Antonio Bianchi

Spedali Civili di Brescia, Brescia, Lombardy, Italy

Are you Antonio Bianchi?

Claim your profile

Publications (86)271.67 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Background and Objective: In 2004, the WHO defined atypical pituitary adenomas those with Ki-67 >3%, excessive p53 expression and increased mitotic activity. As the usefulness of this classification is controversial, we reviewed our typical and atypical pituitary adenomas (TPAs and APAs) to compare the clinical and prognostic features. Patients and Methods: We retrospectively reviewed 343 consecutive pituitary adenomas. APAs represented 18.7% of cases. All patients were operated on in the Department of Neurosurgery at our institution and followed up at the Hypothalamic-Pituitary Disease Unit of the same institution. Median follow-up time was 75 months (range: 7-345 months). Results: Younger age at diagnosis, ACTH- and PRL- immunohistochemical positivity correlated to higher risk of APAs, while TPAs and APAs did not differ for gender, tumor size and recurrence risk and disease-free survival time (DFST). Among the 219 patients that underwent radical surgery, Ki-67 expression≥1.5% was associated to a higher risk of recurrence and to a worse DFST, even after correction for age at diagnosis, gender, immunohystochemical classification, tumor size, invasiveness and Knosp classification (p = 0.01; HR: 2.572; 95% CI: 1.251-5.285). PAs with Ki-67 > 1.5% showed a worse DFST as compared to PAs with Ki-67 < 1.5% (HR: 2.166; 95% CI: 1.154-4.064). Conclusion: In this series, APAs and TPAs didn't differ for recurrence and DFST. PAs with Ki-67≥1.5% showed a higher recurrence risk and a worse DFST as compared to PAs with Ki-67 < 1.5%. We suggest that a Ki-67≥1.5% may be useful as prognostic marker, though this will need to be confirmed by prospective, multi-centre data. © 2015 S. Karger AG, Basel.
    Neuroendocrinology 01/2015; · 4.93 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In this study, we aimed at evaluating the association between radiological vertebral fractures and levo-thyroxine (l-T4) replacement doses in adult patients with hypopituitarism.
    European Journal of Endocrinology 06/2014; 170(6):893-9. · 3.69 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective: Acromegaly is associated with an increased prevalence of vertebral fractures (VFs) in close relationship with growth hormone (GH) hypersecretion. Two isoforms of the GH receptor have been identified; the two isoforms differ by the expression or not of the protein fragment encoded by exon 3 of the GHR gene. Deletion of the exon 3 may influence functional properties of the GHR and affect fracture risk in acromegalic patients. Design: A cross-sectional study was designed to investigate the association between the d3-GH receptor isoform and the prevalence of VFs in patients with acromegaly. Methods: We studied 109 acromegalic patients (M/F: 48/61); 73 with controlled/cured acromegaly and 36 with active disease. GHR genotype was assessed in each patient. All patients were evaluated for VFs and bone mineral density (BMD) at lumbar spine and hip. Serum IGF1 levels and bone metabolism markers were measured. A multivariate analysis was performed to establish risk factors for VFs in our population. Results: d3-GHR carriers showed increased prevalence of VFs than patients expressing full length GHR (35/55 vs 12/54; p < 0.001). The association between GHR deletion and VFs was demonstrated both in patients with active and with controlled/cured disease. In 35 patients prospectively evaluated, 13 (37.1%) developed incident VFs. The incidence of VFs was significantly higher in patients harbouring GHR deletion as compared in those with fl gene (p = 0.04). In multivariate analysis, male sex (OR 3.250, p = 0.041), IGF-1 levels (OR 1.183, p = 0.031), length of active diseases (OR 1.038, p = 0.001) and d3-GHR genotype (OR 3.060, p = 0.015), were all confirmed as risk factors of VFs in our population. Conclusions: This study suggests for the first time that exon 3 deletion of GHR may predispose patients with active and controlled acromegaly to higher risk of VFs.
