Rosario Pivonello

University of Naples Federico II, Napoli, Campania, Italy

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Publications (236)972.41 Total impact

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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: 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;
  • The lancet. Diabetes & endocrinology. 05/2014; 2(5):352-4.
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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; · 3.40 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: 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; · 3.54 Impact Factor
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    ABSTRACT: Guidelines for the management of osteoporosis induced by endogenous hypercortisolism are not available. Both the American College of Rheumatology and the International Osteoporosis Foundation recommend to modulate the treatment of exogenous glucocorticoid-induced osteoporosis (GIO) based on the individual fracture risk profile (calculated by FRAX) and dose of glucocorticoid used, but it is difficult to translate corticosteroid dosages to different degrees of endogenous hypercortisolism, and there are no data on validation of FRAX stratification method in patients with endogenous hypercortisolism. Consequently, it is unclear whether such recommendations may be adapted to patients with endogenous hypercortisolism. Moreover, patients with exogenous GIO take glucocorticoids since suffering a disease that commonly affects bone. On the other hand, the correction of coexistent risk factors, which may contribute to increase the fracture risk in patients exposed to glucocorticoid excess, and the removal of the cause of endogenous hypercortisolism, may lead to the recovery of bone health. Although the correction of hypercortisolism and of possible coexistent risk factors is necessary to favor the normalization of bone turnover with recovery of bone mass; in some patients, the fracture risk could not be normalized and specific anti-osteoporotic drugs should be given. Who, when, and how the patient with endogenous hypercortisolism should be treated with bone-active therapy is discussed.
    Osteoporosis International 12/2013; · 4.04 Impact Factor
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    ABSTRACT: To confirm the efficacy of preoperative workup, the authors analyse the results of a multicentre study in a surgical series of patients diagnosed with an adrenal incidentaloma. The retrospective review of a prospectively collected database was conducted. The data was obtained by six surgical units operating in the Campania Region, Italy. Five-hundred and six (506) adrenalectomies performed between 1993 and 2011 on 498 patients were analysed. Final histology in patients with a preoperative diagnosis of incidentaloma and studied according to guidelines (230/282 patients group A) was compared with final histology coming from patients presenting the same preoperative diagnosis but studied not according to guidelines (52/282 patients group B). In group A preoperative diagnosis was confirmed at final histology in 76/81 (93.8%) cases of subclinical functioning lesions presenting as an incidentaloma. The preoperative detection of pheochromocytoma and primary adrenocortical cancer (ACC) reached 91.6% and 84.6% respectively. In group B conversion rate to open surgery was higher than in group A (p = 0.02). One pheochromocytoma was missed at preoperative diagnosis whereas one ACC smaller than 4 centimetres (cm) and coming from an incidental lesion was discovered. In both groups a significant association between increasing dimensions of incidentaloma and cancer has been observed (p = 0.001). This surgical series confirm the high efficacy of suggested guidelines. A significant preoperative detection rate of adrenal lesions presenting as incidentaloma is observed. The unnecessary number of adrenalectomies performed in understudied patients, causing higher morbidity, was not associated to a higher detection rate of primary adrenocortical cancer.
    BMC Surgery 11/2013; 13(1):57. · 1.97 Impact Factor
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    ABSTRACT: Cushing's disease (CD) is a severe endocrine condition caused by an adrenocorticotropin (ACTH)-producing pituitary adenoma that chronically stimulates adrenocortical cortisol production and with potentially serious complications if not or inadequately treated. Active CD may produce a fourfold increase in mortality and is associated with significant morbidities. Moreover, excess mortality risk may persist even after CD treatment. Although predictors of risk in treated CD are not fully understood, the importance of early recognition and adequate treatment is well established. Surgery with resection of a pituitary adenoma is still the first line therapy, being successful in about 60-70 % of patients; however, recurrence within 2-4 years may often occur. When surgery fails, medical treatment can reduce cortisol production and ameliorate clinical manifestations while more definitive therapy becomes effective. Compounds that target hypothalamic-pituitary axis, glucocorticoid synthesis or adrenocortical function are currently used to control the deleterious effects of chronic glucocorticoid excess. In this review we describe and analyze the molecular basis of the drugs targeting the disease at central level, suppressing ACTH secretion, as well as at peripheral level, acting as adrenal inhibitors, or glucocorticoid receptor antagonists. Understanding of the underlying molecular mechanisms in CD and of glucocorticoid biology should promote the development of new targeted and more successful therapies in the future. Indeed, most of the drugs discussed have been tested in limited clinical trials, but there is potential therapeutic benefit in compounds with better specificity for the class of receptors expressed by ACTH-secreting tumors. However, long-term follow-up with management of persistent comorbidities is needed even after successful treatment of CD.
