F. Pecori Giraldi
University of Milan
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Featured researches published by F. Pecori Giraldi.
International Journal of Andrology | 2010
F. Pecori Giraldi; Paola Toja; Barbara Filippini; J. Michailidis; Massimo Scacchi; M. Stramba Badiale; F. Cavagnini
Symptoms and signs of male hypogonadism span all organ systems, including the cardiovascular apparatus. The electrocardiographic QT interval reflects cardiac ventricular repolarization and, if prolonged, increases the risk of malignant arrhythmias. QT interval duration is similar in boys and girls during childhood, but shortens in males after puberty and experimental studies suggest that testosterone is a major contributor to shortening of QT interval in men. The aim of the present pilot study was to assess the duration of ventricular repolarization in adult males with primary or secondary hypogonadism. Standard ECG recordings were performed in 26 men (mean age 39.2 +/- 2.17 years) with pituitary or testicular hypogonadism and repeated in 15 patients during testosterone replacement. Twenty-six age-matched control men were also analysed. Measured QT intervals were corrected for heart rate according to Bazzetts formula (QTc = QT/radical RR interval). The prevalence of prolonged QTc was considerably higher in hypogonadal patients (four of 26 men) than in control men (none, p < 0.05) and in the general, healthy population (<2.5%). QTc interval normalized on hormone replacement therapy in the four patients presenting prolonged QTc in the hypogonadal state. Heart rate and left ventricular mass did not differ among the two groups and no known QT-prolonging factor was apparent in patients with abnormal QTc interval. In conclusion, a high number prolonged QT interval measurements was observed in hypogonadal men who may therefore be at increased risk for cardiac arrhythmias. This observation reveals an additional feature of male hypogonadism, which may benefit from testosterone replacement therapy.
Journal of Neuroendocrinology | 2007
F. Pecori Giraldi; L. G. Bucciarelli; Andrea Saccani; Massimo Scacchi; Samantha Pesce; Marco Losa; F. Cavagnini
Ghrelin is a brain‐gut peptide with wide‐ranging endocrine, metabolic, cardiovascular and neural effects. Ghrelin, like its synthetic counterparts, the growth hormone (GH) secretagogues, has been shown to markedly stimulate adrenocorticotrophic hormone (ACTH) and cortisol secretion in humans and the ACTH‐releasing effect of GH secretagogues is even greater in patients with pituitary ACTH‐secreting tumours. Furthermore, these tumours synthesize ghrelin itself, suggesting an intrapituitary ghrelin circuit. The aim of the present study was to evaluate the effect of ghrelin on ACTH secretion by human pituitary corticotroph tumours in vitro to test the functionality of this circuit. Nine ACTH‐secreting pituitary tumours (four microadenomas, five macroadenomas) were collected during surgery and incubated with 10–100 nM human ghrelin or with 10 nM human corticotrophin‐releasing hormone (CRH). Control experiments were performed in rat anterior pituitary primary cultures. ACTH secretion was assessed after 4 h and 24 h incubation by immunometric assay. After 4 h of incubation with ghrelin, medium ACTH concentrations were two‐ to ten‐fold higher compared to ACTH concentrations in unstimulated wells. The ACTH‐releasing effect of ghrelin was significantly less than the response elicited by 10 nM CRH (up to 40‐fold) Similar results were obtained after 24 h of incubation and a superimposable response pattern was observed in rat anterior pituitary primary cultures. The present study demonstrates that the endogenous GH secretagogue, ghrelin, stimulates ACTH secretion directly from human tumoural corticotrophs, as well as from normal rat pituitary, and indicates that the marked ACTH release elicited by ghrelin in patients with Cushings disease in vivo is due, at least in part, to its action on the pituitary tumour. However, the reversal of the response pattern reported in vivo, with ghrelin proving a lesser stimulant than CRH in vitro, suggests that additional, suprapituitary mechanisms are involved in the in vivo response. Moreover, these data uphold the concept of a functional intratumoural ghrelin paracrine circuit in human corticotroph adenomas.
