Discontinuing long-term GH replacement therapy--a randomized, placebo-controlled crossover trial in adult GH deficiency.
BACKGROUND
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.


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


METHODS
We conducted a randomized, double-blind, placebo-controlled 4-month crossover trial in a referral center.


METHODS
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.


METHODS
Patients received GH or placebo.


METHODS
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).


CONCLUSIONS
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.
Department of Endocrinology, Sahlgrenska University Hospital, and Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE-41345 Göteborg, Sweden. helena.filipsson@telia.com
Helena
H
Filipsson Nyström
Edna J L
EJ
Barbosa
Anna G
AG
Nilsson
Lise-Lott
LL
Norrman
Oskar
O
Ragnarsson
Gudmundur
G
Johannsson
D015502:Absorptiometry, Photon; D000328:Adult; D000368:Aged; D000886:Anthropometry; D001794:Blood Pressure / Q000502:physiology; D001823:Body Composition / Q000187:drug effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D017097:Electric Impedance; D005260:Female; D005951:Glucose Tolerance Test; D019382:Human Growth Hormone / Q000008:administration & dosage* / Q000172:deficiency / Q000627:therapeutic use*; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009043:Motor Activity / Q000502:physiology; D053580:Muscle Strength / Q000187:drug effects / Q000502:physiology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology; D010900:Pituitary Diseases / Q000188:drug therapy / Q000209:etiology / Q000523:psychology; D011788:Quality of Life; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*; D014057:Tomography, X-Ray Computed
D011994:Recombinant Proteins; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I