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ABSTRACT: The results of dexamethasone suppression tests (DST) in the screening of subclinical hypercortisolism are not readily comparable. Aim of the present study was to review the effectiveness of overnight 1-mg DST and 8-mg DST to look for functional autonomy of clinically inapparent adrenal adenomas. Sixty-eight consecutive patients with clinically inapparent adrenal adenomas were enrolled. All patients underwent 1-mg DST. The 8-mg DST was performed in the 11 patients who had post 1-mg DST cortisol >138 nmol/l and in 11 patients who had post 1-mg DST cortisol between 50 and 138 nmol/l. The a priori probability to have autonomous cortisol secretion was defined by the presence of at least two alterations of the hypothalamic-pituitary-adrenal axis among reduced ACTH concentrations, elevated urinary free cortisol (UFC) or elevated midnight serum cortisol. Cortisol levels >138 nmol/l after the 1-mg DST increases the post-test probability of adrenal functional autonomy to 55%, whereas cortisol levels <50 nmol/l reduce the post-test probability to 8%. Cortisol levels recorded after the 8-mg DST were nonsignificantly lower than after the 1-mg DST and all the patients with cortisol >138 nmol/l after the 1-mg DST maintained cortisol above this cut-point. The 1-mg DST should be considered as the more effective test to detect autonomous cortisol secretion by a clinically inapparent adrenal adenoma when cortisol levels are >138 nmol/l, while cortisol levels <50 nmol/l reduce remarkably the post-test probability of this event. The 8-mg DST seems to replicate by large the results of the 1-mg DST.
Journal of endocrinological investigation 01/2011; 34(1):e1-5. · 1.57 Impact Factor
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ABSTRACT: Several studies suggest that intense exercise may increase the athlete's thrombotic tendency. Available data on those metabolic alteration are still conflicting and their clinical significance is still worth of interest. The aim of the present study was to investigate if widely used markers of cardiac damage such as NT-proBNP levels are affected by homocysteine concentrations during sustained sport activities.
Seventy-eight competitive, non-professional athletes were enrolled in the study; 70 healthy age matched subjects, recruited from blood donors, served as controls. Besides the general clinical determinations, the assessed variables included homocysteine, folate, vitamin B12, total and HDL cholesterol, LDH, CPK, NT-proBNP and IL-6.
The percentages of athletes with normal and elevated homocysteine levels resulted 46% and 54%, respectively. Mean NT-proBNP levels were significantly higher in athletes than in controls (1176.66 + or - 442.15 pg/mL versus 450.34 + or - 180.39 pg/mL). No correlation was found between homocysteine and NT-proBNP values.
The previously described "sport related" homocysteine is not related to other markers of cardiovascular stress such as NT-proBNP. Available data suggest that both hyperhomocysteinemia and high NT-proBNP levels in healthy young athletes could be interpreted as markers of metabolic and morphologic adaptation to training rather than a risk factor for cardio-vascular diseases.
The Journal of sports medicine and physical fitness 12/2009; 49(4):440-7. · 0.85 Impact Factor
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ABSTRACT: Automated haematological analysers still represent the gold standard for the study of reticulocyte maturation even if this technique is based on structural properties and staining affinity rather than on functional aspects. On the contrary, flow cytometry allows the simultaneous analysis of multiple cellular characteristics including functional features. Aim was to investigate whether simultaneous analysis of different reticulocyte parameters using flow cytometry may add functional information when considering their pattern of maturation. Thirty-nine healthy donors (H) and 31 haemodialysed patients on treatment with rHuEpo (HDT) were analysed. Reticulocyte counts and their stages of maturation were studied both with ADVIA 2120 and by flow cytometry. TO/CD71 scattergraph reticulocyte analysis designed a peculiar distribution which was similar among the same group of subjects (H or HDT), but different between H and HDT. distribution of the percentage of reticulocytes in low, medium and high boxes calculated by ADVIA 2120 did not show any difference between H and HDT groups, while the analysis using flow cytometry pointed out statistically significant differences between H and HDT groups in the three boxes where the TO+/CD71+ reticulocytes were localized. The present study suggests that TO/CD71 analysis was reproducible and could detect different pattern of maturation of a particular clinical setting.
