Steen Joop Bonnema

Risk of Malignancy in Thyroid Incidentalomas Detected by 18F-Fluorodeoxyglucose Positron Emission Tomography: A Systematic Review

BACKGROUND The expanding use of (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) has led to the identification of increasing numbers of patients with an incidentaloma in the thyroid gland. We aimed to review the proportion of incidental thyroid cancers found by (18)F-FDG PET or PET/computed tomography imaging. METHODS Studies evaluating thyroid carcinomas discovered incidentally in patients or healthy volunteers by (18)F-FDG PET were systematically searched in the PubMed database from 2000 to 2011. The main exclusion criteria were known thyroid disease, lack of assigned diagnoses, investigation of diffuse uptake only, or investigation of patients with head and neck cancer, or cancer in the upper part of the thorax. RESULTS Twenty-two studies met our criteria comprising a total of 125,754 subjects. Of these, 1994 (1.6%) had unexpected focal hypermetabolic activity, while 999 of 48,644 individuals (2.1%) had an unexpected diffuse hypermetabolic activity in the thyroid gland. A diagnosis was assigned in 1051 of the 1994 patients with a focal uptake, 366 of whom (34.8%) had thyroid malignancy. Likewise, a diagnosis was assigned in 168 of 999 patients with a diffuse uptake, 7 of whom (4.4%) had thyroid malignancy. In the eight studies reporting individual maximum standardized uptake values (SUV(max)), the mean SUV(max) was 4.8 (standard deviation [SD] 3.1) and 6.9 (SD 4.7) in benign and malignant lesions, respectively (p<0.001). CONCLUSIONS Incidentally found thyroid nodules, using (18)F-FDG PET, are at high risk of harboring malignancy if uptake is focal. SUV are significantly higher in malignant than in benign nodules. The pronounced inhomogeneity and other shortcomings of the studies are discussed.

Effects of antithyroid drugs on radioiodine treatment: systematic review and meta-analysis of randomised controlled trials

Objective To determine the effect of adjunctive antithyroid drugs on the risk of treatment failure, hypothyroidism, and adverse events after radioiodine treatment. Design Meta-analysis. Data sources Electronic databases (Cochrane central register of controlled trials, Medline, Embase) searched to August 2006 and contact with experts. Review methods Three reviewers independently assessed trial eligibility and quality. Pooled relative risks for treatment failure and hypothyroidism after radioiodine treatment with and without adjunctive antithyroid drugs were calculated with a random effects model. Results We identified 14 relevant randomised controlled trials with a total of 1306 participants. Adjunctive antithyroid medication was associated with an increased risk of treatment failure (relative risk 1.28, 95% confidence interval 1.07 to 1.52; P=0.006) and a reduced risk for hypothyroidism (0.68, 0.53 to 0.87; P=0.006) after radioiodine treatment. We found no difference in summary estimates for the different antithyroid drugs or for whether antithyroid drugs were given before or after radioiodine treatment. Conclusions Antithyroid drugs potentially increase rates of failure and reduce rates of hypothyroidism if they are given in the week before or after radioiodine treatment, respectively.

Management of the nontoxic multinodular goitre: A European questionnaire study

The optimum management strategy for the patient with a multinodular nontoxic goitre is still a matter of debate. Our aim was to assess the attitudes towards management of such patients throughout Europe by means of a questionnaire.

