Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China
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Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China
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Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China
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Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China
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Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China
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Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China
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Background
Thyroid eye disease (TED) is an autoimmune orbital disease, with intravenous glucocorticoid (IVGC) therapy as the first-line treatment. Due to uncertain response rates and possible side effects, various prediction models have been developed to predict IVGC therapy outcomes.
Methods
A thorough search was conducted in PubMed, Embase, and Web of Science databases. Data extraction included publication details, prediction model content, and performance. Statistical analysis was performed using R software, including heterogeneity evaluation, publication bias, subgroup analysis, and sensitivity analysis. Forest plots were utilized for result visualization.
Results
Of the 12 eligible studies, 47 prediction models were extracted. All included studies exhibited a low-to-moderate risk of bias. The pooled area under the receiver operating characteristic curve (AUC) and the combined sensitivity and specificity for the models were 0.81, 0.75, and 0.79, respectively. In view of heterogeneity, multiple meta-regression and subgroup analysis were conducted, which showed that marker and modeling types may be the possible causes of heterogeneity (P < 0.001). Notably, imaging metrics alone (AUC = 0.81) or clinical characteristics combined with other markers (AUC = 0.87), incorporating with multivariate regression (AUC = 0.84) or radiomics analysis (AUC = 0.91), yielded robust and reliable prediction outcomes.
Conclusion
This meta-analysis comprehensively reviews the predictive models for IVGC therapy response in TED. It underscores that integrating clinical characteristics with laboratory or imaging indicators and employing advanced techniques like multivariate regression or radiomics analysis significantly enhance the efficacy of prediction. Our research findings offer valuable insights that can guide future studies on prediction models for IVGC therapy in TED.
Unit of Endocrinology, Department of Medical Specialties, Azienda Ospedaliero-Universitaria of Modena, Modena, Italy
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Unit of Endocrinology, Department of Medical Specialties, Azienda Ospedaliero-Universitaria of Modena, Modena, Italy
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Unit of Endocrinology, Department of Medical Specialties, Azienda Ospedaliero-Universitaria of Modena, Modena, Italy
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Department of Endocrinology, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
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Department of Endocrinology and Diabetes Care and Prevention Unit, IRCCS Sant’Orsola-Malpighi Polyclinic, Bologna, Italy
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Department of Endocrinology and Diabetes Care and Prevention Unit, IRCCS Sant’Orsola-Malpighi Polyclinic, Bologna, Italy
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Department of Endocrinology and Diabetes Care and Prevention Unit, IRCCS Sant’Orsola-Malpighi Polyclinic, Bologna, Italy
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Unit of Endocrinology, Department of Medical Specialties, Azienda Ospedaliero-Universitaria of Modena, Modena, Italy
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Unit of Endocrinology, Department of Medical Specialties, Azienda Ospedaliero-Universitaria of Modena, Modena, Italy
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Objective
Many cases of subacute thyroiditis (SAT) have been described related to SARS-CoV-2 infection, but no prospective data about follow-up are known. This prospective, longitudinal, 3-year, multicentre study aims to explore the clinical peculiarities and outcome of SAT in relation to SARS-CoV-2 infection, ascertained with antibody dosage.
Methods
All patients receiving SAT diagnosis from November 2020 to May 2022 were enrolled. Data on anamnesis, physical examination, blood tests (TSH, freeT4, freeT3, thyroglobulin, anti-thyroid antibodies, C-reactive protein, erythrocyte sedimentation rate, complete blood count), and thyroid ultrasound were collected. At baseline, the presence of IgG against the SARS-CoV-2 spike protein or nucleocapsid was investigated. Patients were evaluated after 1, 3, 6, and 12 months.
Results
Sixty-six subjects were enrolled. At baseline, 54 presented with pain, 36 (67%) for at least 15 days. Serum SARS-CoV-2 IgG measurements documented that 7 out of 52 subjects (13.5%) had infection before SAT diagnosis (COVID+). No significant differences between the COVID+ and COVID− groups were found at baseline, except for respiratory symptoms and fever, which were more common in COVID+ (P = 0.039 and P = 0.021, respectively). Among the 41 subjects who completed follow-up, COVID+ and COVID− did not differ for therapeutic approach to SAT or outcome, all having an improvement in neck pain, inflammation parameters, and ultrasound features.
Conclusion
This is the first prospective study investigating any difference both at diagnosis and at follow-up between SAT presentation in patients with previous SARS-CoV-2 infection and those without. Our data demonstrate that SARS-CoV-2 does not impact on SAT onset, evolution, and outcome.
Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam, The Netherlands
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Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam, The Netherlands
Amsterdam Reproduction & Development Research Institute, Amsterdam, The Netherlands
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Amsterdam Public Health Research Institute, Amsterdam UMC, The Netherlands
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Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, The Netherlands
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Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, The Netherlands
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Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam, The Netherlands
Amsterdam Reproduction & Development Research Institute, Amsterdam, The Netherlands
Department of Laboratory Medicine, Endocrine Laboratory, Amsterdam UMC Location Vrije Universiteit Amsterdam, Boelelaan, Amsterdam, The Netherlands
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Laboratory Specialized Diagnostics & Research, Department of Laboratory Medicine, Amsterdam UMC, University of Amsterdam, Meibergdreef, Amsterdam, The Netherlands
Amsterdam Public Health Research Institute, Meibergdreef, Amsterdam, The Netherlands
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Background
Subclinical thyroid diseases are often the subject of debate concerning their clinical significance, the appropriateness of diagnostic testing, and possible treatment. This systematic review addresses the variation in international guidelines for subclinical hyperthyroidism, focusing on diagnostic workup, treatment, and follow-up recommendations.
Methods
Following the PRISMA guidelines, we searched PubMed, Embase, and guideline-specific databases and included clinical practice guidelines with recommendations on subclinical hyperthyroidism. Guideline recommendations were extracted, and quality assessment was performed using selected questions of the Appraisal of Guidelines for Research & Evaluation (AGREE) II instrument.
Results
Of the 2624 records screened, 22 guidelines were included, which were published between 2007 and 2021. Guideline quality was generally intermediate to low. Diagnostic approaches differed substantially, particularly in the extent of recommended testing. Treatment initiation depended on TSH levels, age, and comorbidities, but the level of detail regarding defining precise comorbidities varied. Recommendations for monitoring intervals for follow-up ranged from 3 to 12 months.
Conclusion
This review underscores the existing variability in (inter)national guidelines concerning subclinical hyperthyroidism. There isa need for clear recommendations in guidelines considering diagnostic workup, treatment, and follow-up of subclinical hyperthyroidism. In order to establish this, future research should focus on determining clear and evidence-based intervention thresholds.
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Atrial fibrillation (AF) is a common condition with a global estimated prevalence of 60 million cases, and the most common cardiac complication of hyperthyroidism, occurring in 5–15% of overtly hyperthyroid patients. Additionally, subclinical hyperthyroidism and high-normal free T4 have been associated with an increased risk in the development of AF. Hyperthyroidism-related AF is a reversible cause of AF, and the majority of patients spontaneously revert to sinus rhythm in 4–6 months during or after restoration of euthyroidism. Therefore, restoring thyroid function is an indispensable element in hyperthyroidism-related AF management. Rate control with beta-blockers consists another first-line therapy, reserving rhythm control in cases of persistent hyperthyroidism-related AF. It is still controversial whether hyperthyroidism is an independent risk factor of stroke in nonvalvular AF. As a result, initiating anticoagulation should be guided by the clinical thromboembolic risk score CHA2DS2-VASc score in the same way it is applied in patients with non-hyperthyroidism-related AF. Treatment with the novel direct oral anticoagulants appears to be as beneficial and may be safer than warfarin in patients with hyperthyroidism-related AF. In this review, we address the epidemiology, prognosis, and diagnosis of hyperthyroidism-related AF, and we discuss the management strategies and controversies in patients with hyperthyroidism-related AF.
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Objective
Cancer is the second most common cause of death worldwide. It is currently debated whether thyroid dysfunction is a modifiable cancer risk factor. Our aim was to evaluate the risk of cancer in patients with hyperthyroidism.
Methods
This is a register-based nationwide cohort study of individuals with a diagnosis of hyperthyroidism. Each hyperthyroid case was matched with four reference individuals according to age and sex. Using Fine and Gray competing risk regression models, we studied the association of hyperthyroidism and subsequent all-cause cancer diagnoses, adjusted for preexisting morbidity. Sub-analyses were stratified for cause of hyperthyroidism (Graves’ disease and toxic nodular goiter, age when diagnosed with hyperthyroidism, sex, and cancer localization (lung, prostate, breast, and colorectal cancer)).
Results
The cohort consisted of 95,469 patients with hyperthyroidism (followed for a median of 10.9 years (range: 5.2–17.2)), and 364,494 reference individuals (followed for a median of 11.2 years (range: 5.4–17.4)). Hyperthyroidism was associated with increased all-cause cancer risk (sub-distribution hazard ratio (SHR): 1.12; 95% CI: 1.10–1.14), as well as an increased risk of breast (SHR: 1.07; 95% CI: 1.02–1.13), lung (SHR: 1.20; 95% CI: 1.16–1.26), and prostate cancer (SHR: 1.10; 95% CI: 1.02–1.19), but not colorectal cancer (SHR: 1.04; 95% CI: 0.99–1.09). Sub-analyses stratified for age when diagnosed with hyperthyroidism and cause of hyperthyroidism yielded similar results.
