Effect of 5 Years of GH Replacement on Atherosclerosis
Effect of 5 Years of GH Replacement on Atherosclerosis
Adult patients with hypopituitarism under adequate conventional hormone replacement therapy
 have reduced life expectancy due to excess vascular events (1-4). Deficiency in GH secretion
 (GHD) is likely to play a major role in determining the excess mortality, since it is
 associated with lipid abnormalities, visceral adiposity, glucose intolerance, insulin
 resistance, hypertension, cardiac abnormalities and increased intima-media thickness (IMT) at
 major arteries (5).

 Beneficial effects of growth hormone (GH) replacement on cardiovascular risk factors have
 been demonstrated in several studies of hypopituitary GHD patients (5). GH replacement
 improves body composition and lipid profile (5): it is accepted that management of
 dyslipidaemia is crucial in primary and secondary prevention of cardiovascular disease and
 part of the excess vascular risk associated with hypopituitarism is likely to be due to
 dyslipidaemia (6). A meta-analysis of blinded, randomized, placebo-controlled trials with low
 doses and long-duration GH treatment showed that GH replacement has beneficial effects on
 cardiovascular risk by improving lean and fat body mass, total and LDL cholesterol levels,
 and diastolic blood pressure (7). Besides, GH replacement also induces improvement in
 cardiovascular markers (8), and cardiac performance (9). In small cohorts of GHD adults,
 beneficial effects of GH replacement for 6-24 mos have also been reported on surrogate
 parameters of atherosclerosis, such as intima-media thickness (IMT) at major arteries
 (10-13), while 6 months of GH deprivation is associated with an impairment of the
 cardiovascular risk profile (12). In a consistent series of men and women with
 hypopituitarism we reported, however, that two years of GH replacement is not adequate to
 normalize IMT levels at common carotid arteries (13).

 To give further insights on the likelihood of reversal of early atherosclerosis in severe GHD
 patients after prolonged GH replacement, we designed this 5-yr prospective, controlled study.
 Only men aged ≤50 yrs and with severe GHD were enrolled to avoid gender and aging
 interference (13). Main outcome measure was IMT at common carotid arteries; secondary measure
 was prevalence of insulin-resistance syndrome according with the American College of
 Endocrinology (14).
This is an observational,5-yr prospective, controlled study. At study entry, all subjects
 underwent serum assay of IGF-I, systolic and diastolic blood pressure (SBP, DBP) measurement,
 total-, and HDL-cholesterol, triglycerides, glucose, and insulin level after an overnight
 fasting, and common carotid arteries ultrasonography. The oral glucose load (oGTT) was
 performed by measuring blood glucose every 30 minutes for 2 hours after the oral
 administration of 75 g of glucose diluted in 250 ml of saline solution. The conversion
 factors (mg/dl to mmol/l) for lipids and glucose were as follows: cholesterol 0.02586,
 triglycerides 0.01129, and glucose 0.05551. According with previous studies (13,19-21) blood
 pressure was measured at the right arm, with the subjects in relaxed sitting position. The
 average of six measurements (three taken by each of two examiners, in the same day, between
 8.00-9.00 in the morning) with a mercury sphygmomanometer was used in all analysis.

 In the patients, all parameters and carotid ultrasonography were re-evaluated after 12, 24,
 36, 48 and 60 months while in controls they were re-evaluated after 60 months.

 At study entry and at study end, in all of the patients and controls the prevalence of
 insulin-resistance syndrome (IRS) was evaluated according with the American College of
 Endocrinology (14) based on the presence of at least two criteria of the following:
 triglycerides levels ≥1.7 mmol/liter, HDL-cholesterol levels ≤1.0 mmol/liter, blood pressure
 above 130/85 mmHg, fasting glucose between 6.1 and 7 mmol/liter or 2 hr after oGTT between
 7.7 and 11.1 mmol/liter.
Inclusion Criteria:

 -  male gender

 -  age <50 yrs to limit the effect of aging;

 -  body mass index <30 Kg/m2;

 -  no familial or personal history of cardiovascular diseases;

 -  no concomitant treatment with drugs known to interfere with glucose or lipid
 metabolism or to influence blood pressure at the time of study entry;

 -  no previous GH treatment

 Exclusion Criteria:

 -  female gender

 -  age >50 yrs;

 -  body mass index ≥30;

 -  familial or personal history of cardiovascular diseases;

 -  previous and present treatments with drugs known to interfere with glucose or lipid
 metabolism or to influence blood pressure;

 -  previous GH treatment in adult age

 -  GHD of childhood onset

 -  GHD due to previous Cushing's disease