Time to reconsider nonsurgical therapy of benign non-toxic multinodular goitre: focus on recombinant human TSH augmented radioiodine therapy

The treatment of benign multinodular goitre (MNG) is controversial, but surgery is recommended in large compressive goitres. While some patients decline surgery others may have contraindications due to comorbidity, since MNG is prevalent in the elderly. Therefore, non-surgical treatment alternatives are needed. Until recently, levothyroxine therapy was the preferred non-surgical alternative, but due to low efficacy and potential side-effects, it is not recommended for routine use in recent international guidelines. Conventional radioiodine ((131)I) therapy has been used for two decades as an effective and safe alternative to surgery in the treatment of symptomatic non-toxic MNG. Since much higher activities of (131)I are employed when treating non-toxic rather than toxic MNG, there has been reluctance in many countries to use this treatment modality. Frequently, the (131)I -uptake in a non-toxic MNG is low, which makes (131)I therapy less feasible. Another challenge is the negative correlation between the initial goitre size and goitre volume reduction (GVR). With its ability to more than double the thyroid (131)I-uptake, recombinant human TSH (rhTSH) increases the absorbed radiation dose and thus enhances the GVR by 35-56% at the expense of up to fivefold higher rate of permanent hypothyroidism. An alternative strategy is to reduce the administered (131)I-activity with a factor corresponding to the rhTSH induced increase in (131)I-uptake. Hereby, the extrathyroidal irradiation can be reduced without compromising efficacy. Thus, although in its infancy, and still experimental, rhTSH-augmented (131)I therapy may profoundly alter the non-surgical treatment of benign non-toxic MNG.

Urinary Markers of Nucleic Acid Oxidation and Long-Term Mortality of Newly Diagnosed Type 2 Diabetic Patients

OBJECTIVE We analyzed data from a cohort of 1,381 newly diagnosed type 2 diabetic patients to test the hypothesis that urinary markers of nucleic acid oxidation are independent predictors of mortality. RESEARCH DESIGN AND METHODS We examined the relationship between urinary excretion of markers of DNA oxidation (8-oxo-7,8-dihydro-2′-deoxyguanosine [8-oxodG]) and RNA oxidation (8-oxo-7,8-dihydroguanosine [8-oxoGuo]) and long-term mortality using Cox proportional hazards regression. RESULTS After multivariate adjustment, the hazard ratios for all-cause and diabetes-related mortality of patients with 8-oxoGuo levels in the highest quartile compared with those in the lowest quartile were 1.44 (1.12–1.85) and 1.54 (1.13–2.10), respectively. Conversely, no significant associations between 8-oxodG and mortality were found in the adjusted analyses. CONCLUSIONS Urinary excretion of the RNA oxidation marker 8-oxoGuo measured shortly after diagnosis of type 2 diabetes predicts long-term mortality independently of conventional risk factors. This finding suggests that 8-oxoGuo could serve as a new clinical biomarker in diabetes.

Randomized prospective study comparing a single radioiodine dose and a single laser therapy session in autonomously functioning thyroid nodules

OBJECTIVE To compare the efficacy of interstitial laser photocoagulation (ILP) with radioiodine in hot thyroid nodules. DESIGN Thirty consecutive outpatients with subclinical or mild hyperthyroidism and a scintigraphically solitary hot nodule with extraglandular suppression were randomized to either one ILP session or one radioiodine ((131)I) dose. METHODS ILP was performed under continuous ultrasound-guidance and with an output power of 2.5-3.5 W. (131)I was given as a single dose based on thyroid volume and a 24-h thyroid (131)I uptake. Thyroid function and nodule volume were evaluated at inclusion and at 1, 3 and 6 months after treatment. RESULTS Normalization of serum TSH was achieved in 7 out of 14 patients in the ILP group and in all 15 patients in the (131)I group (P=0.0025). In the ILP group, mean thyroid nodule volume reduction was 44+/-5% (s.e.m.; P<0.001), and in the (131)I group 47+/-8% (P<0.001), within 6 months, without between-group difference (P=0.73). The mean reduction of total thyroid volume was 7+/-5% in the ILP group (P=0.20) and 26+/-8% (P=0.006) in the (131)I group (P=0.06 between-group). Two patients in the (131)I group developed hypothyroidism but no major side effects were seen. CONCLUSIONS This first randomized study, comparing ILP with standard therapy, demonstrates that ILP and (131)I therapy approximately halves thyroid nodule volume within 6 months; but in contrast to (131)I, extranodular thyroid volume is unaffected by ILP and no patient developed hypothyroidism. Using the present design, ILP seems inferior to (131)I therapy in normalization of serum TSH. The potential value of ILP as a non-surgical alternative to (131)I needs further investigation.

