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Department of Clinical Research, University of Southern Denmark, Odense, Denmark
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Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, Denmark
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Department of Clinical Research, University of Southern Denmark, Odense, Denmark
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Introduction: Analytical problems should be considered in case of a discrepancy between the results of biochemical tests and the clinical findings. Macro-hormones often artefactually elevate biochemical tests. Case Presentation: A young male was referred with persistently elevated TSH (148 mIU/L) measured by a sandwich electrochemiluminescence immunoassay, ECLIA (Cobas; Roche, Basel, Switzerland). The patient’s complaints were unspecific, and he appeared clinically euthyroid. The plasma levels of free T4 and free T3 were within the normal range, thyroid autoantibodies were negative, and thyroid ultrasonography was normal. During a short trial of thyroid hormone substitution, the level of TSH decreased to near-normal levels, but hyperthyroid symptoms emerged. TSH analysed by a different immunoassay (Architect; Abbott, Chicago, IL, USA) yielded similar results. In addition, serial dilutions were performed showing linearity, without detection of heterophilic antibody interference. Gel filtration chromatography confirmed the presence of macro-TSH. Conclusion: The patient harboured macro-TSH, which is a rare condition. The complex binding of TSH to other plasma proteins, most often immunoglobulins, results in elevated plasma TSH. However, the biologically active fraction of TSH is normal, reflected by clinical and biochemical euthyroidism.
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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.
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OPEN, Odense Patient Data Explorative Network, Odense University Hospital, Odense, Denmark
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Introduction: Benign nodular goiter may be associated with swallowing difficulties, but insight into the associated pathophysiology is limited. The aim of this study was to investigate the effect of surgery on the degree of esophageal compression, and its correlation to swallowing difficulties. Methods: Esophageal compression and deviation were evaluated blindly on magnetic resonance imaging (MRI) of the neck, prior to and 6 months after thyroid surgery for symptomatic benign goiter. Goiter symptoms and swallowing difficulties were measured by the Goiter Symptom Scale of the Thyroid-Specific Patient-Reported Outcome (ThyPRO) questionnaire. Cohen’s d was used for evaluating effect sizes (ES). Results: Sixty-four patients completed the study. Before surgery, median goiter volume was 57 (range 14–642) mL. The smallest cross-sectional area of the esophagus (SCAE) increased from a median of 95 (47–147) to 137 (72–286) mm<sup>2</sup> (ES = 1.31, p < 0.001). Median esophagus width increased from 15 (range 10–21) to 17 (range 12–24) mm (ES = 0.94, p < 0.001) after surgery, while no statistically significant change was observed for the sagittal dimension (anterior-to-posterior), thus reflecting an increasingly ellipsoid esophageal shape. Median esophageal deviation decreased moderately after surgery from 4 (0–23) to 3 (0–10) mm (ES = 0.54, p = 0.005). The goiter symptom score improved considerably from (mean ± SD) 40 ± 21 to 10 ± 10 points (ES = 1.5, p < 0.001) after surgery, and the improvements were associated with improvements in SCAE (p = 0.03). Conclusions: In patients with goiter, thyroidectomy leads to substantial improvements in esophageal anatomy, as assessed by MRI, and this correlates with improved swallowing symptoms. This information is valuable in qualifying the dialogue with goiter patients, before deciding on the mode of therapy. Clinicaltrials.gov (NCT03072654).
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Background: Thyroid nodule image reporting and data systems (TIRADS) provide the indications for fine-needle aspiration (FNA) based on a combination of nodule sonographic features and size. We compared the TIRADS-based recommendations for FNA with those based on the personal expertise of qualified US investigators in the diagnosis of thyroid malignancy. Methods: Seven highly experienced ultrasound (US) investigators from 4 countries evaluated, online, the US video recordings of 123 histologically verified thyroid nodules. Technical resources provided the operators with a diagnostic approach close to the real-world practice. Altogether, 4,305 TIRADS scores were computed. The combined diagnostic potential of TIRADS (TIRSYS) and the personal recommendations of the investigators (PERS) were compared against 3 possible goals: to recognize all malignant lesions (allCA), nonpapillary plus non-pT1 papillary cancers (nPnT1PCA), or stage II-IV cancers (st2-4CA). Results: For allCA and nPnT1PCA, TIRSYS had lower sensitivity than PERS (69.8 vs. 87.2 and 83.5 vs. 92.6%, respectively, p <0.01), while in st2-4CA the sensitivities were the same (99.1 vs. 98.6% and TIRSYS vs. PERS, respectively). TIRSYS had a higher specificity than PERS in all 3 types of cancers (p < 0.001). PERS recommended FNA in a similar proportion of lesions smaller or larger than 1 cm (76.9 vs. 82.7%; ns). Conclusions: Recommendations for FNA based on the investigators’ US expertise demonstrated a better sensitivity for thyroid cancer in the 2 best prognostic groups, while TIRADS methodology showed superior specificity over the full prognostic range of cancers. Thus, personal experience provided more accurate diagnoses of malignancy, missing a lower number of small thyroid cancers, but the TIRADS approach resulted in a similar accuracy for the diagnosis of potentially aggressive lesions while sparing a relevant number of FNAs. Until it is not clearly stated what the goal of the US evaluation is, that is to diagnose all or only clinically relevant thyroid cancers, it cannot be determined whether one diagnostic approach is superior to the other for recommending FNA.
