Rosario Pivonello

University of Naples Federico II, Napoli, Campania, Italy

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Publications (283)1118.49 Total impact

  • Annamaria Colao · Renata S Auriemma · Rosario Pivonello
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    ABSTRACT: In nearly all cases, acromegaly is caused by excess GH from a pituitary adenoma, resulting in elevated circulating levels of GH and, subsequently, IGF-1. Treatment goals are to eliminate morbidity and restore the increased mortality to normal rates. Therapeutic strategies aim to minimize tumor mass and normalize GH and IGF-1 levels. Somatostatin analogues are the medical treatment of choice in acromegaly, as first-line or post-surgical therapy, and have proven efficacy in pituitary tumor volume reduction (TVR). Here we review the effects of somatostatin analogue therapy on pituitary tumor volume in patients with acromegaly. TVR with somatostatin analogues may be mediated by direct anti-proliferative effects via activation of somatostatin receptors, or by indirect effects, such as angiogenesis inhibition, and is more pronounced when they are administered as first-line therapy. Various studies of first-line treatment with octreotide LAR have shown significant TVR in ≥73 % of patients. First-line treatment with lanreotide Autogel has shown evidence of TVR, although more studies are needed. In a recent randomized, double-blind, 12-month trial in 358 medical-treatment-naïve acromegaly patients, significant TVR was achieved by 81 % of patients administered pasireotide LAR and 77 % administered octreotide LAR. Pre-operative somatostatin analogue therapy may also induce TVR and improve post-operative disease control compared with surgery alone. TVR is progressive with prolonged treatment, and decreased IGF-1 levels may be its best predictor, followed by age and degree of GH decrease. However, TVR does not always correlate with degree of biochemical control. Somatostatin analogues (first- or second-line treatment) are the mainstay of medical therapy and, as first-line medical therapy, are associated with significant pituitary TVR in most patients.
    Pituitary 08/2015; DOI:10.1007/s11102-015-0677-y · 3.20 Impact Factor
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    ABSTRACT: Introduction: In patients with acromegaly, somatostatin analogs (SSA) represent the first choice medical treatment. The long-acting SSA have been found to be effective in controlling growth hormone and IGF-I levels in a high percentage of patients, resulting in an improvement in the quality of life; moreover, these peptide analogs have a proven safety record and are generally well tolerated. Areas covered: The most commonly reported adverse events include injection-site discomfort and erythema, gastrointestinal (GI) disturbances such as diarrhea, abdominal pain, nausea and vomiting, biliary sludge or gallstones, and abnormal glucose metabolism. Most SSA-related adverse events are transient and of mild-to-moderate intensity, and the prevalence of such effects markedly and progressively decreases during treatment, so that treatment discontinuations due to adverse events are rare and commonly related to GI disturbances. Cholelithiasis represents the most serious complication of SSA, but is generally asymptomatic, and has been reported in 3 - 56% of patients. Whereas the effect of SSA on glucose metabolism is still controversial, several pieces of evidence have confirmed a modest and transient negative impact on glucose homeostasis. Also the novel SSA pasireotide has shown a safety profile as expected for a SSA, except for the degree of hyperglycemia. Expert opinion: On the basis of these findings, a close and careful monitoring of gallbladder ultrasound and glucose levels is recommended in patients receiving SSA for medical treatment of acromegaly.