    European Journal of Endocrinology 05/2014; · 3.69 Impact Factor
  • Endocrine Abstracts. 04/2014;
  • Endocrine 04/2014; · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Ki-67 Labeling Index is an immunocytochemical marker of cell proliferation. The correlation of Ki-67 expression with pituitary adenomas recurrence has been investigated and is highly debated. Aim of this study was to evaluate whether Ki-67 correlates with recurrence even in patients with an apparently completely removed pituitary adenoma. We retrospectively reviewed the database of the Hypothalamic-Pituitary Disease Unit at the Catholic University of Rome, collected between 2003 and 2011. Inclusion criteria were: patients who underwent surgery at the Department of Neurosurgery with an apparently complete removal of a pituitary adenoma; Ki-67 histological evaluation by the same operator and values of <3 %. All patients underwent endocrine evaluation of the hypothalamic-pituitary function, ophthalmologic and neuro-radiological examinations, during the preoperative period and follow-up. Out of 490 patients recorded on the database of the Hypothalamic-Pituitary Disease Unit at the Catholic University of Rome, 191 cases met the inclusion criteria. Recurrence was observed in 49 cases (25.7 % of the patients who had undergone radical excision). Optional cut-off value was identified at Ki-67 values of 1.50 %. This was associated with worse disease-free survival time, even after correction for age at treatment, gender, positivity to p53, functional classification and Knosp grading. Ki-67 labeling index may be useful in postoperative management, even in patients who underwent radical PA removal. We suggest a Ki-67 cut-off value of 1.5 % to plan an adequate clinical follow-up.
    Pituitary 07/2013; · 2.22 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Pegvisomant (PEGV) is widely used, alone or with somatostatin analogs (SSA), for GH-secreting pituitary tumors poorly controlled by SSAs alone. No information is available on specific indications for or relative efficacies of PEGV + SSA versus PEGV monotherapy. Aim of our study was to characterize real-life clinical use of PEGV vs. PEGV + SSA for SSA-resistant acromegaly (patient selection, long-term outcomes, adverse event rates, doses required to achieve control). A retrospective analysis of data collected in 2005--2010 in five hospital-based endocrinology centers in Rome was performed. Sixty-two adult acromegaly patients treated >=6 months with PEGV (Group 1, n = 35) or PEGV + SSA (Group 2, n = 27) after unsuccessful maximal-dose SSA monotherapy (>=12 months) were enroled. Groups were compared in terms of clinical/biochemical characteristics at diagnosis and before PEGV or PEGV + SSA was started (baseline) and end-of-follow-up outcomes (IGF-I levels, adverse event rates, final PEGV doses). Group 2 showed higher IGF-I and GH levels and sleep apnea rates, higher rates residual tumor tissue at baseline, more substantial responses to SSA monotherapy and worse outcomes (IGF-I normalization rates, final IGF-I levels). Tumor growth and hepatotoxicity events were rare in both groups. Final daily PEGV doses were similar and significantly increased with treatment duration in both groups. PEGV and PEGV + SSA are safe, effective solutions for managing SSA-refractory acromegaly. PEGV + SSA tends to be used for more aggressive disease associated with detectable tumor tissue. With both regimens, ongoing monitoring of responses is important since PEGV doses needed to maintain IGF-I control are likely to increase over time.
    Journal of Experimental & Clinical Cancer Research 06/2013; 32(1):40. · 3.27 Impact Factor
    This article is viewable in ResearchGate's enriched format
  • [Show abstract] [Hide abstract]
    ABSTRACT: Context.Cross-sectional studies showed an elevated prevalence of vertebral fractures in acromegaly. However, no data are available on incident vertebral fractures in this clinical setting.Objective.To investigate the incidence and risk factors of vertebral fractures in patients with acromegaly.Design.Three-year prospective study.Setting.Referral centers.Subjects.88 patients with acromegaly (33 females, 55 males; mean age 50, range 21-88) and 106 control subjects, matched for sex and age (43 females and 63 males, mean age 55 years, range: 33-79), attending out-patient bone clinics.Main Measures.Patients and control subjects were evaluated for incidence of vertebral fractures using a quantitative morphometric approach on spine X-ray, which was performed at baseline and after 3 years of follow-up. At the same time-points, patients with acromegaly were also evaluated for bone mineral density (BMD) with DXA at lumbar spine and femoral neck.Results.After 3-year follow-up, 37 patients with acromegaly (42.0%) and 4 control subjects (3.8%) experienced incident vertebral fractures (p<0.001). The incidence of vertebral fractures was significantly higher in patients with active disease as compared to those who had controlled/cured acromegaly at the study entry (62.5% vs. 25.0%; p<0.001). Risk of incident vertebral fractures was significantly associated with hypogonadism, change in femoral neck BMD and prevalent vertebral fractures at the study entry only in patients with controlled/cured acromegaly, whereas in patients with active disease the fracture risk was not influenced by the above clinical factors but it was significantly associated with duration of active acromegaly.Conclusions.This prospective study demonstrates an high rate of incident vertebral fractures both in patients with active and controlled acromegaly.