Conclusion
In this register-based study, patients with hyperthyroidism had an increased risk of cancer, in particular lung, prostate, and breast cancer. Whether a causal link exists remains to be proven.
Institute of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden
Wallenberg’s Centre of Molecular and Translational Medicine, Region Västra Götaland, Sweden
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Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden
Department of Endocrinology, Sahlgrenska University Hospital, Göteborg, Sweden
Gothenburg Centre for Person Centred-Care (GPCC), Göteborg, Sweden
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Background
Mood disorders are common in Graves’ disease despite treatment. The pathogenic mechanisms involved are unknown and so is whether previous psychiatric disease influences these symptoms.
Methods
This is a longitudinal study conducted in Sweden on 65 women with newly diagnosed Graves’ disease and 65 matched controls. Participants were examined during hyperthyroidism and after 15 months of treatment. Examinations included blood sampling, and psychiatric testing with the Comprehensive Psychopathological Rating Scale for Affective Syndromes and the Structured Clinical Interview for DSM-IV – Axis I Disorders. We also performed two analyses of a national population-based registry to determine previous psychiatric diagnoses and previous prescriptions of psychoactive drugs in (i) all patients we asked to participate and (ii) all Swedish women given a diagnosis of hyperthyroidism during 2013–2018, comparing them to matched controls.
Results
There was no increased previous psychiatric comorbidity in Graves’ patients compared to controls. There was no higher prevalence of psychiatric diagnoses and prescriptions of psychoactive drugs between (i) included GD patients compared to those who declined participation and (ii) women with a hyperthyroidism diagnosis in 5 years prior to their diagnosis, compared to matched controls. Depression scores and anxiety scores were higher in patients compared to controls both during hyperthyroidism (depression (median (IQR): 7.5 (5.0–9.5) vs 1.0 (0.5–2.5) P < 0.001), anxiety: 7.7 (5.0–11) vs 2.5 (1.0–4.0) P < 0.001) and after treatment (depression: 2.5 (1.5–5.0) vs 1.5 (0.5-3.5) P < 0.05), anxiety: 4.0 (2.5–7.5) vs 3.0 (1.5-5.0) P < 0.05). Patients with a previous psychiatric condition, mild eye symptoms, and a younger age had more anxiety at 15 months compared to patients without these symptoms and a higher age (all p<0.05).
Conclusion
Graves’ disease affects patients’ mood despite treatment. A previous psychiatric condition, mild eye symptoms, and a younger age increase the vulnerability for long-lasting symptoms and require specific attention.
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Background
Thyroperoxidase (TPOAb) and thyroglobulin (TgAb) antibodies are highly prevalent in Graves’ disease (GD), but their significance is controversial.
Methods
We retrospectively analyzed TPOAb and TgAb levels and evolution in 136 patients with newly diagnosed GD between 2000 and 2022, treated with anti-thyroid drugs (ATD) in a block-and-replace (B+R) regimen for at least 12 months and followed up for at least 1 year after ATD discontinuation or until disease relapse.
Results
At diagnosis, 98 out of 136 (72%) patients were TPOAb positive and 73 out of 136 (54%) patients were TgAb positive. The presence of TPOAb or TgAb antibodies at diagnosis was generally not related to GD presentation and did not influence the risk of relapse (P = 0.304 and P = 0.348, respectively). There was less TED (thyroid eye disease) in TgAb-positive patients than TgAb-negative patients at diagnosis (11 out of 73 (15.1%) versus 21 out of 63 (33.3%) P = 0.012). In contrast, the presence of TPOAb at diagnosis was not associated with TED (P = 0.354). The absence of TgAb at diagnosis (P = 0.05) and time to euthyroidism (P = 0.009), but not smoking or TRAb levels, were associated with TED in multivariate logistic regression. TPOAb and TgAb levels during treatment and after its discontinuation were not predictive of relapse, except for lower titers of TgAb at 18 months in patients who relapsed (P = 0.034).
Conclusion
In GD patients treated with a first course of ATD in a B+R regimen we observed lower titers of TgAb at the end of treatment in patients who relapsed and a significant protection against TED in patients with positive TgAb at diagnosis, irrespectively of TPOAb.
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Background
Central hyperthyroidism is characterized by elevated free thyroid hormone and unsuppressed thyroid-stimulating hormone (TSH), and this laboratory feature includes TSH-secreting pituitary adenoma (TSHoma) and resistance to thyroid hormone β (RTHβ). Central hyperthyroidism combined with Graves’ disease (GD) has been rarely reported.