    Endocrine 11/2013; · 1.42 Impact Factor
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    ABSTRACT: Diabetes mellitus (DM) is one of the most frequent complications of Cushing syndrome (CS). Aim of the study was to define the changes in insulin sensitivity and/or secretion in relation to glucose tolerance categories in newly diagnosed CS patients. Cross-sectional study on 140 patients with CS. 113 women (80 with pituitary disease and 33 with adrenal disease, aged 41.7±15.7 yr) and 27 men (19 with pituitary disease and 8 with adrenal disease, aged 38.1±20.01 yr) at diagnosis were divided according to glucose tolerance into normal glucose tolerance (CS/NGT), impaired fasting glucose and/or impaired glucose tolerance (CS/prediabetes) and diabetes (CS/DM). 71 patients belonged to CS/NGT (49.3%), 26 (18.5%) to CS/prediabetes and 43 (30.8%) to CS/DM. Significant increasing trends in the prevalence of family history of diabetes (p<0.001), metabolic syndrome (p<0.001), age (p<0.001) and waist circumference (p=0.043) and decreasing trends in HOMAβ (p<0.001)and Oral Dispositional Index (DIo) (p<0.002) were observed among the groups. No significant trend in fasting insulin, AUC INS, ISI-Matsuda and VAI was detected. Impairment of glucose tolerance is characterized by the inability of β-cells to adequately compensate insulin resistance through increased insulin secretion. Age, genetic predisposition and lifestyle, in combination with duration and degree of hypercortisolism, strongly contribute to the impairment of glucose tolerance in the natural history of CS. A careful phenotypic evaluation of glucose tolerance defects in patients with CS proves useful for the identification of patients at high risk for metabolic complications.
    European Journal of Endocrinology 11/2013; · 3.14 Impact Factor
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    ABSTRACT: Heterozygous de novo mutations in SOX2 have been reported in approximately 10-20% of patients with unilateral or bilateral anophthalmia or microphthalmia. An additional phenotype of hypopituitarism, with anterior pituitary hypoplasia and hypogonadotropic hypogonadism, has been reported in patients carrying SOX2 alterations. We report a novel heterozygous mutation in the SOX2 gene in a male affected with congenital bilateral anophthalmia, hypogonadotrophic hypogonadism and growth hormone deficiency. The mutation we describe is a cytosine deletion in position 905 (c905delC) which causes frameshift and an aberrant C-terminal domain. Our report highlights the fact that subjects affected with eye anomalies and harboring SOX2 mutations are at high risk for gonadotropin deficiency, which has important implications for their clinical management.