International journal of laboratory hematology 02/2009; 32(1 Pt 2):65-73. · 1.30 Impact Factor
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ABSTRACT: In recent years, increased awareness and availability of proper diagnostic tools have made subclinical endocrine disease an emerging issue. The clinical impact of subtle alterations of hormonal secretion and/or action depends on the sensitivity of target cells, which shows wide interindividual variability, and within the same individual, varies among tissues and changes in particular microenvironments, e.g. when inflammation is present. Subclinical hypercortisolism is a typical example of this new approach which privileges hormonal action rather than secretion. In the present paper, we concisely review the mechanisms of genomic and non-genomic actions of glucocorticoids (GC), and the determinants of GC sensitivity, with special attention to those more investigated in relation to bone metabolism: GC receptor (GR) types, isoforms and polymorphisms, and 11beta-hydroxysteroid dehydrogenase (11beta-HSD) shuttle. Detailed knowledge of the mechanisms of GR action has opened the way to the development of novel selective GR modulators or selective GR agonists, which show promise of being efficacious for specific treatments of disease having fewer side effects. Exogenous GC excess due to the therapeutic use of GC is the most frequent cause of secondary osteoporosis. Variability of therapeutic or detrimental effects among patients and in the same patient as a function of the clinical course is nowadays recognized to depend on numerous factors. While intermediate to high doses are likely to overcome inter-individual differences in sensitivity, assessment of clinical efficacy and monitoring of adverse effects are of special importance for chronic users of low-dose GC; in these patients prediction of individual response seems still far from clinical practice. In the next future evaluation of GR polymorphisms and 11beta-HSD activities are likely to become important components of a comprehensive approach aimed to "tailor" the therapeutic strategy to the individual risk/benefit ratio.
Journal of endocrinological investigation 07/2008; 31(7 Suppl):7-15. · 1.57 Impact Factor
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D Generali,
A Dovio,
M Tampellini,
M Tucci,
S Tedoldi,
M Torta,
S Bonardi,
G Allevi,
S Aguggini,
M Milani,
A L Harris,
A Bottini,
L Dogliotti, A Angeli,
A Berruti
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ABSTRACT: Persistent circadian rhythm of bone turnover in bone metastatic breast cancer suggests greater skeletal retention of bisphosphonates if administered in the night. We assessed differential effects of night vs morning administration of zoledronic acid (ZA) on bone turnover. Forty-four breast cancer patients with bone metastases were randomised to receive intravenous ZA (4 mg) at 1100 or 2300 hours every 28 days for four times. Urinary concentration N-telopeptide of type-I collagen (NTX) and deoxypyridinolines, and serum C-telopeptide of type-I collagen (CTX), bone alkaline phosphatase (ALP), osteocalcin and Parathyroid hormone (PTH) was measured in the morning at baseline and after 4, 7, 14, 28, 56 and 84 days. Urinary ZA concentration was also measured. Zoledronic acid caused significant decreases of NTX and CTX (P<0.001), without any difference in percent changes between night and morning arms. Bone ALP and osteocalcin were also significantly affected by ZA (P=0.001), without any difference between arms. Parathyroid hormone significantly increased in both the arms; PTH increase was lower in the night arm (P=0.001). From the second administration onwards, urinary ZA level was significantly higher in the night arm (P<0.01). Administration of ZA at two opposite phases of the circadian cycle causes similar changes of bone-turnover marker levels, but has differential effects on the level of serum PTH.
