Thyroid and Glucose and Energy Metabolism

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.
Candidates are screened with a medical history and physical examination, blood tests,
electrocardiogram (EKG) and neck ultrasound to visualize any remaining thyroid tissue.

At the first clinic visit, participants have blood tests, an echocardiogram (ultrasound test
to assess heart function), and vascular endothelial function evaluation (test using
nitroglycerin, a medicine given to patients having chest pain or a heart attack, and
ultrasound to measure blood vessel dilation). They are then randomly assigned to take either
T4 or T3 thyroid hormone medication. After 10 days, patients return to the hospital for a
checkup and blood test, and to complete questionnaires about their feeling of well-being and
eating habits. Thyroid medications are adjusted, if needed. Follow-up visits are scheduled
until the patient's thyroid hormone levels are have stabilized and they have maintained the
same dose for at least 30 days.

Patients are then hospitalized for 5 days for the following tests and procedures:

- Blood tests to analyze thyroid hormones, lipids, glucose, electrolytes, clotting
factors, kidney function, red cells, and DNA. (Day 1)

- DEXA scan (an x-ray test) to determine percentage of body fat tissue. (Day 1)

- Thyrotropin releasing hormone (TRH) stimulation test to indicate how well the body
responds to T4 or T3: A small amount (5 micrograms) of TRH is injected into a vein,
causing the release of another hormone called thyrotrophic stimulating hormone. Blood
samples are collected immediately before and after the TRH injections. This test is
done three times over 3 days with increasing doses of TRH. (Days 1, 2, and 3)

- Subcutaneous fat tissue microdialysis to understand how T3 and T4 affect the activity
of fat tissue. The medication isoproterenol is injected in fat tissue under the skin of
the abdomen, and fluid samples are collected from the area over a 2-hour period using
the same small needle. (Day 2)

- Cardiovascular tests, including exercise stress test using a stationary bicycle; and
repeat echocardiogram, EKG, and vascular endothelial function evaluation. (Day 3)

- Questionnaires on well being and eating habits. (Day 3)

- Euglycemic-hyperinsulinemic clamp to measure the effects of insulin. Catheters (plastic
tubes) are placed in a vein in one arm and in the hand on the opposite side of the
body. Insulin is infused through the catheter in the arm. Glucose is measured every 5
minutes from the catheter in the hand and given through the catheter in the arm to
maintain levels in the normal range. (Day 4,)

- Indirect calorimetry to study how the body uses sugar to generate energy. During the
euglycemic-hyperinsulinemic clamp test a plastic transparent hood is placed over the
head to collect the air breathed.

- Skeletal muscle biopsy to find out how T3 and T4 affect muscle strength and its ability
to store glucose. Under local anesthesia, a small piece of muscle tissue is surgically
removed. This test is optional. (Day 5)

- Fat tissue biopsy to find out how T3 and T4 affect fat tissue size and its ability to
store glucose. Under local anesthesia, a small piece of fat tissue in the abdomen is
surgically removed. This test is optional. (Day 5)

At the conclusion of these tests, patients are discharged from the hospital and enter the
second phase of the study, in which all the procedures described above, from thyroid
stabilization through the 5-day hospitalization, are repeated. This time, however, patients
who were taking T3 now take T4, and vice versa. The time interval between the two
hospitalizations depends on how quickly the thyroid hormone medical dose can be adjusted.