    The Journal of Clinical Endocrinology and Metabolism 06/2013; · 6.31 Impact Factor
  • Source
    Nuclear Medicine and Molecular Imaging. 06/2013;
  • [Show abstract] [Hide abstract]
    ABSTRACT: To report an unusual case of biopsy-proven autoimmune hypophysitis with predominant hypothalamic involvement associated with empty sella, panhypopituitarism, visual disturbances and antipituitary antibodies positivity. We present the history, physical findings, hormonal assay results, imaging, surgical findings and pathology at presentation, together with a 2-year follow-up. A literature review on the hypothalamic involvement of autoimmune hypophysitis with empty sella was performed. A 48-year-old woman presented with polyuria, polydipsia, asthenia, diarrhea and vomiting. The magnetic resonance imaging (MRI) revealed a clear suprasellar (hypothalamic) mass, while the pituitary gland appeared atrophic. Hormonal testing showed panhypopituitarism and hyperprolactinemia; visual field examination was normal. Pituitary serum antibodies were positive. Two months later an MRI documented a mild increase of the lesion. The patient underwent biopsy of the lesion via a transsphenoidal approach. Histological diagnosis was lymphocytic "hypothalamitis". Despite 6 months of corticosteroid therapy, the patient developed bitemporal hemianopia and blurred vision, without radiological evidence of chiasm compression, suggesting autoimmune optic neuritis with uveitis. Immunosuppressive treatment with azathioprine was then instituted. Two months later, an MRI documented a striking reduction of the hypothalamic lesion and visual field examination showed a significant improvement. The lesion is stable at the 2-year follow-up. For the first time we demonstrated that "hypothalamitis" might be the possible evolution of an autoimmune hypophysitis, resulting in pituitary atrophy, secondary empty sella and panhypopituitarism. Although steroid treatment is advisable as a first line therapy, immunosuppressive therapy with azathioprine might be necessary to achieve disease control.
    Pituitary 05/2013; · 2.22 Impact Factor
  • Endocrine Abstracts. 03/2013;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Double pituitary adenomas represent up to 2.6 % of pituitary adenomas in large surgical series and up to 3.3 % of patients with Cushing's disease have been found to have double or multiple pituitary adenomas. We report the case of a 60-year-old male patient whose medical history began in 2002 with erectile dysfunction; hyperprolactinemia was found and MRI showed a 6-mm area of delayed enhancement in the lateral portion of the right pituitary lobe. Treatment with cabergoline was started with normalization of prolactin levels; the following MRI, performed in 2005 and 2008, showed shrinkage of the pituitary lesion. In 2005, the patient began to manifest weight gain, hypertension, and facial plethora, but no further evaluations were done. In January 2010, the patient came to our attention and underwent multiple tests that suggested Cushing's disease. A new MRI was negative. Bilateral inferior petrosal sinus sampling showed significant pituitary-to-peripheral ratio and, in May 2010, the patient underwent exploratory pituitary surgery with evidence of a 1-2-mm white-coloured midline area compatible with pituitary adenoma that was surgically removed. Post-operatively, the patient's clinical conditions improved with onset of secondary hypoadrenalism. The histologic examination confirmed a pituitary adenoma (immunostaining was found to be positive for ACTH and negative for prolactin). We report the case of an ACTH-producing microadenoma metachronous to a prolactin secreting microadenoma although not confirmed histologically, shrunk by medical treatment. A review of data in the literature regarding double or multiple pituitary adenomas has also been done.
