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Several European countries have seen major health issues after a switch from one levothyroxine brand to another, as well as following the introduction of several levothyroxine formulation changes. While the relationship between these health issues and brand or formulation changes merits further investigation, the current position statement on behalf of both health-care providers and patients summarizes recent events in several European countries and provides a number of recommendations to limit the burden for patients, so as to prevent increased health-care consumption and health-care expenses in this context.
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Given the fact that a large number of radiological examinations using iodine-based contrast media (ICM) are performed in everyday practice, clinicians should be aware of potential ICM-induced thyroid dysfunction (TD). ICM can induce hyperthyroidism (Hyper) or hypothyroidism (Hypo) due to supraphysiological concentrations of iodine in the contrast solution. The prevalence of ICM-induced TD varies from 1 to 15%. ICM-induced Hyper is predominantly found in regions with iodine deficiency and in patients with underlying nodular goiter or latent Graves’ disease. Patients at risk for ICM-induced Hypo include those with autoimmune thyroiditis, living in areas with sufficient iodine supply. Most cases of ICM-induced TD are mild and transient. In the absence of prospective clinical trials on the management of ICM-induced TD, an individualized approach to prevention and treatment, based on patient’s age, clinical symptoms, pre-existing thyroid diseases, coexisting morbidities and iodine intake must be advised. Treatment of ICM-induced Hyper with antithyroid drugs (in selected cases in combination with sodium perchlorate) should be considered in patients with severe or prolonged hyperthyroid symptoms or in older patients with underlying heart disease. It is debated whether preventive therapy with methimazole and/or perchlorate prior to ICM administration is justified. In ICM-induced overt Hypo, temporary levothyroxine may be considered in younger patients with symptoms of Hypo, with an underlying autoimmune thyroiditis and in women planning pregnancy. Additional clinical trials with clinically relevant endpoints are warranted to further aid in clinical decision-making in patients with ICM-induced TD.
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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 Clinical Research, University of Southern Denmark, Odense, Denmark
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Background: Graves disease (GD) is an autoimmune condition characterized by the presence of antibodies against the thyrotropin receptor (TRAB), which stimulate the thyroid gland to produce excess thyroid hormone. Theoretically, TRAB could stimulate highly differentiated thyroid cancer tissue and/or metastases to produce thyroid hormone. Case: A 68-year-old male, with weight loss and palpitations, was diagnosed with thyrotoxicosis. A later MRI, due to persistent shoulder pain, revealed multiple bone metastases. A biopsy was diagnostic for follicular variant of papillary thyroid carcinoma, and total thyroidectomy was performed. One week after thyroidectomy the patient was admitted with severe hyperthyroidism. TRAB was >40 IU/mL (normal <0.7 IU/mL). High-dose antithyroid drug treatment was followed by high-dose radioactive iodine-131 (RAI) and local radiotherapy covering the right shoulder. Antithyroid drug treatment continued until after the fourth RAI dose. Hypothyroidism did not occur until following the fifth RAI treatment. Summary and Conclusions: We present a patient initially diagnosed with thyrotoxicosis and subsequently with metastatic follicular variant of papillary thyroid cancer. It is suggested that TRAB stimulated the highly differentiated extrathyroidal metastatic thyroid tissue to produce excessive amounts of thyroid hormone, delayed diagnosis, and potential aggravation of the course of thyroid cancer.
Department of Clinical Research, University of Southern Denmark, Odense, Denmark
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Department of Clinical Research, University of Southern Denmark, Odense, Denmark
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Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Department of Data and Data Support, Region Zealand, Sorø, Denmark
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Department of Clinical Research, University of Southern Denmark, Odense, Denmark
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Faculty of Health Science, University of Copenhagen, Copenhagen, Denmark
Department of Cardiology, University Hospital Nordsjælland, Hillerød, Denmark
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Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Steno Diabetes Center Copenhagen, Herlev, Denmark
Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
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Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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Department of Clinical Research, University of Southern Denmark, Odense, Denmark
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Objective
Some studies suggest that hypothyroidism is associated with increased oxidative stress. Urinary excretion of 8-oxo-7,8-dihydroguanosine (8-oxoGuo) and 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) represents whole-body RNA and DNA oxidation, respectively. These biomarkers have only been explored sparsely in patients with thyroid disorders.
Methods
In 45 Danish women with newly diagnosed hypothyroidism, we compared 8-oxoGuo and 8-oxodG before or shortly after initiating levothyroxine with the excretion rates at euthyroidism. We also compared the excretion of 8-oxoGuo and 8-oxodG in the patients after restored euthyroidism with 18 healthy control subjects.
Results
Compared with baseline, none of the biomarkers changed significantly in the patients after becoming euthyroid. The geometric mean of 8-oxoGuo was 1.63 (95% CI: 1.49–1.78) nmol/mmol creatinine at baseline and 1.67 nmol/mmol at euthyroidism (95% CI: 1.53–1.83) (P = 0.39), while that of 8-oxodG was 1.28 nmol/mmol creatinine at baseline (95% CI: 1.14–1.44) and 1.32 nmol/mmol at euthyroidism (95% CI: 1.18–1.48), respectively (P = 0.47). The relative mean differences were 0.97 (95% CI: 0.91–1.04) for 8-oxoGuo and 0.97 (95% CI: 0.88–1.06) for 8-oxodG. At baseline, multiple linear regression revealed a positive association between free thyroxine and both biomarkers (8-oxoGuo, P < 0.001; 8-oxodG, P = 0.04). Furthermore, 8-oxoGuo was positively associated with age (P = 0.04) and negatively associated with thyrotropin (P = 0.02). In the control group, the geometric mean of 8-oxoGuo was 1.23 nmol/mmol creatinine (95% CI: 1.07–1.42), while that of 8-oxodG was 1.04 nmol/mmol creatinine (95% CI: 0.88–1.23). Thus, compared with control subjects, euthyroid patients showed a significantly higher level of both 8-oxoGuo (P < 0.001) and 8-oxodG (P = 0.03).
Conclusion
In hypothyroid women, no significant effect of levothyroxine treatment on the oxidative stress biomarkers 8-oxoGuo and 8-oxodG could be demonstrated. However, the excretion of these biomarkers was significantly higher than in healthy controls.