British Journal of Cancer 06/2008; 98(11):1753-8. · 5.04 Impact Factor
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M Tucci,
A Mosca,
G Lamanna,
F Porpiglia,
M Terzolo,
F Vana,
C Cracco,
L Russo,
G Gorzegno,
M Tampellini,
M Torta,
G Reimondo,
M Poggio,
R M Scarpa, A Angeli,
L Dogliotti,
A Berruti
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ABSTRACT: Bone metabolic disruption that occurs in bone metastatic prostate cancer could lead to disturbances of calcium metabolism. The prognostic role of either hypocalcemia or hypercalcemia was assessed in a consecutive series of hormone-refractory bone metastatic prostate cancer patients. Serum calcium was measured in 192 patients. The presence of hypocalcemia and hypercalcemia was related with baseline biochemical and clinical characteristics and the role of these two calcium disturbances in predicting prognosis and adverse skeletal-related events (SREs) was assessed. As compared to normocalcemic patients, hypocalcemic patients (n=51) had higher tumor load in bone (P=0.005), higher plasma chromogranin A (CgA, P=0.01), serum alkaline phosphatase (P=0.01), urinary N-telopeptide (NTX, P=0.002) and lower hemoglobin values (P=0.01), while hypercalcemic patients (n=16) had higher plasma CgA (P=0.001) and serum lactate dehydrogenase values (P=0.001), higher bone pain (P=0.003) and a lower frequency of pure osteoblastic lesions (P=0.001). Hypercalcemia was significantly associated with poor prognosis: hazard ratio (HR), 1.9 (95% confidence Interval (CI) 1.2-3.3) and higher risk to develop SREs HR, 2.5 (95% CI 1.2-5.2, P=0.01), while hypocalcemia was not associated with poor prognosis. The prognostic role of hypercalcemia was maintained in multivariate analysis after adjusting for validated prognostic parameters: HR, 2.72 (95% CI 1.1-6.8, P=0.03). These data suggest that serum calcium levels should be taken into account in the clinical decision-making process of bone metastatic prostate cancer patients. Patients with asymptomatic hypercalcemia could benefit of a strict follow-up and an immediate bisphosphonate treatment. Further prospective clinical trials are needed to confirm this finding.
Prostate cancer and prostatic diseases 04/2008; 12(1):94-9. · 2.10 Impact Factor
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ABSTRACT: In endurance sport the delivery of oxygen to muscles plays a critical role. Indeed, muscle performance declines during prolonged and intense activity as a consequence of the shift from the aerobic to the anaerobic metabolism with an increase of lactate. To enhance the aerobic capacity 2 alternatives may be used: increasing either the transport or the delivery of oxygen. In this setting, blood doping is the practice of illicitly using a drug or blood product to improve athletic performance. Based on this definition, blood doping techniques may include: 1) blood transfusion (autologous or omologous); 2) erythropoiesis-stimulating substances [recombinant human erythropoietin (alpha, beta, omega), darbepoietin-alpha, continuous erythropoiesis receptor activator, hematide]; 3) blood substitutes (hemoglobin-based oxygen carriers, perfluorocarbon emulsions); 4) allosteric modulators of hemoglobin (RSR-13 and RSR-4); 5) gene doping (human erythropoietin gene transfection); 6) gene regulation (hypoxia-inducible transcription factors pathway). In the present overview we will briefly describe the above-mentioned techniques with the aim of underlining potential hematological alternatives to gene doping for increasing aerobic capacity in sport.
Journal of endocrinological investigation 03/2008; 31(2):185-92. · 1.57 Impact Factor
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A Dovio,
D Generali,
M Tampellini,
A Berruti,
S Tedoldi,
M Torta,
S Bonardi,
M Tucci,
G Allevi,
S Aguggini,
A Bottini,
L Dogliotti, A Angeli
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ABSTRACT: The variability of serum osteoprotegerin (OPG) and soluble RANKL (sRANKL) along the 24-h cycle was assessed in 20 healthy women. No rhythmic variations of serum OPG, sRANKL or sRANKL/OPG ratio were detected as a group phenomenon. Timing of sampling is unlikely to influence the results of measurements of circulating OPG and sRANKL.
Physiological bone turnover shows diurnal variations. The aim of the study was to assess variability of OPG and sRANKL serum levels along the 24-h cycle.
Blood was collected from 20 healthy women (median age 31 years, range 25-65 years) at 4-h intervals between 08:00 and 24:00 and at 2-h intervals between 24:00 and 08:00. Serum albumin, cortisol, osteocalcin (OC), C-terminal telopeptide of type I collagen (CTX), OPG and total sRANKL were measured. Temporal variations were assessed by the COSINOR model.
Circadian rhythms of cortisol and albumin documented a normal synchronization within the circadian structure. Serum OC and CTX showed rhythmic variations, peaking at night-time. Rhythmic variations of serum OPG, sRANKL and sRANKL/OPG ratio were not detected as a group phenomenon. On an individual basis, rhythmic changes were detected in ten patients for OPG and eight patients for sRANKL, with very small amplitudes and heterogeneous acrophases.