    Endocrine 01/2013; · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Preoperative determination of Ki-67 expression, an important prognostic factor for grading nonfunctioning pancreatic endocrine tumors (NF-PETs), remains an important clinical challenge. To prospectively evaluate the feasibility, yield, and clinical impact of EUS-guided fine-needle tissue acquisition (EUS-FNTA) with a large-gauge needle to obtain tissue samples for histologic diagnosis and Ki-67 analysis in patients with suspected NF-PETs. Prospective cohort study. Tertiary-care academic medical center. Consecutive patients with a single pancreatic lesion suspicious for NF-PET on imaging. EUS-FNTA with a 19-gauge needle. Feasibility and yield of EUS-FNTA for diagnosis and Ki-67 expression determination. Thirty patients (mean [± SD] age 55.7 ± 14.9 years), with a mean (± SD) lesion size of 16.9 ± 6.1 mm were enrolled. EUS-FNTA was successfully performed without complications in all patients, with a mean (± SD) of 2.7 ± 0.5 passes per patient. Adequate samples for histologic examination were obtained in 28 of the 30 patients (93.3%). Ki-67 determination could be performed in 26 of these 28 patients (92.9%, 86.6% overall), 12 of whom underwent surgical resection. Preoperative and postoperative Ki-67 proliferation indexes were concordant in 10 patients (83.3%), whereas 2 patients were upstaged from G1 to G2 or downstaged from G2 to G1, respectively. Single center study with a single operator. In patients with suspected nonfunctioning low-grade to intermediate-grade pancreatic neuroendocrine tumors (p-NETs), retrieval of tissue specimens with EUS-FNTA by using a 19-gauge needle is safe, feasible, and highly accurate for both diagnosis and Ki-67 determination. A Ki-67 proliferative index acquired through this technique might be of great help for further therapeutic decisions.
    Gastrointestinal endoscopy 09/2012; 76(3):570-7. · 4.90 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To describe demographic and hormonal characteristics, comorbidities (diabetes mellitus and hypertension), therapeutic procedures and their effectiveness, as well as predictors of morbidity and mortality in a nationwide survey of Italian acromegalic patients. Retrospective multicenter epidemiological study endorsed by the Italian Society of Endocrinology and performed in 24 tertiary referral Italian centers. The mean follow-up time was 120 months. A total of 1512 patients, 41% male, mean age: 45±13 years, mean GH: 31±37 μg/l, IGF1: 744±318 ng/ml, were included. Diabetes mellitus was reported in 16% of cases and hypertension in 33%. Older age and higher IGF1 levels at diagnosis were significant predictors of diabetes and hypertension. At the last follow-up, 65% of patients had a controlled disease, of whom 55% were off medical therapy. Observed deaths were 61, with a standardized mortality ratio of 1.13 95% (confidence interval (CI): 0.87-1.46). Mortality was significantly higher in the patients with persistently active disease (1.93; 95% CI: 1.34-2.70). Main causes of death were vascular diseases and malignancies with similar prevalence. A multivariate analysis showed that older age, higher GH at the last follow-up, higher IGF1 levels at diagnosis, malignancy, and radiotherapy were independent predictors of mortality. Pretreatment IGF1 levels are important predictors of morbidity and mortality in acromegaly. The full hormonal control of the disease, nowadays reached in the majority of patients with modern management, reduces greatly the disease-related mortality.
