Visualisation of coronary arteries for the analysis of premature atherosclerosis in patients with adult-onset growth hormone deficiency

Patients with a hypopituitarism (and a growth hormone deficiency) are probably
prone for an increased cardiovascular mortality. As a feature of premature
cardiovascular disease in these patients, the intima media thickness (IMT) from
carotid arteries is found to be increased. Additionally, a proatherogenic
phenotype (such as a dyslipidemia, increased levels of pro-inflammatory markers
and a protrombogenic profile) is present. After start of recombinant human
growth hormone substitution, the intima media thickness is reduced already
after 6 months of treatment (sic!). This decrease in atherosclerotic burden is
remarkable (but shown by two independent research groups) and needs therefore
additional analysis.

Hypothesis:

1. Patients who suffer from a hypopituitarism and an adult-onset growth hormone
deficiency (AGHD) express more atherosclerotic disease in the coronary system
(compared with a historically formed control subjects, present as a database in
the cardiology department from the UMC Utrecht)
2. Atherosclerotic disease in the coronary system wil be in regression after
one year substitution with recombinant human growth hormone (in line with
previously published results with regard to carotid IMT)
3. Patients with a hypopituitarism and AGHD display additional proatherogenic
mechanisms: 2.1 disturbances in antioxidant capacity of the high-density
lipoprotein (HDL) fraction, 2.2 disturbances in the differentiation of
endothelial progenitor cells with a less capacity to repair damaged
endothelium, 2.3 an increase of metalloproteinases as part of the
pro-inflammatory profile in circulation .

After inclusion in the study, patients will have a multi-slice coronary CT scan
to analyse atherosclerotic burden in the coronary system. In additional,
additional venous blood will be collected to analyse the different questions as
mentioned under hypothesis 3. Both multi-slice coronary CT scan and venous
blood collection will be repeated after one year GH substitution (substitution
of GH is part of regular care). The obtained results will be analysed in a
transectional analysis (concerning multi-slice coronary CT scan before GH
substitution) and as an effect of GH intervention.

Patients will be treated with recombinant GH (daily dosage titrated upon plasma
IGF-1 levels; adjusted for sex and age) in line with international consensus
guidelines (regular care)/treatment)

The efforts will consist of two additional visits in one year to the UMC
Utrecht to have a multi-slice coronary CT scan and a venous blood puncture. The
efforts are therefore reduced at a minimum level. The risks are quite
minimized because no experimental methods are used. All techniques are part of
daily patient care. An emotional burden may exist in the knowledge of
atherosclerotic burden. However, patients could indicate a "not want to know
teh results". On the other hand, a pronounced expression of atherosclerotic
disease could give rise to addional care with a focus on prevention of
cardiovascular morbidity (such as life style adaptation and reduction of
present cardiovascular risk factors)