Hyperthyroidism and thyrotoxicosis
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Aims
Thyroid eye disease (TED) is an autoimmune orbital disorder that diminishes the quality of life (QOL) in affected individuals. Graves’ ophthalmopathy (GO)-QOL questionnaire effectively assesses TED’s effect on patients. This study aims to investigate the factors influencing visual functioning (QOL-VF) and physical appearance (QOL-AP) scores in Chinese TED patients using innovative data analysis methods.
Methods
This cross-sectional study included 211 TED patients whose initial visit to our clinic was from July 2022 to March 2023. Patients with previous ophthalmic surgery or concurrent severe diseases were excluded. GO-QOL questionnaires, detailed medical histories and clinical examinations were collected. The distribution of GO-QOL scores was analyzed, and linear regression and machine learning algorithms were utilized.
Results
The median QOL-VF and QOL-AP scores were 64.29 and 62.5, respectively. Multivariate linear regression analysis revealed age (P = 0.013), ocular motility pain (P = 0.012), vertical strabismus (P < 0.001) and diplopia scores as significant predictors for QOL-VF. For QOL-AP, gender (P = 0.013) and clinical activity (P = 0.086) were significant. The XGBoost model demonstrated superior performance, with an R 2 of 0.872 and a root mean square error of 11.083. Shapley additive explanations (SHAP) analysis highlighted the importance of vertical strabismus, diplopia score and age in influencing QOL-VF and age, clinical activity and sex in QOL-AP.
Conclusion
TED significantly affects patient QOL. The study highlights the efficacy of XGBoost and SHAP analyses in identifying key factors influencing the QOL in TED patients. Identifying effective interventions and considering specific demographic characteristics are essential to improving the QOL of patients with TED.
Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka, Japan
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Objective
As thionamide is associated with various adverse effects, we re-evaluated the practical efficacy of potassium iodide (KI) therapy for Graves’ hyperthyroidism (GD).
Methods
We administered KI (mainly 100 mg/day) to 324 untreated GD patients and added methimazole (MMI) only to those remaining thyrotoxic even at 200 mg/day. When the patient became hypothyroid, MMI, if taken was stopped, then levothyroxine (LT4) was added without reducing the KI dose. Radioactive iodine (RI) therapy or thyroidectomy was performed whenever required. We evaluated the early effects of KI at 2–4 weeks and followed patients for 2 years.
Results
At 2 weeks, serum thyroid hormone levels decreased in all 324 patients. At 4 weeks, fT4, fT3, and both fT4 and fT3 levels became normal or low in 74.7%, 50.6%, and 50.6% of patients, respectively. In a cross-sectional survey over 2 years, GD was well-controlled with KI or KI + LT4 (KI-effective) in >50% of patients at all time points. Among 288 patients followed for 2 years, 42.7% remained ‘KI-effective’ throughout the 2 years (KI Group), 30.9% were well-controlled with additional MMI given for 1–24 months, and 26.4% were successfully treated with ablative therapy (mainly RI). Among ‘KI-effective’ patients at 4 weeks, 76.5% were classified into the KI Group. No patients experienced adverse effects from KI.
Conclusion
KI therapy was useful in the treatment of GD. A sufficient dose of KI was effective in >50% of GD patients from 4 weeks to 2 years, and 42.7% (76.5% of ‘KI-effective’ patients at 4 weeks) remained ‘KI-effective’ throughout the 2 years.
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Objective
Thyrotoxic periodic paralysis is a rare manifestation of thyrotoxicosis. Here, we describe the clinical and biochemical features and treatment outcomes of this disorder.
Methods
This retrospective study was conducted at a tertiary care centre in southern India. The clinical and biochemical features, treatment received, and therapeutic outcomes of all patients with thyrotoxicosis and acute flaccid paralysis without any other identifiable causes (cases for the study) were compared with an equal number of consecutively selected patients who presented with thyrotoxicosis but without features of paralysis (controls for the study) during the same period.
Results
In total, 41 cases and controls were included in this study. The proportion of males was 92.6% and 43.9% in the cases and controls, respectively. The mean age was 32.8 (±7.6) years (cases) and 39.7 (±11.3) years (controls). In the cases, 20% of patients presented without clinical thyrotoxic features. Graves’ disease was the most common aetiology of thyrotoxicosis in both groups (92.6% of cases and 87.8% of controls). The prevalence of goitre was significantly higher among controls (90.2%) than among cases (53.7%). The mean serum potassium, free T4, total T4 and total T3 levels were significantly lower in the cases than in the controls. In these cases, two patients had an additional aetiology for persistent hypokalaemia, likely Gitelman’s syndrome.
Conclusion
This is one of the largest series of thyrotoxic periodic paralysis cases in India. In subjects with thyrotoxicosis, serum potassium, free T4, total T4 and total T3 levels were significantly lower in those with periodic paralysis than in those without.
FMTS, Université de Strasbourg, Faculté de Médecine, France
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iCUBE, CNRS UMR, Illkrich, France
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Université Paul Sabatier, Inserm, Toulouse, France
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Objective
Subclinical hyperthyroidism (SCH) is common and associated with atrial fibrillation (AF) risk in the elderly. Current guidelines rely on a low level of evidence.
Methods
Randomized clinical trial including patients 50 years and older, with thyroid-stimulating hormone (TSH) <0.4 mU/L and normal thyroid hormone concentrations. All patients showed autonomy on thyroid scan. They were randomized either to receive radioiodine (I-131) or to be monitored and treated only if they underwent AF or evolved toward overt hyperthyroidism. Primary outcome was the onset of new AF. Secondary outcomes were treatment-induced hypothyroidism rate and health-related quality of life.
Results
One hundred forty-four patients (mean age: 65.3 ± 8.9 years, 76% females) were randomized, 74 to surveillance and 70 to treatment. Four patients in the surveillance group and one in the treatment group developed AF (P = 0.238). However, the patient who developed AF in the treatment group maintained TSH <0.4 mU/L at AF onset. A post-hoc analysis was carried out and showed that when normalization of TSH was considered, the risk of AF was significantly reduced (P = 0.0003). In the surveillance group, several patients showed no classical characteristics associated with AF risk, including age >65 years or TSH < 0.1mU/L. Of 94 patients treated using radioiodine, 25% developed hypothyroidism during follow-up.
Conclusion
Due to recruitment difficulties, this study failed to demonstrate that SCH treatment can significantly reduce the incidence of AF in patients older than 50 years with thyroid autonomy even if all the patients who developed AF maintained TSH <0.4 mU/L. This result must be balanced with the increased risk of radioiodine-induced hypothyroidism.
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.
