B Ambrosi

University of Milan, Milano, Lombardy, Italy

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Publications (194)897.44 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Context. The long-term consequences of subclinical hypercortisolism (SH) in patients with adrenal incidentalomas (AI) are unknown. Setting-Patients. In this retrospective multicentric study, 206 AI patients with a ≥5 yrs follow-up (median, range: 72.3, 60-186 months) were enrolled. Intervention-Main Outcome Measure. The adrenocortical function, adenoma size, metabolic changes and incident cardiovascular events (CVE) were assessed. We diagnosed SH in 11.6% of patients, in the presence of cortisol after 1mg-dexamethasone suppression test (1mg-DST) >5 μg/dL (138 nmol/L) or ≥2 out of: low ACTH, increased urinary free cortisol and 1mg-DST >3 μg/dL (83 nmol/L). Results. At baseline, age, CVE and type-2 diabetes (T2DM) prevalence were higher in patients with than in patients without SH (62.2±11yrs vs 58.5±10yrs; 20.5% vs 6%; 33.3% vs 16.8%, respectively, P<0.05). SH and T2DM were associated with prevalent CVE (OR 3.1, 95%CI 1.1-9.0 and OR 2.0, 95%CI 1.2-3.3, respectively) regardless of age. At the end of the follow-up, SH was diagnosed in 15 patients without SH at baseline. An adenoma size >2.4 cm was associated with the risk of developing SH (SN 73.3%, SP 60.5%, P=0.014). Weight, glycemic, lipidic and blood pressure control worsened in 26%, 25%, 13% and 34% of patients, respectively. A new CVE occurred in 22 patients. SH was associated with the worsening of ≥2 metabolic parameters (OR 3.32, 95%CI 1.6-6.9) and with incident CVE (OR 2.7, 95%CI 1.0-7.1) regardless of age and follow-up. Conclusion. SH is associated with the risk of incident CVE. Beside the clinical follow-up, in patients with an AI >2.4 cm also a long-term biochemical follow-up is required, for the risk of SH development.
    The Journal of Clinical Endocrinology and Metabolism 12/2014; DOI:10.1210/jc.2013-3527 · 6.31 Impact Factor
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    ABSTRACT: We describe a patient affected by Cushing's disease due to the presence of double pituitary adenomas, one located within the anterior pituitary and the other in the infundibulum associated with a remnant of Rakthe's pouch. Cure was achieved only after the infundibulum lesion was surgically removed. CASE REPORT: A 38-year-old female presented with unexplained weight gain, hirsutism, amenorrhea, asthenia, recurrent cutaneous micotic infections and alopecia. Hormonal studies indicated Cushing's disease and MRI showed an enlarged pituitary gland with a marked and homogeneous enhancement after injection of gadolinium and an enlarged infundibulum with a maximum diameter of 8 mm. As a venous sampling of the inferior petrosal sinus after 10 mu g iv desmopressin stimulation revealed a central to peripheral ACTH ratio consistent with a pituitary ACTH-secreting tumor, transphenoidal explorative surgery was performed and a 4-mm pituitary adenoma immunopositive for ACTH was disclosed and removed. Since postoperative hormonal evaluation showed persistent hypercortisolism, confirmed by dynamic tests, the patient again underwent surgery by transcranial access and the infundibulum mass was removed. Histology and immunochemistry were consistent with an ACTH-secreting adenoma. A few months after the second operation, cushingoid features were significantly reverted and symptoms improved. CONCLUSION: Although Cushing's patients bearing multiple adenomas have already been documented, the presence of two adenomas both immunohistochemically positive for ACTH is a very rare cause of Cushing's disease and this is the first report of a case of double ACTH-producing adenomas, one located in the pituitary gland and one attached to the stalk.
    Hormones (Athens, Greece) 11/2014; 13(4). DOI:10.14310/horm.2002.1503 · 1.24 Impact Factor
  • Journal of endocrinological investigation 11/2014; 5(6):409-15. DOI:10.1007/BF03350542 · 1.55 Impact Factor
  • Journal of endocrinological investigation 07/2014; 33(7):509-10. DOI:10.1007/BF03346635 · 1.55 Impact Factor
  • L Barbetta, C Dall'Asta, B Ambrosi
    Journal of endocrinological investigation 07/2014; 23(7):491-2. DOI:10.1007/BF03343762 · 1.55 Impact Factor
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    ABSTRACT: Abstract Not Available.