    Gene 11/2013; · 2.20 Impact Factor
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    ABSTRACT: Cushing's disease (CD) is a severe endocrine condition caused by an adrenocorticotropin (ACTH)-producing pituitary adenoma that chronically stimulates adrenocortical cortisol production and with potentially serious complications if not or inadequately treated. Active CD may produce a fourfold increase in mortality and is associated with significant morbidities. Moreover, excess mortality risk may persist even after CD treatment. Although predictors of risk in treated CD are not fully understood, the importance of early recognition and adequate treatment is well established. Surgery with resection of a pituitary adenoma is still the first line therapy, being successful in about 60-70 % of patients; however, recurrence within 2-4 years may often occur. When surgery fails, medical treatment can reduce cortisol production and ameliorate clinical manifestations while more definitive therapy becomes effective. Compounds that target hypothalamic-pituitary axis, glucocorticoid synthesis or adrenocortical function are currently used to control the deleterious effects of chronic glucocorticoid excess. In this review we describe and analyze the molecular basis of the drugs targeting the disease at central level, suppressing ACTH secretion, as well as at peripheral level, acting as adrenal inhibitors, or glucocorticoid receptor antagonists. Understanding of the underlying molecular mechanisms in CD and of glucocorticoid biology should promote the development of new targeted and more successful therapies in the future. Indeed, most of the drugs discussed have been tested in limited clinical trials, but there is potential therapeutic benefit in compounds with better specificity for the class of receptors expressed by ACTH-secreting tumors. However, long-term follow-up with management of persistent comorbidities is needed even after successful treatment of CD
    Endocrine 11/2013; · 2.25 Impact Factor
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    ABSTRACT: Context:Adrenocortical cancer (ACC) is a rare cancer with poor prognosis and scant treatment options. In ACC, no personalized approach has emerged but no extensive molecular screening has been performed to date.Objective:The objective of the study was to evaluate the presence of a large number of potentially targetable molecular events in a large cohort of advanced ACC.Design, Setting, and Participants:We used hot spot gene sequencing (Ion Torrent, 40 patients) and comparative genomic hybridization (CGH; 28 patients; a subset of the entire cohort) in adult stage III-IV ACC samples to screen for mutations and copy number abnormalities of potential interest for therapeutic use in 46 and 130 genes, respectively.Results:At least one copy number alteration or mutation was found in 19 patients (47.5%). The most frequent mutations were detected on TP53, ATM, and CTNNB1 [6 of 40 (15%), 5 of 40 (12.5%), and 4 of 40 (10%), respectively]. The most frequent copy number alterations identified were: amplification of the CDK4 oncogene (5 of 28; 17.9%) and deletion of the CDKN2A (4 of 28; 14.3%) and CDKN2B (3 of 28; 10.7%) tumor suppressor genes. Amplifications of FGFR1, FGF9, or FRS2 were discovered in three subjects (10.7%). Associated alterations were: deletions of CDKN2A, CDKN2B with ATM mutations, and TP53 mutations with CTNNB1 mutations.Conclusions:No simple targetable molecular event emerged. Drugs targeting the cell cycle could be the most relevant new therapeutic approach for patients with advanced ACC. Inhibitors of the fibroblast growth factor receptor pathway could also be a therapeutic option in a subset of patients, whereas other targeted therapies should be considered on a case-by-case basis.
    The Journal of clinical endocrinology and metabolism 08/2013; · 6.50 Impact Factor
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    ABSTRACT: Objective: In humans, glucocorticoid excess may cause neuropsychiatric symptoms, including psychosis and cognitive impairment, and glucocorticoid signaling hyperactivation may sensitize to substance of abuse. The aim of this work was to evaluate whether exposure to glucocorticoid excess triggers molecular changes in dopaminergic and opioidergic systems within relevant forebrain areas. Methods: We acutely exposed Sprague-Dawley rats to dexamethasone, a glucocorticoid analogue, or vehicle and evaluated the mRNA expression of dopamine D1 and D2 receptors and enkephalin within the cortex, the striatum, and the midbrain. Results: Dexamethasone reduced mRNA expression of D1 receptor and enkephalin in the cortex. In the striatum, dexamethasone reduced the expression of D1 receptor mRNA, but not that of D2 receptor and enkephalin. No significant changes in D2 receptor mRNA expression were observed in the midbrain. Basal distribution of D1 and D2 receptor mRNA showed a clear-cut striatal/cortical gradient, while this distribution was less obvious for enkephalin mRNA. Dexamethasone increased the cortico-striatal separation in terms of D1 and D2 receptor mRNA expression. Discussion: These molecular changes may represent adaptive mechanisms to dexamethasone-induced potentiation of dopaminergic and opioidergic transmission, mostly in cortical areas.
