Thyroid and Glucose and Energy Metabolism

Phase 2

Completed

Conditions: Thyroid Diseases

Interventions: Drug: Liothyronine and Levothyroxine

Registration Number: NCT00106119

Lead Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Brief Summary: 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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 18

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Liothyronine and Levothyroxine	Liothyronine and Levothyroxine	Hypothyroid patients treatment with Levothyroxine and Liothyronine in 2 crossover, randomized phases

Primary Outcome Measures

Name	Time	Method
Insulin-mediated Glucose Disposal Rate at Liothyronine Treatment Phase	One month of therapy
Insulin-mediated Glucose Disposal Rate at Levothyroxine Treatment Phase	One month of therapy.

Secondary Outcome Measures

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