Effects of growth hormone (GH) replacement therapy in GH deficient adult childhood cancer survivors on organ size and microvascularisation of kidney and skin.

Survival of children treated for brain tumors has improved dramatically in the
last decades. This is a result of improved neurosurgical techniques,
radiotherapy and chemotherapy. However, this success is accompanied by some
serious late effects of both disease and treatment. One of the late effects of
radiotherapy invariably is growth hormone deficiency (GHD). The radiation
effects are dose and time dependent. GHD is always seen within 2 years after a
radiation dose of > 35 Gy at the pituitary-hypothalamic region. With radiation
doses of 27-35 Gy approximately 50% will develop GHD within 2 years. However,
the other 50% will develop GHD several years later. At this point adulthood may
already been reached.
GHD results during childhood in attenuated growth. When the final height has
not been reached, delayed growth is the most important clue to GHD. This clue
disappeares when GHD becomes apparent only during adolescence or adulthood. GHD
also leads to adverse metabolic effects like a reduced peak bone mass and
dyslipidemia with central obesity.
It is unknown if and how GH contributes to the development of organs and
microcirculation during normal growth. This is important to know because
microcirculation is critical for normal organ function. In view of their age
and their life expectancy it is important to optimize normal organ size and
function.

The primary objective is to study the effects of GH substitution therapy in
adult GH deficient survivors of childhood cancer.
Primary endpoints are organ size, renal function and capillary density of the
skin.

50 patients with GHD as a late consequence of radiotherapy for childhood cancer
will be asked to participate in this study. Regular care involves growth
hormone substitution therapy for these patients. In order to describe the
effects of growth hormone therapy, at baseline (before start GH) and after one
year of GH treatment visceral organ size (especially kidney size) will be
determined by means of CT scan. In addition, renal function (GFR and ERPF) and
capillary density of the skin will be measured.

1 year of growth hormone substitution therapy.

The nature and extent of the burden consists of two one-day visits to the
day-care centre for determination of the FGR and ERPF. For this test an i.v.
drip with light radioactive fluid will be inserted. To prevend the uptake of
the radioactive fluid in the thyroid gland, the patient will drink a mixture of
10 drops of iodine and orange juice. Bloodpressure and pulse will be checked
during the examination, 5 times blood will be drawn (80 mL) and the patient has
to produce urine on 3 separate occasions during this test. After this test
capillary microscopy is performed by looking at the nail under the microscope.
This is a non invasive procedure with a duration of approximately 10 minutes.
In addition a CT scan is performed of the abdomen. All these tests are
incorporated in normal clinical care and no associated side effects are to be
expected.
Several questionaires on health, general wellbeing and cognition will be
answered.

These tests are repeated after one year of growth hormone substitution therapy.

During the treatment year 2 visits to our outpatient clinic will be scheduled.
In addition, on 5 occasions 10 mL of blood will be drawn. Results be be
discussed in another 3 telephone calls.