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

No link between season of birth and subsequent development of Graves’ disease or toxic nodular goitre. A nationwide Danish register-based study

Background: Season of birth, an exogenous indicator of early life environment, has been linked with a higher risk of adverse health outcomes such as autoimmune thyroiditis, multiple sclerosis and schizophrenia later in life. Whether the development and cause of hyperthyroidism is influenced by season of birth is unclarified. We aimed, at a nationwide level, to investigate whether season of birth influences the risk of hyperthyroidism due to Graves’ disease (GD) and/or toxic nodular goitre (TNG). Method: Register-based nationwide cohort study. By record-linkage between Danish health registers, 36,087 and 20,537 patients with GD and TNG, respectively, were identified. Each case was matched with four controls without thyroid disease, according to age and sex. Differences in month of birth across the year were evaluated by the Walter–Elwood test. Hazard ratios, for the risk of GD and TNG in individuals born in a certain month or season of the year, were calculated using Cox regression models. Results: Neither for GD nor for TNG could we demonstrate a significant difference in birth rate across months or seasons of the year (Walter–Elwood’s test; X2 = 5.92 and X2 = 1.27, P = 0.052 and P = 0.53, respectively). Conclusion: Irrespective of its cause, our findings do not support the hypothesis that season of birth is significantly related to the development of hyperthyroidism

The enigma of persistent symptoms in hypothyroid patients treated with lexothroxine : A narrative review

A significant minority of patients with hypothyroidism report persistent symptoms despite achieving normal thyroid biochemistry after levothyroxine (L-T4) replacement. Four principal lines of thinking, which are not mutually exclusive, may explain this enigma. The ‘low tissue liothyronine hypothesis’ emphasizes the potential imperfections of L-T4 replacement therapy that may lead to hypothyroidism in some tissues such as the brain, while others (eg hypothalamus) are euthyroid. The ‘Somatic Symptom and Related Disorders hypothesis’ draws attention to an incidental coexistence of a diagnosis of Somatic Symptom and Related Disorders in patients with treated hypothyroidism. The ‘autoimmune neuroinflammation hypothesis’ highlights the potential consequences of inflammatory mediators due to thyroid autoimmunity (the commonest cause of hypothyroidism) on the brain. The ‘comorbidities and psychosocial hypothesis’ implicates a variety of physical and psychosocial factors that have been noted to be associated with a diagnosis of hypothyroidism, which may be primarily the cause of persistent complaints. Over the past twenty years, a great deal of time and effort has been expended pursuing the ‘low tissue liothyronine hypothesis’, which has failed to yield results that translate to patient benefits. This has skewed the balance in clinical practice, in favour of pursuing answers relating to L-T4 and liothyronine combination treatment, while the alternative explanations have been downplayed and potentially useful interventions have been given insufficient attention

Use of thyroid hormones in hypothyroid and euthyroid patients: a THESIS* questionnaire survey of Polish physicians. *THESIS: Treatment of hypothyroidism in Europe by specialists: an international survey

Introduction: Over the past several years new evidence on the management of hypothyroidism has emerged, which has influenced recommendations from professional bodies. The presentation of hypothyroid patients has also changed, and new cases are increasingly diagnosed by indiscriminate screening, often identifying cases with minor biochemical disturbances. Little is known about the physician responses and attitudes to this changing landscape. THESIS (Treatment of Hypothyroidism in Europe by Specialists: an International Survey) is a large-scale survey of European physicians who treat patients with hypothyroidism. Here we document current practices of Polish physicians relating to the use of thyroid hormones in hypothyroid and euthyroid patients.  Material and methods: Members of the Polish Society of Endocrinology were invited to participate in the web-based THESIS survey. Results: In total 423 (54.6% of the 774 invited) physicians completed the survey. The majority of respondents (74.2%) would prescribe thyroid hormones for euthyroid patients for certain indications, such as female infertility with elevated thyroid antibodies (63.4%), simple goitre (40.9%), unexplained fatigue (12.1%), obesity (9.7%), hypercholesterolaemia (9.0%), and depression (9.2%). Nearly all physicians (96.0%) declared that the treatment of choice for hypothyroidism is levothyroxine (LT4). However, around one-third (30.3%) were also using LT4 and liothyronine (LT3) combination treatment; LT3 alone was rarely prescribed (1.7%), and none prescribed desiccated thyroid extract. The majority of respondents preferred LT4 tablets. Among alternative formulations, liquid LT4 was most commonly recommended for patients unable to take LT4 in the fasting state (26.0%) and patients with malabsorption (19.9%). Respondents considered prescribing dietary supplements (such as selenium and iodine) in hypothyroid patients with coexisting autoimmune thyroiditis (29.6%) or at the patients’ request (32.2%). LT4 + LT3 combination therapy was used by 32.2% when symptoms persisted notwithstanding normal serum TSH concentration. Psychosocial factors, comorbidities, and the burden of chronic disease were considered as the most likely causes of persistent symptoms. Conclusions: Apart from clinical practice recommendations, other factors influence the thyroid hormone therapy patterns. Moreover, certain areas of clinical practice were identified (the use of thyroid hormones in euthyroid subjects and the use of dietary supplements), which are not in accordance with the current evidence.

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