Thyroid and Glucose and Energy Metabolism

February 20, 2015 updated by: Kong Chen, Ph.D., National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Peripheral Thyroid Hormone Conversion and Glucose and Energy Metabolism

This study will examine how two thyroid preparations-levothyroxine (T4) and liothyronine (T3)-affect fat and cholesterol metabolism, blood sugar regulation, and thyrotropin secretion in patients who have had their thyroid gland removed. Results of the study may help in the development of better therapies to optimize blood sugar and cholesterol levels in some patients.

Patients 18 years of age or older who have had most or all of their thyroid gland removed and are taking long-term thyroid hormone medication may be eligible for this study after screening.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Thyroid hormone action plays an important role in the regulation of many physiologic processes, among them glucose and lipid metabolism. Interestingly, the clinical presentation of thyroid dysfunction is extremely variable, with relatively poor correlation between circulating hormone levels and clinical features. This finding suggests that the local, intracellular concentration of the active hormone liothyronine (T3), regulated by peripheral conversion of the pro-hormone levothyroxine (T4), is an important determinant in the maintenance of the thyroidal homeostasis.

The aim of the present study is the evaluation of the role of peripheral thyroid hormone conversion in the regulation of glucose and lipid metabolism by assessing the differential response to T4 or T3 treatment in subjects devoid of endogenous thyroid hormone production. T3 administration bypasses peripheral metabolism and therefore will allow us to assess the role of the peripheral thyroid hormone conversion in the regulation of the hormone action at the end-organ level.

Fifty hypothyroid subjects will be initially randomized to either of the thyroid hormone replacements liothyronine (T3) or levothyroxine (T4) treatment period (one arm cross-over design, with treatment sequence randomized), aimed to maintain serum TSH levels greater than or equal to 0.5 less than or equal to 1.5 mU/L, indicating full replacement. After a 30-day period of steady-state replacement the study subjects will be admitted to the Clinical Center and, after a three-day period of stabilization and an overnight fast, will undergo the following tests: escalating dose TRH stimulation test, indirect calorimetry, graded exercise tolerance test, DEXA scan, and echocardiogram.

Patients will also undergo skeletal muscle biopsy and subcutaneous adipose tissue biopsy and microdialysis, as well as a two-step euglycemic hyperinsulinemic clamp with measurement of splanchnic gluconeogenesis. Fasting venous blood samples will be collected for the determination of the parameters of lipid, glucose and energy metabolism.

After discharge, the patients will switch to the other form of thyroid hormone replacement therapy (second period) . The therapy will be adjusted in order to achieve the same therapeutic goal for TSH concentrations (greater than or equal to 0.5 less than or equal to 1.5 mU/L), analogous to that achieved during the first phase of the study (TSH less than or equal to 0.5 mU/L difference between T3 and T4 phases). After reaching a 30-day period of steady-state replacement, study subjects will be re-admitted to the Clinical Center and the previously described evaluation procedures will be repeated.

Study Type

Interventional

Enrollment (Actual)

18

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Bethesda, Maryland, United States, 20892
        • National Institutes of Health Clinical Center, 9000 Rockville Pike

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 63 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

  • INCLUSION CRITERIA:

Age greater than or equal to 18 years, male or female.

History of total or near total thyroidectomy or hypothyroidism on replacement therapy.

For non-thyroidectomized patients, at least three-year history of replacement therapy (at least 1.2 mcg/Kg LT4/body weight), and less than 5% uptake at 24H on (123)I thyroid scan while on replacement therapy.

Written informed consent.

EXCLUSION CRITERIA:

BMI less than or equal to 20 or greater than or equal to 30 kg/m(2).

Metastatic thyroid cancer or history of thyroid cancer with high risk of recurrence requiring suppressive thyroid hormone therapy (Singer 1996).

Significant thyroid residual greater than 1 mL as measured by ultrasound (limited to thyroidectomized patients) or greater than 5 percent uptake at 24H on (123)I thyroid scan while on replacement therapy (limited to hypothyroid patients not undergone total thyroidectomy).

