Hyperthyroidism and thyrotoxicosis
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Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden
The National Task Force in Hyperthyroidism, Swedish National System for Knowledge-Driven Management, Umeå, Sweden
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Department of Endocrinology and Diabetes, Örebro University Hospital, Örebro, Sweden
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Thyroid Federation International, Kungsbacka, Sweden
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Swedish Thyroid Association, Stockholm, Sweden
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Swedish Thyroid Association, Stockholm, Sweden
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Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden
The National Task Force in Hyperthyroidism, Swedish National System for Knowledge-Driven Management, Umeå, Sweden
Sweden and Wallenberg Center for Molecular and Translational Medicine, Västra Götaland Region, Göteborg, Sweden
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Patients with Graves' disease (GD) not only need appropriate medical care, but they also need to be cared for. The aim of this review is to examine the literature on GD patient needs, expectations, perceptions, and quality of life. We will also present methods for patient care, define gaps in knowledge, and suggest factors that can be introduced into the regular care of GD patients. Patient information, teamwork with thyroid/contact nurses, education of personnel and patients, quality of life measurements, and the formation of a rehabilitation program have enough evidence to be implemented into regular care. However, visualizing patient needs through person-centered care requires further evaluation in GD patients before being implemented in routine care. We conclude that considerable improvement in nursing can be achieved in relation to GD.
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Background
Graves' disease (GD) among children has attracted wide attention. However, data on long-term follow-up are scarce, especially in China. This study aimed to investigate the prognosis after regular treatments of GD and to identify possible influencing factors.
Methods
A total of 204 newly diagnosed GD children in the Children's Hospital of Nanjing Medical University between 2013 and 2019 were included in this study. The cases involved were divided into remission group, relapse group, and continuing treatment group according to therapy outcomes. Relationships between prognosis and possible influencing factors in remission and relapse groups were analyzed.
Results
All 204 cases were treated with methimazole at presentation with GD. Due to severe complications, 4 (2.0%) cases changed medication to propylthiouracil. Of all the GD children included, 79 (38.7%) had remission, and 40 (50.6%) relapsed after remission. For each additional month before free thyroxine fell into the reference range with treatment, the risk of relapse increased 1.510 times (adjusted odds ratio (OR)=2.510, 95%CI: 1.561–4.034) compared to those in the remission group. On the contrary, the risk of relapse was reduced by 0.548 times for each additional hour of sleep duration per day (adjusted OR=0.452, 95%CI: 0.232–0.879).
Conclusion
GD children have a high relapse rate after remission, and most of them occur within 1 year. Thyroid function should be reexamined regularly after drug withdrawal. The response to medication and lifestyle of GD children may affect the prognosis.
Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine and School of Medicine, Seoul, Republic of Korea
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Division of Endocrinology and Metabolism, Department Internal Medicine, Dankook University College of Medicine, Cheonan, Republic of Korea
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Objective
This study evaluated the efficacy of antithyroid drugs (ATDs) and risk factors associated with the recurrence of Graves’ hyperthyroidism using a comprehensive retrospective cohort.
Methods
We included 1829 patients newly diagnosed with Graves’ hyperthyroidism, with sufficient follow-up data. Clinical outcomes of the patients and risk factors associated with recurrence-free survival, including the changes in thyrotropin receptor antibody, were evaluated.
Results
The median age of the patients was 44.5 years, and 69% were female. Among the patients, 1235 had a chance to withdraw ATD after a median of 23 (interquartile range (IQR) 17.0–35.5) months of treatment. The first remission rate was 55.6% during a median of 72.7 months of follow-up. After the first recurrence, 95% of patients underwent the second course of ATD treatment for a median of 21.1 (IQR 14.8–31.7) months, and the remission rate was 54.1%. During a median of 67 months of follow-up, 7.7% of patients underwent surgery, and 10.5% underwent radioactive iodine therapy. Approximately 30% were still on ATD therapy for recurrent disease or prolonged low-dose maintenance. Younger age (<45 years), male sex, and fluctuating or smoldering of TRAb levels were independent risk factors of the first recurrence after ATD treatment.
Conclusions
ATD treatment is an acceptable option for the initial treatment of Graves’ hyperthyroidism as well as for recurrent disease. The optimal treatment period for ATD treatment needs to be determined using the individual risk factors of recurrence.
Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal
Institute of Biomedical Sciences Abel Salazar, University of Porto, Porto, Portugal
Faculty of Medicine, University of Porto, Porto, Portugal
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Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal
Faculty of Medicine, University of Porto, Porto, Portugal
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Faculty of Medicine, University of Porto, Porto, Portugal
North Lisbon University Hospital Center, Lisbon, Portugal
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University Hospital Center of São João, Porto, Portugal
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University Hospital Center of São João, Porto, Portugal
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Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal
Faculty of Medicine, University of Porto, Porto, Portugal
University Hospital Center of São João, Porto, Portugal
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Faculty of Medicine, University of Porto, Porto, Portugal
University Hospital Center of São João, Porto, Portugal
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Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal
Faculty of Medicine, University of Porto, Porto, Portugal
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Objective
To understand whether thyroid cells can be directly infected by the SARS-CoV-2 virus and to establish a putative correlation with the expression of the host entry machinery: ACE-2, TMPRSS2, and furin.
Methods
We assessed the presence of SARS-CoV-2 virus at the gene level by RT-PCR, viral RNA transcripts localization by in situ hybridization, and by detecting viral proteins by immunohistochemistry for the nucleocapsid and the spike proteins. Furthermore, we also described the immunoexpression of key host factors for virus entry in the COVID-19 thyroid samples.
Results
We performed RT-PCR for SARS-CoV-2 in all autopsy specimens and detected viral genome positivity in 13 of 15 thyroid tissues and in a lung specimen. In 9 of the 14 positive samples, we were also able to confirm SARS-CoV-2 signal by in situ hybridization. Immunohistochemistry for the viral nucleocapsid and spike protein was also positive for ten and nine of the RT-PCR-positive cases, respectively, but revealed a lower sensitivity. We also described, for the first time in a COVID-19 series, the immunohistochemical expression of ACE-2, TMPRSS2, and furin in the thyroid.
Conclusions
Our results obtained in thyroid specimens from deceased COVID-19 patients indicate that thyrocytes can be directly infected by SARS-CoV-2 since we detected the presence of SARS-CoV-2 genome in follicular cells. Nevertheless, we did not find a clear correlation between the presence of viral genome and the expression of the host factors for virus entry, namely ACE-2, TMPRSS2, and furin.
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A 22-year-old male with a history of ulcerative colitis and nephrotic syndrome treated with immunomodulatory agents including vedolizumab and mycophenolic acid developed hyperthyroidism 2 weeks following the first administration of BNT162b2 vaccine (Pfizer-BioNTech COVID-19 vaccine). Graves’ disease (GD) was diagnosed based on the elevated thyrotropin-receptor antibody, thyroid scintigraphy and ultrasound. To this day, four cases of new-onset GD following SARS-CoV-2 vaccine were reported in patients with no previous history of thyroid disease. Two cases of recurrence of GD following SARS-CoV-2 vaccine were also reported. Although the underlying mechanisms of vaccine-induced autoimmunity remain to be clarified, there is a rationale for the association between SARS-CoV-2 vaccination and the development of Th1-mediated diseases, at least in predisposed individuals. The BNT162b2 vaccine could be a trigger for GD in some patients. However, the benefit/risk ratio remains by far in favour of SARS-CoV-2 vaccination considering the potentially higher risk of severe infection in these patients.
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Objective
Destructive thyroiditis is the most common endocrine immune-related adverse event (iRAEs) in patients treated with anti-PD1/PD-L1 agents. Given its self-limited course, current guidelines recommend no treatment for this iRAE. Nevertheless, in patients with enlarged thyroid volume and a poor performance status, thyrotoxicosis may be particularly severe and harmful. The aim of the study is to evaluate if steroid treatment might be useful in improving thyrotoxicosis in subjects with a poor performance status.
Methods
We conducted a retrospective study, comparing the course of thyrotoxicosis of four patients treated with oral prednisone at the dosage of 25 mg/day (tapered to discontinuation in 3 weeks) and an enlarged thyroid volume to that of eight patients with similar thyroid volume who were left untreated.
Results
The levels of thyroid hormones were lower in subjects treated compared to those untreated at time of 7, 14, 21, 28, 35, 42, 60 and 90 days (P < 0.05 at each time). The time to remission of thyrotoxicosis was 24 days in patients treated with steroids and 120 days in untreated patients (P < 0.001). At 6 months, the rate of evolution to hypothyroidism was similar in the two groups (4/4 in the steroid group vs 7/8 in the untreated group, P = 0.74) and no difference was found in tumor progression (P = 0.89).
Conclusions
Our preliminary data suggest that in patients with a poor performance status experiencing a severe destructive thyrotoxicosis induced by PD-1 blockade, a short period of administration of oral prednisone is effective in obtaining a quick reduction of the levels of thyroid hormones.
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Objective
We investigated whether a positive thyroid peroxidase antibody (TPO Ab) status before radioactive iodine (RAI) therapy in patients with Graves’ hyperthyroidism is a predictive factor for developing hypothyroidism post RAI.
