At admission, every patient had a medical interview and underwent a physical examination. Blood samples of all patients were taken after overnight fasting. IGF-1 and GH were measured. According to guidelines, nadir GH in the oral glucose tolerance test was measured in all non-diabetic patients. In patients with diabetes mellitus and in those, who had already been treated with somatostatin analogues, random GH was calculated as an arithmetic mean of five measurements of blood samples obtained every 30 min. MRI scan of the pituitary gland was also performed routinely in all patients with acromegaly unless there were no contraindications. Treatment naïve acromegaly was diagnosed when all of the following criteria were fulfilled:

IGF-1 elevated above the age-adjusted upper norm limit

Lack of suppression of GH below 1 ng/mL in 75 g oral glucose tolerance test (patients without diabetes) or random GH levels above 2.5 ng/mL (patients with diabetes)

A pituitary gland tumour visualised in magnetic resonance imaging (MRI) or computed tomography (CT) (in patients with contraindications for MRI).

Previously treated patients who achieved age-normalisation of IGF-1 and normalisation of GH (GH < 1 ng/mL in 75 g OGTT or random GH < 2.5 ng/mL in diabetic patients) were classified as a stable/controlled group. Acromegaly was considered active/uncontrolled (non-remission group) when IGF-1 and GH were elevated in patients who had already been treated. Patients who could not be classified according to the above-mentioned criteria were excluded from the analysis. Tumour invasiveness was defined as the infiltration of surrounding tissues.
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