Metabolic Effects of Synthetic Thyroid Hormone for Thyroid Cancer Treatment
Condition: Malignant Struma Ovarii; Papillary Thyroid Cancer; Hurthle Cell Thyroid Cancer; Follicular Thyroid Cancer; Tall Cell Variant Thyroid Cancer
MeSH terms: Thyroid Neoplasms; Thyroid Cancer, Papillary; Adenocarcinoma, Follicular; Struma Ovarii; Thyroid Diseases
Study type: Observational

Summary: 
      Background:

      - Thyroid hormone is produced by the thyroid gland, an organ at the base of the neck. Thyroid
      hormone controls the body's metabolism and the function of many organs. The thyroid gland
      produces two forms of thyroid hormone: T4 and T3. People who have thyroid cancer are treated
      with thyroid hormone therapy (synthetic T4, levothyroxine), which at times needs to be
      stopped to allow for cancer treatments. At these times, a different form of thyroid hormone
      (synthetic T3, liothyronine) is used to reduce the symptoms caused by low levels of thyroid
      hormone. Researchers want to know more about how changes in T3 hormone affect the body and
      organ function.

      Objectives:

      - To study how changes in T3 hormone levels affect the body and organ function.

      Eligibility:

      - Individuals at least 18 years of age who have had most or all of their thyroid removed to
      treat thyroid cancer who need to stop taking their regular thyroid hormone dose in
      preparation for the treatment of thyroid cancer.

      Design:

        -  The study involves a screening visit and a baseline evaluation. It also includes an
           11-day inpatient hospital stay.

        -  Participants will be screened with a physical exam and medical history. They will also
           have blood tests and a neck ultrasound.

        -  Participants will be evaluated with a physical exam, blood tests, and the following
           procedures:

        -  Glucose tolerance test to measure blood sugar

        -  Tests of body fat, muscle strength, and calorie burning levels

        -  Imaging studies of the heart, liver, and thigh muscles

        -  Quality of life questionnaires

        -  Food preference and diet questionnaires

        -  After 4 weeks of treatment with T3 hormone, participants will have an 11-day inpatient
           hospital stay to study the effect of thyroid hormone on their metabolism. The stay will
           involve the same tests done in the baseline evaluation.
    

Detailed description: 
      In human adults thyroid hormone action plays a critical role in the modulation of metabolism
      and the function of virtually all organ/systems. The specificity of the hormonal action is
      ultimately the result of the interaction of the active hormone, triiodothyronine (T3), with
      the receptors isoforms and the co-activators and co-repressors specific for the various cells
      target of the hormonal action. Circulating and tissue levels of T3 are the result of the
      secretion of T3 and its precursor, thyroxine (T4), from the thyroid gland, the peripheral
      conversion of T4 into T3, and the degradation of these hormones. This complex system has only
      been partially studied in humans and very little is known regarding the kinetics of T3, and
      in particular on the correlation between circulating levels of T3 and end-organ target tissue
      thyroid hormone action.

      The aim of this protocol is to characterize the pharmacokinetics of T3 and its biological
      effects at various concentrations in a cohort of thyroidectomized patients undergoing thyroid
      hormone replacement therapy withdrawal for the management of thyroid cancer.

      Sixteen patients with a clinical indication for thyroid hormone withdrawal in preparation for
      131I therapy or 123I diagnostic scan for follow-up and management of differentiated thyroid
      cancer will be recruited for this study. After enrollment in the study, the patients baseline
      characteristics will be determined during an outpatient visit while receiving levothyroxine
      (L-T4) therapy. The L-T4 therapy then will be suspended and substituted with an equivalent
      thrice daily liothyronine (L-T3) therapy for one month. Patients will be admitted to the NIH
      Clinical Center on the day prior to withdrawal of the T3 therapy until the diagnostic scan or
      the administration of radioactive iodine. During the hospitalization for this research
      protocol, which is expected to last eleven days, the following studies will be performed:
      serial blood sampling for circulating thyroid hormones to obtain pharmacokinetic parameters
      of L-T3, lipids, glucose and insulin, resting energy expenditure, echocardiogram, skeletal
      muscle strength measurement, cardiac, hepatic and skeletal muscles MRI, and quality of life
      and well-being questionnaires. The pharmacokinetic parameters of L-T3 will also be assessed
      with the first dose after the diagnostic scan or the administration of radioactive iodine.

      The results obtained from this study will help in understanding the effects of thyroid
      hormone on metabolism, and may lead to important information on how to optimize the duration
      of the thyroid hormone therapy withdrawal for the treatment of thyroid cancer.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        primary clinical
      
Keywords: Hypothyroidism; Thyroid Cancer; Triiodothyronine (T3); Energy Expenditure; Thyroid Hormone