Journal of Endocrinological Investigation | 2004
Pietro Putignano; F. Pecori Giraldi; F. Cavagnini
Glucocorticoids are important regulators of glucose, lipid and protein metabolism, acting mainly in the liver, adipose tissue and muscle. Chronic glucocorticoid excess is associated with clinical features, such as insulin resistance, visceral obesity, hypertension, and dyslipidemia, which also represent the classical hallmarks of the metabolic syndrome. Elevenß-hydroxysteroid dehydrogenase type 1 (11ß-HSD-1), a key intracellular enzyme which catalyses the conversion of inactive cortisone to active cortisol, has been implicated in the development of the metabolic syndrome. The shift of this reaction towards cortisol generation may lead to tissutal overexposure to glucocorticoids even with normal circulating cortisol levels. The most robust evidence in support of a pathogenetic role of this enzyme in the development of the metabolic syndrome has been reported in experimental animals, whereas results of human studies are less convincing with several case control and cross-sectional studies showing an association between with 11ß-HSD-1 setpoint and individual features of the metabolic syndrome. However, recent data suggest a tissue-specific rather than systemic alteration of this shuttle, with down-regulation in liver but up-regulation in adipose tissue and skeletal muscle of obese subjects. New techniques based on direct tissutal estimates of cortisol/cortisone ratios are clearly needed to precisely assess the role of enzyme in all target tissues. If confirmed, these results would prompt the development of selective and tissuespecific 11ß-HSD-1 inhibitors to decrease insulin resistance and treat the metabolic syndrome, thus contrasting the harmful effects of glucocorticoid excess in peripheral tissues
Clinical Endocrinology | 1993
Cecilia Invitti; F. Pecori Giraldi; A. Tagliaferri; Massimo Scacchi; A. Dubini; Francesco Cavagnini
OBJECTIVE Galanin is believed to play a role in the control of prolactin (PRL) secretion in the rat. Such a role is uncertain in humans where the neuropeptide is expressed by the corticotrophs. However, in clinical conditions of enhanced ACTH secretion, increased PRL levels are often observed. Therefore, we evaluated the effect of galanin infusion on serum PRL levels in patients with Cushings disease and in control subjects. For comparison, the PRL responses to TRH and metoclopramide were also investigated in the same patients.
Journal of Endocrinological Investigation | 2006
Massimo Scacchi; Elena Valassi; A. I. Pincelli; Letizia Maria Fatti; F. Pecori Giraldi; Paola Ascoli; R. Viarengo; B. Cestaro; F. Cavagnini; R. Cazzola
Objective: Adult GH deficiency (GHD) syndrome is characterized by increased risk of atherosclerosis and hence of cardio- and cerebrovascular mortality. Oxidative stress appears to play an important role in early atherogenesis. Oxidized LDL represents an important predictor of cardiovascular risk and is mainly responsible for oxidative damage of the endothelium. Its concentrations are increased in GHD, but the association between this abnormality and oxidative stress is still unclear, due to the discordant results yielded by the few available studies. Design and methods: In 13 GHD patients, plasma lipid peroxide concentrations were measured before and after a 4-month treatment with recombinant human GH (rhGH) and compared with those of 13 age-and sex-matched controls. In the same subjects, the so-called “lag-time”, an index of anti-oxidant activity and thus of plasma oxidative balance, was also measured using a fluorescence kinetics method. Results: Before treatment, peroxide levels were significantly higher in patients than in controls (374.0±31.52 vs 268.0±8.51 U.C., p<0.01), whereas the lag-time was significantly lower (113.0±10.70 vs 168.0±7.80 min, p<0.01). RhGH administration to patients resulted both in a significant decrease in lipid peroxide levels (from 374.0±31.52 to 336.0±33.17 U.C., p<0.01) and a significant prolongation of lag-time (from 113.0±10.70 to 144.0±15.00 min, p<0.01). After treatment, both parameters were no longer significantly different in patients and controls. Lagtime and peroxide levels at baseline did not show any correlation with IGF-I concentrations in GHD patients. After replacement therapy, however, lag-time was positively (r2= 0.62, p<0.01), and peroxide levels negatively (r2=0.41, p<0.05), correlated with IGF-I levels. Conclusions: These data support the view that adult GHD syndrome is characterized by an unbalance between pro- and anti-oxidant factors with marked preponderance of the former. This abnormality, likely contributing to the increased atherogenic risk of GHD patients, is corrected by short-term GH administration at a dose able to increase, although not to fully normalize, IGF-I levels.
