Dose Response Relationship for Single Doses of Corticotropin Releasing Hormone (CRH) in Normal Volunteers and in Patients With Adrenal Insufficiency
Dose Response Relationship for Single Doses of Corticotropin Releasing Hormone (CRH) in Normal Volunteers and in Patients With Adrenal Insufficiency
Corticotropin Releasing Hormone (CRH) is a hypothalamic hormone made up of 41 amino acids.
 Amino acids are proteins that when combined make up different substances, like hormones. The
 order of amino acids in CRH, has been determined, meaning that the hormone can now be
 synthetically reproduced in a laboratory setting.

 When CRH is released from the hypothalamus it stimulates the pituitary gland to secrete
 another hormone, ACTH. ACTH then causes the adrenal glands to make a third hormone, cortisol.
 This process is known as the hypothalamic-pituitary-adrenal axis. Problems can occur in any
 of the steps of this process and result in a variety of diseases (Cushing's Syndrome and
 adrenal insufficiency).

 Researchers hope that CRH created in a laboratory setting, ovine CRH (oCRH) can be used to
 help diagnose and treat conditions of the HPA axis. This study will test the relationship for
 single doses of oCRH in normal volunteers and patients with disorders of the HPA axis. The
 oCRH will be injected into the patients vein as a single injection or slowly through an IV
 line over 24 hours. The participants will have blood tests taken to measure hormone levels
 before, during, and after receiving the oCRH.
Corticotropin-releasing hormone (CRH) is a 41 amino acid hypothalamic peptide whose chemical
 structure has recently been determined after more than two decades of intensive research.
 This peptide stimulates secretion of ACTH by the corticotroph cells of the pituitary gland.
 As with the previously discovered hypothalamic hormones, CRH has important diagnostic and
 therapeutic applications. This study seeks to explore these clinical applications by
 determining the dose-response relationship for single doses of ovine CRH (oCRH) in normal
 volunteers and in patients with disorders of the hypothalamic-pituitary-adrenal axis. CRH is
 administered intravenously at doses up to 10 pg/kg, given as a bolus or up to 1 ug/kg/b as a
 continuous infusion lasting up to 24 hours. Plasma levels of ACTH, cortisol and CRH are
 measured before, during and after CRH administration.
INCLUSION CRITERIA:

 The normal volunteers are obtained through the NIH volunteer program or are NIH employees.
 Normal volunteers are in excellent health and are receiving no chronic medications.

 We now routinely test patients with hypocortisolism or hypercortisolism in our clinic and
 ward.