Neoplasms

Gland and Hormone Related Diseases

All Conditions

Thyroid Neoplasms

Thyroid Diseases

Hyperthyroidism

Hypothyroidism

Endocrine System Diseases

Endocrine Gland Neoplasms

Head and Neck Neoplasms

All Drugs and Chemicals

Anti-Infective Agents

Antineoplastic Agents

Hormones

polysaccharide-K

Skin Biopsy

This study will examine whether and how levothyroxine (Synthroid, a synthetic thyroid hormone) affects the way the body handles other drugs. If levothyroxine does affect the metabolism of other drugs, the dose of those medications may need to be increased to enhance their action or decreased to avoid adverse reactions.

Patients 18 years of age and older with thyroid cancer who are participating in NIH protocol #77-DK-0096 and are receiving long-term suppression therapy with levothyroxine may be eligible for this study. This is not a study of thyroid cancer or of potential new drugs to treat it. Thyroid cancer patients are being studied because their treatment regimen provides an opportunity to study drug metabolism while patients are both on and off levothyroxine therapy.

Participants come to the NIH Clinical Center on two occasions: once while they are regularly taking their levothyroxine, and once while they are off the medication in preparation for their radioactive iodide diagnostic scan for the procedures outlined below. The time interval between the two clinic visits depends on whether the first visit is while the patient is on or off medication. Participants are asked to fast overnight before each visit and to abstain from certain foods and beverages for 48 to 72 hours before the visit. At each visit, patients undergo the following procedures:

* Medication history, limited physical examination, and blood draw for laboratory tests, including a test to look for genes important in eliminating medications from the body.
* Insertion of a catheter (thin plastic tube) into an arm vein for collecting blood samples.
* Shave skin biopsy (optional) to explore how proteins in the skin that metabolize and transport drugs are affected by thyroid hormone. For this procedure, the skin is cleaned, numbed with medicine, and a small sample of the top layer is removed with a razor blade. The wound heals in 2 to 3 days.
* Medication dosing. Participants take all of the following substances by mouth at the same time: 1) 200 mg of caffeine, a compound commonly found in chocolate, soda/pop, coffee, tea and non-prescription products to prevent sleep; 2) 30 mg of dextromethorphan, a non-prescription cough suppressant; 3) 40 mg of omeprazole, a prescription drug for heartburn and stomach ulcers; 4) 8 mg of midazolam, a prescription drug used to cause relaxation and drowsiness; and 5) 120 mg of fexofenadine, a non-sedating prescription antihistamine used to treat allergies.
* Blood and urine sampling. Fifteen blood samples of about 5 mL (1 teaspoon) each are collected through the catheter and urine is collected over the next 24 hours to determine what happens to the test drugs in the body.

Participants may resume their normal diet 4 hours after taking the study medications.

Interaction between thyroid hormones and commonly prescribed drugs has been well documented, resulting in augmentation or attenuation of the action of either compound. Phase I drug metabolism is mediated mostly by enzymes belonging to the cytochrome p450 superfamily. Studies in animals and cell cultures have shown that thyroid hormones play an important role in the constitutive expression of the p450 enzymes, thus potentially altering the metabolism and the effects of a variety of drugs. P-glycoprotein is expressed in the major organs associated with drug absorption, distribution, and elimination from the body (e.g. intestine, kidney, liver, skin, and the blood-brain barrier). Expression of intestinal P-glycoprotein in humans also appears to be influenced by thyroid hormones. We intend to study the effect of thyroid hormones on the activity of CYP1A2, CYP2C19, CYP2D6, CYP3A4 and P-glycoprotein by using a five-drug cocktail (caffeine, omeprazole, dextromethorphan, midazolam, and fexofenadine) administered in patients with thyroid cancer, both on thyroid hormone suppression therapy (in conditions of subclinical hyperthyroidism) and off this treatment (in conditions of hypothyroidism) at the time of their routine radioactive iodine scan. Additionally we will perform two skin biopsies in order to assess the pattern of expression of metabolic enzymes and drug transport proteins on and off thyroid hormone suppression therapy.

The Effect of Thyroid Hormone on Drug Elimination in Cancer Patients

The Effects of Thyroid Hormone on Cytochrome P450 and P-Glycoprotein Activity in Thyroid Cancer Patients

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Thyroid Cancer, Papillary

Adenocarcinoma, Follicular

Goiter

Leukemia-Lymphoma, Adult T-Cell

Struma Ovarii

Adenocarcinoma

Adenocarcinoma, Papillary

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Teratoma

Neoplasms, Germ Cell and Embryonal

Papillary Thyroid Carcinoma

Thyroid Cancer, Follicular

Adult T-cell Leukemia/lymphoma

Hurthle Cell Thyroid Cancer

Micronutrients

Iodine

Cadexomer iodine

Adults with clinical indication for withdrawal from thyroid hormone replacement therapy in preparation for nuclear medicine imaging or therapeutic procedures with radioactive iodine

Kong Y Chen, Ph.D.

