Search

Background:Pituitary tumors account for approximately 10–15% of intracranial neoplasms. Aim:Using the cDNA microarray method, we have previously compared expression under two distinct conditions: a pool of 4 clinically non-functioning pituitary adenomas (NFPA) and a spinal cord metastasis of a non-functioning pituitary carcinoma, in order to gain biological insights into genomic changes of pituitary neoplasias. In the present study, we further investigated the mRNA expression of 3 selected genes previously described as being involved in other neoplasias based on a series of 60 pituitary adenomas: CRABP1(cellular retinoic acid binding protein 1), GRP (gastrin-releasing peptide), and RERG (Ras-related, estrogen-regulated, growth inhibitor). Material and methods:The expression of CRABP1, GRP, and RERG was determined by quantitative RT-PCR. Results:A significantly higher content of CRABP1mRNA was observed in NFPA compared to functioning adenomas, and PRL-secreting adenomas showed a lower expression of this gene compared to normal pituitary. A lower expression of GRP mRNA was detected in NFPA compared to normal pituitary and also to functioning adenomas. RERG mRNA was overexpressed in NFPA in comparison to functioning adenomas and to normal pituitary. Among the functioning adenomas, only the ACTH-secreting adenomas presented a higher expression of RERG mRNA compared to normal pituitary. Conclusions:The findings of differential expression of CRABP1in prolactinomas and of RERG in NFPA compared to normal pituitary suggests that retinoic acid and estrogen receptor, respectively, could be involved in the tumorigenesis of these adenomas subtypes. Additional studies are required to further confirm this hypothesis.

GH secretagogues (GHS) have been used for the differential diagnosis of ACTH-dependent Cushing’s syndrome (CS) since 1997 due to their ability to increase ACTH and cortisol levels in Cushing’s disease. The aim of this study was to correlate ACTH response to GH-releasing peptide-6 (GHRP-6) in vivowith GH secretagogue receptor type 1a (GHSR-1a) mRNA expression in a patient with lung carcinoid tumor. The patient was a 26-yr-old male with diagnosis of ACTH-dependent CS. He presented negative responses to human CRH and desmopressin tests; yet, a significant increase in ACTH after the GHRP-6 test was observed. Sellar magnetic resonance imaging (MRI) showed slight posterior hypointensity, but bilateral petrosal sinus sampling did not show central gradient. Computed tomography (CT) and MRI of thorax/abdomen/cervical were negative and 111In-pentetreotide scintigraphy depicted abnormal uptake on the right lung. The patient was submitted to right thoracotomy for exeresis of lung nodule and hilar lymph node which were characterized as atypical lung carcinoid tumor and he presented clinical and laboratorial remission after surgery. GHSR-1 a mRNA expression was studied with real-time quantitative PCR and tumor data were compared with fragments of normal lung and pituitary. There was a higher GHSR-1 a expression in the lung carcinoid tumor as compared with normal tissues. The ACTH response to GHRP-6 in a patient with ectopic ACTH production by a lung carcinoid tumor was associated with GHSR-1a expression in the tumor tissue, suggesting an association between GHSR-1a mRNA overexpression and the in vivoresponse to GHS.

Diagnostic strategies, malignancy predictors and long-term survival were retrospectively evaluated in patients with hyperinsulinemic hypoglycemia (64 insulinomas). Lower median glycemia was 30 (range 20–53) mg/dl [1.6 (1.1–2.9) mmol/l] with concurrent insulin of 48 (13.2–217) μU/ml and 15 (2–46) μU/ml measured by radioimmunoassay (RIA) and immunofluorimetric assay (IFMA), respectively. All patients with insulinomas had a positive prolonged fast within 48 h. Sensitivity of localization methods was: ultrasonography (US) 23%, computed tomography (CT) 28%, magnetic resonance imaging (MRI) 65%, endoscopic US 75%, arteriography 38%, portal venous sampling 67%, selective arterial calcium stimulation 67%, intraoperative US 94% and palpation 92%. Nine patients (14%) had malignant insulinomas. Age at diagnosis (mean±SD, 53.8±19 vs 39.4±16.3 yr; p=0.03), insulin (1372±730 vs 785±659% (percentage of the method’s diagnostic cut-off; 6 and 3 μU/ml for RIA and IFMA, respectively; p=0.007) and C-peptide levels (9.8±2.9 vs 3.9±2.8 ng/ml (3.2±0.9 vs 1.3±0.9 nmol/l; p=0.006), and tumor size (6.2±4.1 vs 1.5±0.6 cm; p=0.0002) were increased in malignant insulinomas. C-peptide level above 6.1 ng/ml (2.0 nmol/l) had a 100% sensitivity and 96% specificity, and tumor size above 2.6 cm yielded a sensitivity of 88% and specificity of 100% in predicting malignancy. Survival of patients with malignant insulinomas was significantly impaired (16 vs 100% at 5 yr; p=0.0000001). The diagnosis of insulinoma can be made within 48 h of fasting. The association between intraoperative US and palpation evidenced the tumor in 95% of the patients. C-peptide and tumor size were reliable malignancy predictors.