A total of 45 subjects with documented biochemical remission of
acromegaly were recruited from the Massachusetts General Hospital
Neuroendocrine Clinical Center, by referring endocrinologists, and
through advertising. All subjects had been treated by surgery or radiation
therapy at least 6 months before study entry and demonstrated biochemical
cure, defined as GH suppression to less than 1 ng/ml during an oral
glucose tolerance test and/or normal serum IGF-I for age. Subjects were
excluded from participation if they were receiving somatostatin analogs,
dopamine agonists, or GH receptor antagonists. Additional exclusion
criteria included unstable cardiovascular disease, uncontrolled hypertension
or diabetes mellitus, cancer, and pregnancy, or breastfeeding
within 1 yr before study enrollment. One subject had received GH therapy
previously and for less than 1 yr, discontinuing it more than 3 yr
before study enrollment. Subjects with hypopituitarism were required to
have been receiving stable hormone replacement therapy doses for at
least 3 months before enrollment. Subjects with adrenal insufficiency
were all receiving 4–5 mg of prednisone or 15–30 mg of hydrocortisone
daily. The range of doses of testosterone replacement in hypogonadal
men was 5 to 7.5 g of a transdermal gel, except for one male subject who
was receiving im testosterone esters at a dose of 200 mg every 2 wk. All
but two (one of whom was receiving transdermal estradiol and the other
oral conjugated equine estrogens) of the women receiving gonadal steroids
were receiving oral contraceptives. Diagnosis of GHD was defined
as a peak GH level of less than 5 ng/ml on GHRH-arginine stimulation
testing, or an IGF-I level more than 2 SD values below the age-specific
normal range in the presence of at least three anterior pituitary deficiencies
(n  5) (23). Subjects were categorized as GH-sufficient based on
peakGHlevels above 9 ng/ml on a GHRH-arginine stimulation test (24,
25). Two additional subjects tested did not qualify as GH-deficient or
GH-sufficient (peakGHlevels5 ng/ml or9 ng/ml) and were included
for analyses in which data were used as continuous variables. One was
a 45-yr-old female, and the other was a 31-yr-old male. GHRH-arginine
testing was performed using the standard protocol for diagnosis ofGHD
in adults with hypopituitarism (GHRH 1g/kg plus arginine 0.5 g/kg to
a maximum of 30 g were administered iv, and GH levels were measured
at baseline and every 30 min for 2 h) (26).
The study was approved by the Partners Healthcare, Inc. Institutional
Review Board, and written informed consent was obtained from all
subjects