History or symptoms compatible with cardiovascular disease, including paroxysmal supraventricular tachycardia, atrial fibrillation, syncopal episodes or use of prescription medications for heart conditions, including antihypertensives.

Allergy to lidocaine, isoproterenol, TRH, levothyroxine, liothyronine, Tylenol #3, oxycodone, nitroglycerin.

Pregnancy or unwillingness to use non-hormonal contraception during the study.

Breastfeeding

Use of hormonal contraceptives or estrogen replacement therapy.

Use of tobacco (smoking, chewing) for the two weeks preceding the hospital admissions (metabolic testing)

Diabetes mellitus, either type I or II.

Hypercholesterolemia (serum levels greater than or equal to 240 mg/dL), hypertriglyceridemia (plasma levels greater than or equal to 220 mg/dL) and/or use of antilipemic therapy.

Liver disease or ALT serum level greater than two fold the upper laboratory reference limit.

Renal insufficiency or estimated creatinine clearance less than or equal to 50 mL/min.

Use of medications/supplements/alternative therapies known to alter thyroid function.

Current history or symptoms compatible with psychosis including major depression (including history of hospitalization for depression, history of attempted suicide, history of suicidal ideation).

Use of antipsychotic medications

History of drug or alcohol abuse within the last 5 years; current use of drugs or alcohol (CAGE greater than 3).

Keloid formation (relative to skeletal muscle and subcutaneous adipose tissue biopsies).

Current or previous clinically significant (requiring medical/surgical intervention) extrathyroidal manifestations of autoimmune thyroid disease (dermopathy, ophthalmopathy, arthropathy).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Liothyronine and Levothyroxine
Hypothyroid patients treatment with Levothyroxine and Liothyronine in 2 crossover, randomized phases
Drug: Liothyronine and Levothyroxine
Hypothyroid patients are treated with Liothyronine and Levothyroxine in 2 crossover, randomized phases
Other Names:
  • T3 and T4

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Insulin-mediated Glucose Disposal Rate at Levothyroxine Treatment Phase
Time Frame: One month of therapy.
One month of therapy.
Insulin-mediated Glucose Disposal Rate at Liothyronine Treatment Phase
Time Frame: One month of therapy
One month of therapy

Secondary Outcome Measures

Outcome Measure
Time Frame
Total Cholesterol at Levothyroxine Treatment Phase
Time Frame: One month of therapy.
One month of therapy.
Total Cholesterol at Liothyronine Treatment Phase
Time Frame: One month of therapy.
One month of therapy.
Triglycerides at Levothyroxine Treatment Phase
Time Frame: One month of therapy.
One month of therapy.
Triglycerides at Liothyronine Treatment Phase
Time Frame: One month of therapy.
One month of therapy.
Resting Energy Expenditure at Levothyroxine Treatment Phase
Time Frame: One month of therapy.
One month of therapy.
Resting Energy Expenditure at Liothyronine Treatment Phase
Time Frame: One month of therapy.
One month of therapy.
Left Ventricle Mass Index at Levothyroxine Treatment Phase
Time Frame: One month of therapy.
One month of therapy.
Left Ventricle Mass Index at Liothyronine Treatment Phase
Time Frame: One month of therapy.
One month of therapy.
Apolipoprotein A-I at Levothyroxine Treatment Phase
Time Frame: One month of therapy.
One month of therapy.
Apolipoprotein A-I at Liothyronine Treatment Phase
Time Frame: One month of therapy.
One month of therapy.
Apolipoprotein B at Levothyroxine Treatment Phase
Time Frame: One month of therapy.
One month of therapy.
Apolipoprotein B at Liothyronine Treatment Phase
Time Frame: One month of therapy.
One month of therapy.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2005

Primary Completion (Actual)

November 1, 2013

Study Completion (Actual)

November 1, 2013

Study Registration Dates

First Submitted

March 19, 2005

First Submitted That Met QC Criteria

March 19, 2005

First Posted (Estimate)

March 21, 2005

Study Record Updates

Last Update Posted (Estimate)

February 23, 2015

Last Update Submitted That Met QC Criteria

February 20, 2015

Last Verified

February 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 050119
  • 05-DK-0119 (Other Identifier: NIH)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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