Methods
We performed a retrospective study of patients with Graves’ hyperthyroidism with known TPO Ab status, receiving the first administration of RAI. Patients from four thyroid outpatient centres in Belgium receiving their first RAI therapy between the years 2011 and 2019 were studied. Clinical, laboratory, imaging, and treatment data were recorded from medical charts. Hypothyroidism and cure (defined as combined hypo- and euthyroidism) were evaluated in period 1 (≥2 and ≤9 months, closest to 6 months post RAI) and period 2 (>9 months and ≤24 months post RAI, closest to 12 months post RAI).
Results
A total of 152 patients were included of which 105 (69%) were TPO Ab-positive. Compared to TPO Ab-negative patients, TPO Ab-positive patients were younger, had a larger thyroid gland, and had more previous episodes of hyperthyroidism. In period 1, 89% of the TPO Ab-positive group developed hypothyroidism and 72% in the TPO Ab-negative group (P = 0.007). In period 2, the observation was similar: 88% vs 72% (P = 0.019). In the multivariate logistic regression analysis, a positive TPO Ab status was associated with hypothyroidism in period 2 (adjusted OR: 4.78; 95% CI: 1.27–20.18; P = 0.024). In period 1, the aOR was 4.16 (95% CI: 1.0–18.83; P = 0.052).
Conclusion
A positive TPO Ab status in patients with Graves’ hyperthyroidism receiving the first administration of RAI is associated with a higher risk of early hypothyroidism.
University of Lille, Lille, France
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University of Lille, Lille, France
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Department of Dermatology, Lille University Hospital, Lille, France
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University of Lille, Lille, France
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Introduction
Immune checkpoint inhibitors (ICI) are used to treat cancers including metastatic melanomas and can induce endocrine side effects. The thyroid is frequently affected with classically transient thyrotoxicosis followed by hypothyroidism. The evolution of thyroid nodules and goiters under ICI therapy is poorly described.
Case presentation
A 72-year-old male presenting with hyperthyroidism due to a toxic nodule in a multinodular goiter (MNG) started ICI therapy combining ipilimumab and nivolumab to treat metastatic melanoma. After an initial worsening of thyrotoxicosis, treated with carbimazole, he developed profound hypothyroidism, persisting after carbimazole discontinuation, needing a long-term levothyroxine supplementation. Ultrasound control performed 6 months after ICIs treatment initiation revealed diffuse thyroid atrophy with involution of all nodules. 123I-scintigraphy confirmed a destructive mechanism.
Discussion
The evolution of MNG and toxic nodules is poorly described in patients treated with ICI since systematic US evaluations are lacking. We describe for the first time a toxic nodule cured by ICI therapy inducing destructive thyroiditis.
Conclusion
Pre-existing nodules and MNG, even if toxic, are not a contraindication for ICI treatment provided the patients are carefully monitored.
Department of Clinical Institute, Aalborg University, Aalborg, Denmark
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Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark
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Department of Clinical Institute, Aalborg University, Aalborg, Denmark
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Department of Clinical Institute, Aalborg University, Aalborg, Denmark
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Purpose
In this prospective multicenter study with patients newly diagnosed with Graves’ hyperthyroidism (GH), we studied the timing and characteristics of adverse drug reactions in patients treated with anti-thyroid drugs (ATD) for up to 48 months.
Methods
Patients with GH were treated with ATD until remission and hereafter with a low-dose regime to keep the patients in remission. The patients were followed with blood samples and recording of adverse events approximately every second month for the first 2 years and every third month for the following 2 years.
Results
We included 208 patients and the patients were treated for a median of 22 (range: 0.5–49) months. Ten percent of the patients experienced adverse drug reactions and 75% of the cases occurred during the first 6 months. After 24 months, the methimazole dose was lowered to 5 mg/day, and after this time point, no further adverse drug reactions were recorded. Skin reactions were the most prominent reaction, comprising 68% of the registered reactions, and no hepatic and bonemarrow affection was recorded.
Conclusion
With this study, we report the frequency, timing of occurrence, and characteristics of adverse drug reactions when treating GH with the ATD drug methimazole for up to 48 months. Long-term low-dose methimazole treatment can be a cost-effective and straightforward treatment option if adverse drug reactions such as severe hepatic and bone marrow affection are kept in mind.
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The clinical and laboratory findings of subacute thyroiditis have been repeatedly reported as being associated with acute Sars-Cov-2 infection and post-COVID-19 syndrome. The exact mechanisms and histopathological correlations underlying thyroid involvement remained unresolved, but current insights suggest either direct viral damage, systemic inflammatory reaction, or an autoimmune response as possible noxious effectors. Here we present findings of immunohistochemical/immunofluorescence detection of Sars-Cov-2 viral proteins (spike/S and nucleocapside proteins) in relation to histoarchitectonic changes of autoptic thyroid tissue obtained from patient who deceased from COVID-19.