    The Journal of Clinical Endocrinology and Metabolism 05/2014; 99(8):jc20141183. DOI:10.1210/jc.2014-1183 · 6.31 Impact Factor
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    ABSTRACT: Objective A polymorphism in the promoter region of the IGF-I gene has been linked to serum IGF-I levels, risk of diabetes and cardiovascular diseases with conflicting results. Aim of this study was to investigate the impact of this polymorphism on the short- (1 yr, n=98) and long- (5 yrs, n=50) term metabolic response to rhGH in GHD adults.Design and Methods Prospective study on GHD adults. Different genotypes were studied by microsatellite method. According to the most frequent 192 bp allele (19 CA-repeats) subjects were divided in homozygous (19/19), heterozygous (19/X) and non-carriers (X/X).Results Basal characteristics of patients as well as their response to rhGH in terms of decrease in BF% and increase in IGF-I levels were not different in the three genotypes groups. Conversely, after 1-year rhGH, a significant worsening of insulin sensitivity (i.e. increase in fasting glucose levels and HOMA-IR) and a significant improvement in lipid profile (i.e. reduction in total- and LDL-cholesterol) was recorded only in homozygous subjects. In the long-term, insulin sensitivity was restored in all the patients, while a significant improvement in lipid profile was observed in homozygous and heterozygous, but not in non-carriers. No difference in rhGH dose among groups was recorded throughout study.Conclusions In GHD adults, the presence of the wild type allele in the IGF-I gene promoter may enhance sensitivity to either negative or positive metabolic changes induced by rhGH.
    European Journal of Endocrinology 11/2013; DOI:10.1530/EJE-13-0600 · 3.69 Impact Factor
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    ABSTRACT: Parathyroid function in Myotonic Dystrophy (DM) patients has been poorly investigated. Parathyroid and muscle parameters were assessed in 31 male DM1 (44±2years), 13 male DM2 (56±2years) and 32 healthy controls. Hyperparathyroidism was diagnosed in 18% of patients without differences between DM types. In all DM patients, hyperparathyroidism was associated with normocalcemia but one with hypercalcemia. DM patients presented significantly higher PTH and lower vitamin D (25OHD) compared with controls, also considering seasonality. Severe vitamin D deficiency (25OHD<10ng/ml) was diagnosed in 40% and hypovitaminosis D (25OHD<30ng/ml) occurred in 88% of DM patients. About one-third of DM1 presented hypophosphatemia associated with elevated PTH levels. Serum 25OHD levels negatively correlated with PTH and with body fat mass. Considering DM1 patients, serum PTH levels positively correlated with CTG triplet repeats. Furthermore, PTH levels negatively correlated with total modified Medical Research Council (MRC) and positively with Muscular Impairment Rating Scale (MIRS). By contrast, in DM2 patients muscle assessment did not show any correlation with parathyroid function. In conclusion, we arrived at the following: 1) severe vitamin D deficiency is common in DM patients and it is associated with secondary hyperparathyroidism; 2) primary hyperparathyroidism, though rare, may occur; 3) increased adiposity in DM may be a risk factor for hypovitaminosis D; and 4) high serum PTH levels may indicate a muscle impairment, at least in DM1.
    Journal of the neurological sciences 06/2013; DOI:10.1016/j.jns.2013.06.008 · 2.26 Impact Factor
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    ABSTRACT: Objective:Effects of GH replacement in patients with GH deficiency (GHD) after a cure for acromegaly so far have been poorly studied, although its prevalence among acromegalic patients may reach the 60%. The aim of the study was to evaluate whether metabolic parameters and quality of life are improved by GH replacement in patients with prior acromegaly and severe GHD.Design and Methods:This was a prospective study on 42 GHD subjects [22 men, mean age (sd): 48 ± 10]: 10 acromegalics treated with recombinant human GH (group A), 12 acromegalics who refused treatment (group B), and 20 subjects operated for nonfunctioning pituitary adenoma on recombinant human GH (group C). Serum IGF-I levels, lipid profile, glucose levels (fasting and after an oral glucose tolerance test), glycosylated hemoglobin, insulin resistance (homeostasis model assessment insulin resistance index), anthropometric parameters (body mass index, waist circumference, body composition), and quality of life (Questions on Life Satisfaction-Hypopituitarism Z-scores) were evaluated at baseline and after 12 and 36 months.Results:At baseline, group B showed higher IGF sd score than group A and C, as well as better quality of life and higher post-oral glucose tolerance test glucose levels than group A. After 12-months, similarly in group A and C, the IGF-I sd score significantly increased, and body composition and lipid profile improved, without deterioration of glucose tolerance. Quality of life significantly improved too, and the baseline difference between group A and B disappeared. Results were confirmed after 36 months.Conclusions:In GHD acromegalic patients, GH therapy improved body composition, lipid profile, and quality of life as in patients with GHD due to nonfunctioning pituitary adenoma, without negative effects on glucose metabolism. GH replacement therapy should be considered in these patients, as in patients with GHD from other causes.
