Graves Disease, Thyroid Cancer
Conditions
Keywords
thyroid hormones, glucose metabolism, lipid metabolism, graves disease, thyroid cancer, hyperthyroidism
Brief summary
The goal of this clinical trial to clarify the impact of changes in thyroid hormone levels on glucose and lipid metabolism. Patients will be included in whom thyroid hormone levels are intentionally changed by treatment. In patients with Graves' disease, thyroid hormone levels will be lowered using medication, while in patients with thyroid cancer, thyroid hormone levels will be raised using medication. Oral glucose tolerance tests will be performed before treatment and at two time points after treatment begins to assess metabolic effects.
Detailed description
This research project aims to clarify the role of changes in thyroid hormone levels in glucose and liver metabolism. Thyroid hormones regulate endogenous glucose production, insulin sensitivity, lipid metabolism, and lipid storage in the liver. They also appear to enhance insulin sensitivity in other tissues. Furthermore, thyroid hormones stimulate lipolysis and reduce total and LDL-cholesterol levels. The impact of thyroid hormones on insulin secretion is controversial, with some trials demonstrating increased secretion and others showing decreased secretion. Most of this evidence is derived from animal trials, and prospective human trials are lacking. Clinical scenarios where thyroid hormone levels are altered through therapeutic interventions will be used. In patients with Graves' disease, hyperthyroidism is pharmacologically reduced, whereas in patients with thyroid carcinoma, hyperthyroidism is pharmacologically induced. Before the start of treatment, two weeks and three months after start of treatment oral glucose tolerance tests will be performed for metabolic characterization. Using this approach, differences in glycemic, insulin sensitivity, insulin secretion, lipids, resting energy expenditure, respiratory quotient, hepatic steatosis, eating and exercise behavior will be assessed.
Interventions
OTHEROral Glucose Tolerance Test
Participants will receive a 75 g oral glucose tolerance (3h) before the start of treatment, two weeks and three months after start of treatment. Body composition will measured by bioimpedance analysis. Before and during the oral glucose tolerance test, indirect calometry will assess metabolic flexibility.
Sponsors
University of Ulm
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
This is a longitudinal mechanistic study evaluating the metabolic effects of changes in thyroid hormone levels on glucose and liver metabolism. Participants include patients with Graves' disease and patients with thyroid carcinoma undergoing standard-of-care thyroid treatment. The only study-specific intervention is repeated metabolic phenotyping using oral glucose tolerance tests (OGTTs) performed at baseline, two weeks, and three months after initiation of therapy. Thyroid hormone modulation occurs as part of routine clinical care and is not assigned by the study protocol.
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* patients with initial diagnosis of graves disease OR * patients with initial diagnosis of thyroid carcinoma
Exclusion criteria
* contraindications for oral glucose tolerance test * Diabetes mellitus * Fasting glucose level ≥ 200 mg/dL * Exogenous insulin administration with action at the time of the test * Current disease with activation of stress hormones * Post-aggressive metabolism * Acute infectious disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Insulin sensitivity | Baseline, 2 weeks, 3 months | Effect of changes in thyroid hormone levels on whole-body insulin sensitivity, assessed from glucose and insulin measurements during the 75 g oral glucose tolerance test. |
| Insulin secretion | Baseline, 2 weeks, 3 months | Effect of changes in thyroid hormone levels on insulin secretion, assessed from glucose and insulin/c-peptide measurements during the 75 g oral glucose tolerance test. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Resting energy expenditure. | Baseline, 2 weeks, 3 months | Effect of changes in thyroid hormone levels on resting energy expenditure assessed by indirect calometry before and during the 75 g oral glucose tolerance test. |
| Respiratory Quotient | Baseline, 2 weeks, 3 months | Effect of changes in thyroid hormone levels on respiratory quotient assessed by indirect calometry before and during the 75 g oral glucose tolerance test. |
| Lipid metabolism | Baseline, 2 weeks, 3 months | Effect of changes in thyroid hormone levels on lipid metabolism assessed from lipid measurements during the 75 g oral glucose tolerance test. |
| Hepatic steatosis | baseline | Presence of hepatic steatosis assessed by liver ultrasound including elastography. |
| Heart rate variability | Baseline, 2 weeks, 3 months | Effect of changes in thyroid hormone levels on heart rate variability assessed by electrocardiography during the 75 g oral glucose tolerance test. |
| Eating behavior | Baseline, 3 months | Effect of changes in thyroid hormone levels on eating behavior assessed by dietary protocols before the start of treatment and 3 months later. |
Countries
Germany
Contacts
CONTACTMartin Heni, Prof
CONTACTRoza Sabia, MD
PRINCIPAL_INVESTIGATORMartin Heni
University of Ulm
Outcome results
None listed