Adult Growth Hormone Deficiency and Cardiovascular Risk

Phase 4

Terminated

Conditions: Growth Hormone Deficiency

Interventions: Procedure: Blood draws
Drug: growth hormone releasing hormone (GHRH) & arginine
Procedure: Carotid ultrasound
Procedure: MRI
Procedure: Endothelial cell biopsy

Registration Number: NCT00720902

Lead Sponsor: Columbia University

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 7

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
B - Growth hormone deficient	Carotid ultrasound	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.
A - Normal growth hormone secretion	Blood draws	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.
A - Normal growth hormone secretion	MRI	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.
B - Growth hormone deficient	Blood draws	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.
B - Growth hormone deficient	MRI	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.
A - Normal growth hormone secretion	growth hormone releasing hormone (GHRH) & arginine	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.
A - Normal growth hormone secretion	Carotid ultrasound	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.
B - Growth hormone deficient	growth hormone releasing hormone (GHRH) & arginine	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.
A - Normal growth hormone secretion	Endothelial cell biopsy	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.
B - Growth hormone deficient	Endothelial cell biopsy	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.

Primary Outcome Measures

Name	Time	Method
Homocysteine Level	Day 1	Homocytsteine levels in GH sufficient and GH deficient participants
C-reactive Protein (CRP) Levels	Day 1	C-reactive protein (CRP) levels in GH sufficient and GH deficient participants
Total Cholesterol Level	Day 1	Total cholesterol levels in GH sufficient and GH deficient participants

Secondary Outcome Measures

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