    The Journal of Clinical Endocrinology and Metabolism 08/2012; 97(11). DOI:10.1210/jc.2012-2477 · 6.31 Impact Factor
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    ABSTRACT: Context: Cushing's syndrome may remain unrecognized among patients referred for metabolic syndrome; thus, a proactive screening has been suggested in certain patient populations with features of the disorder. However, conflicting data have been reported on the prevalence of Cushing's syndrome in patients with type 2 diabetes. Objective: Our aim was to evaluate the prevalence of unsuspected Cushing's syndrome among outpatients with type 2 diabetes. Design and Setting: This was a cross-sectional prospective study in 24 diabetes clinics across Italy. Patients: Between June 2006 and April 2008, 813 patients with known type 2 diabetes without clinically overt hypercortisolism were evaluated. Follow-up of the study was closed in September 2010. Patients were not selected for characteristics conferring a higher pretest probability of hypercortisolism. Patients underwent a first screening step with the 1-mg overnight dexamethasone suppression test. Results: Forty patients failed to suppress serum cortisol less than 5.0 μg/dl (138 nmol/liter) and underwent a standard 2-d, 2-mg dexamethasone suppression test, after which six patients (0.6% of the overall series) failed to suppress cortisol less than 1.8 μg/dl (50 nmol/liter), receiving a definitive diagnosis of Cushing's syndrome that was adrenal dependent in five patients. Four patients were cured, being able to discontinue, or reduce, the glucose-lowering agents. Conclusions: The present data do not support widespread screening of patients with type 2 diabetes for Cushing's syndrome; however, the disorder is less rare than previously thought when considering epidemiology of type 2 diabetes. Our results support a case-finding approach in patients with uncontrolled diabetes and hypertension despite appropriate treatment.
    The Journal of Clinical Endocrinology and Metabolism 07/2012; 97(10):3467-75. DOI:10.1210/jc.2012-1323 · 6.31 Impact Factor
  • Journal of endocrinological investigation 12/2011; 34(11):889-90. DOI:10.1007/BF03346735 · 1.55 Impact Factor
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    ABSTRACT: BACKGROUND AND AIM: Growth Hormone Deficiency (GHD) is characterized by increased visceral fat accumulation. Echocardiographic epicardial fat thickness is a new marker of visceral adiposity. Aim of the present study was to evaluate whether epicardial fat thickness can significantly change and therefore serve as a marker of visceral fat reduction after short-term rhGH replacement therapy in patients with adult-onset GHD. METHODS AND RESULTS: Echocardiographic epicardial fat thickness was measured in 18 patients (10 M, 8 F, age 48 ± 11.8 yrs, BMI 29 ± 5.9 kg/m(2)) with adult-onset GHD, at baseline and after 6 and 12 months of rhGH therapy and in 18 healthy matched controls, at baseline. Echocardiographic epicardial fat thickness, conventional anthropometric and metabolic parameters, body fat percentage and quality of life were also evaluated. Epicardial fat thickness in adult GHD patients was higher than in controls (9.8 ± 2.8 vs 8 ± 3 mm, p < 0.05). Epicardial fat thickness significantly decreased after 6-months of rhGH replacement therapy (from 9.8 ± 2.8 to 7.0 ± 2.3 mm, P < 0.01, i.e. -29% from baseline). After 12 months of rhGH replacement therapy, epicardial fat thickness showed a further significant decrease (from 7.0 ± 2.3 to 5.9 ± 3.1 mm, P < 0.01, i.e. -40% from baseline). No significant changes in BMI or waist circumference after 6 or 12 months of rhGH therapy were observed. CONCLUSIONS: Echocardiographic epicardial fat thickness may represent a valuable and easy marker of visceral fat and visceral fat changes during rhGH replacement treatment in patients with adult-onset growth hormone deficiency.