Institute of Public Health, University of Copenhagen
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National Research Centre for the Working Environment, Copenhagen
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Department of Palliative Medicine, Bispebjerg Hospital
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Purpose: To evaluate the relationship between thyroid variables and health-related quality of life (QoL) in patients with autoimmune hypothyroidism, using the thyroid-specific QoL questionnaire ThyPRO. Methods: In a cross-sectional study, responses to the ThyPRO from 199 outpatients with autoimmune hypothyroidism were analyzed in relation to thyroid volume, thyroid function and markers of thyroid autoimmunity. Based on a classical QoL framework, we hypothesized that physiological dysfunction caused specific physical and psychological symptoms, which affected functioning and well-being, and consequently participation in life and QoL. These hypotheses were tested through multiple regression and multivariate path analysis models. Results: None of the thyroid function tests were associated with QoL scores. However, in the pairwise regression, the thyroid peroxidase antibody (TPOAb) level was associated with several QoL outcomes: Goitre Symptoms (p = 0.024), Depressivity (p = 0.004), Anxiety (p = 0.004), Emotional Susceptibility (p = 0.005) and Impaired Social Life (p = 0.047). In the multivariate model, the TPOAb level was related to Goitre Symptoms (r = 0.17, p = 0.019), Depressivity (r = 0.24, p = 0.001), and Anxiety (r = 0.23, p = 0.002), but no longer to Emotional Susceptibility or Impaired Social Life, indicating that the effect on these were mediated through an effect on the symptom scales (i.e. Goitre Symptoms, Depressivity and Anxiety). Conclusion: Health-related QoL, evaluated with state-of-the-art QoL methodology, was related to TPOAb level but not to thyroid function. This raises the hypothesis that autoimmunity, independent of thyroid function, impacts on QoL in patients with autoimmune hypothyroidism, especially in terms of psychological symptoms. Longitudinal studies, in initially untreated patients, are needed to test this hypothesis.
OPEN, Odense Patient Data Explorative Network, Odense University Hospital, Odense, Denmark
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Objective: A large goiter may cause compression of the trachea. The aim of this study was to investigate the impact of thyroidectomy on tracheal anatomy and airflow and to correlate this with changes in health-related quality of life (HRQoL) in patients with benign nodular goiter. Methods: Magnetic resonance images of the neck and respiratory flow-volume curves, including both inspiration and expiration, were performed prior to and 6 months following surgery. HRQoL was measured by selected scales from the thyroid-specific patient-reported outcome (ThyPRO). Cohen’s effect size (ES) was calculated as mean change divided by standard deviation at baseline. ES of 0.2–0.5 were defined as small, 0.5–0.8 as moderate, and values >0.8 as large. Results: Sixty-five patients completed all examinations. Median goiter volume was 58 mL (range, 14–642 mL) before surgery with surgical removal of a median of 43 g (range, 8–607 g). Six months after surgery, tracheal narrowing and deviation were diminished by a median of 26% (ES = 0.67, p < 0.001) and 33% (ES = 0.61, p < 0.001), respectively. Correspondingly, each 10% decrease in goiter volume resulted in 1.0% less tracheal narrowing (p < 0.001). Concomitantly, a small improvement was seen in forced inspiratory flow at 50% of forced vital capacity (ES = 0.32, p < 0.001). A reduction in tracheal narrowing was associated with improvements in the Impaired Daily Life scale (0.33 points per 1% decrease in tracheal narrowing, p = 0.03) of the ThyPRO questionnaire. Conclusions: In patients with symptomatic benign nodular goiter, thyroidectomy resulted in substantial improvements in tracheal anatomy and improvements in inspiratory flow, which were followed by gains in HRQoL. This information is pertinent when counseling patients before choice of treatment.
