Rosario Pivonello

Erasmus MC, Rotterdam, South Holland, Netherlands

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Publications (250)1021.48 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Report the efficacy and safety of pasireotide sc in patients with Cushing's disease during an open-ended, open-label extension to a randomized, double-blind, 12-month, Phase III study. 162 patients entered the core study. 58 patients who had mean UFC ≤ ULN at month 12 or were benefiting clinically from pasireotide entered the extension. Patients received the same dose of pasireotide as at the end of the core study (300-1,200 μg bid). Dose titration was permitted according to efficacy or drug-related adverse events. 40 patients completed 24 months' treatment. Of the patients who entered the extension, 50.0 % (29/58) and 34.5 % (20/58) had controlled UFC (UFC ≤ ULN) at months 12 and 24, respectively. The mean percentage decrease in UFC was 57.3 % (95 % CI 40.7-73.9; n = 52) and 62.1 % (50.8-73.5; n = 33) after 12 and 24 months' treatment, respectively. Improvements in clinical signs of Cushing's disease were sustained up to month 24. The most frequent drug-related adverse events in patients who received ≥1 dose of pasireotide (n = 162) from core baseline until the 24-month cut-off were diarrhea (55.6 %), nausea (48.1 %), hyperglycemia (38.9 %), and cholelithiasis (31.5 %). No new safety issues were identified during the extension. Reductions in mean UFC and improvements in clinical signs of Cushing's disease were maintained over 24 months of pasireotide treatment. The safety profile of pasireotide is typical for a somatostatin analogue, except for the frequency and degree of hyperglycemia; patients should be monitored for changes in glucose homeostasis. Pasireotide represents the first approved pituitary-targeted treatment for patients with Cushing's disease.
    Pituitary 12/2014; · 2.22 Impact Factor
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    ABSTRACT: Cushing's syndrome is associated with increased mortality, mainly due to cardiovascular complications, which are sustained by the common development of systemic arterial hypertension and metabolic syndrome, which partially persist after the disease remission. Cardiovascular diseases and hypertension associated with endogenous hypercortisolism reveal underexplored peculiarities. The use of exogenous corticosteroids also impacts on hypertension and cardiovascular system, especially after prolonged treatment. The mechanisms involved in the development of hypertension differ, whether glucocorticoid excess is acute or chronic, and the source endogenous or exogenous, introducing inconsistencies among published studies. The pleiotropic effects of glucocorticoids and the overlap of the several regulatory mechanisms controlling blood pressure suggest that a rigorous comparison of in-vivo and in-vitro studies is necessary to draw reliable conclusions. This review, developed during the first 'Altogether to Beat Cushing's syndrome' workshop held in Capri in 2012, evaluates the most important peculiarities of hypertension associated with CS, with a particular focus on its pathophysiology. A critical appraisal of most significant animal and human studies is compared with a systematic review of the few available clinical trials. A special attention is dedicated to the description of the clinical features and cardiovascular damage secondary to glucocorticoid excess. On the basis of the consensus reached during the workshop, a pathophysiology-oriented therapeutic algorithm has been developed and it could serve as a first attempt to rationalize the treatment of hypertension in Cushing's syndrome.
    Journal of hypertension. 11/2014;
  • Endocrinology & Metabolism Clinics of North America 11/2014; · 2.86 Impact Factor
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    ABSTRACT: Introduction: Acromegaly is characterized by increased release of growth hormone (GH) and IGF-I generally induced by a pituitary adenoma. Therapies for acromegaly aim at controlling tumor growth and normalizing hormonal excess, and include surgery, pharmacotherapy, and radiotherapy.Area covered: This review focuses on efficacy and tolerability of the GH receptor antagonist pegvisomant (PEG), widely used in acromegaly as second- or third-line treatment, mainly after unsuccessful surgery and/or radiotherapy, or in patients with a proven resistance to conventional somatostatin analogs (SSA). The response to PEG takes into account control of IGF-I excess and improvement of clinical symptoms directly related to IGF-I hypersecretion, whereas PEG does not exert a direct action on GH oversecretion and tumor mass. The response to PEG treatment depends on proper dose adjustment and patient compliance, as it is approved as daily subcutaneous injection. However, PEG can be added to SSA in patients non- or partly responders to SSA, or converted from daily to weekly administration with similar effectiveness of daily monotherapy.Expert opinion: PEG is safe and well tolerated, and main safety focuses are on the potential risk of increased GH and pituitary tumor size, liver enzyme elevation, and injection site reactions.
