Adult Growth Hormone Deficiency and Cardiovascular Risk

• Percentage of total body fat, trunk fat and lean body mass by DEXA [ Time Frame: once ] [ Designated as safety issue: No ]
• Insulin sensitivity as assessed by fasting insulin and glucose levels and by an oral glucose tolerance test [ Time Frame: once ] [ Designated as safety issue: No ]
• Endothelial function as assessed by flow mediated dilatation and endothelial cell biopsy [ Time Frame: once ] [ Designated as safety issue: No ]
• Carotid intimal-medial thickness studies as assessed by ultrasound [ Time Frame: once ] [ Designated as safety issue: No ]
• Intramyocellular and intrahepatic lipid content using MRI and MR spectroscopy [ Time Frame: once ] [ Designated as safety issue: No ]

This protocol will assess the cardiovascular risk associated with growth hormone deficiency in adults. We will use multiple modalities to assess risk for heart attacks or strokes including blood work, ultrasound, MRI and endothelial cell biopsies in both patients who are growth hormone deficient and in patients with normal growth hormone secretion. We hypothesize that adults with growth hormone deficiency will have results suggestive of an increased risk for cardiovascular disease.

Subjects will first be tested for possible growth hormone deficiency. This will be done by administering two intravenous medications that should stimulate growth hormone secretion and we will measure growth hormone in the blood every 30 minutes following the administration. Once we have the results on enough subjects we will split the cohort into those subjects who are growth hormone deficient and those who have normal growth hormone. The two groups will each undergo various tests all designed to assess some component of cardiovascular risk. Ultimately we will compare the results of each test to see if those who are growth hormone deficient have an increased risk for cardiovascular disease.

• Procedure: Blood draws
  Subjects will have serum cardiovascular markers assessed
• Drug: Growth hormone releasing hormone (GHRH) and arginine
  Subjects will receive GHRH and arginine intravenously and then have blood drawn at frequent intervals over a 90 minutes to assess growth hormone secretion.
• Procedure: Carotid ultrasound
  Subjects will have an ultrasound of their neck to assess their carotid arteries to look for intima-medial thickness.
• Procedure: MRI
  Subjects will have MRI and MR spectroscopy of the abdomen and lower extremities to assess for fat in internal organs and muscle.
• Procedure: Endothelial cell biopsy
  Subjects will undergo endothelial cell biopsies to harvest endothelial cells to study. It will occur once and takes approximately 20 minutes. Patients will have an iv placed and then a sterile wire is passed back and forth in the iv a couple of times. Three wires are passed.

• Active Comparator: A
  Patients who have undergone transsphenoidal surgery for a pituitary adenoma and have normal growth hormone secretion.
  Interventions:

  • Procedure: Blood draws
  • Drug: Growth hormone releasing hormone (GHRH) and arginine
  • Procedure: Carotid ultrasound
  • Procedure: MRI
  • Procedure: Endothelial cell biopsy
• Active Comparator: B
  Patients who have undergone transsphenoidal surgery for pituitary adenoma who are growth hormone deficient.
  Interventions:

  • Procedure: Blood draws
  • Drug: Growth hormone releasing hormone (GHRH) and arginine
  • Procedure: Carotid ultrasound
  • Procedure: MRI
  • Procedure: Endothelial cell biopsy

Inclusion Criteria:

• Adults 19 years or older who have undergone transsphenoidal surgery for a clinically non-secreting pituitary adenoma

Exclusion Criteria:

• Currently taking growth hormone, radiation therapy in the past 5 years, changes in dose of other pituitary hormone replacement therapy in past 3 months, taking hydrocortisone (or its equivalent) at a dose of > 30 mg/day, pregnant or nursing women