    Expert Opinion on Drug Safety 08/2015; 14(8):1213-1226. DOI:10.1517/14740338.2015.1059817 · 2.91 Impact Factor
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    ABSTRACT: In Kallmann syndrome (KS), congenital hypogonadism is associated with olfactory impairment. To evaluate flavor perception-related disability in KS patients, 30 patients with KS, 12 with normosmic hypogonadism (nIHH), 24 with acquired anosmia (AA), and 58 healthy controls entered the study. All participants completed questionnaires concerning dietary habits, olfaction-related quality of life (QoL), and self-determined olfactory, flavor, and taste abilities prior to undergoing standardized olfactometry and gustometry. Each subject underwent flavor testing, using orally administered aqueous aromatic solutions, identifying 21 different compounds by choosing each out of 5 alternative items. Flavor score (FS) was calculated as the sum of correct answers (range 0-21). Flavor perception by self-assessment was similar between KS, nIHH, and controls, and was mostly reduced only in AA. FS was similar between KS (5.4 ± 1.4) and AA (6.4 ± 1.9), and lower than in nIHH (16.2 ± 2.4, p < 0.001) and controls (16.8 ± 1.7, p < 0.0001). FS showed strong reproducibility, and correlated with olfactory scores in the overall population. KS and AA patients identified aromatics eliciting trigeminal stimulation better than pure odorants. Olfaction-related QoL was more impaired in AA than in KS. We report significant flavor impairment in KS. This contrasts with routine clinic evidence; KS patients, in contrast with AA, do not complain of flavor perception impairment, perhaps owing to the congenital nature of the dysfunction. Flavor perception impairment should be considered a specific KS disability, because of important detrimental effects on physical and mental health and on QoL. KS patients should also be advised of this impairment in order to prevent accidental and life-threatening events.
    Endocrine 07/2015; DOI:10.1007/s12020-015-0690-y · 3.88 Impact Factor
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    ABSTRACT: Ectopic Cushing's Syndrome (ECS) can be a diagnostic challenge with the hormonal source difficult to find. This study analyzes the accuracy of imaging studies in ECS localization. Systematic review of medical literature for ECS case series providing individual patient data on at least one conventional imaging technique (CT/MRI) and one of (111)In-pentetreotide (OCT), (131)/(123)I-Metaiodobenzylguanidine (MIBG), (18)F-fluoro-2-deoxyglucose (FDG-PET), (18)F-fluorodopa (F-DOPA-PET), (68)Ga-DOTATATE-PET/CT or (68)Ga-DOTATOC-PET/CT scan ((68)Ga-SSTR-PET/CT). Evidence Summary: The analysis comprised 231 patients (female 50.2%; 42.6±17 years). Overall, 52.4% had 'overt' (121/231), 18.6% 'occult' and 29% 'covert' ECS. Tumors were located in the lung (55.3%), mediastinum-thymus (7.9%), pancreas (8.5%), adrenal glands (6.4%), gastrointestinal tract (5.4%), thyroid (3.7%) and other sites (12.8%), and primary tumors were mostly bronchial neuroendocrine tumors [NETs] (54.8%), pancreatic-NETs (8%), mediastinum-thymus-NETs (6.9%) gastrointestinal NETs (5.3%), pheochromocytoma (6.4%), neuroblastoma (3.2%), and medullary thyroid carcinoma (3.2%). Tumors were localized by CT in 66.2% (137/207), MRI in 51.5% (53/103), OCT in 48.9% (84/172), FDG-PET in 51.7% (46/89), F-DOPA-PET in 57.1% (12/21), MIBG in 30.8% (4/13), (68)Ga-SSTR-PET/CT in 81.8% (18/22) of cases. Molecular imaging discovered 79.1% (53/67) of tumors unidentified by conventional radiology, with OCT the most commonly used, revealing the tumor in 64%, followed by FDG-PET in 59.4%. F-DOPA-PET was used only in 7 coverts (sensitivity 85.7%). Notably, (68)Ga-SSTR-PET/CT had 100% sensitivity among covert cases. Nuclear medicine improves the sensitivity of conventional radiology when tumor site identification is problematic. OCT offers a good availability/reliability ratio and FDG-PET was proven useful; (68)Ga-SSTR-PET/CT use was infrequent, despite offering the highest sensitivity.