    European Journal of Endocrinology 05/2012; 167(2):189-98. · 3.69 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Surgical cure cannot be achieved in most patients with invasive non-functioning pituitary macroadenoma (NFPA). Short-term residual tumor treatment with somatostatin analogs has produced disappointing results. This prospective case-control study assessed the efficacy of chronic treatment with long acting octreotide (octreotide LAR) on tumor volume in patients harboring post-surgical NFPA residue. The study population comprised 39 patients with NFPAs not cured by surgery. All patients underwent somatostatin receptor scintigraphy at least 6 months after the last surgery. Patients with a positive pituitary level octreoscan at (n = 26) received octreotide LAR (20 mg every 28 days) for ≥12 months (mean follow-up 37 ± 18 months) (Treated group). Moreover, a fragment of tumor tissue from patients in the treated group was retrospectively collected to assess the immunohistochemical expression of somatostatin receptor subtypes (SSTRs). The patients with a negative octreoscan (n = 13) formed the control group (mean follow-up 37 ± 16 months). Hormonal, radiological and visual field parameters were periodically assessed. In the treated group, all tumors expressed at least one SSTR subtype. The SSTR5 subtype was the most abundant, followed by SSTR3. The tumor residue increased in five of 26 patients (19%) in the treated group and in seven of 13 controls (53%). Visual field and pituitary function did not change in any patient. This study indicates that SSTR5 and SSTR3 are the most frequently expressed SSTR subtypes in NFPAs and supports a potential role of SSTR subtypes in stabilization of tumor remnant from NFPAs.
    Pituitary 12/2011; · 2.22 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The GH receptor (GHR) plays a key role in the the function of the GH/IGF-I axis and is the major effector of human growth. A common polymorphic variant consisting of genomic exon 3 deletion or retention (d3-GHR and full-length GHR, respectively), described in 2000, has been linked with increased receptor activity due to enhanced signal transduction. Subsequent pharmacogenetic studies have addressed a possible role of GHR polymorphism on the response to recombinant human GH treatment first in short children and then in adults, many of them suggesting that growth response to GH may be influenced, at least in some aspects, by this polymorphism. Similar studies, performed in patients with acromegaly, assumed an influence of the d3- GHR variant in the relationship between GH and IGF-I levels. More recently, some studies have investigated the relation between GHR genotype and treatment with the GHR antagonist pegvisomant, suggesting a better clinical response to therapy related to d3-GHR genotype. This review provides a summary of the main pharmacogenetic studies performed on this current and still open topic.
    Journal of endocrinological investigation 12/2011; 34(11):861-8. · 1.65 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Introduction  Nonalcoholic fatty liver disease (NAFLD) has been described in adult GH deficiency syndrome. Furthermore, chronic liver disease can be associated with significant changes in levels of IGF-I, GH-binding protein (GHBP), IGF-binding proteins (IGFBPs) and acid-labile subunit (ALS). However, the effect of liver steatosis on the GHBP production has not been investigated yet. Aim of the study  To explore whether GH secretion and/or levels of IGF-I, IGFBP-3, ALS and GHBP could be altered in obese patients in relation to the presence of liver steatosis. Materials and methods  A total of 115 obese patients (BMI > 30) were enrolled in the protocol (65 patients with liver steatosis and 50 age- and BMI-matched controls). In all patients, the following parameters were studied: serum levels of glucose, insulin, the HOMA index, IGF-I, GHBP, IGFBP-3, ALS and GH after GHRH and arginine stimulation test. Results  As expected, patients with NAFLD had blood glucose, insulin, HOMA-R significantly higher than controls, indicating a more severe insulin-resistance state in NAFLD. Furthermore, patients with NAFLD had higher levels of GHBP and IGFBP-3 and lower GH peak and IGF-I levels as compared to controls. No difference was found in ALS levels between the groups. In a multivariate analysis, GHBP was positively associated with hepatic steatosis while IGF-1 was negatively associated with hepatic steatosis. Conclusions  This study demonstrates that in patients with NAFLD, the GHBP levels are increased, and that the GH/IGF-I axis is significantly altered probably leading to reduced IGF-I bioavailability at tissue level.