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Institute of Public Health, University of Copenhagen, Odense, Denmark
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National Research Centre for the Working Environment, Copenhagen, Odense, Denmark
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Department of Palliative Medicine, Bispebjerg Hospital, Odense, Denmark
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Background and Objective: Graves' disease has been associated with an increased psychiatric morbidity. It is unclarified whether this relates to Graves' disease or chronic disease per se. The aim of our study was to estimate the prevalence of anxiety and depression symptoms in patients with Graves' disease compared to patients with another chronic thyroid disease, nodular goitre, and to investigate determinants of anxiety and depression in Graves' disease. Methods: 157 cross-sectionally sampled patients with Graves' disease, 17 newly diagnosed, 140 treated, and 251 controls with nodular goitre completed the Hospital Anxiety and Depression Scale (HADS). The differences in the mean HADS scores between the groups were analysed using multiple linear regression, controlling for socio-demographic variables. HADS scores were also analysed dichotomized: a score >10 indicating probable ‘anxiety'/probable ‘depression'. Determinants of anxiety and depression symptoms in Graves' disease were examined using multiple linear regression. Results: In Graves' disease levels of anxiety (p = 0.008) and depression (p = 0.014) were significantly higher than in controls. The prevalence of depression was 10% in Graves' disease versus 4% in nodular goitre (p = 0.038), anxiety was 18 versus 13% (p = 0.131). Symptoms of anxiety (p = 0.04) and depression (p = 0.01) increased with comorbidity. Anxiety symptoms increased with duration of Graves' disease (p = 0.04). Neither thyroid function nor autoantibody levels were associated with anxiety and depression symptoms. Conclusions: Anxiety and depression symptoms were more severe in Graves' disease than in nodular goitre. Symptoms were positively correlated to comorbidity and duration of Graves' disease but neither to thyroid function nor thyroid autoimmunity.
Department of Clinical Research, University of Southern Denmark, Odense, Denmark
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Institute of Clinical Medicine, Faculty of Health and Clinical Sciences, Copenhagen University, Copenhagen, Denmark
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QualityMetric Inc, Johnston, Lincoln, Rhode Island, USA
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Internal Medicine Research Unit, University Hospital of Southern Jutland, Aabenraa, Denmark
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Institute of Clinical Medicine, Faculty of Health and Clinical Sciences, Copenhagen University, Copenhagen, Denmark
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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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Purpose
We investigated whether selenium supplementation improves quality-of-life (QoL) in patients with autoimmune thyroiditis (ID:NCT02013479).
Methods
We included 412 patients ≥18 years with serum thyroid peroxidase antibody (TPOAb) level ≥100 IU/mL in a multicentre double-blinded randomised clinical trial. The patients were allocated 1:1 to daily supplementation with either 200 μg selenium as selenium-enriched yeast or matching placebo tablets for 12 months, as add-on to levothyroxine (LT4) treatment. QoL, assessed by the Thyroid-related Patient-Reported-Outcome questionnaire (ThyPRO-39), was measured at baseline, after 6 weeks, and after 3, 6, 12, and 18 months.
Results
In total, 332 patients (81%) completed the intervention period, of whom 82% were women. Although QoL improved during the trial, no difference in any of the ThyPRO-39 scales was found between the selenium group and the placebo group after 12 months of intervention. In addition, employing linear mixed model regression no difference between the two groups was observed in the ThyPRO-39 composite score (28.8 (95% CI: 24.5–33.6) and 28.0 (24.5–33.1), respectively; P = 0.602). Stratifying the patients according to duration of the disease at inclusion, ThyPRO-39 composite score, TPOAb level, or selenium status at baseline did not significantly change the results. TPOAb levels after 12 months of intervention were lower in the selenium group than in the placebo group (1995 (95% CI: 1512–2512) vs 2344 kIU/L (1862–2951); P = 0.016) but did not influence LT4 dosage or free triiodothyronine–free thyroxine ratio.
Conclusion
In hypothyroid patients on LT4 therapy due to autoimmune thyroiditis, daily supplementation with 200 μg selenium or placebo for 12 months improved QoL to the same extent.