    The Journal of Clinical Endocrinology and Metabolism 07/2015; DOI:10.1210/JC.2015-1589 · 6.21 Impact Factor
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    ABSTRACT: In GSDIa, glucose 6-phosphate (G6P) accumulates in the endoplasmic reticulum (ER); in GSDIb, G6P levels are reduced in ER. G6P availability directly modulates the activity of 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1), an ER-bound enzyme playing a key role in the development of the metabolic syndrome (MS). To evaluate the prevalence of MS and Insulin Resistance (IR) in GSDIa and GSDIb patients. This was a prospective study. All the enrolled patients were followed at the Department of Pediatrics "Federico II" University of Naples for 10 years. Clinical and biochemical parameters of MS and the presence of IR were recorded. The results were correlated with the biochemical parameters of GSDI-related metabolic control. 10 GSDIa patient (median age 12.10 ± 1.50), 7 GSDIb patients (median age 14.90 ± 2.20 were enrolled in the study. They were compared to 20 and 14 age and sex matched controls, respectively. 10 GSDIa patients (median age 24.60 ± 1.50) and 6 GSDIb patients (median age 25.10 ± 2.00) completed the 10-year-follow-up. At the end of the study the patients' data were compared to 10 and 6 age and sex matched controls, respectively. At study entry, 20 % GSDIa patients had MS and 80 % showed 2 criteria for MS. GSDIa patients showed higher HOMA-IR than controls and GSDIb patients (p < 0.001, p < 0.05), respectively. Baseline ISI was lower in GSDIa than controls (p < 0.001). QUICKI was significantly lower in GSDIa than in controls (p < 0.001). At the end of the study 70 % of GSDIa patients had MS and 30 % showed 2 criteria for MS. HOMA-IR was higher in GSDIa than controls (p < 0.01). Baseline ISI was higher in GSDIb than controls (p < 0.005) and GSD1a (p < 0.05). QUICKI was lower in GSD1a patients than in controls (p < 0.03). VAI was higher in GSDIa patients than controls (p < 0.001) and GSDIb patients (p = 0.002). Our data showed high prevalence of IR and MS in GSDIa patients. We speculate a possible role of 11βHSD1 modulation by G6P availability. We suggest a routine metabolic assessment in GSDIa patients.
    Orphanet Journal of Rare Diseases 07/2015; 10(1):91. DOI:10.1186/s13023-015-0301-2 · 3.36 Impact Factor
  • Rosario Pivonello · Monica De Leo · Alessia Cozzolino · Annamaria Colao
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    ABSTRACT: Cushing's disease (CD), or pituitary-dependent Cushing's syndrome (CS), is a severe endocrine disease caused by a corticotroph pituitary tumor, associated with increased morbidity and mortality. The first-line treatment for CD is pituitary surgery, which is followed by disease remission in around 75%, and relapse in around 15%, of patients during the ten-year period after surgery. Patients with persistent or recurrent CD require additional treatments, including pituitary radiotherapy, adrenal surgery and/or medical therapy. Pituitary radiotherapy is effective in controlling cortisol excess in a large percentage of patients, but it is associated with a considerable risk of hypopituitarism. Adrenal surgery is followed by a rapid and definitive control of cortisol excess nearly in the totality of patients, but it induces adrenal insufficiency. Medical therapy has recently acquired a more important role compared to the past, due to the recent employment of novel compounds able to control cortisol secretion or action. Currently, medical therapy is used as a presurgical treatment, particularly for severe disease, or as post-surgical treatment, in case of failure or incomplete surgical tumor resection, or as bridging therapy before, during and after radiotherapy while waiting for disease control or, in selected cases, as primary therapy, mainly when surgery is not an option. The adrenal-directed drug ketoconazole is the most commonly used drug, mainly because of its rapid action, whereas the glucocorticoid receptor antagonist, mifepristone, is highly effective in controlling clinical comorbidities, mainly glucose intolerance, thus being a useful treatment for CD when it is associated with diabetes mellitus. Pituitary-directed drugs have the advantage of acting at the site responsible for CD, the pituitary tumor. Among this group of drugs, the dopamine agonist cabergoline and the somatostatin analogue pasireotide result in disease remission in a consistent subgroup of patients with CD. Recently, pasireotide has been approved for the treatment of CD when surgery has failed or when surgery is not an option, and mifepristone has been approved for the treatment of CS when associated with impairment of glucose metabolism in case of lack of a surgical indication. Recent experience suggests that the combination of different drugs may be able to control cortisol excess in a great majority of patients with CD.