    Expert Opinion on Orphan Drugs. 10/2014;
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    ABSTRACT: Thyrotropin-secreting pituitary adenomas (TSHomas) represent a rare subtype of pituitary tumors. Neurosurgery (NCH) is still considered the first-line therapy. In this study we aimed to investigate the outcome of different treatment modalities, including first line somatostatin analogs (SSA) treatment, with a specific focus on neurosurgery-related complications.
    Pituitary 10/2014; · 2.22 Impact Factor
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    ABSTRACT: Contexte Le syndrome de Kallmann (KS) associe un hypogonadisme hypogonadotrophique à une diminution de l’odorat par une anomalie du développement des structures olfactives. La perception du goût, liée à l’olfaction, n’a jamais été étudiée. Objectif Évaluer les goût chez des KS. Patients Comparativement à 50 sujets témoins, ont été évalués 20 malades avec KS et 20 avec anosmie acquise (AA), appariés. Méthodes (1) Chaque sujet a fait une auto-estimation de son odorat et de son sens gustatif (échelle semi-quantitative graduée à 10 niveaux) ; (2) ils ont ensuite eu un test olfactif (TDI) ; puis (3) un test de perception gustative (TPG) : 20 extraits aromatiques dilués, étaient administrés oralement dans une solution aqueuse à température ambiante pour éviter les biais physiques (aspect visuel, texture) de la perception gustative. Chaque sujet devait identifier le goût correct au sein de 5 items. Le score final était la somme des réponses correctes (0 à 21). Résultats Le TDI a révélé une anosmie chez tous les sujets KS et AA et une olfaction normale chez les contrôles. Par rapport aux témoins (16,7 ± 1,9), le taux de réponses correctes au TPG était spectaculairement diminué chez les KS (5,4 ± 1,4) et les AA (6,4 ± 1,9) (p < 0,0001 pour chaque). Le TPG était très significativement corrélé au TDI. Conclusion Nous montrons pour la première fois une nouvelle atteinte neurosensorielle chez les KS. Celle-ci n’est pas exprimée spontanément contrairement aux sujets AA. La souffrance face à ce handicap, forte chez les AA, semble absente chez les KS.
    Annales d Endocrinologie 10/2014; Volume 75(Issues 5–6):272. · 0.66 Impact Factor
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    Journal of endocrinological investigation 09/2014; · 1.65 Impact Factor
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    ABSTRACT: mTOR-pathway has been recently suggested as a new potential target for therapy in adrenocortical carcinomas (ACC). The aim of the current study is to describe the expression of the mTOR-pathway in normal (NA) and pathological adrenals, and to explore whether there are correlation between the expression of these proteins and the in vitro response to sirolimus. At this purpose, the mTOR, S6K1 and 4EBP1 mRNA expression was evaluated in 10 NA, 10 hyperplasia (AH), 17 adenomas (ACA) and 17 ACCs by qPCR whereas total(t)/phospho(p)-mTOR, t/p-S6K and t/p-4EBP1 protein expression was assessed in 3 NAs, 3 AHs, 6 ACAs and 20 ACCs by immunohistochemistry. The effects of sirolimus on cell survival and/or cortisol secretion in 12 (adrenocortical tumors) AT human primary cultures were also evaluated. In the NA and AH a layer specific expression of t and p mTOR, S6K1 and 4EBP1 was observed. S6K1 mRNA levels were lower in ACCs compared with NA, AH and ACA (p<0.01). A subset of ATs presented a moderate-high staining of the evaluated proteins. In ACCs median t-S6K1 protein expression was lower than ACAs (p<0.01). Moderate-high staining of p-S6K1 and/or p-4EBP1 was observed in most ATs. A subset of ACCs not having moderate-high staining had higher Weiss than others (p<0.029). In primary AT cultures sirolumus significantly reduced cell survival or cortisol secretion only in sporadic cases. In conclusion, these data suggest the presence of an activated mTOR-pathway in a subset of AT and a possible response to sirolimus only in certain ACC cases.
