Replacement GH Therapy After Bariatric Surgery in Patients With Very Severe Obesity

The objectives of the study are:

• To evaluate the GH/GF-I status is correlation with body composition in very severe obese patients. IGF-I levels were classified as deficient when the standard deviation score from the mean was <-2 for age and gender.
• To evaluate the efficacy of a medical treatment with recombinant GH replacement therapy in very severe obese patients after LASGB on the Fat mass (%), free fat mass (%), percent decrease of fat mass. In line with GHD diagnosis, obese patients with persistent GHD after bariatric surgery will be randomized to be treated with or without recombinant GH therapy with replacement doses, in addition to the controlled trial of dietary management, as routinely performed after LASGB.

Study protocol The study protocol includes two different arms: a correlation observational longitudinal open study (Phase I), and a treatment study (Phase II).

PHASE I: In the correlation study a clinical, biochemical and instrumental evaluation will be performed in 20-30 patients with very severe obesity (grade III) with GHD followed-up in a multi-disciplinary approach at the Unit of Endocrinology of the Departments of Molecular and Clinical Endocrinology and Oncology and at the Physiology Nutrition Unit of the Department of Neuroscience and the Department of Surgery of "S. Giovanni Bosco" Hospital of Naples, according to the current criteria of the National Institute of Health (27). The clinical examination will focus on the GH/IGF-I status effects on body composition changes before and after LASGB. The clinical examination will determine anthropometric indexes (weight, height, BMI, waist circumference). The biochemical evaluation will include the measurement of lipid profile, fasting plasma glucose and insulin, liver test function, FT3, FT4, GHRH + Arginine test to detect GHD, plasma IGF-I levels. The instrumental evaluation will include DEXA Total Body and bioimpedance analysis to determine body composition, and liver ultrasounds.

PHASE II: In the medical treatment protocol very severe obese patients with persistent GHD after LASGB will be inclosed. Starting from 15-day, GHD patients were re-evaluated by GHRH + Arginine test. After evaluation, the patients with persistent GHD will be randomized to be treated with Recombinant GH replacement therapy (Group A: Recombinant GH replacement therapy at the initial dose 0.15-0.30 mg/die; dose adjustment will be made according to IGF-I levels; Group B: no GH treatment). In both subgroups, the diet will arranged to fit an energy intake of 5.7 MJ/day (55% carbohydrate, 25% fat, 20% protein, 30 g fiber) and a moderate-intensity activity (brisk walking for 30-45 min/day) will be encouraged.

The evaluation of medical treatment efficacy will be based on the analysis of changes in anthropometric indexes, IGF-I levels, liver function test, body composition assessed by DEXA Total Body and bioimpedance analysis, liver ultrasounds. At 3 and 6 months, the patients of both subgroups A and B will be clinically re-evaluated, plasma samples for metabolic, liver function tests, and endocrine profile will be obtained, body composition and liver ultrasounds will be determined. At the end of the 6-months period of treatment and observation, the GH response to a subsequent GHRH + Arginine will be re-tested to confirm or to exclude GHD. All the patients with persistent GHD will continue recombinant GH therapy.

Inclusion criteria

• Age between 18-50 yrs
• Normal glucose tolerance during standard oral glucose tolerance test (OGTT)
• Inclusion criteria for bariatric surgery proposed by the 1991 National Institutes of Health Consensus Development Panel Report.

Exclusion criteria

• Liver or renal failure, cancer, acute or chronic inflammatory diseases
• Chronic treatment with any type of medications
• organic pituitary deficiency
• Bulimia Nervosa of the DSM-IV
• Ulcers or malignancies excluded by oesophagus-gastro-duodenoscopy.