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.

Condition	Treatment or Intervention	Phase
Healthy Pituitary Disease Thyroid Disease	Drug: TRH (Thyrotropin Releasing Hormone)	Phase II

Further Study Details: 

Expected Total Enrollment:  99999

Thyrotropin releasing hormone (TRH) is a neuropeptide used in the diagnostic evaluation of patient with dysfunction of the hypothalamic-pituitary-thyroid (HPT) axis. In healthy individuals, administration of TRH intravenously results in pituitary secretion of thyrotropin [thyroid-stimulation 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.

The purpose of this study is to test the safety and activity of a new preparation of TRH produced by the Pharmaceutical Development Section of the Clinical Center Pharmacy at the NIH. This preparation is similar to a previously commercially available preparation. Normal, health adults will be recruited to undergo a standard TRH test using the new preparation. TSH, prolactin and thyroid hormones are measured after the administration of TRH. After the safety, activity and diagnostic comparability are established, the preparation will be used for routine diagnostic testing and research studies in adults and children.

Genders Eligible for Study:  Both

Accepts Healthy Volunteers

Criteria

INCLUSION CRITERIA:
Healthy Volunteer Study:
1. Healthy males and females between the ages of 18 and 65 years.
Diagnostic Study Protocol:
1. 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:
Healthy Volunteer Study:
1. Hypertension;
2. Coronary artery disease;
3. History of asthma;
4. History of seizures;
5. Chronic liver, kidney, thyroid or pituitary disease;
6. Use of medications for chronic conditions, contraception or hormone replacement;
7. Pregnancy;
8. Known allergy to TRH.
Diagnostic Study Protocol:
1. Uncontrolled hypertension;
2. Uncontrolled seizure disorder;
3. Unstable coronary disease;
4. Known allergy to TRH.
Research Protocols:
1. Untreated hypertension;
2. Coronary artery disease;
3. History of asthma;
4. History fo seizures
5. Pregnancy;
6. Known allergy to TRH.

Maryland
      National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), 9000 Rockville Pike,  Bethesda,  Maryland,  20892,  United States; Recruiting

Study ID Numbers:  030098; 03-DK-0098
Record last reviewed:  January 4, 2005
Last Updated:  January 10, 2005
Record first received:  February 7, 2003
ClinicalTrials.gov Identifier:  NCT00054756
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08