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