    Endocrine reviews 06/2015; 36(4):er20131048. DOI:10.1210/er.2013-1048 · 21.06 Impact Factor
  • 05/2015; DOI:10.1530/endoabs.37.EP94
  • 05/2015; DOI:10.1530/endoabs.37.EP48
  • 05/2015; DOI:10.1530/endoabs.37.GP.19.08
  • 05/2015; DOI:10.1530/endoabs.37.GP.01.03
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    ABSTRACT: Vitamin D (25(OH)D) levels have been associated with cardiovascular disease. Thus, the aim of our study was to investigate the association of 25(OH)D levels with coronary heart disease (CHD) in 698 consecutive type 2 diabetic outpatients. 698 consecutive type 2 diabetic outpatients (25.2 % men, age 66 ± 9 years) and 100 (90 % men, age 65 ± 13 years) age-matched non-diabetic volunteers were enrolled. 25(OH)D assay and the main cardiovascular risk factors were explored. 25(OH)D concentration was 22 ± 10 ng/ml in control subjects and 18.23 ± 10 ng/ml in diabetic patients (p < 0.01). The prevalence of hypovitaminosis D was higher in diabetic patients than in control subjects (90 vs. 83 %, p < 0.01). Diabetic subjects with hypovitaminosis D had higher prevalence of high values of A1C (p < 0.01), BMI (p < 0.01), LDL cholesterol (p < 0.01), triglycerides (p < 0.01), and glycemia (p < 0.01) than their vitamin D-sufficient counterparts. 25(OH)D and HDL cholesterol were lower (p < 0.01), while BMI (p < 0.01), age (p < 0.01), systolic (p < 0.01) and diastolic blood pressure (p < 0.01), diabetes duration (p < 0.01), A1C (p < 0.01), glycemia (p < 0.01), fibrinogen (p < 0.01), triglycerides (p < 0.01), and total (p < 0.01) and LDL cholesterol (p < 0.01) were higher in diabetic subjects with CHD than diabetic subjects without CHD. At the logistic regression analysis, the association of vitamin D with CHD was lost, while sex (p = 0.026), diabetes duration (p = 0.023), and age (p = 0.024) were the most powerful predictors of CHD. The current study demonstrates that 25(OH)D does not have a direct effect on CHD but may have an indirect effect mediated by cardiovascular risk factors such as diabetes duration, age, and sex.
    Endocrine 05/2015; DOI:10.1007/s12020-015-0609-7 · 3.88 Impact Factor
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    ABSTRACT: Endogenous Cushing's syndrome (CS), a rare endocrine disorder characterized by cortisol hypersecretion, is associated with psychiatric and neurocognitive disorders. Major depression, mania, anxiety, and neurocognitive impairment are the most important clinical abnormalities. Moreover, patients most often complain of impairment in quality of life, interference with family life, social, and work performance. Surprisingly, after hypercortisolism resolution, despite the improvement of the overall prevalence of psychiatric and neurocognitive disorders, the brain volume loss at least partially persists and it should be noted that some patients may still display depression, anxiety, panic disorders, and neurocognitive impairment. This brief review aimed at describing the prevalence of psychiatric and neurocognitive disorders and their characterization both during the active and remission phases of CS. The last section of this review is dedicated to quality of life, impaired during active CS and only partially resolved after resolution of hypercortisolism.