    Current Molecular Pharmacology 07/2013;
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    ABSTRACT: Objective Acromegalic patients have increased mortality. The objective of the study was to compare the effect of different therapies for acromegaly on mortality.Design&Methods Mortality of 438 consecutive acromegalic patients was compared to that of the general population by standardized mortality ratio(SMR);the effect of different therapies on survival was evaluated by Cox regression analysis.ResultsTwenty patients(4·5%) died between 1999 and 2009.Age and sex-adjusted SMR was 0·70(95% C.I., 0·43-1·08).Cox regression analysis revealed that, in the whole population, both general risks factors(age and the physical status), and specific factors for acromegaly(macroadenoma, hypopituitarism and uncontrolled disease) were associate with death. The most compromised patients at diagnosis had higher mortality(p=0·001), which occurred also in patients with controlled acromegaly.Death occurred in 2·4%(adenomectomy), 2·6%(adenomectomy followed by somatostatin analogues, SSA) and 11·4%(SSA as primary therapy) patients.The risk of death was higher in patients receiving SSA as primary therapy(Hazard Ratio, HR 5·518, 95% C.I., 1·058-28·767, p=0·043) than in all patients submitted to adenomectomy; however, a higher risk of death occurred only in diabetic patients treated with SSA alone(HR, 21·936, 95% CI, 1·557-309·04, p=0·022).Radiotherapy was associated with increased mortality, which occurred in patients with the more locally advanced disease.Conclusions Therapies of acromegaly and comorbidities have lowered mortality to the level of the general population;SSA alone or following pituitary adenomectomy was comparable to curative neurosurgery on survival in non-diabetic patients; on the contrary, SSA as primary therapy, may be less effective than adenomectomy in reducing mortality in diabetic patients.
    European Journal of Endocrinology 07/2013; · 3.14 Impact Factor
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    ABSTRACT: Cabergoline (CAB) has been found to be associated with increased risk of cardiac valve regurgitation in Parkinson's disease (PD), whereas several retrospective analyses failed to detect a similar relation in hyperprolactinemic patients. The current study aimed at investigating cardiac valve disease before and after 24 and 60 months of continuous treatment with CAB only in patients with hyperprolactinemia. Forty patients (11 men, 29 women, aged 38.7±12.5 years) newly diagnosed with hyperprolactinemia entered the study. Cumulative CAB dose ranged 12-588 mg (median 48 mg) at 24 months, and 48-1260 mg (median 149 mg) at 60 months. All patients underwent a complete trans-thoracic echocardiographic examination. Valve regurgitation was assessed according to the American Society of Echocardiography. At baseline the prevalence of trace mitral, aortic, pulmonic and tricuspid regurgitation was respectively 20%, 2.5%, 10% and 40%, with no patient showing clinically relevant valvulopathy. After 24 months, no change in the prevalence of trace mitral (p=0.78) and pulmonic (p=0.89) regurgitation and of mild aortic (p=0.89) and tricuspid (p=0.89) regurgitation was found as compared to baseline. After 60 months, the prevalence of trace tricuspid regurgitation only was slightly increased as compared to 24 months (37,5%; p=0.82) but none of the patients developed significant valvulopathy. No correlation was found between cumulative dose and prevalence or grade of valve regurgitation at both evaluations. Prolactin levels normalized in all patients but one. CAB does not increase the risk of significant cardiac valve regurgitation in prolactinomas after the first five years of treatment.
    European Journal of Endocrinology 07/2013; · 3.14 Impact Factor
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    ABSTRACT: Introduction: Pasireotide, a novel multireceptor targeted somatostatin analog is the first drug approved for treatment of adult patients with Cushing's disease (CD) for whom pituitary surgery is not an option or has not been curative. Areas covered: The review describes published data on efficacy and safety of pasireotide in CD patients. In particular, the review focuses on a Phase III study (CSOM230B2305) evaluating the outcomes of treatment with pasireotide at the doses of 600 and 900 µg twice daily for 12 months in 162 CD patients. This clinical trial reported a decrease in urinary free cortisol levels in the majority of patients, with a substantial reduction in nearly half and a normalization in > 25% of patients included in the study, accompanied by an improvement in clinical picture as well as a significant reduction in pituitary tumor size. Hyperglycemia appears as the most important side effect, requiring a careful monitoring and a prompt administration of glucose-lowering medications. Expert opinion: Pasireotide seems to have a promising role as medical option for CD patients who experienced a failure or not candidate for neurosurgery; its employment will probably induce in the near future significant changes in the therapeutic approach to CD.