    Endocrine Related Cancer 08/2014; · 5.26 Impact Factor
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    ABSTRACT: [(111)In-DTPA0]octreotide scintigraphy allows the in vivo visualization of several types of SS receptor (SSR)-expressing tumors. Among these, thymomas have been recently detected. Here we report on 2 patients admitted for myasthenia gravis and radiological evidence of thymic mass. Although these patients had similar clinical presentation, in vivo SSR scintigraphy displayed a difference in the degree of the [(111)In-DTPA0]octreotide uptake. Considering that both thymic masses had comparable volume, [(111)In-DTPA0]octreotide level was significantly higher in one of the 2 tumors (tumor/background ratio of 5.7 vs 2.6). The SSR subtype expression pattern was studied in vitro on the surgically resected specimens by ligand binding techniques, quantitative reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry. According to the recent World Health Organization classification, the 2 tumors were classified A and B2 thymomas respectively. In membrane homogenates, we found a higher number of high affinity [125I-Tyr11]-SS-14 binding sites in the B2 thymomas (23.5+/-2.5 vs 12.0+/-0.4 fmol/mg membrane protein; p<0.05). RT-PCR analysis showed sst1, sst2A and sst3 mRNA in the 2 thymoma tissues, whereas SS mRNA was detectable only in the A thymoma. Quantitative evaluation of RT-PCR data showed a comparable expression of the relative amount of sst2A mRNA in both tumors, whereas a significant higher expression of sst3 mRNA in the B2 thymoma. Sst2A immunoreactivity was localized mainly on the endothelium of intratumoral vessels, whereas sst3 was present on either tumoral epithelial cells or normal reactive thymocytes. The expression of sst2A receptors in these tumors is in line with the in vivo visualization by [(111)In-DTPA0]octreotide, which is considered a sst2-preferring ligand. However, since radioligand uptake was significantly higher in the B2 thymoma, which expressed the largest sst3 mRNA levels, it might be possible that this subtype is involved in determining the tumor visualization during SSR scintigraphy. Apart from the affinity of the radioligand for the receptor, also the efficacy of the internalization of the radioligand-receptor complex might play a role in radioactivity accumulation during in vivo SSR scintigraphy. In fact, although octreotide binds with lower affinity to sst3 receptors, this subtype displayed the highest amount of agonist-dependent receptor internalization compared to the other SSR subtypes. Moreover, sst3 was localized on both tumor cells and reactive thymocytes, and these latter cells are characterized by a very active turnover of membrane molecules. Finally, although more cases need to be evaluated, the lack of detection of SS mRNA in the tumor presenting a more aggressive phenotype (B2 thymoma) might have physiopathological or prognostic significance.
    Journal of endocrinological investigation 07/2014; 24(7):522-8. · 1.55 Impact Factor
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    ABSTRACT: The aim of the current study was to evaluate the effectiveness of a long-term treatment with sodium valproate in 19 patients with Cushing's disease. Before therapy beginning, the patients were subjected to acute test with 600 mg sodium valproate. Then, they were subjected to a 3-month therapy with sodium valproate at the dose of 600 mg/day before surgery (presurgical study). The 7 patients not surgically cured were subjected again to a 3-month therapy with sodium valproate at the dose of 600 mg/day after surgery (postsurgical study). Circulating ACTH and cortisol and urinary free cortisol levels were evaluated before and monthly after the beginning of the therapy. A decrease of plasma ACTH and serum cortisol levels greater than 50% of baseline was considered as positive response to acute test whereas the normalization of plasma ACTH, serum cortisol and urinary free cortisol levels and the clinical remission were considered as positive response to the long-term treatment. At acute test, 8 patients were considered responders and 11 patients non-responders. In no patient plasma ACTH, serum cortisol and urinary free cortisol were normalized during the long-term treatment. Urinary free cortisol levels significantly decreased (483.2 +/- 33.8 vs 699.4 +/- 67.0 micrograms/24 h), whereas plasma ACTH (302.8 +/- 17.7 vs 183.3 +/- 25.0 ng/l) and serum cortisol (466.5 +/- 23.2 vs 356.7 +/- 19.6 micrograms/l) significantly increased during sodium valproate administration in the 19 patients enrolled in the presurgical study. Plasma ACTH (247.7 +/- 22.3 vs 168.6 +/- 15.0 ng/l), serum cortisol (387.4 +/- 35.8 vs 282.0 +/- 16.0 micrograms/l) and urinary free cortisol (370.9 +/- 70.6 vs 261.3 +/- 37.8 micrograms/24 h) levels significantly increased in the 7 patients enrolled in the postsurgical study. No patient had clinical remission of Cushing's disease. In conclusion, the current study showed that long-term therapy with sodium valproate is not useful in the therapeutic management of Cushing's disease neither as alternative nor as adjunctive therapy to surgery.