The absence of consistent rhythmic variations of circulating OPG and sRANKL levels may reflect the absence of rhythmic variations of their expression in the bone microenvironment. Were this the case, the nocturnal rise of bone resorption should be accounted for by different, not RANKL/OPG-mediated factors. Since circulating OPG and sRANKL may derive from sources other than bone, rhythmicity could be masked by non-rhythmic or non-synchronized rhythmic expression in these sources. Timing of sampling is unlikely to influence the results of measurements of circulating OPG and sRANKL.
Osteoporosis International 02/2008; 19(1):113-7. · 4.58 Impact Factor
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P Mulatero,
G Leotta,
M Terzolo,
P Maffei,
S Monticone,
E Saglio,
A Viola,
F Tosello,
E C Degli Uberti, A Angeli,
F Veglio
High Blood Pressure & Cardiovascular Prevention 09/2007; 14(3):145.
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ABSTRACT: Hyperhomocysteinemia is a well-established risk factor for cardiovascular diseases. The aims of this study were to longitudinally investigate, in a group of elite athletes, plasma homocysteine levels and to search for relationships with the muscular workload and the vitamin status. One hundred and three athletes (59 males and 44 females, respectively) were evaluated in different periods: namely the recovery period, the training period, and the competition period; 84 subjects (37 males and 47 females), served as controls. The evaluation sessions consisted in blood sampling and medical examination. The percentages of athletes with normal and elevated homocysteine levels, defined by levels below or above the limit of 15 mumol/l, were 68.0% and 32.0%, respectively, in the recovery period, and these percentages remained unchanged during the following periods. In the control group, relevant percentages were 92.9% and 7.1%, respectively. The comparison between plasma homocysteine of male and female, evaluated in the recovery period, showed significantly higher levels in the former group (18.8+/-18.0 micromol/l vs 10.7+/-5.9 micromol/l, p<0.001 respectively), as well as a higher proportion of individuals with hyperhomocysteinemia (24/59 vs 9/44, p<0.05). The correlation analyses showed a weak but significant negative correlation between homocysteine and folate in the three periods considered, while no significant relationship was observed between homocysteine and creatine-kinase. We found excess prevalence of hyperhomocysteinemia in elite athletes of winter sports. A strategy to understand which mechanisms in these athletes subserve hyperhomocysteinemia is essential in order to reduce the potential risk for future cardio-vascular morbidity and mortality.
Journal of endocrinological investigation 06/2007; 30(5):367-75. · 1.57 Impact Factor
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ABSTRACT: Adrenal cysts are infrequently observed, since less than 500 cases have been reported in Western literature. Adrenal cysts are conventionally divided into four categories: epithelial, parasitic, endothelial, and hemorrhagic. They are characterized by different etiological and pathological features. Some authors suggest that endothelial and hemorrhagic cysts are related and may represent a spectrum of lesions. We report herein the case of an adrenal hemorrhagic pseudocyst that simulated adrenocortical cancer and argue on the clinical clues for a differential diagnosis with other adrenal tumors.
Journal of endocrinological investigation 04/2007; 30(3):256-8. · 1.57 Impact Factor
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Experimental and Clinical Endocrinology & Diabetes 03/2007; 115(3):166-70. · 1.69 Impact Factor
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ABSTRACT: To overcome the limitation of the currently adopted direct method to detect recombinant Human Erythropoietin (rHuEpo) abuse in sport, indirect analysis of blood parameters are increasingly used as part of the anti-doping strategies. The aim of the present work is to identify whether immunophenotype modifications on erythroid cells may be indicative of previous rHuEPO administration. The study was conducted on dialyzed patients under treatment with rHuEPO (DPT). Dialyzed patients without rHuEPO therapy (DP) and volunteer donors (H) were used as controls. The analysis of erythroid cells immunophenotype, performed using a multiparametric flow cytometry technique, showed a peculiar pattern of CD71 expression following rHuEPO treatment. In particular CD71 showed an increased expression in mature and intermediate reticulocytes and a surprisingly decreased expression in immature reticulocytes. In conclusion, the analysis of reticulocyte maturation stages with TO/CD71 double staining may be considered as a valid alternative indirect method for the detection of rHuEPO abuse.
