Consequence of Lifetime Isolated Growth Hormone Deficiency
Status:
Completed
Trial end date:
2009-12-01
Target enrollment:
Participant gender:
Summary
Growth hormone (GH) deficiency (GHD) in adulthood has been associated with changes in body
composition (e.g. increased abdominal obesity, and reduced muscle mass), in organ functions
(e.g. reduced cardiac systolic function), in metabolic parameters linked to increased risk of
cardiovascular disease (e.g. increased serum total and LDL cholesterol, C reactive protein,
and plasma fibrinogen), and with reduced bone density. These observations have been used to
define the "adult GHD syndrome" and to advocate GH replacement therapy in GHD adults.
However, most of the studies have been performed in patients who have had hypothalamic or
pituitary diseases, and/or have undergone brain irradiation. Such patients are often
chronically sick, and commonly lack other pituitary hormones, whose replacement therapies may
not fully restore the physiological functions of the under-active glands. Reliable data on
the existence of the AGHD syndrome and its response to GH therapy can be only obtained by
studying patients that are otherwise healthy. However, isolated GH deficiency (IGHD) is a
rare disease. In addition, up to 50% of patients who have been diagnosed with IGHD in
childhood are no longer GH deficient as adults, making such study difficult to perform due to
the scarcity of patients population. We have identified a very large homogeneous population
of patients who have IGHD due to a homozygous mutation in the GHRH-receptor (GHRHR) gene that
resides in a rural area of Brazil. None of the adult dwarf patients has ever been treated
with hGH replacement. This population represents a unique model to study the effect of
isolated lifetime lack of GH. We propose studies of physiological and metabolic parameters in
subjects who are homozygous for this mutation and compare them with normal subjects residing
in the same community.
The primary goal of this proposal is to determine the consequences of life-long lack of GH on
body composition, muscle strength, cardiovascular status, cardiovascular risk factors,
thyroid status and bone density and metabolism, and to test which of these parameters are
reversed by a 6-month course of GH replacement therapy. In addition, we want to test the
hypothesis that heterozygosity for this GHRHR mutation causes a phenotype that may be
intermediate between the one present in homozygous normal subjects and in homozygous affected
GHD patients. This is relevant because inactivating mutations in the GHRHR are being
described with increasing frequency in populations of different genetic background,
suggesting that individuals with faulty single GHRHR alleles may be present in significant
numbers in the general population.
Phase:
N/A
Details
Lead Sponsor:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)