Adult Growth Hormone Deficiency and Cardiovascular Risk

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Assessment of Cardiovascular Risk Markers in GH Deficient Patients With Nonsecreting Pituitary Adenomas

Conditions
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Growth Hormone Deficiency

Intervention / Treatment
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* Procedure: Blood draws
* Drug: growth hormone releasing hormone (GHRH) & arginine
* Procedure: Carotid ultrasound
* Procedure: MRI
* Procedure: Endothelial cell biopsy


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: A - Normal growth hormone secretion<br>Patients who have undergone transsphenoidal surgery for a pituitary adenoma and have normal growth hormone secretion: Subjects will undergo a clinical exam with vital signs and blood draws, anthropometric measurements and skin fold thickness assessments. Subjects will also undergo GH stimulation testing with growth hormone releasing hormone (GHRH) & arginine, MRI and MR spectroscopy, carotid ultrasound, and have an endothelial cell biopsy. | Procedure: Blood draws<br>* Subjects will have serum cardiovascular markers assessed<br>Drug: growth hormone releasing hormone (GHRH) & arginine<br>* Subjects will receive GHRH and arginine intravenously and then have blood drawn at frequent intervals over a 90 minutes to assess growth hormone secretion.<br>Procedure: Carotid ultrasound<br>* Subjects will have an ultrasound of their neck to assess their carotid arteries to look for intima-medial thickness.<br>Procedure: MRI<br>* Subjects will have MRI and MR spectroscopy of the abdomen and lower extremities to assess for fat in internal organs and muscle.<br>Procedure: Endothelial cell biopsy<br>* 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.<br>|
| Active Comparator: B - Growth hormone deficient<br>Patients who have undergone transsphenoidal surgery for pituitary adenoma who are growth hormone deficient: Subjects will undergo a clinical exam with vital signs and blood draws, anthropometric measurements and skin fold thickness assessments. Subjects will also undergo GH stimulation testing with growth hormone releasing hormone (GHRH) & arginine, MRI and MR spectroscopy, carotid ultrasound, and have an endothelial cell biopsy. | Procedure: Blood draws<br>* Subjects will have serum cardiovascular markers assessed<br>Drug: growth hormone releasing hormone (GHRH) & arginine<br>* Subjects will receive GHRH and arginine intravenously and then have blood drawn at frequent intervals over a 90 minutes to assess growth hormone secretion.<br>Procedure: Carotid ultrasound<br>* Subjects will have an ultrasound of their neck to assess their carotid arteries to look for intima-medial thickness.<br>Procedure: MRI<br>* Subjects will have MRI and MR spectroscopy of the abdomen and lower extremities to assess for fat in internal organs and muscle.<br>Procedure: Endothelial cell biopsy<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| C-reactive Protein (CRP) Levels | C-reactive protein (CRP) levels in GH sufficient and GH deficient participants | Day 1 | 
| Homocysteine Level | Homocytsteine levels in GH sufficient and GH deficient participants | Day 1 | 
| Total Cholesterol Level | Total cholesterol levels in GH sufficient and GH deficient participants | Day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Fat Measured by DXA DEXA | Percentage of total body fat and trunk fat as measured by DXA | Day 1 | 
| Lean Body Mass by DXA DEXA | Lean body mass as measured by DXA | Day 1 | 
| Insulin Sensitivity as Assessed by Fasting Insulin Levels | Insulin sensitivity as assessed by fasting insulin levels | Day 1 | 
| Glucose Levels as Assessed by an Oral Glucose Tolerance Test | Glucose levels as assessed by an oral glucose tolerance test | Day 1 | 
| Endothelial Function as Assessed by Flow Mediated Dilatation and Endothelial Cell Biopsy | Endothelial function as assessed by flow mediated dilatation and endothelial cell biopsy for measurement of inflammatory markers. | Day 1 | 
| Carotid Intimal-medial Thickness Studies as Assessed by Ultrasound | Carotid intimal-medial thickness studies will be measured by ultrasound | Year 1 | 
| Intramyocellular Lipid Content Using MRI and MR Spectroscopy | Intramyocellular lipid content using MRI and MR spectroscopy of the soleus muscle was performed. | Day 1 | 
| Intrahepatic Lipid Content Using MRI and MR Spectroscopy | Intrahepatic lipid (IHL) content using MRI and MR spectroscopy of the liver was performed. | Day 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Growth hormone