    Journal of endocrinological investigation 07/2014; 20(7):387-92. · 1.55 Impact Factor
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    ABSTRACT: Background Mortality in acromegaly strictly depends on optimal control of GH and IGF-I levels. Modern medical therapy with somatostatin analogs (SSA) and GH-receptor antagonist (GHRA) is not available in many countries due to funding restrictions. This retrospective, comparative, cohort study investigated the impact of different treatment modalities on disease control (GH and IGF-1) and mortality in acromegaly patients. Methods Two cohorts of patients with acromegaly from Bulgaria (n=407) and Campania, Italy (n=220) were compared, and mortality rates were evaluated during a 10 year period (1999-2008). Results: The major difference in treatment approach between cohorts was higher usage of SSA and GHRA in Italy, leading to a decreased requirement of radiotherapy. Significantly more Italian than Bulgarian patients had achieved disease control (50.1% vs. 39.1%, p=0.005) at the last follow-up. Compared with the general population, the Bulgarian cohort had decreased life expectancy with standardized mortality ratio (SMR) of 2.0 (95% CI 1.54-2.47) that was restored to normal in patients with disease control - SMR 1.25 (95% CI 0.68-1.81). Irradiated patients had higher cerebrovascular mortality - SMR 7.15 (95% CI 2.92 -11.37). Internal analysis revealed an independent role of age at diagnosis and last GH value on all-cause and radiotherapy on cerebrovascular mortality. Normal survival rates were seen in the Italian cohort: SMR 0.66 (95% CI 0.27-1.36). Conclusions: Suboptimal biochemical control was associated with higher mortality in the Bulgarian cohort. Modern treatment options that induce a strict biochemical control and reduce the necessity of radiotherapy might influence life expectancy. Other factors, possibly management of comorbidities, could contribute to survival rates.
    European journal of endocrinology / European Federation of Endocrine Societies. 05/2014;
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    The lancet. Diabetes & endocrinology. 05/2014; 2(5):352-4.
  • Endocrine Abstracts. 04/2014;
  • Endocrine Abstracts. 04/2014;
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    ABSTRACT: Signs and symptoms of Cushing's disease are associated with high burden of illness. In this analysis, we evaluated the effect of pasireotide treatment on signs and symptoms in patients with Cushing's disease. Phase III study with double-blind randomization of two pasireotide doses. Patients (n=162) with persistent/recurrent or de novo Cushing's disease and urinary free cortisol (UFC) levels ≥1.5x upper limit of normal (ULN) were randomized to receive subcutaneous pasireotide (600/900μg bid). At month 3, patients with UFC≤2xULN and not exceeding the baseline value continued their randomized dose; all others received 300μg bid uptitration. At month 6, patients could enter an open-label phase until month 12 with a maximal dose of 1200μg bid. Changes in signs and symptoms of hypercortisolism over 12 months' treatment in patients still enrolled in the study and with evaluable measurements were assessed in relation to degree of UFC control. Reductions in blood pressure were observed even without full UFC control and were greatest in patients who did not receive antihypertensive medications during the study. Significant reductions in total cholesterol and LDL-cholesterol were observed in patients who achieved UFC control. Reductions in BMI, weight and waist circumference occurred during the study even without full UFC control. Adverse effects were typical of somatostatin analogues except for hyperglycaemia-related events, which were experienced by 72.8% of patients. In the largest Phase III study of medical therapy in Cushing's disease, significant improvements in signs and symptoms were seen during 12 months of pasireotide treatment, as UFC levels decreased. This article is protected by copyright. All rights reserved.
    Clinical Endocrinology 02/2014; · 3.35 Impact Factor
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    ABSTRACT: Pregnancy is becoming a relatively common event in patients with pituitary tumors (PT), due to the increasing availability of medical treatments, which control pituitary diseases associated with the development of PT. However, the presence of PT and its treatment may be a disturbing factor for pregnancy, and pregnancy significantly influences the course and the management of PT. This review summarizes the knowledge about the management of PT during pregnancy and the occurrence of pregnancy in patients with pre-existent PT, focusing on secreting PT characterized by hormonal excess and on clinically non-functioning PT often associated to hormone deficiency, which configure the hypopituitaric syndrome.
