Thyroid and Glucose and Energy Metabolism
Condition: Thyroid Diseases
MeSH terms: Thyroid Diseases
Intervention: Liothyronine and Levothyroxine
Intervention description: Hypothyroid patients are treated with Liothyronine and Levothyroxine in 2 crossover, randomized phases
Phase: Phase 2
Study type: Interventional
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 18.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Levothyroxine; Liothyronine; Lipid Metabolism; Gluconeogensis; Thyrotropin Releasing Hormone; Deiodinase; Replacement Thyroid Hormone Therapy; Thyroidectomy; Near Total Thyroidectomy

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.
    

Eligibility criteria:

        -  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).