Neurocognitive and Metabolic Effects of Mild Hypothyroidism
| Status: | Completed |
|---|---|
| Conditions: | Endocrine |
| Therapuetic Areas: | Endocrinology |
| Healthy: | No |
| Age Range: | 20 - 75 |
| Updated: | 8/24/2018 |
| Start Date: | August 2008 |
| End Date: | August 2013 |
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.
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.
Thyroid hormone is essential for neurocognitive and metabolic function, and patients with
overt thyroid dysfunction have well-described alterations in mood, cognition, energy
expenditure, and body composition. However, it is not clear that patients with more mild
degrees of thyroid dysfunction have clinically significant alterations in these parameters.
In addition, recent data suggest that variations in thyroid function within the laboratory
reference range may also affect these parameters.
Patients with hypothyroidism are routinely treated with levothyroxine (L-T4) as replacement
therapy. Physicians monitor the L-T4 dose by measuring serum thyroid stimulating hormone
(TSH) levels, with the goal of a normal level. However, many patients with normal TSH levels
continue to report symptoms, primarily in neurocognitive and metabolic areas. For this
reason, patients with hypothyroidism often request higher L-T4 doses, but the clinical
consequences of this are unknown.
In the present study, otherwise healthy subjects with treated hypothyroidism and normal TSH
levels, ages 20-75 years, will be enrolled in a 7-11 month study. At baseline, the following
tests will be performed to measure health status, psychological symptoms, mood, memory, body
composition, and energy expenditure: the Short Form Health Survey-36 (SF-36), Profile of Mood
States (POMS), Affective Lability Scale (ALS), Letter Cancellation Test (LCT), Trail Making
Test, Iowa Gambling Task (IGT), N-Back Test, Subject-Ordered Pointing, Paragraph Recall,
Pursuit Rotor, Motor Sequence Learning Test, resting energy expenditure (REE) and thermic
effect of food (TEF) by indirect calorimetry, total energy expenditure (TEE) by doubly
labelled water, physical activity energy expenditure (PAEE) by accelerometry, diet intake by
24-hour diet recalls, and body composition by dual energy x-ray absorptiometry (DEXA).
Following these baseline measurements, subjects will receive either their usual doses of
L-T4, 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 L-T4 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.
overt thyroid dysfunction have well-described alterations in mood, cognition, energy
expenditure, and body composition. However, it is not clear that patients with more mild
degrees of thyroid dysfunction have clinically significant alterations in these parameters.
In addition, recent data suggest that variations in thyroid function within the laboratory
reference range may also affect these parameters.
Patients with hypothyroidism are routinely treated with levothyroxine (L-T4) as replacement
therapy. Physicians monitor the L-T4 dose by measuring serum thyroid stimulating hormone
(TSH) levels, with the goal of a normal level. However, many patients with normal TSH levels
continue to report symptoms, primarily in neurocognitive and metabolic areas. For this
reason, patients with hypothyroidism often request higher L-T4 doses, but the clinical
consequences of this are unknown.
In the present study, otherwise healthy subjects with treated hypothyroidism and normal TSH
levels, ages 20-75 years, will be enrolled in a 7-11 month study. At baseline, the following
tests will be performed to measure health status, psychological symptoms, mood, memory, body
composition, and energy expenditure: the Short Form Health Survey-36 (SF-36), Profile of Mood
States (POMS), Affective Lability Scale (ALS), Letter Cancellation Test (LCT), Trail Making
Test, Iowa Gambling Task (IGT), N-Back Test, Subject-Ordered Pointing, Paragraph Recall,
Pursuit Rotor, Motor Sequence Learning Test, resting energy expenditure (REE) and thermic
effect of food (TEF) by indirect calorimetry, total energy expenditure (TEE) by doubly
labelled water, physical activity energy expenditure (PAEE) by accelerometry, diet intake by
24-hour diet recalls, and body composition by dual energy x-ray absorptiometry (DEXA).
Following these baseline measurements, subjects will receive either their usual doses of
L-T4, 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 L-T4 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.
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
We found this trial at
1
site
3181 Southwest Sam Jackson Park Road
Portland, Oregon 97239
Portland, Oregon 97239
503 494-8311
Oregon Health and Science University In 1887, the inaugural class of the University of Oregon...
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