Journal of biological regulators and homeostatic agents 02/2007; 21(3-4):79-88. · 5.18 Impact Factor
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International Journal of Integrative Biology. 01/2007;
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Annals of the New York Academy of Sciences 12/2006; 586(1):17 - 28. · 3.15 Impact Factor
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ABSTRACT: Aims of the study were: to determine the differences in the mechanical, hormonal and lactate responses to a high-intensity isokinetic exercise in two groups of endurance-trained athletes (EA, n = 11) and sedentary subjects (SED, n = 11); to evaluate the relationships between the hormonal and lactate responses; to evaluate the effects of the training status on the pituitary responsiveness to the exercise.
EA and SED completed, for each leg, 4 sets of 20 maximal concentric contractions of the knee extensor muscle groups at 180 degrees s-1 angular velocity. Blood and saliva for hormonal and lactate determinations were sampled before, immediately after the test and during the subsequent recovery of 2 hours.
The exercise was completed by all subjects and elicited significant mechanical and biochemical responses both in EA and in SED subjects. No differences were found between the two groups both in the mechanical performances and in the increases of lactate and hormones of the pituitary-adrenal axis or in the comparison of the slopes of adrenocorticotropic hormone (ACTH), cortisol, and dehydroepiandrosterone recovery after the peak. The correlation analyses showed significant positive relationships between lactate peak values and percentages of change for ACTH (r2 = 0.16, P < 0.05), salivary cortisol (r2 = 0.42, P < 0.01), and serum cortisol (r2 = 0.56, P < 0.001).
The adrenocortical activation was found, in this particular setting, at least partly dependent on the muscular lactate production, while no effect of the training status on the pituitary responsiveness to exercise was evident, as it was indirectly confirmed by no abnormalities in the rates of hormonal recovery after the exercise session.
The Journal of sports medicine and physical fitness 10/2006; 46(3):494-500. · 0.85 Impact Factor
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ABSTRACT: Adreno-cortical carcinoma (ACC) is a rare cancer with poor prognosis. Complete surgical resection of the primary tumor and, when feasible, of the local and distant metastases offers the best prospects for long-term survival; conversely, the role of systemic therapy in patients developing unresectable metastatic disease is unclear. We describe the case of a young female patient (36 yr) who presented with an androgen-releasing metastatic ACC. Treatment consisted of five courses of chemotherapy with etoposide, doxorubicin and cisplatin (EDP scheme) plus oral mitotane, which caused the complete disappearance of distant metastases and reduction of the primary tumor, as documented by serial computed tomography (CT) scans of the chest and the abdomen. Moreover, during treatment, clinical and biochemical resolution of the hypersecretory status occurred. The left adrenal gland was then removed and histopathological examination showed extensive tumor necrosis and the absence of viable cancer cells. The patient is currently alive without evidence of recurrence 3 yr after surgery. This report shows that chemotherapy plus mitotane could result in complete pathological remission, which may be a surrogate for long-term progression- free survival in metastatic ACC patients.
Journal of endocrinological investigation 07/2006; 29(6):560-2. · 1.57 Impact Factor
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ABSTRACT: The focus of this work was to study the serum interleukin-6 (IL-6) response to total hip replacement. Twenty-one patients received an uncemented total hip prosthesis. Venous samples for IL-6 determination were drawn before and after surgery. The IL-6 response was significant, and a peculiar heterogeneity of response was apparent: the medians of peak levels (82.3 pg/ml) and of areas under the response curve (51.8 pg/ml) distinguished between IL-6 high responders (HR) and IL-6 low responders (LR; p<0.0001). No difference was found in the gender composition of these groups, whereas the HR patients were older than the LR patients (p<0.05). The amount of IL-6 increase was found to correlate with patient age, whereas its slope was found to correlate with the duration of the surgical procedure. Moreover, the HR group presented a higher degree of hyperthermia in the days after surgery compared with the LR patients, without evidence of differences in postoperative complications, time to mobilisation, or length of stay in hospital. The main finding of our study was the evidence of a remarkable variability between individuals in the IL-6 response to surgery. Future studies are needed to identify the factors involved in the regulation of the cytokine response to surgery.