Journal of Neuroendocrinology | 2011
F. Pecori Giraldi; Luca Pagliardini; Maria Francesca Cassarino; Marco Losa; Giovanni Lasio; F. Cavagnini
Patients with Cushing’s disease are known to present a variable secretory response to stimulatory and inhibitory challenges. Evaluation of the secretory behaviour of pituitary adrenocorticotrophic hormone (ACTH)‐secreting adenomas in vitro aids in the comprehension of its behaviour in vivo; however, given the small size of these tumours and the consequent paucity of material available to in vitro studies, a comprehensive study on the secretory behaviour of human corticotroph tumours has not yet been performed. The present study aimed to assess the spectrum of responses to the two main corticotroph modulators, corticotrophin‐releasing hormone (CRH) and dexamethasone, in a large series of human ACTH‐secreting pituitary tumours. Seventy‐two ACTH‐secreting pituitary tumours were collected during surgery and established in culture. Specimens were incubated with 10 nm CRH and/or 10 nm dexamethasone for 4 h and 24 h. Secretion in unstimulated, control wells was set at 100% and changes in ACTH concentrations by at least 20% were considered as responses. Parallel experiments in 12 rat anterior pituitary primary cultures were evaluated. A marked ACTH increase was observed during incubation with CRH in 70% of tumoural specimens at 4 h (range 124–3500% of control wells) and in 57% at 24 h (range 122–3323%). Dexamethasone reduced ACTH secretion in almost 50% of tumours (range 78–2% of control at 4 h; 76–3% at 24 h), whereas it did not affect ACTH medium levels in 30% of specimens and induced a paradoxical ACTH increase in 20% of tumours (range 130–327% of control at 4 h; 156–348% at 24 h). By comparison, CRH uniformly increased ACTH levels in rat anterior pituitary primary cultures (mean 745 ± 84% at 4 h; 347 ± 25% at 24 h), whereas dexamethasone decreased ACTH levels by 40–50% in all experiments. In conclusion, the present study of a large series of human ACTH‐secreting pituitary tumours in vitro revealed a considerable variability in the responses to CRH and dexamethasone. This finding indicates the existence of multiple corticotroph tumoural phenotypes and may account for the different responses to physiological and pharmacological modulators in vivo.
Journal of Neuroendocrinology | 2010
F. Pecori Giraldi; Samantha Pesce; Paola Maroni; Luca Pagliardini; Giovanni Lasio; Marco Losa; F. Cavagnini
Prepro‐thyrotrophin‐releasing hormone (TRH) (178–199), a 22‐amino acid cleavage product of the TRH prohormone, has been postulated to act as an adrenocorticotrophin hormone (ACTH)‐release inhibitor. Indeed, although in vitro evidence indicates that this peptide may inhibit basal and stimulated ACTH secretion in rodent anterior pituitary primary cultures and cell lines, not all studies concur and no study has as yet evaluated the effect of this peptide in Cushing’s disease. The present study aimed to test the effect of preproTRH(178–199) in human tumoural corticotrophs. Twenty‐four human ACTH‐secreting pituitary tumours (13 macroadenomas, 11 microadenomas) were collected during surgery and incubated with 10 or 100 nm preproTRH(178–199). ACTH secretion was assessed after 4 and 24 h of incubation by immunometric assay and expressed relative to levels observed in control, unchallenged wells (= 100%). Parallel experiments were performed in rat anterior pituitary primary cultures. A clear inhibition of ACTH secretion at 4 and 24 h was observed in 12 specimens (for 10 nm ppTRH: 70 ± 4% control at 4 h and 83 ± 5% control at 24 h; for 100 nm ppTRH: 70 ± 4% control at 4 h and 85 ± 5% control at 24 h), whereas a mild and short‐lasting stimulatory effect was observed in three tumours and no changes in ACTH secretion in the remaining nine tumoural specimens. The inhibitory effect of preproTRH(178–199) was more evident in macroadenomas and significantly correlated with sensitivity to dexamethasone inhibition. Significant inhibition of ACTH secretion by preproTRH(178–199) in rat pituitary cultures was observed after 24 h of incubation. The present study conducted in a large series of human corticotroph tumours shows that preproTRH(178–199) inhibits tumoural ACTH secretion in a sizable proportion of specimens, in close relation to the size of the tumour and its sensitivity to glucocorticoid negative feedback. This appears a promising avenue of research and further studies are warranted to explore the full scope of preproTRH(178–199) as a regulator of ACTH secretion.
