Growth hormone deficiency in patients in long-term remission of adrenal Cushing's syndrome

Several studies have demonstrated impaired growth hormone (GH) secretion as
well as absent or blunted GH response to stimuli in patients with active
Cushing*s syndrome. Although the exact pathophysiology of this effect is not
fully understood, it has been postulated that prolonged exposure to
supraphysiological levels of cortisol is the major cause of this abnormality.
Following cure of Cushing*s syndrome and thus resolution of hypercortisolism,
recovery of GH secretory status is often seen, but certainly not in all
patients. Because most patients with CS have Cushing*s disease caused by a
pituitary adenoma it is thought that damage of the pituitary gland by surgery
of radiotherapy is the cause of this lasting GH deficiency. However, lasting GH
deficiency after treatment of adrenal CS has also been reported in one small
study (Tzanela et al 2003). Recently we observed unexpected low insulin growth
factor type-1 levels in our patients that have been treated for adrenal CS in
the past. We therefore hypothesize that GH deficiency in patients that are in
remission of CS may be a remaining effect of the supraphysiological levels of
cortisol that they were exposed to for a substantial period.
To examine this hypothesis we plan to assess the GH response to an insulin
tolerance test (ITT) or an Arginine/GHRHtest in patients who are in long-term
remission of Cushing*s syndrome due to adrenal adenoma. In this group of
patients, GH deficiency cannot be explained by pituitary damage due to surgery,
radiotherapy or a pituitary adenoma in situ.

To assess the presence of GH deficiency in patients who are in long-term
remission of Cushing*s syndrome due to adrenal adenoma.

Observational pilot study in which 16 patients who are in remission of
Cushing*s syndrome due to adrenal adenoma will be included.
They will undergo an ITT or an Arginine/GHRH test if there are
contra-indications for the first.

Following venapuncture a local haematoma can occur. During the ITT
hypoglycaemia is induced which may cause the following side-effects; sweating,
palpitations, and rarely convulsions and even of loss of consciousness due to
severe hypoglycemia. The glucose level in the blood as well as the wellbeing of
the patient will be monitored closely. A physician and a nurse will be present
during the test. Beside the patient*s bed a vial of glucose 50% will be ready
for use. It will be administered intravenously if the patient is showing signs
of impaired consciousness.
During the Arginine/GHRH test the administration of the Arginine can cause a
warm feeling. Very rarely an anaphylactic reaction can occur. All drugs to
treat this reaction will be available in the testingroom. Both the ITT and the
Arginine/GHRH test are well validated tests to investigate GH-response and are
used frequently in normal clinical practice.
This patientgroup could benefit from undergoing this test. Nowadays there is a
treatment for patients with GH deficiency.