnant women who gave birth to very sick preterm newborns that required admission to the Neonatal Intensive Care Unit (NICU). The mothers were asymptomatic during pregnancy and unaware of their subclinical disease. The newborns’ complications, considered initially as consequences of prematurity or infection, subsequently revealed transient autoimmune disease in two of the cases (myasthenia gravis and hyperthyroidism) and a severe form of thrombophilia in the third case. Results: The newborns’ diagnosis preceded maternal diagnosis and contributed to the identification of the maternal pathology; adequate treatment was prescribed, with favorable short- and long-term outcomes. Conclusions: Prenatal exams and investigations throughout pregnancy are a good opportunity to detect subclinical diseases or predispositions. As newborns usually develop non-specific signs, one should have experience and pay attention to differentiating among etiologies. Our paper takes a reversed approach to the usual medical diagnosis pathway: from infant to mother instead of from mother to infant, proving that inter-specialty collaboration can work bi-directionally. Full article

Introduction: Graves’ disease (GD) is an autoimmune disorder affecting the thyroid gland, leading to systemic manifestations such as hyperthyroidism, Graves’ orbitopathy, and pretibial myxedema. Contrary to previous beliefs that hyperthyroidism protects against thyroid cancer, recent studies reveal an increased incidence of thyroid malignancies in GD patients, particularly differentiated thyroid carcinomas and, in rare cases, medullary thyroid carcinoma (MTC). Case series: This case series presents three female GD patients diagnosed with MTC, highlighting the complexities of diagnosis and management. All patients exhibited thyroid nodules with suspicious ultrasonographic features, elevated plasma calcitonin levels, and required total thyroidectomy. Histological examination confirmed MTC. Discussion: These cases underscore the importance of routine calcitonin screening in GD patients with thyroid nodules to facilitate early detection and improve prognosis. Our findings suggest that while the coexistence of GD and MTC is likely incidental, vigilant monitoring and comprehensive evaluation are crucial for timely intervention. Conclusions: This study advocates for integrating calcitonin testing into the standard diagnostic protocol for GD patients presenting with thyroid abnormalities. Full article

The effectiveness of newborn screening (NBS) for congenital hypothyroidism (CH) relies on timely screening, confirmation of diagnosis, and initiation and ongoing monitoring of treatment. The objective of this study was to ascertain the extent to which infants with CH have received timely and appropriate management within the first 3 years of life, following diagnosis through NBS in Alberta, Canada. Deidentified laboratory data were extracted between 1 April 2014 and 31 March 2019 from Alberta Health administrative databases for infants born in this time frame. Time to lab collection was anchored from date of birth. Timeliness was assessed as the frequency of monitoring of Thyroid Stimulating Hormone (TSH) and appropriateness as the frequency of children maintaining biochemical euthyroidism. Among 160 term infants, 95% had confirmation of diagnosis by 16 days of age. The cohort had a median of 2 (range 0–5) TSH measurements performed in the time interval from 0 to 1 month, 4 (0–12) from 1 to 6 months, 2 (0–10) from 6 to 12 months, and 7 (0–21) from 12 to 36 months. Approximately half were still biochemically hypothyroid (TSH > 7 mU/L) at 1 month of age. After becoming euthyroid, at least some period of hypo- (60%) or hyperthyroidism (TSH < 0.2 mU/L) (39%) was experienced. More work needs to be performed to discern factors contributing to prolonged periods of hypothyroidism or infrequent lab monitoring. Full article