Case Report
We describe three patients with TSHoma combined with GD and one patient with GD combined with RTHβ and pituitary adenoma. These three patients with TSHoma combined with GD showed elevated thyroid hormone, while TSH level was normal or elevated, and TSH receptor antibodies were positive. After thyrotoxicosis was controlled, they all underwent transsphenoidal surgery. We also describe a patient with an initial presentation of GD who developed hypothyroidism after anti-hyperthyroidism treatment and TSH was inappropriately significantly increased. His head magnetic resonance imaging revealed a pituitary adenoma. Genetic testing confirmed a heterozygous mutation in the thyroid hormone receptor β gene c.1148G>A (p.R383H). After levothyroxine and desiccated thyroid tablet treatment, the TSH level decreased to normal.
Conclusion
These four cases highlight the need to consider the diagnosis of GD combined with central hyperthyroidism when faced with inconsistent thyroid function test results, illuminating the specific diagnostic and therapeutic challenges of coexisting primary and central hyperthyroidism. Finally, we propose clinical management for central hyperthyroidism combined with GD.
Department of Neurology, Sahlgrenska University Hospital, Gothenburg, Sweden
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Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
Wallenberg’s Centre of Molecular and Translational Medicine, Region Västra Götaland, Sweden
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Department of Pedagogical, Curricular and Professional Studies, Faculty of Education, University of Gothenburg, Gothenburg, Sweden
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Wallenberg’s Centre of Molecular and Translational Medicine, Region Västra Götaland, Sweden
Department of Endocrinology, Sahlgrenska University Hospital, Gothenburg, Sweden
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Objective
Mental fatigue, depression, anxiety, and cognitive complaints are common in Graves’ disease (GD). Our aims were to assess the relationship between these variables in patients with GD during both hyperthyroidism and a long stable euthyroidism.
Methods
A prospective longitudinal case-control study where 65 premenopausal women diagnosed with GD and 65 matched controls were assessed twice with 15 months in between. The first visit for patients was in overt hyperthyroidism and the second after treatment.
Results
During the hyperthyroid phase, mental fatigue, depression, and anxiety were significantly increased for GD patients compared to controls (all P < 0.001). Among GD patients, 89% reported mental fatigue and among controls 14%. No difference in cognitive tests was found. After 15 months, significant improvements for GD patients after treatment were found for the items of mental fatigue, depression, and anxiety (all P < 0.001), but these were unchanged in controls. GD patients reported residual mental fatigue (38%), 23% without depression, and 15% mental fatigue combined with depression. Self-reported cognitive complaints were pronounced while cognitive tests did not reveal any deficiencies.
Conclusion
Mental fatigue and emotional distress are common in the hyperthyroid phase. These improve with treatment but are still more common in GD patients after 15 months of therapy than in controls. The residual mental fatigue is shown to be a phenomenon distinct from depression in this study. This indicates the importance of assessing mental fatigue in GD patients and underlines the need for rehabilitation and healthcare support as fatigue will have consequences for work ability.
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Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar Universitário de São João, Porto, Portugal
Department of Surgery and Physiology, Cardiovascular Research Unit, Faculty of Medicine from the University of Porto, Porto, Portugal
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Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar Universitário de São João, Porto, Portugal
Institute for Research Innovation in Health, University of Porto, Porto, Portugal
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Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar Universitário de São João, Porto, Portugal
Department of Surgery and Physiology, Cardiovascular Research Unit, Faculty of Medicine from the University of Porto, Porto, Portugal
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Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar Universitário de São João, Porto, Portugal
Institute for Research Innovation in Health, University of Porto, Porto, Portugal
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Aim
The prevalence of thyroid nodules and the risk of thyroid cancer in patients with Graves’ disease is uncertain. We aimed to evaluate the prevalence of thyroid nodules and cancer in patients with Graves’ disease.
Methods
Retrospective observational study of adult subjects with Graves' disease (positive autoantibodies thyrotropin receptor antibodies (TRAbs)) between 2017 and 2021 at our center was done. We evaluated the prevalence of thyroid nodules and cancer in this population and characterized the predictive factors for thyroid malignancy using linear and logistic regression models.
Results
We evaluated a total of 539 patients with Graves' disease during a median follow-up of 3.3 years (25th–75th percentiles 1.5–5.2 years). Fifty-three percent had thyroid nodules and 18 (3.3%) were diagnosed with thyroid cancer (12 papillary microcarcinomas). All tumors were classified using TNM classification as T1, and only one had lymph node metastasis; there were no recordings of distant metastasis. Sex, age, body mass index, smoking, TSH, and TRAbs levels were not significantly different between patients with and without thyroid cancer. Patients with multiple nodules on ultrasound (OR 1.61, 95%CI 1.04–2.49) and with larger nodules (OR 2.96, 95%CI 1.08–8.14, for 10 mm increase in size) had a greater risk of thyroid cancer diagnosis.
Conclusion
Patients with Graves’ disease had a high prevalence of thyroid nodules and their nodules had a significant risk of thyroid cancer. The risk was higher in those with multiple and larger nodules. Most had low-grade papillary thyroid cancer. More studies are needed to clarify the clinical relevance of these findings.
