The Impact of Goiter and Thyroid Surgery on Goiter Related Esophageal Dysfunction. A Systematic Review

Background: Patients with goiter referred for thyroidectomy report swallowing difficulties. This might be associated with esophageal compression and deviation as this is present in a significant number of patients. Studies on how goiter and subsequently its treatment affect the esophagus are sparse and point in various directions. Our aim was to investigate, through a systematic review, the impact of goiter and thyroidectomy on esophageal anatomy, esophageal physiology, and subjective swallowing dysfunction.Methods: The search period covered 1 January 1975 to 1 July 2018, using the scientific databases PubMed and EMBASE. Inclusion criteria were adult patients with goiter who were either observed or underwent thyroidectomy. Search terms were variations of the terms for goiter, esophagus, swallowing, and dysphagia. From an initial 3,040 titles, 55 full text evaluations led to the final inclusion of 27 papers. Seventeen papers investigated, prospectively, the impact of thyroidectomy on the esophagus, while five observational and five retrospective studies were also included.Results: Esophageal anatomy impairment: Esophageal deviation occurred in 14% and esophageal compression in 8–27% of goiter patients. The prevalence increased with goiter size and with the extent of substernal extension. The smallest cross-sectional area of the esophagus increased by median 34% after thyroidectomy. Esophageal physiology changes: Goiter patients had increased esophageal transit time, positively correlated with goiter size, but unrelated to esophageal motility disturbances. Decrease in the upper esophageal sphincter pressure occurred early after surgery, and normalized within 6 months. Swallowing related patient-reported outcomes: Evaluated by validated questionnaires, swallowing symptoms worsened in the early period after thyroidectomy, but improved after 6 months, as compared to baseline.Conclusions: Thyroidectomy relieved patients with goiter from dysphagia, within 6 months of surgery probably via increase in the cross-sectional area of the esophagus. Attention to the impact by goiter on the esophagus is needed, and balanced and individualized information about the potential benefits and risks of thyroid surgery is crucial in the management of patients with goiter

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

BACKGROUND: Patients 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/DESIGN: The 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. DISCUSSION: In 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 REGISTRATION: ClinicalTrials.gov ID: NCT02013479

Selenium supplementation for patients with Graves' hyperthyroidism (the GRASS trial):Study protocol for a randomized controlled trial

BACKGROUND: Graves’ hyperthyroidism is an autoimmune disease causing hyperfunction of the thyroid gland. The concentration of selenium is high in the thyroid gland and two important groups of enzymes within the thyroid are selenoproteins, that is, they depend on selenium. Selenium may have beneficial effects on autoimmune hypothyroidism and on Graves' orbitopathy, but the effects of selenium on Graves' hyperthyroidism is unknown. We hypothesize that adjuvant selenium may be beneficial in the treatment of Graves' hyperthyroidism. The objective is to investigate if selenium supplementation plus standard treatment with anti-thyroid drugs versus standard treatment with anti-thyroid drugs will lead to a decrease in anti-thyroid drug treatment failure (that is, failure to remain euthyroid, without further treatment, one year after cessation of anti-thyroid drug treatment), faster and longer lasting remission (that is, anti-thyroid drug treatment success), and improved quality of life in patients with Graves’ hyperthyroidism. METHODS AND DESIGN: The trial is an investigator-initiated, randomised, blinded, multicentre clinical trial. Inclusion criteria are: age 18 years or older; diagnosis of active Graves' hyperthyroidism within the last two months; and informed consent. Exclusion criteria are major co-morbidity; previous radioactive iodine treatment; ongoing anti-thyroid drug treatment for more than two months; treatment with immunomodulatory drugs; known allergy towards the components in the selenium and placebo pills; pregnancy or breast-feeding; and intake of selenium supplementation above 70 μg per day. We plan to include 492 participants, randomised (1:1) to two tablets of 100 μg selenium once daily for the 24 to 30 months intervention period versus two identical placebo tablets once daily. The primary outcome is the proportion of participants with anti-thyroid drug treatment failure (see above) at the end of the intervention period (24 to 30 months). Secondary outcomes are: thyroid-specific quality of life during the first year after randomisation; level of thyroid stimulating hormone-receptor antibodies at 18 months after randomisation and at the end of the intervention period (24 to 30 months); hyperthyroid symptoms during the first year after randomisation; eye symptoms during the first year after randomisation, and at the end of the intervention period (24 to 30 months); adverse reactions during the intervention period; and serious adverse events during the intervention period. DISCUSSION: It was of great importance to the initiators of this trial, that the results would be directly applicable to daily clinical practice. Therefore, it was designed as a pragmatic trial: the patients follow their usual treatment at their usual hospitals. In order to still collect high quality data on the clinical course and quality of life, an elaborate trial management system was designed to keep track of patient input, need for trial personnel input and action, and to collect data from medical chart systems. Meticulous follow-up on missing responses to the QoL measurements has been incorporated into the system, to minimise missing quality of life data. Monitoring of adverse reactions and events is achieved by thorough instruction of the participants, surveillance of patient-reported outcomes, and integration with national databases regarding hospitalizations. A very long intervention period was necessary, since patients are not considered in remission until one year after stopping anti-thyroid drugs. Usually, patients are treated for 12 to 18 months with anti-thyroid drugs, yielding a total intervention period of 24 to 30 months. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01611896