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Growth hormone control may be important
HIV lipodystrophy treatment
Study describes new approach to treating
AIDS-associated syndrome
BOSTON - July 10, 2004 - Increasing the body's production
of growth hormone may be an effective treatment for HIV lipodystrophy,
a syndrome involving the redistribution of fat and other metabolic
changes in those receiving combination drug therapy for HIV infection.
Researchers from Massachusetts General Hospital (MGH) report that
administration of growth-hormone-releasing hormone to a group of
men with HIV lipodystrophy significantly improved fat distribution
with no negative side effects. The study appears in the July 14
Journal of the American Medical Association, a special HIV/AIDS
issue published in conjunction with the International AIDS Conference
in Bangkok.
"This study is an initial proof of principal that augmenting
low growth hormone levels in this way has the potential to reverse
the abnormal body composition seen in these individuals," says
Steven Grinspoon, MD, of the MGH Neuroendocrine Unit and Program
in Nutritional Metabolism, the report's senior author. "At
the current time, there is no established treatment for this syndrome."
The combination drug strategy known as highly active antiretroviral
therapy (HAART) can significantly reduce virus levels and help maintain
health in HIV-infected individuals, but more than half may develop
lipodystrophy. Typical symptoms of the syndrome include a loss of
subcutaneous fat in the face, arms, and legs and increased fat deposits
in the abdomen and upper back. The metabolic aspects of the syndrome
- changes in cholesterol and other blood lipids, and development
of insulin resistance - could also increase the risk of cardiovascular
disease.
It recently has been discovered that men with lipodystrophy do not
secrete normal levels of growth hormone. Although growth-hormone
(GH) injections can reduce fat deposits that develop in other GH-deficiency
situations, high-dose injections have a number of significant side
effects, including insulin resistance, already a problem for lipodystrophy
patients.
In a healthy body, secretion of GH is controlled by a feedback mechanism,
which shuts down the process if hormone concentrations exceed normal
blood levels. Directly injecting GH could bypass this natural control
mechanism, allowing blood levels to rise too high. In an attempt
to raise GH levels in a more natural manner, the MGH team devised
a strategy using growth-hormone-releasing hormone (GHRH).
They enrolled 31 men with HIV lipodystrophy for a 12-week, randomized,
double-blinded study. Participants injected themselves twice daily
with either GHRH or a placebo injection. To track GH secretion,
the researchers measured blood levels of insulin-like growth factor-1
(IGF-1). As part of the natural feedback system, IGF-1 levels rise
in response to GH blood levels, which turns off further hormone
secretion. Body composition was measured by x-ray and CT scan studies,
and blood tests followed other metabolic markers.
At the end of the study period, participants in the GHRH group had
significant increases in their IGF-1 levels compared with the placebo
group, indicating more normal GH production and regulation. In addition,
body composition of those in the GHRH group returned to a more normal
pattern, with increases in subcutaneous fat in the extremities and
less fat deposited deep within the abdomen. Although there were
no significant differences in total fat mass, those in the GHRH
group had significant increases in lean body mass.
As the reseachers hoped, the increased GH levels resulting from
GHRH therapy did not significantly change blood levels of insulin
and glucose. Cholesterol and triglyceride levels also remained stable.
In addition, both participants and their physicians noted improvement
in lipodystrophy symptoms in the GHRH group, and those participants
also expressed significantly greater satisfaction with their overall
appearance.
"The novel part of this study was use of a natural secretion
inducer to produce normal hormone levels," Grinspoon says.
"The significant redistribution of fat away from the abdomen
reflects a change toward a more healthy cardiovascular profile,
an important health benefit with minimal risk due to the achievement
of normal growth hormone levels." Grinspoon is an associate
professor of Medicine at Harvard Medical School.
The researchers note that further studies should investigate longer-term
therapy in a larger, more diverse population. They also are studying
other GH-secretion inducers and theorize that this approach could
be useful for other GH-deficiency syndromes. Although GHRH remains
investigational for lipodystrophy, the study was performed with
the approval of the Food and Drug Administration.
The study's first author is Polyxeni Koutkia, MD, of the MGH Neuroendocrine
Unit and Program in Nutritional Metabolism. Co-authors are Bridget
Canavan, Martin Torriani, MD, and John Kissko, all of the MGH; and
Jeff Breau of Massachusetts Institute of Technology. The research
was supported by grants from the National Institute for Diabetes,
Digestive and Kidney Diseases, and the study drug was provided by
Serono, Inc., which had no additional input into the study.
Massachusetts General Hospital, established in 1811, is the original
and largest teaching hospital of Harvard Medical School. The MGH
conducts the largest hospital-based research program in the United
States, with an annual research budget of more than $400 million
and major research centers in AIDS, cardiovascular research, cancer,
cutaneous biology, medical imaging, neurodegenerative disorders,
transplantation biology and photomedicine. In 1994, MGH and Brigham
and Women's Hospital joined to form Partners HealthCare System,
an integrated health care delivery system comprising the two academic
medical centers, specialty and community hospitals, a network of
physician groups, and nonacute and home health services.
Media Contact: Sue
McGreevey, MGH Public Affairs
Physician Referral Service: 1-800-388-4644
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