    Journal of endocrinological investigation 02/2014; 37(2):99-112. · 1.65 Impact Factor
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    ABSTRACT: Hepatocellular carcinoma (HCC) is the sixth most common malignancy worldwide. Different signalling pathways have been identified to be implicated in the pathogenesis of HCC; among these, GH, IGF and somatostatin (SST) pathways have emerged as some of the major pathways implicated in the development of HCC. Physiologically, GH-IGF-SST system plays a crucial role in liver growth and development since GH induces IGF1 and IGF2 secretion and the expression of their receptors, involved in hepatocytes cell proliferation, differentiation and metabolism. On the other hand, somatostatin receptors (SSTRs) are exclusively present on the biliary tract. Importantly, the GH-IGF-SST system components have been indicated as regulators of hepatocarcinogenesis. Reduction of GH binding affinity to GH receptor, decreased serum IGF1 and increased serum IGF2 production, overexpression of IGF1 receptor, loss of function of IGF2 receptor and appearance of SSTRs are frequently observed in human HCC. In particular, recently, many studies have evaluated the correlation between increased levels of IGF1 receptors and liver diseases and the oncogenic role of IGF2 and its involvement in angiogenesis, migration and, consequently, in tumour progression. SST directly or indirectly influences tumour growth and development through the inhibition of cell proliferation and secretion and induction of apoptosis, even though SST role in hepatocarcinogenesis is still opened to argument. This review addresses the present evidences suggesting a role of the GH-IGF-SST system in the development and progression of HCC, and describes the therapeutic perspectives, based on the targeting of GH-IGF-SST system, which have been hypothesised and experimented in HCC.
    Infectious Agents and Cancer 01/2014; 9:27. · 2.07 Impact Factor
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    ABSTRACT: Background: Glycogen storage disease type 1 (GSD1) is a rare and genetically heterogeneous metabolic defect of gluconeogenesis due to mutations of either the G6PC gene (GSD1a) or the SLC37A4 gene (GSD1b). Osteopenia is a known complication of GSD1. Objectives: The aim of this study was to investigate the effects of poor metabolic control and/or use of GSD1-specific treatments on bone mineral density (BMD) and metabolism in GSD1 patients. Methods: In a multicenter, cross-sectional case-control study, we studied 38 GSD1 (29 GSD1a and 9 GSD1b) patients. Clinical, biochemical and instrumental parameters indicative of bone metabolism were analyzed; BMD was evaluated by dual-emission X-ray absorptiometry and quantitative ultrasound. Results: Both GSD1a and GSD1b patients showed reduced BMD compared with age-matched controls. In GSD1a patients, these abnormalities correlated with compliance to diet and biochemical indicators of metabolic control. In GSD1b patients, BMD correlated with the age at first administration and the duration of granulocyte colony-stimulating factor (G-CSF) therapy. Conclusions: Our data indicate that good metabolic control and compliance with diet are highly recommended to improve bone metabolism in GSD1a patients. GSD1b patients on G-CSF treatment should be carefully monitored for the risk of osteopenia/osteoporosis. © 2013 S. Karger AG, Basel.
    Hormone Research in Paediatrics 12/2013; · 1.55 Impact Factor
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    ABSTRACT: Introduction: Hyperprolactinaemia has been implicated in the pathogenesis of obesity and glucose intolerance and is reportedly associated with impaired metabolic profile. The current study aimed at investigating the effects of 12 and 60-month treatment with cabergoline (CAB) on metabolic syndrome (MetS ) in patients with prolactinomas. Patients and Methods: Sixty-one patients with prolactinomas (13 men, 48 women, 41 with microadenoma, 20 with macroadenoma), aged 34.4 ± 10.3 years, entered the study. In all patients, PRL and metabolic parameters were assessed at diagnosis and after 12 and 60 months of continuous CAB treatment. MetS was diagnosed according to NCEP-ATP III criteria. Results: Compared to baseline, CAB induced a significant decrease in PRL with complete normalization in 93% of patients after 60-month treatment. At baseline, MetS prevalence was significantly higher in patients with PRL above (34.5%) than in those with PRL lower (12.5%) than the median (129 μg/l, p = 0.03). MetS prevalence significantly decreased after 12 (11.5%, p = 0.039) and 60 (5.0%, p = 0.001) months compared to baseline (28.0%). At both evaluations, lipid profile significantly improved compared to baseline. Fasting insulin and HOMA-IR significantly decreased after 1 years-CAB (p = 0.012 and p = 0.002, respectively), and further improved after 60 months (p = 0.000). Visceral adiposity index (VAI) significantly decreased after 60 month-treatment (p = 0.000) compared to baseline. At 5-years evaluation, CAB dose was the best predictor of percent decrease in FI (t = 2.35, p = 0.022). Conclusions: CAB significantly reduces MetS prevalence and improves the adipose tissue dysfunction index. The improvement in PRL, insulin sensitivity and other metabolic parameters might reflect the direct effect of CAB. © 2014 S. Karger AG, Basel.