Journal of Endocrinological Investigation | 2005
F. Pecori Giraldi; Letizia Maria Fatti; F. Cavagnini
Isolated ACTH deficiency is a rare disorder often presenting with long-standing aspecific symptoms combined with unusual clinical presentations. We here describe a patient in whom pericardial effusion was part of the clinical presentation and fully resolved on steroid at replacement dosage, highlighting the possibility of hypoadrenalism as an additional cause of pericardial effusion of unknown origin.
Journal of Endocrinological Investigation | 2011
F. Pecori Giraldi; F. Cassarino; Luca Pagliardini; V. Asnaghi; F. Cavagnini
Proopiomelanocortin (POMC) is crucial for several life-essential functions and its regulation has been studied extensively in the past decades. The first studies provided the framework for POMC promoter activity, namely the identification for the major response elements contained in the promoter, e.g., the glucocorticoid response element, the Nur response element, while subsequent studies showed the importance of cooperation and interplay between transcription factors to achieve optimal promoter activity. The involvement of constitutive repressors of POMC transcription, such as Bmp4, provided the latest clues to our understanding of POMC promoter activity. This increased knowledge benefits the clinician as it allows genetic testing and early recognition of patients with congenital ACTH deficiency due to mutations in TPIT and paves the way to new medical treatments in Cushing’s disease. The present review will illustrate the current standing on regulation of the human POMC promoter, focusing on its activity in corticotropes.
General and Comparative Endocrinology | 2012
F. Pecori Giraldi; Luca Pagliardini; Maria Francesca Cassarino; F. Martucci; Antonella Sesta; Luigi Castelli; E. Montanari; H.A. Schmid; F. Cavagnini
SOM230 (pasireotide, Signifor), a recently developed somatostatin analog, has been tested in ACTH-secreting pituitary tumors with promising results. No study has yet evaluated whether this analog also directly affects adrenal steroid production. The aim of the current study was to evaluate whether SOM230 modulates corticosteroid secretion by normal adrenals in vitro. Primary cultures from normal human and rat adrenals were incubated with 10-100 nM SOM230 with and without 10nM ACTH. Dose-response studies with 1 nM-1 μM SOM230 were performed on rat adrenals. Cortisol/corticosterone levels in medium were measured after 4 and 24h. SOM230 (10nM) significantly increased corticosteroid levels after 24h incubation in both human (36.4 ± 0.43 ng/well vs 27.7 ± 3.17 ng/well, p<0.05) and rat (16.2 ± 1.16 ng/well vs 11.6 ± 0.92 ng/well p<0.05) adrenals; lesser effects were observed with 100 nM SOM (33.4 ± 2.59 ng/well vs 27.7 ± 3.17 ng/well p<0.05; 13.4 ± 0.82 ng/well vs 11.6 ± 0.92 ng/well, N.S. vs baseline secretion for human and rat adrenals, respectively). Dose-response curves confirmed maximal effect at 10nM SOM230. The corticosteroid secretory response to ACTH was unaffected by SOM230 co-incubation. In conclusion, SOM230 exerts a moderate stimulatory effect on adrenal corticosteroid secretion in vitro. This argues against a direct adrenal involvement in the clinical efficacy of SOM230 in patients with ACTH-secreting pituitary tumors and widens the known range of action of SOM230.