International Orthopaedics 06/2006; 30(3):172-6. · 2.03 Impact Factor
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S Bovio,
A Cataldi,
G Reimondo,
P Sperone,
S Novello,
A Berruti,
P Borasio,
C Fava,
L Dogliotti,
G V Scagliotti, A Angeli,
M Terzolo
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ABSTRACT: Adrenal incidentalomas, defined as masses discovered incidentally during imaging investigation of non-adrenal disorders, have become a rather common finding in clinical practice. The prevalence is not well characterized and varies among studies. The aim of the present study was to perform a prospective evaluation of the prevalence of adrenal incidentalomas among subjects undergoing computerized tomography (CT) scan of the chest in a screening program of lung cancer (Tic TAC study) in Piedmont, a region of Northwestern Italy. This evaluation included 520 subjects (382 males and 138 females, aged between 55-82 yr), referred to our hospital from April to December 2001. Twenty-three patients with adrenal masses were identified: 21 adrenal adenomas, 1 myelolipoma, and 1 metastasis of lung cancer. Therefore, the overall prevalence of adrenal lesions was 4.4%, and that of benign adrenal masses was 4.2%. This prevalence is higher than those found in previous CT scan series reported in the literature, probably because of the use of high-resolution CT scanning technology. Another factor that influenced our results is that subject age is skewed towards the decades characterized by a greater occurrence of adrenal masses. The outcome of this study confirms that we are presently able to identify incidentally discovered adrenal masses more often than in early years and that the prevalence of adrenal incidentalomas on CT images is approaching that of autopsy series. The present study provides a reliable estimate of the prevalence of adrenal incidentaloma with currently used CT scanners. Notwithstanding that our subjects were at increased risk of lung cancer, the rate of adrenal metastases was low. We think that the present results can be generalized even if we may disclose the lack of histological diagnosis.
Journal of endocrinological investigation 05/2006; 29(4):298-302. · 1.57 Impact Factor
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ABSTRACT: Physical exercise is associated with increases of serum and salivary levels of cortisol. The concomitant increase in serum lactate has been implicated as one of the mechanisms responsible for adrenocortical activation. We evaluated the responses of serum lactate and serum and salivary cortisol to an acute bout of high-intensity isokinetic exercise in eleven non-competitive and twenty competitive athletes (NCA and CA, respectively). The latter group was composed of endurance- and power-trained athletes (EA and PA, respectively). Aims of the study were to determine interindividual differences in the lactate and cortisol responses as a function of type and intensity of training and to search for relationships both between lactate and cortisol production and between serum and salivary cortisol levels. The isokinetic exercise test elicited significant cortisol and lactate responses. No difference was evident in the lactate responses between NCA and CA, while the PA showed a higher response during and after the exercise in comparison to EA (peak levels immediately after the exercise: PA 15.0 +/- 1.5 mmol/l vs. EA 11.1 +/- 2.6 mmol/l, p < 0.01). Serum cortisol was higher in the CA in comparison to the NCA group at 30 and 120 minutes after the termination of the exercise, while no differential response was evident between EA and PA groups. Salivary cortisol response was higher in the CA group in comparison to NCA immediately after the exercise and at 90 and 120 minutes after the termination and was higher in PA in comparison to EA at 60, 90, and 120 minutes after the termination (peak levels at 60 minutes: PA 51.2 +/- 18.5 nmol/l vs. EA 27.5 +/- 20.8 nmol/l, p < 0.05). No significant correlations were found between serum or salivary cortisol and lactate levels. The relationship between serum and salivary cortisol was markedly non-linear, the slope of the serum-saliva regression line being lower for serum cortisol concentrations over 500 nmol/l than for concentrations below that value (0.019 and 0.037, respectively, p < 0.01). We have confirmed in this particular setting the existence of an important adrenocortical response that can be reliably and non invasively assessed by a serial saliva sampling and have supported the concept that cortisol and lactate responses to a high-intensity isokinetic exercise are independent. The interindividual differences in cortisol changes are likely to be related to the training status and mode as well as to the correspondence between the evaluation protocol and the discipline individually performed.
International Journal of Sports Medicine 11/2005; 26(9):747-55. · 2.43 Impact Factor
