Giovanni Acerbi

Microvascular density and vascular endothelial growth factor expression in normal pituitary tissue and pituitary adenomas

Microvessel density (MVD) represents a measure of angiogenesis and may be used as an indicator of neoplastic aggressiveness. Vascular endothelial growth factor (VEGF) plays a pivotal role as angiogenic promoter by stimulating endothelial cell proliferation and migration and enhancing vascular permeability. The aim of this study was to investigate MVD and VEGF expression in human pituitary adenomas and normal pituitary gland tissues by immunohistochemistry, and to correlate data with clinical characteristics. Fragments from 46 pituitary adenomas (18 non-functioning, 12 ACTH-secreting, 12 GH-secreting, 4 PRL-secreting) and 19 specimens of normal anterior pituitary gland obtained at surgery were evaluated. MVD in normal anterior pituitary was significantly higher than in tumors (69.2±28.5 vs 29.3±19.7; p<0.0001). Within adenomas, no difference was found in MVD when different histotype, size, sex, age, rate of recurrence or medical pre-surgical treatment were considered. The degree of vascularity was somewhat related only to clinical invasiveness, as evaluated by pre-surgical MRI grading (grade 0 p<0.05 vs grade 1 and vs grade 2). No statistically significant difference in VEGF expression was found between normal tissue and adenomas and among tumors of different histotype (p= 0.3978). Size, sex, age, rate of recurrence and medical pre-surgical treatment did not influence VEGF expression. No correlation was found between MVD and VEGF expression. In conclusion, MVD was reduced in pituitary adenomas with respect to normal gland. VEGF expression is however well preserved in adenomas and this might contribute to adequate tumoral vascular supply with complex mechanisms other than endothelial cells proliferation.

Prevalence of stroke and transient ischaemic attack in the elderly population of an Italian rural community

Objectives: To evaluate the prevalence of stroke and transient ischaemic attack in the elderly population, including the oldest residents, of a rural Italian community. Methods: A door-to-door survey was performed between April and October 2001 in 2390 subjects aged 65 years and over. A symptom questionnaire validated by medical records and neurological examination was employed. Results: Complete information was available for 2260 subjects. The overall prevalence of stroke was 8.2% in males and 5.1% in females. In the very elderly, this increased to 10.7% in males and 10% in females and decreased only in males aged 90 years or over. The overall prevalence of transient ischaemic attack was 7% in males and 4.9% in females. This, too, increased with age, reaching 10.2% in males and 7.4% in females and decreased only in subjects of both sexes aged 85 years or over. Conclusions: An actual estimate of the high prevalence of cerebrovascular disease in the elderly population, even in very old subjects, was thus achieved. Appropriate health care services consequently need to be planned.

Clinical aspects and therapeutic outcome in thyrotropin-secreting pituitary adenomas: a single center experience.

Background and aim: The management of pituitary adenomas secreting TSH has evolved considerably over the last decades. We report the clinical features, management, and outcome of a large monocentric series. Material and methods: A monocentric retrospective cohort of 26 patients admitted to our Department of Endocrinology between 1983 and 2007, followed for a period up to 204 months. The diagnosis of TSH-secreting adenoma was based on clinical and biochemical findings of central hyperthyroidism. Evaluation of basal and dynamic pituitary function, magnetic resonance imaging or computerized tomography scan were performed in all patients. Twenty-two patients, of whom 15 pre-treated by somatostatin analogs (SSA), underwent trans-sphenoidal surgery and were regularly re-evaluated. Results: The number of cases increased over the years. Age at diagnosis, micro- to macroadenoma ratio, and mean estimated latency between first symptoms and diagnosis did not appreciably change over time. Latency was significantly shorter in macroadenomas. Following surgery, 55% of patients obtained remission (success rate of 40 and 67% in macro- and microadenomas, respectively). SSA pre-treatment led to an apparent although not statistically-significant increase in success rate in micro- but not in macroadenomas. Conclusions: In a monocentric group of 26 TSH-secreting adenomas the high ratio between micro- and macroadenomas remained stable over time with a significantly shorter diagnosis latency in macroadenomas. A more precocious recognition of the tumors and possibly the use of presurgical SSA allowed a high remission rate. A varied combination of neurosurgery, SSA, radiotherapy, and thyroid ablation led to the control of the disease in all the patients studied.

Peroxisome proliferator-activated receptor (PPAR)γ is highly expressed in normal human pituitary gland

Objective: Expression of peroxisome proliferator-activated receptor (PPAR)γ in normal pituitary seems to be restricted to ACTH-secreting cells. The aim of the study was to evaluate the expression of PPARγ in normal human pituitary tissue and to study its localization in the pituitary secreting cells. Materials and methods: Normal pituitary tissue samples were obtained form 11 patients with non-secreting adenoma who underwent surgical excision of the tumor. Expression of PPAR? was evaluated by immunostaining and western blotting; localization of PPAR? in each pituitary secreting cell lineage was evaluated by double immunofluorescence using confocal microscopy. Pituitary non-functioning adenomas served as Controls. Results: PPARγ was highly expressed in all pituitary samples with a (mean±SD) 81±6.5% of stained cells; expression of PPARγ was confirmed by western blotting. Non-functioning pituitary adenomas had 74±11% PPAR? positive cells. Expression of PPARγ was either in cytoplasm or nuclei. In addition, treatment of GH3 cells, with a PPARγ ligand was associated with traslocation of the receptor from cytoplasm into the nucleus. Double immunostaining revealed that every pituitary secreting cell (GH, TSH, LH, FSH, PRL and ACTH) had PPARγ expressed. Discussion: The present study demonstrated that PPARγ is highly expressed in every normal pituitary secreting cell lineage. It can translocate into the nucleus by ligand binding; however, its role in pituitary hormone regulation remains to be elucidated.

