Desiccated Thyroid Extract Versus Synthetic T3/T4 Combination (ThyrolarTM) Versus L-T4 Alone in the Therapy of Primary Hypothyroidism With Special Attention to the Gene Polymorphism
Desiccated Thyroid Extract Versus Synthetic T3/T4 Combination (ThyrolarTM) Versus L-T4 Alone in the Therapy of Primary Hypothyroidism With Special Attention to the Gene Polymorphism
The proposed study design is a prospective, randomized, double-blind, crossover study. After
 informed consent is obtained, patients will be randomized to receive either desiccated
 thyroid in capsules, or L-T4/L-T3 (ThyrolarTM) in capsules, or L-T4 alone capsules. All study
 participants, physician investigators, those administering the neurocognitive tests and those
 analyzing test results will be blinded throughout the study.

 Subjects will undergo memory testing, a disease specific symptom questionnaire, a general
 mental health assessment, a complete physical examination, baseline EKG, and biochemical
 testing consisting of serum TSH, free T4, total T4, total T3, free T3, T3 resin uptake,
 reverse T3, sex hormone binding globulin (SHBG), serum iodine, a lipid panel, insulin,
 glucose and leptin. This testing and DXA scan of body composition will be performed at
 baseline and after each 3 month treatment period. Deiodinase type 2 (DIO2) polymorphisms
 analyses - will also be performed at the beginning of the study and the results will be
 blinded to the investigators performing the memory testing.

 After 5-6 weeks on the study medication, TSH levels will be checked and the medication
 adjusted to maintain TSH level between 0.46-4.68 mIU/L. Once the TSH level is in the desired
 range, subjects will continue the medication for an additional 6 weeks. Subjects will then be
 crossed-over to the other treatment arm for 3 months. Again, testing will be performed after
 each treatment period. Finally the subjects will again switched over to the 3rd arm and
 testing will be performed after treatment period.

 A cross-over design is preferred because we are assessing subjective symptoms such as
 clinical well-being and other parameters. Therefore, we will be able to evaluate the
 effectiveness of L-T4/T3 (ThyrolarTM) vs DTE vs T4 alone in the same patientssubjects. This
 is also supported by the previous study by Escobar-Morreale et al.

 Additionally, the Wechsler memory scale, DEXA for body composition, measurment of reverse T3,
 insulin, leptin, and DIO2 polymorphisms analysis will be included for the research portion of
 this study. Further, the frequency of serum blood draws, for research purposes, will be at
 intervals of 0, 6, 12, 18, 24, 30 and 36 weeks.
Inclusion Criteria:

 -  Subjects will be between the ages of 18 to 65 and will have been on levothyroxine for
 primary hypothyroidism for at least 6 months

 -  Department of Defense beneficiaries living within 60 miles of Besthesda, MD

 Exclusion Criteria:

 -  Subjects will be excluded if they have the following problems: pregnancy, plan for
 pregnancy in the next 12 months, cardiac disease, especially coronary artery disease,
 chronic obstructive lung disease, malabsorption disorder, gastrointestinal surgeries,
 significant renal or liver dysfunction, seizure disorders, thyroid and non-thyroid
 active cancers, uncontrolled psychosis, psychotropic medication use, steroid use,
 amiodarone, chemotherapy for cancer, iron supplement more than 325mg per day,
 carafate/ proton pump inhibitor use, cholestyramine use, and those with recent orders
 who are expected to move out of the geographic area, age less than 18 years old or
 older than 65 years old. Patients scheduled for deployment will be excluded.

 -  Subjects with subclinical hypothyroidism will be excluded. If we include patients with
 subclinical hypothyroidism, it will be difficult to assess the outcomes. This is
 because only a very small percentage of patients with subclinical hypothyroidism
 benefit from thyroid hormone therapy and therefore, a cross-over study as done in this
 project will not show a difference between the therapies.

 -  Females of child-bearing age will be screened with initial assessment for pregnancy as
 part of standard of care (eg history of amnenorrhea and/or positive pregnancy testing
 via hCG). There is no experience in using desiccated thyroid extract in pregnant women
 and there is no published paper in this area. Desiccated thyroid extract is rated
 Category-A drug in pregnancy which means there are no known risks to the fetus.