Effects of Pharmacologic Block of Type-1 Deiodinase on Thyroid Hormone Action and on the Circulating Levels of T3 in Hypothyroid Patients
Colección de datos
Recopilados desde hoy en adelante - ProspectivoEnfermedades del Sistema Endocrino
+ Enfermedades de la Tiroides
+ Hipotiroidismo
Resumen
Fecha de inicio: 4 de enero de 2013
Fecha en la que se inscribió al primer participante.Thyroid hormone action is an important regulator of the metabolism and the function of many organs. The active form of thyroid hormone is T3, and its blood and tissue levels are the result of the secretion of T3 and its precursor, thyroxine (T4), from the thyroid gland, of the peripheral conversion of T4 into T3, and of the degradation of these hormones. In hypothyroid patients (particularly patients who underwent total thyroidectomy), the levels of T3 are entirely dependent on the exogenously administered T4 (Levothyroxine, L-T4) which is converted to T3 or to the inactive form, rT3, by enzymes called deiodinases. This complex system has only been partially studied in humans and very little is known about the correlation between circulating levels of T3 and end-organ target tissue thyroid hormone action. The aim of this protocol is to characterize the contribution of the two activating deiodinases (type-1 and type-2) to the blood levels and biological effects of T3. To achieve this goal we intend to study hypothyroid patients treated with adequate replacement of L-T4 therapy while simultaneously blocking the activity of the type-1 deiodinase with propylthiouracil (PTU). Twenty hypothyroid patients who underwent total thyroidectomy or are affected by hypothyroidism and are on L-T4 therapy with normal TSH values will be recruited. After enrollment in the study, the patients eligibility will be determined during an outpatient visit. Patients will be admitted to the NIH Clinical Center for a 9-day period and will receive PTU at a dose of 200 mg four times daily for seven days. During the hospitalization for this research protocol, the following studies will be performed: serial blood sampling for circulating thyroid hormones to obtain pharmacokinetic parameters of T3, lipids, glucose and insulin; body composition; resting energy expenditure at room temperature and during exposure to mild cold; echocardiogram and EKG; skeletal muscle strength measurement and cardiac MRI. The results obtained from this study will help in further characterizing the effects of thyroid hormone on metabolism, and may lead to important information on how to optimize the thyroid hormone replacement therapy for the treatment of hypothyroidism.
Protocolo
Esta sección proporciona detalles del plan del estudio, incluyendo cómo está diseñado y qué se está evaluando.Elegibilidad
Los investigadores buscan pacientes que cumplan ciertos criterios, conocidos como criterios de elegibilidad: estado general de salud o tratamientos previos.Cualquier sexo
Sexo biológico de los participantes elegibles para inscribirse.A partir de 18 años
Rango de edades de los participantes que pueden unirse al estudio.Voluntarios sanos no permitidos
Indica si personas sanas, sin la condición que se estudia, pueden participar.Condiciones
Patología
Criterios
PARTICIPANT INCLUSION CRITERIA: Study subjects will be adults older than 18 years who do not have any endogenous thyroid hormone production (i.e. status post total thyroidectomy, or in individuals who have a residual remnant greater than 2 mL, an uptake in the thyroid gland less than 5% while on therapy on 123I uptake scan) and on L-T4 replacement at a minimum dose of 1.6 microg/Kg in a steady state of euthyroidism. EXCLUSION CRITERIA: <TAB>Thyroid uptake > 5% at 24 hours on (123)I thyroid scan while on replacement therapy (in patients with thyroid gland residue > 2 mL by ultrasound). <TAB>Patients who have lipid disorders requiring pharmacologic intervention. <TAB>Any elevation of AST or ALT above upper limit of normal range. <TAB>Any reduction of the WBC count below the lower limit of normal range. <TAB>History of, and/or current diabetes mellitus (fasting glucose >126 mg/dL or current pharmacologic treatment). <TAB>Hypertension requiring pharmacologic intervention. <TAB>Female patients who are on hormonal contraceptives or are breastfeeding. <TAB>Use of beta blocker medications and amiodarone. <TAB>Pregnancy (women of child-bearing age must have a negative pregnancy test prior to inclusion). <TAB>History of vasculitis, viral hepatitis (except A), granulocytopenia. <TAB>Known allergy or serious adverse event to PTU. <TAB>Current use of prescription medication or certain non-prescription medications and dietary supplements known to affect thyroid function and/or metabolism, or alter the pharmacokinetics of PTU. Should study volunteers receive other pharmacologic interventions a clinical pharmacist will be consulted to evaluate potential drug-drug interactions. <TAB>Presence of persistent diarrhea or malabsorption syndromes that would interfere with the patient s ability to adequately absorb medications. <TAB>Inability to obtain venous access for sample collection, or basal hemoglobin of less than or equal to 12 g/dl.
Plan de Estudio
Conoce todos los tratamientos administrados en este estudio, su descripción detallada y en qué consisten.Objetivos del Estudio
Objetivos Primarios