Low Dose Growth Hormone (GH) on Insulin Sensitivity and Cortisol Production Rates

The study will be double-blinded. One hundred subjects will be screened for eligibility initially, and 24 subjects will be enrolled with 12 subjects being randomized to receive the low GH dose (0.1 mg/day) treatment and 12 subjects to receive Placebo treatment for 3 months, allowing a 10% drop-out rate. The subjects will be taught by either by the Endocrine Nurse Specialists to self-administer the GH by subcutaneous injections using a Genotropin pen device.

Visit 1, Initial Screening Assessment (as out-patient)

• Physical examination, weight, height, and waist circumference measurements
• Fasting blood glucose levels

Visit 2, Baseline Assessment (as in-patient)

• Physical examination, weight, height, and waist circumference measurements
• Fasting blood tests for glucose, insulin, C-peptide, free IGF-I, total IGF-I, IGF-2, IGFBPs -1 and -3, non-esterified fatty acid and lipid profiles
• MRS, abdominal CT and DEXA scans
• One-step 3-hour hyperinsulinaemic euglycaemic clamp
• Cortisol production rates and urine cortisol collections
• Fat biopsies will be taken at the end of the assessment of cortisol production rates

Visit 3, Interim Assessment (Month 1) (as out-patient)

• Documentation of any adverse effects
• Fasting blood tests for glucose, insulin, C-peptide, free IGF-I, total IGF-I, IGF-2, IGFBPs -1 and -3

Visit 4, Final Assessment (Month 3) (as in-patient)

• Physical examination, weight, height, and waist circumference measurements
• Fasting blood tests for glucose, insulin, C-peptide, free IGF-I, total IGF-I, IGF-2, IGFBPs -1 and -3, non-esterified fatty acid and lipid profiles
• MRS, abdominal CT and DEXA scans
• One-step 3-hour hyperinsulinaemic euglycaemic clamp
• Cortisol production rates and urine cortisol collections
• Fat biopsies will be taken at the end of the assessment of cortisol production rates

Any extra blood remaining from the samples of blood drawn may be banked indefinitely with confidential identifiers, and may be given to researchers in the future to examine for other potential causes of diabetes and heart diseases in adults. These blood samples, however, will not be used for genetic studies.

Inclusion criteria

• Age range 18 to 75 years
• BMI should not exceed 40 kg/m2
• Confirmed GH deficient with at least one provocative test, e.g. insulin tolerance test and/ or GHRH/arginine
• Not received any GH therapy within last 6 months
• On a stable standardized hydrocortisone replacement dose regimen (twice a day at 8 AM and 4 PM),
• If any other pituitary hormone deficiencies are present, patient must be on optimal pituitary hormone replacement therapy, e.g. Thyroxine, testosterone and oestrogen replacement
• Normal renal and hepatic function
• Prepared to self-inject

Exclusion criteria

• Untreated or subclinically hypo/hyperthyroid
• Untreated or subclinically treated hypocortisolism
• Type 1 or 2 diabetes mellitus
• Subjects with evidence of nephropathy from any cause
• Subjects with evidence of retinopathy from any cause
• Any other medical illnesses that may affect the interpretation of the results
• Pregnant
• Emotional/social instability likely to prejudice study completion
• Previous history of known malignancy
• Recurrent or severe unexplained hypoglycaemia
• Known or suspected drug/alcohol abuse