    Frontiers in Neuroscience 04/2015; 9:129. DOI:10.3389/fnins.2015.00129 · 3.66 Impact Factor
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    ABSTRACT: PurposeThe aim of this prospective study was to measure the thickness of the circumpapillary retinal nerve fibre layer (cpRNFL) and the ganglion cell complex (GCC) using spectral domain optical coherence tomography (SD-OCT) in a cohort of consecutive de novo patients with pituitary macroadenomas without chiasmal compression.Patients and methodsTwenty-two consecutive patients with pituitary macroadenoma without chiasmal compression (16 men, 6 women, aged 45.2±14.6 years, 43 eyes) entered the study between September 2011 and June 2013. Among them, 31.8% harboured a growth hormone-secreting pituitary adenoma, 27.3% a prolactin-secreting pituitary adenoma, 27.3% a corticotrophin-secreting pituitary adenoma, and 13.6% a non-secreting pituitary tumour. Eighteen subjects (nine females, nine males, mean age 36.47±6.37 years; 33 eyes) without pituitary adenoma, with normal ophthalmic examination, served as controls. In both patients and controls, cpRNFL and GCC thicknesses were measured by SD-OCT.ResultsPatients were significantly older (P=0.02) than controls. Best corrected visual acuity, intraocular pressure, colour fundus photography, and automatic perimetry test were within the normal range in patients and controls. Conversely, cpRNFL (P=0.009) and GCC (P<0.0001) were significantly thinner in patients than in controls. The average GCC (r=0.306, P=0.046) significantly correlated with the presence of arterial hypertension. OCT parameters did not differ significantly between patients with a tumour volume above the median and those with a tumour volume below the median.Conclusion Pituitary macroadenomas, even in the absence of chiasmal compression, may induce GCC and retinal nerve fibre layer thinning. SD-OCT may have a role in the early diagnosis and management of patients with pituitary tumours.Eye advance online publication, 27 March 2015; doi:10.1038/eye.2015.35.
    Eye (London, England) 03/2015; 29(6). DOI:10.1038/eye.2015.35 · 2.08 Impact Factor
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    ABSTRACT: Dear Editor,The points raised by Molfino et al. [1] in their comment to our article [2] open a new scenario for the management of skeletal fragility in patients with endogenous hypercortisolism. Sarcopenia is a well-known complication of glucocorticoid excess [3] potentially involved in the pathogenesis of fragility fractures [4]. However, the clinical challenge is to understand whether and how sarcopenia reverts after resolution of hypercortisolism. Most of the considerations highlighted in our recent paper [2] concerning the outcome of skeletal fragility in patients with cured hypercortisolism may be also applied to sarcopenia. As a matter of fact, there is evidence to suggest that muscle structure and function may persist abnormal for several months after remission of hypercortisolism [5], prompting the search for specific therapeutic approach to sarcopenia.As correctly indicated by Molfino et al., adequate nutrition, physical activity [6], and vitamin D supplementation [7] have ana ...
