Massimo Giovanelli

Early results of surgery in patients with nonfunctioning pituitary adenoma and analysis of the risk of tumor recurrence

OBJECT Nonfunctioning pituitary adenomas (NFPAs) are benign tumors of the pituitary gland that typically cause visual and/or hormonal dysfunction. Surgery is the treatment of choice, but patients remain at risk for tumor recurrence for several years afterwards. The authors evaluate the early results of surgery and the long-term risk of tumor recurrence in patients with NFPAs. METHODS Between 1990 and 2005, 491 previously untreated patients with NFPA underwent surgery at the Università Vita-Salute. Determinations of recurrence or growth of the residual tumor tissue during the follow-up period were based on neuroradiological criteria. RESULTS Residual tumor after surgery was detected in 173 patients (36.4%). Multivariate analysis showed that invasion of the cavernous sinus, maximum tumor diameter, and absence of tumor apoplexy were associated with an unfavorable surgical outcome. At least 2 sets of follow-up neuroimaging studies were obtained in 436 patients (median follow-up 53 months). Tumors recurred in 83 patients (19.0%). When tumor removal appeared complete, younger age at surgery was associated with a risk of tumor recurrence. In patients with incomplete tumor removal, adjunctive postoperative radiotherapy had a marked protective effect against growth of residual tumor. CONCLUSIONS Complete surgical removal of NFPAs can be safely achieved in > 50% of cases. Visual symptoms and, less frequently, pituitary function may improve after surgery. However, tumor can recur in patients after apparently complete surgical removal. In patients with incomplete tumor removal, radiation therapy is the most effective adjuvant therapy for preventing residual tumor growth.

Radiosurgery and the prevention of regrowth of incompletely removed nonfunctioning pituitary adenomas

OBJECT The authors studied the efficacy of gamma knife radiosurgery (GKS) in the prevention of regrowth of nonfunctioning pituitary adenomas (NPA). METHODS One hundred nineteen patients were included in this study and were divided into two groups. All patients had undergone surgery in our department and recurrent or residual adenoma was demonstrated on postoperative MR imaging. Group A consisted of 68 patients who were followed without additional treatment. Group B was composed of 51 patients who received GKS within 1 year after microsurgery. There was no significant demographic difference between the two groups. In Group B the mean margin dose was 16.5 ± 0.3 Gy (range 13-21 Gy). Fifty one and one tenth percent of patients in Group A were recurrence free at 5 years and 89.8% in Group B (p < 0.001). In Group B patients, tumor volume decreased from a baseline value of 2.4 ± 0.2 cm3 to 1.6 ± 0.2 cm3 at last follow up (p < 0.001). CONCLUSIONS The results of this study suggest that GKS is effective in controlling growth of residual NPA for at least 5 years following initial maximal surgical debulking compared with no radiation therapy. Thus, GKS is recommended after microsurgery when visible tumor can be detected on imaging studies.

Correlation between clinical characteristics and proliferative activity in patients with craniopharyngioma

Objectives: The aim of the study was to correlate the Ki-67 and cyclin A labelling index (LI) with clinical characteristics and risk of recurrence of craniopharyngiomas. Methods: 47 consecutive patients were studied, 21 female and 26 male, aged 34.3 (2.8) years. Immunohistochemical analysis was performed on paraffin wax embedded material using monoclonal antibodies directed against the proliferation associated nuclear antigen Ki-67 and cyclin A. Results: The median Ki-67 LI was 8.6% (interquartile range, 4.4%–14.0%). Ki-67 LI was significantly higher in tumours with a heavy inflammatory reaction and diabetes insipidus at presentation, whereas other clinical and histological features were not associated with the proliferation index. There was a strong linear correlation between Ki-67 LI and cyclin A LI (r = 0.77; p<0.0001); therefore, cyclin A LI showed the same clinical and histological relations described for Ki-67 LI. Recurrence of craniopharyngioma occurred in 13 of 46 patients (28.3%). The median Ki-67 LI in the 13 recurrent craniopharyngiomas (9.0%) was not significantly different from that of non-recurring tumours (7.9%). Cyclin A LI was also not associated with the risk of relapse. Conclusions: This study confirms the great variability of proliferative activity in craniopharyngiomas. Ki-67 and cyclin A LIs were associated with the presence of a heavy inflammatory reaction and diabetes insipidus, but did not correlate with the long term risk of tumour regrowth.

