Study of Thyrotropin-Releasing Hormone in Normal Volunteers and in Patients With Thyroid or Pituitary Abnormalities

Study Overview
=================
Brief Summary
-----------------
This study will determine the safety and activity of a new formulation of thyrotropin-releasing hormone (TRH), a drug used for diagnosing and evaluating patients with certain thyroid gland abnormalities. Normal thyroid gland function depends on proper chemical signaling between the thyroid gland, the hypothalamus (the part of the brain where TRH is made), and the pituitary (another part of the brain). The TRH test helps assess this interaction. Production of the only FDA-approved preparation of TRH was stopped in July 2002. As a result, to have a continuous source of TRH available for NIH clinical and research purposes, the NIH Clinical Center (CC) Pharmacy Department produced a pharmaceutical grade formulation of TRH for patient use. This study will test the CC formulation in healthy volunteers to show that its activity and side effects are similar to those of the previously available commercial test preparation. It will then be studied in CC patients for whom the diagnostic test is recommended. Healthy volunteers between 18 and 65 years of age and all patients requiring TRH evaluation of hypothalamic-pituitary-thyroid gland interaction may be eligible for this study. Patients include those with pituitary reserve, inconsistent thyroid function test, inappropriate TSH secretion, or pre- and post-operative evaluation of pituitary tumors. Normal volunteers will be screened with a medical history, physical examination, and blood tests. Women of child-bearing potential will be given a pregnancy test; pregnant and breast-feeding women may not participate. The TRH test procedure will be the same for healthy volunteers and patients. All participants fast from midnight before the morning of the test. In the morning, a catheter (flexible plastic tube) is inserted into an arm vein for easy injection of the TRH and collection of blood samples. Blood pressure is monitored before and during the test. A blood sample is drawn, and then TRH is given through the catheter over a 1-minute period. Another nine blood samples are collected over a 3-hour period from the time of the TRH injection for measuring levels of various hormones. A total of less than 4 tablespoons of blood is taken for the test.

Detailed Description
-----------------
Thyrotropin releasing hormone (TRH) is a neuropeptide used in the diagnostic evaluation of patients with dysfunction of the hypothalamic-pituitary-thyroid (HPT) axis. In healthy individuals, administration of TRH intravenously results in pituitary secretion of thyrotropin [thyroid-stimulating hormone (TSH)], which in turn stimulates the thyroid gland release of thyroid hormones; thyroxine (T4) and triiodothyronine (T3). TRH stimulates the secretion of other pituitary hormones under normal physiologic as well as pathologic conditions. Under this protocol, TRH is used for routine diagnostic testing and research studies in adults and children. It is produced by the Pharmaceutical Development Section of the Clinical Center Pharmacy at the NIH. The safety, activity and comparability of this preparation were demonstrated in a small group of normal volunteers prior to its release for diagnostic and research use.

Official Title
-----------------
Study of Thyrotropin Releasing Hormone in Patients With Thyroid or Pituitary Abnormalities

Conditions
-----------------
Healthy, Pituitary Disease, Thyroid Disease

Intervention / Treatment
-----------------
* Drug: TRH (Thyrotropin Releasing Hormone)


Participation Criteria
=================
Eligibility Criteria
-----------------
DIAGNOSTIC STUDY PROTOCOL Inclusion Criteria: -All adults and children requiring dynamic testing of the hypothalamic-pituitary axis for the evaluation of pituitary reserve, inconsistent thyroid function test, inappropriate TSH secretion, or pre-and post-operative evaluation of pituitary adenomas (glycoprotein hormone secreting tumors, growth hormone secreting tumors and TSH secreting tumors). Exclusion Criteria: Uncontrolled hypertension; Uncontrolled seizure disorder; Unstable coronary disease; Known allergy to TRH. RESEARCH PROTOCOLS -TRH is available for use in other IRB approved research protocols either using the standard diagnostic testing protocol or the modified TRH test. Exclusion Criteria: Untreated hypertension; Coronary artery disease; History of asthma; History of seizures; Pregnancy; Known allergy to TRH.

Ages Eligible for Study
-----------------
Minimum Age: 2 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Thyrotropin Releasing Hormone<br>Subjects receiving TRH (Thyrotropin Releasing Hormone) | Drug: TRH (Thyrotropin Releasing Hormone)<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| TSH Response to TRH | Serum TSH Levels in Response to TRH Administration | 180 minutes from infusion | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Hypothalamic Releasing Factor, Neuropeptide, Diagnostic Testing, Pituitary Tumors, Central Hypothyroidism, Pituitary Disorder, Thyroid Disorder, Healthy Volunteer