    Osteoporosis International 03/2015; 26(5). DOI:10.1007/s00198-014-2876-1 · 4.17 Impact Factor
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    ABSTRACT: Pasireotide is the first medical therapy officially approved for the treatment of adult patients with Cushing's disease (CD) who experienced a failure of pituitary surgery or are not candidates for surgery and require medical therapeutic intervention. The current study aimed at investigating the effects of long-term treatment with pasireotide (up to 24 months) on tumor mass in a group of patients with CD, participating to a phase III study. Fourteen CD patients entered the phase III clinical trial CSOM230B2305 at Naples Center, and eight (seven women, one man, aged 38.9 ± 17.6 years), including seven with a microadenoma and one with a macroadenoma, received treatment with pasireotide at the dose of 600-1200 µg bid for at least 6 months, and were considered for the analysis of the study. These eight patients were subjected to the evaluation of pituitary tumor volume by pituitary MRI, together with the evaluation of urinary cortisol levels, at baseline and every 6 months for the entire period of treatment. Pasireotide treatment induced full disease control in 37.5 % and partial disease control in 37.5 % after 6 months, whereas full and partial disease control after 12 months was obtained in 28.6 % and in 57.1 % of patients, respectively. A significant (>25 %) reduction in tumor volume was found in 62.5 % and in 100 % of patients, after 6 and 12 months, respectively. In particular, after 6 months, a slight tumor shrinkage (between 25.1 and 50 %) was observed in 25 %, moderate (50.1-75 %) in 25 %, and marked (>75 %) in 12.5 % of patients, whereas after 12 months, a slight tumor shrinkage was observed in 43 %, moderate in 14 %, and marked in 43 % of patients. In 25 % of patients (two patients), a marked tumor shrinkage was recorded, with tumor mass disappearance in one case; this tumor shrinkage was associated to rapid and sustained biochemical remission up to 24 months of continuous pasireotide treatment. These two cases represent the first cases with a documentation of such a notable effect of pasireotide on tumor mass. Pasireotide induces significant tumor shrinkage in 62.5 % of patients after 6 months and in 100 % of patients after 12 months, and occasionally induces a radiological disappearance of the tumor. This evidence supports and strengthens the role of pasireotide as medical treatment specifically addressed to patients with CD, particularly in those who had unsuccessful pituitary surgery, or are not candidates for surgery.
    Endocrine 03/2015; DOI:10.1007/s12020-015-0557-2 · 3.88 Impact Factor
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    ABSTRACT: The prevalence of erectile dysfunction (ED) and its correlates in men with acromegaly has never been investigated. The aim of this study was to evaluate sexual function in men with acromegaly. Multicenter-based, retrospective analysis of a nonselected series of 57 acromegalic subjects (mean age: 52.7 ± 14.2 years) was performed. Acromegalic subjects reporting ED (n = 24) were compared with matched ED patients without acromegaly or pituitary disease (controls), selected from a cohort of more than 4,000 subjects enrolled in the Florence Sexual Medicine and Andrology Unit. Patients were interviewed using Structured Interview on Erectile Dysfunction (SIEDY) structured interview, a 13-item tool for the assessment of ED-related morbidities. Several clinical and biochemical parameters were taken. Penile color Doppler ultrasound (PCDU) was performed in a subgroup of 37 acromegalic subjects. ED was reported by 42.1% of acromegalic subjects. After adjusting for age and testosterone, acromegalic subjects with ED had a higher prevalence of hypertension and more often reported an impairment of sleep-related erections and a longer smoking habit. Accordingly, acromegaly-associated ED was characterized by a higher organic component and worse PCDU parameters. No relationship between ED and testosterone levels or other acromegaly-related parameters was found. However, acromegalic subjects with severe ED reported a longer disease duration. In a case-control analysis, comparing acromegalic subjects with ED-matched controls free from acromegaly (1:5 ratio), acromegalic men had a worse ED problem and a higher organic component of ED, as derived from SIEDY score. In line with these data, acromegalic patients with ED had a higher prevalence of major adverse cardiovascular events history at enrollment and lower PCDU parameters. Subjects with complicated acromegaly are at an increased risk of developing ED, especially those with cardiovascular morbidities. Our data suggest including a sexual function evaluation in routine acromegaly follow-up. Lotti F, Rochira V, Pivonello R, Santi D, Galdiero M, Maseroli E, Balestrieri A, Faustini-Fustini M, Peri A, Sforza A, Colao A, Maggi M, and Corona G. Erectile dysfunction is common among men with acromegaly and is associated with morbidities related to the disease. J Sex Med **;**:**-**. © 2015 International Society for Sexual Medicine.
