ThyrBar: Thyroid in Bariatric Surgery

Sponsor

University Hospitals Coventry and Warwickshire NHS Trust (Other)

Overall Status

Completed

CT.gov ID

NCT03048708

Collaborator

(none)

Enrollment

Arms

Duration (Months)

Study Details

Study Description

Brief Summary

This study is expected to provide novel data regarding potential structural and functional changes of the thyroid gland in morbidly obese adults following significant weight loss through bariatric surgery. These data will complement evidence from epidemiological studies regarding the association of obesity and alterations in thyroid function. Potentially this study may justify further longer-term studies regarding the effects of weight gain and/or weight loss on the morphology of the thyroid gland and could help to form recommendations regarding follow-up investigations for the thyroid in morbidly obese patients.

Condition or Disease	Intervention/Treatment	Phase
Thyroid Obesity Insulin Resistance Autoimmune Thyroiditis	Procedure: Bariatric surgery	N/A

Detailed Description

Alterations in thyroid function are reported in obesity. Thyroid hormones and thyroid-stimulating hormone (TSH) concentrations have been variously described as normal, elevated, or low in morbidly obese patients compared with normal weight controls. However, it is a common observation that a significant proportion of patients with morbid obesity display slightly increased serum levels of TSH, while even relatively mild elevations of serum TSH are associated with an increase in the occurrence of obesity. Of note, abnormalities in thyroid function and TSH mostly normalize after weight loss, suggesting that these biochemical alterations are reversible. Despite uncertainty regarding the underlying mechanisms, it has been suggested that neither autoimmunity nor iodine deficiency seems to play a critical role. Several alternative mechanisms leading to hyperthyrotropinemia have been hypothesized, which include impaired feedback due to decreased number of triiodothyronine (T3) receptors in the hypothalamus, and variations in peripheral deiodinase activity. Leptin, in addition to regulating body weight and satiation, has also been shown to mediate the production of pro-TRH in cultured fetal rat hypothalamic neurons. Partial regulation of TSH by leptin has been also reported in humans. In addition, peripheral thyroid hormone metabolism appears to be reflected by the ratio of T3 to reverse T3 (rT3) (T3/rT3-ratio). We have shown that the T3/rT3-ratio is significantly increased in insulin resistant patients compared to their insulin sensitive partners despite comparable TSH values. Given that obesity is strongly associated with insulin resistance, and thyroid hormones are known to modulate carbohydrate metabolism, e.g. by affecting cellular glucose uptake, possible changes in the T3/fT3 ratio following weight loss after bariatric surgery could be of interest.

Data from cross-sectional studies further indicate that the thyroid structure of obese patients can be also affected, independent of the existence of autoimmune thyroiditis as indicated by the presence of auto-antibodies such as TPO. Ultrasound (US) scans are able to accurately characterize the echographic structure of thyroid tissue, in addition to estimation of thyroid volume and identification of non-palpable thyroid nodules. The typical normal thyroid parenchyma has a distinct high echo density due to the follicle structure, which contrasts well with tissue of the collar muscles. The interface between thyroid cells and the colloid exhibits elevated acoustic impedance, causing high-frequency acoustic waves to be reflected back to the US probe. However, in autoimmune thyroid diseases both lymphocytic infiltration and disruption of normal tissue architecture cause a reduction in thyroid echogenicity, whereas other tissues close by such as muscle tissue appear to remain unaffected. Only few previous studies reported on the morphology of the thyroid gland in adults with morbid obesity. Given that thyroid function has been reported to return to normal after weight loss, research questions are also raised about the potential reversibility of thyroid structural abnormalities following substantial weight loss in previously morbidly obese patients.

Study Design

Study Type:

Interventional

Actual Enrollment :

10 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Diagnostic

Official Title:

Changes in Thyroid Function Tests and Texture Following Bariatric Surgery Induced Weight Loss

Study Start Date :

Jun 1, 2011

Actual Primary Completion Date :

Dec 1, 2013

Actual Study Completion Date :

Aug 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Obese patients treated with bariatric surgery Patients with morbid obesity who were eligible for and willing to have bariatric surgery performed	Procedure: Bariatric surgery patients who had received treatment with bariatric surgery for medical reasons
No Intervention: Obese patients not treated with bariatric surgery Age and BMI matched patients with morbid obesity who either were not eligible for or were not willing to have bariatric surgery performed - no sufficient number of matched patients has completed the study; the arm of obese patients not treated with bariatric surgery has been discarded for the purpose of the analyses

Arm

Intervention/Treatment

Experimental: Obese patients treated with bariatric surgery

Patients with morbid obesity who were eligible for and willing to have bariatric surgery performed

Procedure: Bariatric surgery

patients who had received treatment with bariatric surgery for medical reasons

No Intervention: Obese patients not treated with bariatric surgery

Age and BMI matched patients with morbid obesity who either were not eligible for or were not willing to have bariatric surgery performed - no sufficient number of matched patients has completed the study; the arm of obese patients not treated with bariatric surgery has been discarded for the purpose of the analyses

Outcome Measures

Primary Outcome Measures

Changes in thyroid morphology and thyroid function tests in morbidly obese patients following significant weight loss after bariatric surgery [> 3 month or when relevant weight loss has been achieved]
Measurement of thyroid ultrasound (grey scale assessment, volume, echogenicity) and thyroid function tests (free T4, free T3, TSH and rT3) at baseline and at least 3 months after surgery when relevant weight loss is achieved

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Obesity (BMI > 40 kg/m2)
Age: 18-65

Exclusion Criteria:

Diagnosis of obesity secondary to primary endocrine or systemic disease (e.g. Cushing's syndrome)
Evidence of clinically relevant thyroid disease
Chronic systematic inflammatory disease (e.g. rheumatoid arthritis)
Pregnancy
Treatment with anti-inflammatory drugs (e.g. corticosteroids)
Type 1 diabetes mellitus