Pharmacogenomic Response to Thyrotropin-Releasing Hormone Stimulation in Healthy Volunteers: The Influence of a Common Type 2 Deiodinase Genetic Polymorphism on Serum T3
Pharmacogenomic Response to Thyrotropin-Releasing Hormone Stimulation in Healthy Volunteers: The Influence of a Common Type 2 Deiodinase Genetic Polymorphism on Serum T3
This study intends to examine how a common genetic pattern affects thyroid function. Recent
 studies have demonstrated that a substance (enzyme) produced by a gene has an important role
 in controlling circulating thyroid hormone levels. A commonly found pattern in this gene
 exists in many individuals and might affect the function of the enzyme. These individuals
 need higher doses of thyroid hormone medication in certain situations (e.g. in the treatment
 of thyroid cancer after the thyroid gland has been removed) than those individuals without
 the variation.

 We intend to study this by looking at the response to a hormone-test in healthy volunteers
 with different genetic patterns.

 We plan to screen healthy volunteers using a blood test to identify their genetic pattern
 relating to the enzyme we are interested in. From this group, forty-five healthy volunteers
 will be recruited for the hormone-test. This test (called the TRH test) uses a hormone
 produced by the brain and stimulates the pituitary and thyroid gland. The response to this
 test will allow us to compare the function of the thyroid system in relation to the genetic
 pattern of the volunteer.

 We hypothesize that the stimulation of the thyroid hormone system will be decreased in
 volunteers with a specific genetic pattern and that these individuals will release less
 active thyroid hormone from the thyroid gland in response to the TRH test.

 This study will provide new information on the effect of a common genetic pattern on thyroid
 hormone function and will help us to better understand the way in which the thyroid hormone
 system operates. Ultimately, the results of this study might help to provide a more
 individualized therapy for patients in need of thyroid hormone replacement.
This study intends to examine how a common genetic pattern affects thyroid function. Recent
 studies have demonstrated that a substance (enzyme) produced by a gene has an important role
 in controlling circulating thyroid hormone levels. A commonly found pattern in this gene
 exists in many individuals and might affect the function of the enzyme. These individuals
 need higher doses of thyroid hormone medication in certain situations (e.g. in the treatment
 of thyroid cancer after the thyroid gland has been removed) than those individuals without
 the variation.

 We intend to study this by looking at the response to a hormone-test in healthy volunteers
 with different genetic patterns.

 We plan to screen healthy volunteers using a blood test to identify their genetic pattern
 relating to the enzyme we are interested in. From this group, forty-five healthy volunteers
 will be recruited for the hormone-test. This test (called the TRH test) uses a hormone
 produced by the brain and stimulates the pituitary and thyroid gland. The response to this
 test will allow us to compare the function of the thyroid system in relation to the genetic
 pattern of the volunteer.

 We hypothesize that the stimulation of the thyroid hormone system will be decreased in
 volunteers with a specific genetic pattern and that these individuals will release less
 active thyroid hormone from the thyroid gland in response to the TRH test.

 This study will provide new information on the effect of a common genetic pattern on thyroid
 hormone function and will help us to better understand the way in which the thyroid hormone
 system operates. Ultimately, the results of this study might help to provide a more
 individualized therapy for patients in need of thyroid hormone replacement.
-  INCLUSION CRITERIA:

 1. Subjects will be healthy male and female adult volunteers, between the ages of 18
 and 65, able to provide informed consent. Patients younger than 18 are excluded
 as this is a purely physiologic study and we are unable to justify any potential
 risk. However, should our preliminary findings show potential clinically relevant
 benefits for children, the protocol could be modified to include them. Patients
 older than 65 are excluded due to intrinsic differences in thyroid hormone
 dynamics, compared with younger subjects, which could confound study
 interpretation.

 EXCLUSION CRITERIA:

 1. BMI less than or equal to 19 or greater than or equal to 35 Kg/m(2)

 2. Hypothyroidism, or TSH levels above the normal limits (current replacement therapy or
 TSH greater than 4.0 mcIU/mL)

 3. Hyperthyroidism, or TSH levels below the normal limits (current or previous therapy or
 TSH less than 0.4 mcIU/mL)

 4. Autoimmune thyroid disease (as defined by a positive anti-TPO, or anti-TSH receptor
 antibody titer)

 5. Hypertension (Blood pressure greater than 140/90 or use of antihypertensive
 medication)

 6. Liver disease or ALT serum concentrations greater than 1.5 times the upper laboratory
 reference limit.

 7. Renal insufficiency or estimated creatinine clearance less than or equal to 50 mL/min
 (MDRD equation).

 8. History of, and/or current Diabetes Mellitus (fasting glucose greater than 126 mg/dL)

 9. Iodine deficiency (spot urine iodine concentration less than 42 mcg/L)

 10. History of, and/or current coronary artery disease

 11. History of, and/or current asthma

 12. History of, and/or current seizures or chronic headache

 13. History of, and/or current depression

 14. History of pituitary tumor

 15. Pregnancy (women of child-bearing potential must have a negative pregnancy test prior
 to inclusion and at the time of TRH testing)

 16. Known allergy to TRH

 17. Current use of prescription medication or certain non-prescription medications and
 dietary supplements which could affect thyroid function and/or metabolism.