    Journal of Sexual Medicine 03/2015; 12(5). DOI:10.1111/jsm.12859 · 3.15 Impact Factor
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    ABSTRACT: In the management of adrenocorticotropic hormone (ACTH)-dependent Cushing's syndrome, inferior petrosal sinus sampling (IPSS) provides information for the endocrinologist, the neurosurgeon, and the neuroradiologist. To the endocrinologist who performs the etiological diagnosis, results of IPSS confirm or exclude the diagnosis of Cushing's disease with 80%-100% sensitivity and over 95% specificity. Baseline central-peripheral gradients have suboptimal accuracy, and stimulation with corticotropin-releasing hormone (CRH), possibly desmopressin, has to be performed. The rationale for the use of IPSS in this context depends on other diagnostic means, taking availability of CRH and reliability of dynamic testing and pituitary imaging into account. As regards the other specialists, the neuroradiologist may collate results of IPSS with findings at imaging, while IPSS may prove useful to the neurosurgeon to chart a surgical course. The present review illustrates the current standpoint of these 3 specialists on the role of IPSS.
    Neurosurgical FOCUS 02/2015; 38(2):E5. DOI:10.3171/2014.11.FOCUS14766 · 2.11 Impact Factor
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    ABSTRACT: Introduction: Hyperprolactinemia and hypogonadism are reportedly associated with an impaired metabolic profile. The current study aimed at investigating the effects of testosterone replacement and cabergoline (CAB) treatment on the metabolic profile in male hyperprolactinemic patients. Patients and methods: Thirty-two men with prolactinomas, including 22 with total testosterone (TT) <8 nmol/l (HG, 69%) and 10 with TT >8 nmol/l (non-HG, 31%), were entered in the study. In all patients, metabolic parameters were assessed at diagnosis and after 12- and 24-month treatment. Results: Compared to non-HG patients, at baseline the HG patients had higher waist circumference (WC). TT significantly correlated with body mass index (BMI). Twelve-month CAB induced PRL normalization in 84%. HG prevalence significantly decreased (28%) and non-HG prevalence significantly increased (72%). Anthropometric and lipid parameters, fasting insulin (FI), insulin sensitivity index (ISI0), homeostatic model assessment of insulin secretion (HOMA-β) and homeostatic model assessment of insulin resistance (HOMA-IR) significantly improved compared to baseline. TT was the best predictor for FI. Percent change (Δ) of TT significantly correlated with ΔCholesterol, ΔWeight and ΔBMI. Compared to non-HG patients, the HG patients had a higher weight, BMI, WC and HOMA-β. In HG, testosterone replacement was started. After 24 months, PRL normalized in 97%. HG prevalence significantly decreased (6%) and non-HG prevalence significantly increased (94%). Anthropometric and lipid parameters, FI, ISI0, HOMA-β and HOMA-IR significantly improved compared to baseline, with FI, ISI0, HOMA-β and HOMA-IR further ameliorating compared to the 12-month evaluation. Compared to non-HG patients, the HG patients still had a higher weight, BMI and WC. Conclusions: In hyperprolactinemic hypogonal men, proper testosterone replacement induces a significant improvement in the metabolic profile, even though the amelioration in the lipid profile might reflect the direct action of CAB.
    Neuroendocrinology 01/2015; 101(1). DOI:10.1159/000371851 · 4.37 Impact Factor
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    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; 18(5). DOI:10.1007/s11102-014-0618-1 · 3.20 Impact Factor

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7k Citations
1,118.49 Total Impact Points


  • 1997–2015
    • University of Naples Federico II
      • • Department of Molecular Medicine and Medical Biotechnology
      • • Department of Neuroscience and Reproductive and Odontostomatological Sciences
      Napoli, Campania, Italy
  • 2014
    • Erasmus MC
      • Department of Internal Medicine
      Rotterdam, South Holland, Netherlands
  • 1999–2004
    • Second University of Naples
      • Faculty of Medicine and Surgery
      Caserta, Campania, Italy
  • 1998
    • Università degli Studi di Torino
      Torino, Piedmont, Italy