Tumor Infiltrating Lymphocytes But Not Serum Pituitary Antibodies Are Associated with Poor Clinical Outcome after Surgery in Patients with Pituitary Adenoma

CONTEXT Serum pituitary antibodies (Pit Abs) and tumor-infiltrating lymphocytes (TILs) have been described in pituitary adenomas, but their clinical significance remains unknown. OBJECTIVE The objective of the study was to assess Pit Abs and TILs prevalence in pituitary adenomas and their influence on clinical outcome. DESIGN This was a prevalence case-control study. PATIENTS AND SETTING Two hundred ninety-one pituitary adenoma cases (110 non-secreting, 30 ACTH-69 GH-71 prolactin- and 13 TSH-secreting adenoma; 177 operated and 114 untreated), 409 healthy controls, and 14 autoimmune hypophysitis were enrolled in a tertiary referral center. INTERVENTION Pit Abs were measured using immunofluorescence in all cases and controls (n = 714). The presence of TILs was evaluated using CD45 staining in a subset of adenomas surgically treated (n = 72). MAIN OUTCOME MEASURE Clinical response of pituitary adenoma after surgery was evaluated. RESULTS Pit Abs prevalence was higher in adenomas (5.1%) than healthy subjects (0.7%, P < 0.0001) and lower than in autoimmune hypophysitis patients (57%, P < 0.0001). Similarly, TILs prevalence was higher in adenomas than normal pituitary (P = 0.01) and lower than in autoimmune hypophysitis (P < 0.0001). No correlation between Pit Abs and TILs was found (P = 0.78). A poor clinical outcome was more common in adenoma patients with TILs (11 of 18, 61%) than in those without (17 of 54, 31%, P = 0.026). Multivariate regression analysis identified the presence of TILs as independent prognostic factor for persistence/recurrence of pituitary adenoma. CONCLUSIONS TILs and Pit Abs are present in a significant number of pituitary adenoma patients. Cell-mediated immunity appears to be predictive of a less favorable clinical outcome.

Spontaneous arteriovenous fistula of the vertebral artery. Three case reports.

Three cases of spontaneous arteriovenous fistulas of the vertebral artery (VAF) are reported. In one case the only symptom was a cervical bruit; in the other two cases, symptoms of multiple cervical radiculopathy were also observed. Definitive diagnostic findings were obtained by Doppler ultrasonography, computed tomography, magnetic resonance imaging, and angiography. Clinical signs of radiculopathy disappeared after endovascular balloon occlusion of the fistula, in about 1 month. In one case the vertebral artery was occluded without clinical consequences.

Microcirculatory Effects of Viatromb® Spray Gel Heparin in Chronic Venous Insufficiency: Evaluation of TcPO2 and PCO2—A Product Evaluation Study

The evolution of microcirculatory methods and the definition of the concept of venous microangiopathy allow the study in a quantitative way of microcirculatory changes produced by pharmacologic treatments at the areas most frequently and severely affected by chronic venous insufficiency (CVI), venous hypertensive microangiopathy, and venous ulcerations. This pilot study compares subjects with CVI, in the area most affected by venous hypertension in a 2-week registry. Elastic compression, compression plus Viatromb® (lyposomal spray gel heparin), Lioton® (gel including heparin), and Viatromb® alone were compared. Subjects were evaluated for laser Doppler flux, transcutaneous partial pressure of oxygen (TcPO2), and partial pressure of carbon dioxide (PCO2) and CVI analogic symptom scale. In the Viatromb® groups (B and D), significant decreases in laser Doppler flux, PCO2, and CVI score were observed. The decrease was proportionally more important in the elastic compression plus Viatromb ® group. Partial pressure of oxygen (PO2) was significantly increased. No significant changes were observed in the Lioton® group. There was a good effect for compression only. These differences are significant, as they can be observed even in small groups (10-15 patients). No treatment side effects were observed, and compliance and tolerability were very good.

Undetectable inferior petrosal sinus levels of PTH-related peptide (PTHrP) in patients with ACTH-dependent Cushing's disease

PTH-related peptide (PTHrP), a member of the PTH family, is widely expressed in foetal and adult tissues, and it has been found in benign and malignant tumors, including GH and PRL-secreting adenomas. Conflicting data are reported in literature on serum PTHrP concentrations in patients with Cushing’s disease. The aim of the present study was to further evaluate peripheral and inferior petrosal sinus (IPS) serum PTHrP concentrations before and after CRH, in a group of consecutive patients with ACTH-dependent Cushing’s disease. Nine patients with active ACTH-dependent Cushing’s disease (8 women and 1 man, age±SD 41±13 yr) were submitted to peripheral and IPS sampling under fluoroscopic control before and after iv administration of CRH. All patients were subsequently submitted to transsphenoidal surgery and an ACTH-secreting microadenoma was found in all cases. In all patients, serum IPS and peripheral ACTH measurement were in keeping with the diagnosis of ACTH-dependent Cushing’s disease. Serum PTHrP concentrations before and after CRH stimulation were below the sensitivity limit of the assay in all samples, and no gradient between IPS and peripheral sampling was observed. Our data, combined with others reported in literature, indicate that PTHrP release by ACTH-secreting tumors is not a common occurrence. Therefore, we conclude that IPS and peripheral PTHrP are of little clinical usefulness.