    Neuroendocrinology 12/2013; · 4.93 Impact Factor
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    ABSTRACT: Introduction: The clinical features and increased mortality associated with Cushing's syndrome result from a chronic excess of circulating cortisol. As LCI699 potently inhibits 11β-hydroxylase, which catalyzes the final step of cortisol synthesis, it is a potential new treatment for Cushing's disease, the most common cause of endogenous Cushing's syndrome. Methods: Adult patients with moderate-to-severe Cushing's disease (UFC levels >1.5xULN) received oral LCI699 for 10 weeks in this proof-of-concept study. LCI699 was initiated at 4 mg/day in two equal doses; the dose was escalated every 14 days to 10, 20, 40 and 100 mg/day until UFC normalized, whereupon the dose was maintained until treatment ended (day 70). The primary endpoint was UFC≤ULN or a ≥50% decrease from baseline at day 70. Results: Twelve patients were enrolled and completed the study. Baseline UFC ranged over 1.6-17.0xULN. All 12 patients achieved UFC≤ULN or a ≥50% decrease from baseline at day 70; 11 (92%) had normal UFC levels at that time. After treatment discontinuation (day 84), UFC was >ULN in 10 patients with available measurements. Mean 11-deoxycortisol, 11-deoxycorticosterone and adrenocorticotropic hormone levels increased during treatment and declined after discontinuation. Mean systolic and diastolic blood pressure decreased from baseline by 10.0 and 6.0 mmHg, respectively. LCI699 was generally well tolerated; most adverse events (AEs) were mild or moderate. The most common AEs included fatigue (7/12), nausea (5/12) and headache (3/12). No serious drug-related AEs were reported. Conclusion: LCI699 was efficacious and well tolerated in patients with Cushing's disease enrolled in this proof-of-concept study.
    The Journal of Clinical Endocrinology and Metabolism 12/2013; · 6.31 Impact Factor

Publication Stats

6k Citations
1,021.48 Total Impact Points


  • 2002–2014
    • Erasmus MC
      • Department of Internal Medicine
      Rotterdam, South Holland, Netherlands
  • 1996–2014
    • University of Naples Federico II
      • • Department of Molecular Medicine and Health Biotechnology
      • • Department of Clinical Medicine and Surgery
      Napoli, Campania, Italy
  • 2013
    • IRCCS Ospedale Casa Sollievo della Sofferenza
      • Department of Endocrinology
      Giovanni Rotondo, Apulia, Italy
  • 2011–2013
    • Università degli Studi di Genova
      • Department of Physics
      Genova, Liguria, Italy
    • Università degli studi di Palermo
      • Department of internal medicine and medical specialties (DIMIS)
      Palermo, Sicily, Italy
  • 2012
    • Università degli Studi del Molise
      Campobasso, Molise, Italy
    • Università degli Studi di Salerno
      • Department of Medicine and Surgery
      Fisciano, Campania, Italy
  • 2009
    • University of Milan
      • Department of Medical Sciences
      Milano, Lombardy, Italy
  • 2001–2004
    • Second University of Naples
      • Faculty of Medicine and Surgery
      Caserta, Campania, Italy
  • 2000
    • Erasmus Universiteit Rotterdam
      • Department of Internal Medicine
      Rotterdam, South Holland, Netherlands
  • 1998
    • Università degli Studi di Torino
      Torino, Piedmont, Italy