Neurocognitive and Metabolic Effects of Mild Hypothyroidism
Condition: Hypothyroidism
MeSH terms: Hypothyroidism
Intervention: L-thyroxine (L-T4)
Intervention description: L-thyroxine (L-T4) is the intervention for each arm/group. In each arm/group, the dose of L-T4 is adjusted to achieve TSH levels in the randomly assigned arm. L-thyroxine at doses appropriate to attain target TSH levels for the different arms for 24 weeks
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 173.0
Sex: All
Minimum age: 20 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Hypothyroidism; Cognition; Metabolism

Summary:

      Patients with hypothyroidism are routinely treated with thyroid hormone (l-thyroxine) for
      replacement therapy. Physicians monitor the thyroid hormone dose by measuring a thyroid
      stimulating hormone (TSH) level in the blood, with the goal of a normal level. However,
      recent data suggest that the "normal" TSH range is too broad, and that patients may still
      have symptoms if their TSH levels are at the top or bottom part of the normal range.

      To study this issue, it is useful to address issues such as general health status,
      psychological symptoms, mood, memory, and metabolic status, since thyroid hormone has major
      effects on the brain and metabolism, and since patients with treated hypothyroidism often
      have symptoms related to these areas.

      In the present study, otherwise healthy subjects with treated hypothyroidism, ages 20-75
      years, will be enrolled in a 7-11month study. At baseline, they will have tests of health
      status, psychological symptoms, mood, memory, body composition, and energy expenditure
      performed. Following these baseline measurements, subjects will receive either their usual
      doses of l-thyroxine, or a slightly higher or lower dose. The doses will be chosen to try to
      achieve either a low-normal TSH level, a high-normal TSH level, or a mildly elevated TSH
      level. Which target TSH the patient is assigned will be determined randomly, and neither the
      subject nor the study contacts will know which dose the patient is receiving. Subjects will
      be seen every 6 weeks during the study for brief visits to make sure they are not having any
      side effects, and to adjust the l-thyroxine doses if the TSH has not yet reached the target
      range. At the 24-week visit (end of study), the subjects will undergo the same tests that
      they had on the baseline visit.

      Results from the study will be examined to see if minor changes in TSH or other thyroid
      hormone levels cause changes in any of the outcomes, and if the degree of TSH change
      correlates with the degree of outcome changes. These results may help physicians caring for
      patients with thyroid disease better determine the optimal dose of thyroid hormone for each
      patient.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Ages 20-75

          -  Primary hypothyroidism on stable dose of L-T4 for > 3 months

          -  Documented elevated TSH off L-T4

          -  Normal TSH level on usual dose of L-T4

          -  No acute or chronic medical or psychiatric illnesses that affect thyroid function,
             mood or cognition

          -  No medication use that affects thyroid function, mood or cognition (oral
             contraceptives or estrogen therapy allowed)

          -  Normal score on screening Mini-Mental State Exam (MMSE) (to test for dementia)

          -  Normal vision by screening examination

          -  Normal hearing by screening examination

          -  Non smoker

        Exclusion Criteria:

          -  Failure to meet any of the above inclusion criteria

          -  Inability to speak and comprehend English

          -  A history of coronary artery disease

          -  Screening hgb <10

          -  Screening wbc > 10,000

          -  Clinically significant abnormalities on screening metabolic set

          -  Screening LDL cholesterol > 160

          -  Screening triglyceride > 300

          -  Significant abnormalities on screening ECG

          -  Pregnancy or intent to become pregnant in next 6 months

          -  Present or recent use of medications that affect thyroid hormone levels or interfere
             with thyroid hormone effects, including beta-blockers, lithium, glucocorticoids, or
             iodine containing agents

          -  MMSE score < 26