Establishing construct validity for the thyroid-specific patient reported outcome measure (ThyPRO): an initial examination

ObjectiveTo establish a reliable and valid scale structure of a patient-reported outcome measuring thyroid-specific quality of life.MethodsThe 98-item ThyPRO questionnaire was administered to patients with benign thyroid diseases at two university hospitals. Multi-trait scaling was performed, evaluating lack of convergent validity (item-own scale polyserial correlation <0.40) or lack of discriminant validity (item-other scale correlation higher than item-own scale correlation) of the hypothesized scale structure. Analyses were repeated in clinical and sociodemographic subgroups and with Pearson correlations. Reliability was estimated by Cronbach’s α, both conventionally and with polychoric correlations.ResultsIn total, 904 patients (69%) responded. Initial multitrait scaling analysis identified 25 scaling errors. Twelve items were omitted from the scale structure, and a re-analysis showed complete convergent validity and only two instances of lack of discriminant validity. Pearson correlations yielded similar results. Across all subgroups, convergent validity was complete, and discriminant validity was found in 99.2% of tests. Lack of discriminant validity was mainly between physical symptoms and psychological and disease-impact scales. Cronbach’s α was acceptable (>0.70, >0.80 with polychoric correlations) for all 13 scales.ConclusionA reliable scale structure displaying complete convergent and almost complete discriminant validity was established in general analyses and in distinct clinical subgroups of patients with benign thyroid diseases.

Association between urinary markers of nucleic acid oxidation and mortality in type 2 diabetes: a population-based cohort study.

OBJECTIVE We recently showed that RNA oxidation, estimated by urinary excretion of 8-oxo-7,8-dihydroguanosine (8-oxoGuo), independently predicted mortality in a cohort of 1,381 treatment-naive patients with newly diagnosed type 2 diabetes. In the present investigation, we analyzed urine collected 6 years after the diagnosis to assess the association between urinary markers of nucleic acid oxidation and mortality in patients with established and treated diabetes. RESEARCH DESIGN AND METHODS We used data from the 970 patients who attended the screening for diabetes complications 6 years after the diagnosis. Cox proportional hazards regression was used to examine the relationship between urinary markers of DNA oxidation (8-oxo-7,8-dihydro-2′-deoxyguanosine [8-oxodG] [n = 938]) and RNA oxidation (8-oxoGuo [n = 936]) and mortality. RESULTS During a median of 9.8 years of follow-up, 654 patients died. Urinary 8-oxoGuo assessed 6 years after the diagnosis was significantly associated with mortality. The multivariate-adjusted hazard ratios for all-cause and diabetes-related mortality of patients with 8-oxoGuo levels in the highest quartile compared with those in the lowest quartile were 1.86 (95% CI 1.34–2.58) and 1.72 (1.11–2.66), respectively. Conversely, 8-oxodG was not associated with mortality. In addition, we found an association between changes in 8-oxoGuo from diagnosis to 6-year follow-up and mortality, with increased risk in patients with an increase and decreased risk in patients with a decrease in 8-oxoGuo. CONCLUSIONS The RNA oxidation marker 8-oxoGuo is an independent predictor of mortality in patients with established and treated type 2 diabetes, and changes in 8-oxoGuo during the first 6 years after diagnosis are associated with mortality.