Background:

- Thyroid hormone is produced by the thyroid gland, an organ at the base of the neck. Thyroid hormone controls the body's metabolism and the function of many organs. The thyroid gland produces two forms of thyroid hormone: T4 and T3. People who have thyroid cancer are treated with thyroid hormone therapy (synthetic T4, levothyroxine), which at times needs to be stopped to allow for cancer treatments. At these times, a different form of thyroid hormone (synthetic T3, liothyronine) is used to reduce the symptoms caused by low levels of thyroid hormone. Researchers want to know more about how changes in T3 hormone affect the body and organ function.

Objectives:

- To study how changes in T3 hormone levels affect the body and organ function.

Eligibility:

- Individuals at least 18 years of age who have had most or all of their thyroid removed to treat thyroid cancer who need to stop taking their regular thyroid hormone dose in preparation for the treatment of thyroid cancer.

Design:

* The study involves a screening visit and a baseline evaluation. It also includes an 11-day inpatient hospital stay.
* Participants will be screened with a physical exam and medical history. They will also have blood tests and a neck ultrasound.
* Participants will be evaluated with a physical exam, blood tests, and the following procedures:
* Glucose tolerance test to measure blood sugar
* Tests of body fat, muscle strength, and calorie burning levels
* Imaging studies of the heart, liver, and thigh muscles
* Quality of life questionnaires
* Food preference and diet questionnaires
* After 4 weeks of treatment with T3 hormone, participants will have an 11-day inpatient hospital stay to study the effect of thyroid hormone on their metabolism. The stay will involve the same tests done in the baseline evaluation.

In human adults thyroid hormone action plays a critical role in the modulation of metabolism and the function of virtually all organ/systems. The specificity of the hormonal action is ultimately the result of the interaction of the active hormone, triiodothyronine (T3), with the receptors isoforms and the co-activators and co-repressors specific for the various cells target of the hormonal action. Circulating and tissue levels of T3 are the result of the secretion of T3 and its precursor, thyroxine (T4), from the thyroid gland, the peripheral conversion of T4 into T3, and the degradation of these hormones. This complex system has only been partially studied in humans and very little is known regarding the kinetics of T3, and in particular on the correlation between circulating levels of T3 and end-organ target tissue thyroid hormone action.

The aim of this protocol is to characterize the pharmacokinetics of T3 and its biological effects at various concentrations in a cohort of thyroidectomized patients undergoing thyroid hormone replacement therapy withdrawal for the management of thyroid cancer.

Sixteen patients with a clinical indication for thyroid hormone withdrawal in preparation for 131I therapy or 123I diagnostic scan for follow-up and management of differentiated thyroid cancer will be recruited for this study. After enrollment in the study, the patients baseline characteristics will be determined during an outpatient visit while receiving levothyroxine (L-T4) therapy. The L-T4 therapy then will be suspended and substituted with an equivalent thrice daily liothyronine (L-T3) therapy for one month. Patients will be admitted to the NIH Clinical Center on the day prior to withdrawal of the T3 therapy until the diagnostic scan or the administration of radioactive iodine. During the hospitalization for this research protocol, which is expected to last eleven days, the following studies will be performed: serial blood sampling for circulating thyroid hormones to obtain pharmacokinetic parameters of L-T3, lipids, glucose and insulin, resting energy expenditure, echocardiogram, skeletal muscle strength measurement, cardiac, hepatic and skeletal muscles MRI, and quality of life and well-being questionnaires. The pharmacokinetic parameters of L-T3 will also be assessed with the first dose after the diagnostic scan or the administration of radioactive iodine.

The results obtained from this study will help in understanding the effects of thyroid hormone on metabolism, and may lead to important information on how to optimize the duration of the thyroid hormone therapy withdrawal for the treatment of thyroid cancer.

Metabolic Effects of Synthetic Thyroid Hormone for Thyroid Cancer Treatment

Pharmacokinetic and Pharmacodynamic Studies of Liothyronine. A Study on the Metabolic Effects of Thyroid Hormone

to study T3 kinetics in thyroidectomized patients treated with liothyronine (L- T3) replacement therapy in preparation for diagnostic or therapeutic nuclear medicine procedures for the follow-up and management of differentiated thyroid cancer

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
The Effect of Thyroid Hormone on Drug Elimination in Cancer Patients	NCT00080574	Thyroid Cancer	Skin Biopsy	-	National Institutes of Health Clinical Center (CC)
Metabolic Effects of Synthetic Thyroid Hormone for Thyroid Cancer Treatment	NCT01441154	Malignant Strum... Papillary Thyro... Hurthle Cell Th... Follicular Thyr... Tall Cell Varia...		18 Years - 99 Years	National Institutes of Health Clinical Center (CC)

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