    Expert Opinion on Orphan Drugs. 07/2013; 1(7).
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    ABSTRACT: Background: Endothelial progenitor cells (EPCs), involved in the repairing mechanisms of vascular damage, are positively correlated to IGF-1 concentrations in healthy adults. However, the levels of EPCs and their role in acromegalic patients have never been investigated. Aim: We conducted a cross-sectional study in order to assess the levels of the different phenotypes of circulating EPC in acromegalic patients. Subjects and methods: The study was performed at the Endocrinology Unit of Federico II University and at the Unit of Metabolic Diseases and Endocrinology of the Second University of Naples. Fifty-five acromegalic patients and 65 healthy controls were studied. EPCs were assessed by flow cytometry and IGF-1 by IRMA. Results: Compared with subjects of the control group, acromegalic patients showed significantly higher levels of EPCs phenotypes expressing KDR antigen, (KDR+, cells per 106 events, median and interquartile range, 44 [28-67] vs 23 [13-40] P=0.006; CD34+KDR+ 25 [18-38] vs 12 [8-17] P <0.001; CD133+KDR+ 17 [13-30] vs 8 [6-12] P <0.001; CD34+KDR+CD133+ 16 [12-25] vs 8 [6-10] P <0.001). There was a positive correlations between CD34+KDR+CD133+ cells count and IGF-1 in acromegaly group (r = 0.79, P <0.001). Conclusions: Acromegalic patients show higher circulating EPCs levels expressing KDR, positively correlated with IGF1, suggesting a role for IGF-1 in regulating the expression of this surface marker in the early phase of EPCs differentiation.
    Journal of endocrinological investigation 06/2013; · 1.65 Impact Factor
  • Ludovica Fs Grasso, Rosario Pivonello, Annamaria Colao
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    ABSTRACT: Introduction: The treatment of acromegaly aims at normalizing growth hormone (GH) and insulin-like growth factor (IGF-I) levels and controlling tumor growth. The approaches to therapy are essentially three: surgery and pharmacotherapy, alone or in combination, and radiotherapy, generally used in more aggressive tumors. Areas covered: This review focuses on the novel drug formulations being developed for medical therapy of acromegaly. Even though many efficient treatments have been made available to manage acromegaly in the last two decades, a significant number of patients remain still uncontrolled. Medical therapy represents an important therapeutic option and can be used as the first-line treatment in many patients. However, roughly 25% of patients might be considered as poor responsive or resistant to conventional long-acting somatostatin analogs (SSA) treatment. Therefore, new longer-acting SSA, oral SSA formulations, new combined therapies with weekly doses of pegvisomant, combination therapy with pegvisomant (PEG) and cabergoline (CAB) or SSA and new approaches have been proposed. New molecules are currently under investigation in clinical trials, such as the SSA multi-receptor ligand, pasireotide, which represents a promising option therapy, especially in patients not adequately controlled with currently available SSA. Further, temozolomide has been suggested as an efficient drug for treating GH-aggressive pituitary tumors resistant to conventional therapy. Expert opinion: All these novel SSA formulations and new molecules implement the available options in therapies of acromegaly to improve disease control. However, further studies are needed to define the exact role of these newer agents. The predicting factors for response to these new therapies should also be determined.
    Expert Opinion on Investigational Drugs 06/2013; · 4.74 Impact Factor

Publication Stats

5k Citations
972.41 Total Impact Points

Institutions

  • 1996–2014
    • University of Naples Federico II
      • • Department of Clinical Medicine and Surgery
      • • Department of Molecular Medicine and Medical Biotechnology
      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
  • 2002–2008
    • Erasmus MC
      • Department of Internal Medicine
      Rotterdam, South Holland, Netherlands
  • 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