Coexistence of TSH-secreting pituitary adenoma and autoimmune hypothyroidism

Objective: TSH-secreting pituitary adenomas account for about 1–2% of all pituitary adenomas. Their diagnosis may be very difficult when coexistence of other diseases masquerades the clinical and biochemical manifestations of TSH-hypersecretion. Clinical presentation: A 41-yr-old female patient, weighing 56 kg, was referred for evaluation of an intra- and suprasellar mass causing menstrual irregularities. Eight yr before, the patient had been given a diagnosis of subclinical autoimmune hypothyroidism because of slightly elevated TSH levels and low-normal free T4 (FT4). Menses were normal. Despite increasing doses of levo-T4 (L-T4; up to 125 µg/day), TSH levels remained elevated and the patient developed mild symptoms of hyperthyroidism. After 7 yr, the menstrual cycle ceased. Gonadotropins were normal, whereas PRL level was elevated at 70 µg/l and magnetic resonance imaging (MRI) of the hypothalamic-pituitary region revealed a pituitary lesion with slight suprasellar extension. The tumor was surgically removed and histological examinations revealed a pituitary adenoma strongly positive for TSH. Three months after surgery the patient was well while receiving L-T4 75 µg/day and normal menses had resumed. MRI of the hypothalamic-pituitary region showed no evidence of residual tumor. At the last follow-up, 16 months after surgery, serum TSH, free T3 (FT3), and FT4 levels were normal. Conclusions: Coexistence of autoimmune hypothyroidism and TSH-secreting pituitary adenoma may cause further delays in the diagnosis of the latter. In patients with autoimmune hypothyroidism, one should be aware of the possible presence of a TSH-secreting pituitary adenoma when TSH levels do not adequately suppress in the face of high doses of L-T4 replacement therapy and elevated serum thyroid hormone levels.

Stereotactic drainage and Gamma Knife radiosurgery of cystic brain metastasis

OBJECT Treatment options for patients with brain metastasis include tumor resection, whole-brain radiation therapy, and radiosurgery. A single treatment is not useful in cases of multiple tumors, of which at least 1 is a cystic tumor. The purpose of this study was to assess the role of stereotactic drainage and Gamma Knife surgery (GKS) in the treatment of cystic brain metastasis. METHODS Between January 2001 and November 2005, 680 consecutive patients with brain metastases underwent GKS at our hospital, 30 of whom were included in this study (18 males and 12 females, mean age 60.6 +/- 11 years, range 38-75 years). Inclusion criteria were: 1) no prior whole-brain radiation therapy or resection procedure; 2) a maximum of 4 lesions on preoperative MR imaging; 3) at least 1 cystic lesion; 4) a Karnofsky Performance Scale score >or= 70; and 5) histological diagnosis of a malignant tumor. RESULTS Non-small cell lung carcinoma was the primary cancer in most patients (19 patients [63.3%]). A single metastasis was present in 13 patients (43.3%). There was a total of 81 tumors, 33 of which were cystic. Ten patients (33.3%) were in recursive partitioning analysis Class I, and 20 (66.6%) were in Class II. Before drainage the mean tumor volume was 21.8 ml (range 3.8-68 ml); before GKS the mean tumor volume was 10.1 ml (range 1.2-32 ml). The mean prescription dose to the tumor margin was 19.5 Gy (range 12-25 Gy). Overall median patient survival was 15 months. The 1- and 2-year survival rates were 54.7% (95% confidence interval 45.3-64.1%) and 34.2% (95% confidence interval 23.1-45.3%). Local tumor control was achieved in 91.3% of the patients. CONCLUSIONS The results of this study support the use of a multiple stereotactic approach in cases of multiple and cystic brain metastasis.

Increased insulin-stimulated endothelin-1 release is a distinct vascular phenotype distinguishing Cushing's disease from metabolic syndrome

Objective  Although much is known about the anti‐inflammatory effects of an acute corticosteroid therapy, little is known about the effects on chronic hypercortisolism on endothelial dysfunction and proinflammatory alterations in patients with Cushings disease (CD).

Acute effects of a single administration of dexamethasone on basal and growth hormone‐releasing hormone stimulated GH secretion in acromegaly

A single administration of dexamethasone causes both an early stimulatory and a late inhibitory effect on GH secretion in normal subjects.