|
Mauras and colleagues conducted a multicenter,
double-blind, placebo-controlled 2-year follow-up study of 58 subjects (mean
age 15.8 ± 1.8 years; 33 males) who were treated for GH-deficiency as children
and who, upon retesting at near adult height, were still GH-deficient (GHD).
The study consisted of 3 phases: a basal phase, a washout phase, and an
assessment phase. Twenty-five subjects were enrolled in the GH group (15 males,
10 females), 15 in the placebo group (9 males, 6 females), and 18 in the
GH-sufficient control group (8 males; 7 females) of which 3 were excluded from
analysis because they had evidence of multiple anterior pituitary hormone
deficiencies. Forty-two subjects completed the study period that included
baseline assessment and follow-up assessments at 2, 4, 8, 12, 16, 20, and 24
months: 21 patients in the GH group, 11 in the placebo group, and 10 in the
control group (assessed only at 12 and 24 months). The primary objective of the
study was to establish the efficacy of GH treatment with regards to body
composition and bone mineral density changes, as well as the safety of a
transition dose (20 µg/kg/d) of GH as replacement therapy in subjects with GHD
during the transition from adolescence to adulthood. Secondary objectives
included exploring the effects of GH treatment on plasma lipids, insulin-like
growth factor (IGF)-I concentration, carbohydrate metabolism, cardiac function,
exercise tolerance, and quality of life (QoL).
The results, in general,
failed to reveal a significantly beneficial effect of GH on measures of either
body composition or bone mass over the 2-year study compared with the placebo
group. There were also no measurable improvements in functional measures of
muscle strength. Cardiovascular assessment revealed normal cardiac function and
exercise tolerance in the study subjects at baseline and throughout the study.
The lipid profile did not change during GH therapy, and measures of
carbohydrate metabolism showed only mild increases in measures of insulin
resistance. QoL measures were unchanged during the 24-month trial. The authors
concluded that GHD adolescents who are in good metabolic status at the time of
discontinuation of GH treatment may be able to discontinue GH for at least 2
years without any deleterious effects, and that replacement treatment in
adulthood needs to be individualized.
Mauras
N, Pescovitz OH, Allada V, Messig M, Wajnrajch MP, Lippe B. for the Transition
Study Group. Limited efficacy of growth hormone (GH) during transition of
GH-deficient patients from adolescence to adulthood: A phase III multicenter,
double-blind, randomized two-year trial. J Clin Endocrinol
Metab. 2005;90:3946 - 3955.
First Editor’s Comment: The investigators
provided several plausible explanations for the finding that treatment of GHD
adolescents in transition to adulthood did not elicit metabolic or QoL
benefits, including the younger age of these research participants than those
in studies showing benefits, the brief length of time off of GH, a possibly
over-liberal threshold for diagnosing persistent GHD (<5 µg/liter), and
sample attrition.
It is
noteworthy that the QoL scores of the GHD participants were indistinguishable
from those of the general population while on GH and prior to the washout phase
of the study. Unfortunately, one can not surmise what the level of functioning
was before initiating treatment years earlier. Without such baseline data, it
would be erroneous to conclude that GH treatment in childhood and adolescence
had any effects on QoL.
Finally, if the results of this well-designed
study can be replicated, then this would come as good news to patients,
families, and clinicians. No one, least of all the adolescent patient, looks
forward to continuing daily injections beyond the period of active linear
growth. Most GHD patients will end this initial phase at some point during
adolescence, a phase of development notoriously difficult from the perspective
of adherence to medical regimens.1 Knowing that no physical or
psychological harm will come to patients by introducing a hiatus in treatment
for at least 2 years provides the opportunity to re-educate the now
increasingly mature patient about the changing hormonal requirements to support
optimal health (physical and QoL).
David E. Sandberg, PhD
Second Editor’s Comment: This work was presented
at the ESPE – LWPES Joint Meeting and reviewed on page
8 of this issue of GGH.
Fima Lifshitz, MD
References - (linked to  )
- La Greca AM, Bearman KJ. Adherence to pediatric treatment regimens. In:
Roberts MC, ed. Handbook of Pediatric Psychology. New York: Guilford
Press; 2003:119 - 140.
|
Current GGH - Vol. 24 No. 1
print version (pdf)
Printer Friendly
Email Paper