    Clinical Endocrinology 11/2011; 77(4):531-6. · 3.35 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: The few epidemiological data available in literature on neuroendocrine tumors (NET)s are mainly based on Registry databases, missing therefore details on their clinical and natural history. Aim: To investigate epidemiology, clinical presentation and natural history of NETs Design & Setting: A large national retrospective survey was conducted in 13 Italian referral centers. Among 1203 NETs, 820 originating in the thorax (T-NET), in the gastro-enteropancreatic tract (GEP-NET) or metastatic NET of unknown primary origin (U-NET) were enrolled in the study. Results: 93% had a sporadic and 7% a MEN1 associated tumor. 63% were GEP-NET, 33% T-NET, 4% U-NET. Pancreas and lung were the commonest primary sites. Poorly differentiated carcinomas were <10%, all sporadic. The incidence of NET had a linear increase from 1990 to 2007 in all the centers. The mean age at diagnosis was 60.0±16.4 yrs, significantly anticipated in MEN1 patients (47.7±16.5 yrs). Association with Cigarette smoking and other non-NET cancer were more prevalent than in the general Italian population. The first symptoms of the disease were related to tumor burden in 46%, endocrine syndrome in 23%, while the diagnosis was fortuity in 29%. Insulin (37%) and serotonin (35%) were the most common hormonal hypersecretions. An advanced tumor stage was found in 42%, more frequently in the gut and thymus. No differences in the overall survival was observed between TNET and GEP-NET and between sporadic and MEN-1 associated tumors at ten years from diagnosis, while survival probability was dramatically reduced in U-NET. Conclusions: The data obtained from this study furnish relevant information on epidemiology, natural history and clinico-pathological features of NET, not available from the few published Register studies.
    Journal of endocrinological investigation 11/2011; · 1.65 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this retrospective study was to evaluate the efficacy, safety, and tolerability of lanreotide autogel given to metastatic well-differentiated (WD) neuroendocrine tumors (NET) patients observed in our Institute between 2005 and 2008. Patients with metastatic NET referred to our tertiary referral center were given lanreotide autogel 120 mg/month by deep sc injection for a period of at least 24 months. The efficacy was evaluated by the relief of disease symptoms, behavior of tumor markers and response rate in terms of time to tumor progression. Safety and tolerability were evaluated by assessing the onset of adverse events and treatment feasibility. Twenty-three patients (13 males), median age 62 yr (range 32-87) were considered for the study. All patients were affected by WD metastatic NET and had tumor progression in the last 6 months before the enrolment in the study. Median duration of response was 28 months (range 6-50 months). Fourteen patients (60.9%) showed flushing and diarrhea which improved by 85.7% and 55.6%, respectively, bronchoconstrinction and abdominal pain also ameliorated. A complete, partial or no-changed response in the tumor markers behavior was observed, respectively, in 42.9%, 22.9%, and 17.1% of cases. According to RECIST (Response Evaluation Criteria In Solid Tumors) criteria (version 1.1), there were 2 partial regression (8.7%) and 15 stable disease (65.3%); 6 patients (26.0%) progressed. No patient complained from any severe adverse reaction. The results of our study suggest that lanreotide autogel is effective in the symptoms, biochemical markers, and tumor progression control of WD metastatic NET and confirm that the treatment is well tolerated.
    Journal of endocrinological investigation 11/2011; 34(9):692-7. · 1.65 Impact Factor
  • American journal of men's health 10/2011; 8(3):224-224. · 1.15 Impact Factor

Publication Stats

973 Citations
271.67 Total Impact Points


  • 2014
    • Spedali Civili di Brescia
      Brescia, Lombardy, Italy
  • 2005–2013
    • Università degli Studi di Brescia
      • Department of Medicine and Surgery
      Brescia, Lombardy, Italy
    • Sapienza University of Rome
      Roma, Latium, Italy
  • 2004–2013
    • Catholic University of the Sacred Heart
      • • Institute of Nuclear Medicine
      • • School of Internal Medicine
      • • Institute of Internal and Geriatric Medicine
      • • Institute of Biochemistry and Clinical Biochemistry
      Milano, Lombardy, Italy
  • 1999–2013
    • The Catholic University of America
      Washington, Washington, D.C., United States
  • 2011
    • Policlinico Universitario Agostino Gemelli
      Roma, Latium, Italy
  • 2002
    • Università degli Studi di Trento
      • Departmental Area of Materials Engineering and Industrial Technologies
      Trient, Trentino-Alto Adige, Italy