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09-17-2014, 09:56 AM
What Happens When Long Term Growth Hormone is Stopped
Study Looked at What Happens When Long Term Growth Hormone Replacement Therapy is Stopped

Discontinuing Long-Term GH Replacement Therapy—A Randomized, Placebo-Controlled Crossover Trial in Adult GH Deficiency


Department of Endocrinology, Sahlgrenska University Hospital, and Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE-41345 Göteborg, Sweden

Abstract

Context: Adult GH deficiency (GHD) is associated with impaired quality of life (QoL) and increased cardiovascular risk. Continued long-term efficacy in terms of QoL and cardiovascular risk factors has been indicated in open surveillance studies.

Objectives: The aim was to study the impact of discontinuation of long-term GH replacement on QoL, body composition, and metabolism.

Design and Setting: We conducted a randomized, double-blind, placebo-controlled 4-month crossover trial in a referral center.

Patients: Sixty adult hypopituitary patients with GHD and more than 3 yr of continuous GH replacement therapy (mean treatment duration, 10 yr) participated in the study.

Intervention: Patients received GH or placebo.

Main Outcome Measurements: We measured QoL using validated questionnaires; body composition using computer tomography, dual-energy x-ray absorptiometry, and bioelectrical impedance spectroscopy; and insulin sensitivity using the short insulin tolerance test.

Results: Mean serum IGF-I decreased from 168± 52 to 98± 47 µg/liter during the placebo period (P< 0.001). Two QoL domains (emotional reactions and positive well-being) in the Nottingham Health Profile and Psychological General Well-Being questionnaires deteriorated during placebo, compared with GH treatment (P< 0.05). Waist circumference and sc and visceral fat mass increased, and extracellular water and muscle area decreased during the placebo period (all P< 0.05). C-reactive protein and total-, low-density lipoprotein-, and high-density lipoprotein-cholesterol increased, and insulin sensitivity improved during placebo, compared to GH treatment (P< 0.05).

Conclusion: After more than 3 yr of GH replacement therapy, a 4-month period of placebo treatment caused self-perceived deterioration in QoL and increased abdominal fat accumulation. Moreover, markers of systemic inflammation and lipid status deteriorated, whereas insulin sensitivity improved. Long-term continuous GH replacement is needed to maintain therapeutic effects of GH on QoL and cardiovascular risk factors.