Acromegaly is a disease caused by excessive growth hormone (GH) production. The majority of cases are due to pituitary gland tumors. There are two theories about the cause of these tumors formation: (1) A mutation in a chromosome of a cell leads to neoplastic transformation and subsequent formation of a tumor. (2) Excessive release of GH-releasing hormone (GHRH) (a factor produced by the hypothalamus that stimulates the growth and function of GH-secreting cells) stimulates GH-producing cells to multiply and produce large amounts of GH. Combinations of these two theories could be also functional. Moreover, GHRH can be produced by the pituitary tumor cells. Our hypothesis is that GHRH plays an important role in the formation of the pituitary tumors that cause acromegaly, and in maintaining the excessive GH secretion in acromegaly. We will attempt to answer this question by administering GHRH-antagonist (GHRH-Ant), a synthetic molecule that blocks the action of GHRH on the GH-producing cells, to patients with acromegaly. Two groups of patients will be studied: (a) Fifteen patients (group A) will have frequent blood sampling for plasma GH for 24 hours on 2 different occasions with the goal to show that without any intervention the GH secretion pattern in acromegaly does not change from day to day so that any changes that we could observe during administration of GHRH-Ant would be meaningful. (b) Ten patients recently diagnosed with acromegaly, who are scheduled to have pituitary surgery (group B) will receive intravenous (i.v.) infusion of GHRH-Ant for 7 days. Plasma GH will be measured every 10 min for 24 h, and the GH responses to factors that cause abnormal GH responses in acromegaly (i.v. thyrotropin-releasing hormone (TRH) and oral glucose) and to i.v. GHRH will be assessed before and at the end of the GHRH-Ant infusion. The effect of GHRH-Ant on the pituitary tumor size will be measured by pituitary MRI scans before and after the GHRH-Ant infusion. At the time of pituitary surgery, a pituitary tumor sample will be obtained to study the effects of GHRH-Ant on the GH production by the tumor cells in the laboratory. If the GHRH-Ant suppresses the secretion of GH and decreases the size of the pituitary tumors, we will conclude that GHRH plays a role in the formation of the pituitary tumors that cause acromegaly and in maintaining abnormal GH secretion in this disease.
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