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.
INCLUSION CRITERIA: 1. Subject has signed the informed consent document; 2. Subject is greater than or equal to 18 years of age; 3. Subjects diagnosed with thyroid cancer participating in protocol 77DK0096; 4. Subjects receiving THST with levothyroxine; 5. Serum TSH less than 0.4 mIU/L while on THST, and more than 20 mIU/L while off THST. EXCLUSION CRITERIA: Subject is pregnant, currently breast-feeding, practicing birth control with hormonal contraceptives, or is on hormone replacement therapy (HRT). Subject is a smoker. Subject has a confounding medical illness (es) that in the judgement of the investigators would pose an added risk for the subject (e.g. severe respiratory disease). Subject has a history of substance abuse within the past 5 years or drug or alcohol use, that may affect enzyme levels and function. Caffeine or caffeine-containing beverages and chocolate bars consumption within 48 hours of scheduled caffeine administration for CYP1A2 phenotyping; scheduled omeprazole administration during or within 14 days of the study; scheduled dextromethorphan administration during or within 30 days of study; scheduled fexofenadine administration during or within 7 days of the study. AST or ALT greater than or equal to 2 times the upper normal reference limit. Concurrent administration of known CYP and/or P-gp inducers (barbiturates, phenytoin, carbamazepine, rifampicin) and inhibitors (amiodarone, atorvastatin, chloroquine, cimetidine, co-trimoxazole, cyclosporine, diltazem, erythromycin, fluoxetine fluvoxamine, isoniazid, itrakonazole, ketokonazole, metronidazole, mexiletine, nefazadone, norfloxacin, verapamil) or use of any alternative/complementary therapies for at least 30 days prior to study or during the study. Non-herbal vitamin and mineral preparations will be allowed. Inability to obtain venous access for sample collection, or basal hemoglobin of equal or less than 10 g/dl. Patients receiving scheduled therapy with alprazolam, triazolam, clonazepam, diazepam, lorazepam, oxazepam, temazepam or chlorodiazepoxide, during or within 30 days of study. Patients consuming grapefruit products (juice or the fresh fruit), apple and orange juice during or within 72 hrs of study. History of intolerance to caffiene, omeprazole, dextromethorphan, midazolam or fexofenadine. The presence of persistent diarrhea or malabsorption syndromes that would interfere with the patient's ability to adequately absorb drugs; and/or Patients receiving monoamine oxidase inhibitors (MAOIs) such as phenelzine, tranylcypromine, and isocarboxazid. Patients with a history of cheloids formation.