Recombinant Human Thyrotropin-Stimulated Radioiodine Therapy of Large Nodular Goiters Facilitates Tracheal Decompression and Improves Inspiration

INTRODUCTION The impact on tracheal anatomy and respiratory function of recombinant human (rh)TSH-stimulated (131)I therapy in patients with goiter is not clarified. METHODS In a double-blinded design, patients (age 37-87 yr) with a large multinodular goiter (range, 99-440 ml) were randomized to placebo (n = 15) or 0.3 mg rhTSH (n = 14) 24 h before (131)I therapy. The smallest cross-sectional area of the trachea (SCAT; assessed by magnetic resonance imaging) and the pulmonary function were determined before, 1 wk, and 12 months after therapy. RESULTS Data on goiter reduction have been reported previously. In the placebo group, no significant changes in the lung function or SCAT were found throughout the study. In the rhTSH group, a slight decrease was observed in the forced vital capacity 1 wk after therapy, whereas the mean individual change in SCAT was significantly increased by 10.5% (95% confidence interval = 0.9-20.0%). A further increase in SCAT to 117 +/- 36 mm(2) (P = 0.005 compared with 92 +/- 38 mm(2) at baseline) was seen at 12 months, corresponding to a mean of 31.4% (95% confidence interval = 16.0-46.8%). The expiratory parameters did not change significantly, whereas forced inspiratory flow at 50% of the vital capacity (FIF50%) increased from initially 3.34 +/- 1.33 liters/sec to ultimately 4.23 +/- 1.88 liters/sec (P = 0.015) in the rhTSH group, corresponding to a median increase of 24.6%. By 12 months, the relative improvements in FIF50% and in SCAT were inversely correlated to the respective baseline values (FIF50%: r = -0.47, P = 0.012; SCAT: r = -0.57, P = 0.001). CONCLUSION On average, neither compression of the trachea nor deterioration of the pulmonary function was observed in the acute phase after rhTSH-augmented (131)I therapy. In the long term, tracheal compression is diminished, and the inspiratory capacity improved, compared with (131)I therapy alone.

The chronic autoimmune thyroiditis quality of life selenium trial (CATALYST): study protocol for a randomized controlled trial

BackgroundPatients with chronic autoimmune thyroiditis have impaired health-related quality of life. The thyroid gland has a high selenium concentration, and specific selenoprotein enzyme families are crucial to immune function, and catalyze thyroid hormone metabolism and redox processes in thyroid cells. Previous randomized controlled trials have found that selenium supplementation decreases thyroid-disease-specific antibody levels. We hypothesize that selenium might be beneficial in the treatment of chronic autoimmune thyroiditis.Methods/DesignThe CATALYST trial is an investigator-initiated randomized, blinded, multicentre clinical trial of selenium supplementation versus placebo in patients with chronic autoimmune thyroiditis. Inclusion criteria: age ≥18 years; serum thyroid peroxidase antibody level ≥100 IU/ml within the previous 12 months; treatment with levothyroxine and written informed consent. Exclusion criteria: previous diagnosis of toxic nodular goitre, Graves’ hyperthyroidism, postpartum thyroiditis, Graves’ orbitopathy; previous antithyroid drug treatment, radioiodine therapy or thyroid surgery; immune-modulatory or other medication affecting thyroid function; pregnancy, planned pregnancy or breastfeeding; allergy towards any intervention or placebo component; intake of selenium supplementation >55 μg/day; inability to read or understand Danish or lack of informed consent. The trial will include 2 × 236 participants. The experimental intervention and control groups will receive 200 μg selenium-enriched yeast or matching placebo tablets daily for 12 months. The experimental supplement will be SelenoPrecise®. The primary outcome is thyroid-related quality of life assessed by the Thyroid Patient-Reported Outcome (ThyPRO) questionnaire. Secondary outcomes include serum thyroid peroxidase antibody concentration; serum triiodothyronine/thyroxine ratio; levothyroxine dosage; adverse reactions and serious adverse reactions and events.DiscussionIn this pragmatic trial, participating patients follow their usual treatment at their usual hospitals. In order to collect high-quality data on the clinical course and quality of life, and to minimize missing data, an elaborate trial management system has been designed. 12 months intervention duration was selected in consideration of the primary outcome, thyroid-related quality of life.Trial registrationClinicalTrials.gov ID: NCT02013479.