    Nutrition, metabolism, and cardiovascular diseases: NMCD 11/2011; DOI:10.1016/j.numecd.2011.09.001 · 3.88 Impact Factor
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    ABSTRACT: In patients with adrenal incidentalomas (AIs), cross-sectional studies suggested the presence of an association between subclinical hypercortisolism (SH) and an increased prevalence of vertebral fractures (VFx) and spinal deformity index (SDI), which is a clinical index of bone quality. No longitudinal studies investigated the incidence of VFx and SDI changes over time in SH. The aim of this study was to evaluate VFx risk and SDI changes in SH over time. One-hundred-three consecutive AI patients were studied at baseline and after 12 and 24 months. Patients were divided into SH(+) (n = 27) and SH(-) (n = 76) groups on the basis of the presence of two or more among urinary free cortisol greater than 70 µg/24 hours, serum cortisol after 1-mg dexamethasone suppression test greater than 3.0 µg/dL, and adrenocorticotropic hormone (ACTH) less than 10 pg/mL in 2 or more of the 3 evaluations. At baseline and after 24 months, bone mineral density (BMD) by dual-energy X-ray absorptiometry and the presence of VFx and SDI by summing the grade of deformity for each vertebra were evaluated. At the end of follow-up, the SH(+) group showed a higher prevalence of VFx (81.5%) as compared with baseline (55.6%, p = .04) and a worsening of SDI (2.11 ± 1.85 versus 1.11 ± 1.47, p = .032) associated with SH regardless of age, gender, body mass index , BMD, baseline SDI, menopause duration [odds ratio (OR) = 12.3, 95% confidence interval (CI) 4.1-36.5, p = .001]. The incidence of new vertebral fractures was higher in the SH(+) group (48%) than in the SH(-) group (13%; p = .001). It is concluded that subclinical hypercortisolism is associated with an increased risk of VFx and a possible deterioration of bone quality.
    Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 08/2011; 26(8):1816-21. DOI:10.1002/jbmr.398 · 6.59 Impact Factor
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    ABSTRACT: Newborns with congenital hypothyroidism (CH) have an increased risk for congenital heart defects (CHD) due to a common embryonic developmental program between thyroid gland and heart and great vessels. Our objective was to investigate the prevalence and origin of thyroid disorders in young patients with CHD. We conducted a prospective observational study between January 2007 and January 2009 in academic Pediatric Cardiosurgery and Endocrinology. Patients included 324 children (164 males, 160 females, aged 0.2-15.4 yrs) with CHD. Subjects underwent hormonal and genetic screening. Serum TSH and thyroid hormone levels were assessed. Two CHD patients were diagnosed with CH at the neonatal screening (1:162). Mild hypothyroidism (serum TSH > 4.0 μU/ml) was diagnosed and confirmed 6 months later [TSH = 5.4 ± 1.5 μU/ml; free T(4) = 1.3 ± 0.2 ng/dl (normal values 0.8-1.9)] in 37 children (11.5%) who were negative at neonatal screening. Hypothyroidism was not related to type of CHD, whereas TSH levels positively correlated with serum N-terminal pro-type B natriuretic peptide levels. Biochemical and ultrasound findings consistent with thyroid autoimmunity were present in three of 37 hypothyroid children (8.1%). One patient had hemiagenesis (2.7%). Variations in candidate genes were screened in CHD patients. NKX2.5 coding sequence was normal in all samples. A 3-Mb microdeletion in 22q11.2 was detected in three patients (8.3%), whereas only known polymorphisms were identified in TBX1 coding sequence. CHD patients have an increased risk for both CH (10-fold higher) and acquired mild hypothyroidism (3-fold higher). Unrecognized mild hypothyroidism may negatively affect the outcome of CHD children, suggesting that thyroid function should be repeatedly checked. Thyroid autoimmunity and 22q11.2 microdeletions account for small percentages of these cases, and still unknown mechanisms underline such a strong association.
    The Journal of Clinical Endocrinology and Metabolism 04/2011; 96(7):E1115-9. DOI:10.1210/jc.2011-0057 · 6.31 Impact Factor
  • The Journal of Clinical Endocrinology and Metabolism 01/2011; 96(1):22-3. DOI:10.1210/jc.2010-2011 · 6.31 Impact Factor
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    Journal of endocrinological investigation 12/2010; 33(11):852-3. DOI:10.1007/BF03350353 · 1.55 Impact Factor
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    ABSTRACT: A relationship between thyroid function and obesity seems likely, mainly influenced by the insulin resistance. Whether variations in TSH and/or thyroid hormones, within a normal range, can influence body weight or if obesity per se can alter thyroid function has not been clarified so far. Further studies are necessary to assess the link between thyroid function and body weight, that must consider not only changes of thyroid hormones, but also body fat distribution, obesity duration and the state of low grade inflammation. It is recognized that thyroid function is linked not only to body mass index, but also to body composition and, particularly, to the amount and percentage of fat mass.
    Minerva medica 10/2010; 101(5):363-70. · 1.20 Impact Factor
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    ABSTRACT: A common polymorphic variant of GH receptor (exon 3 deletion, d3GHR) has been linked with increased response to recombinant human GH (rhGH) in some patients with or without GH deficiency (GHD). The aim of the study was to investigate the impact of the GHR genotype on the phenotype of GHD adults and on the metabolic effect of rhGH therapy. Prospective study of GHD patients evaluated before and during short- (1 year, n=100) and long-term (5 years, n=50) rhGH therapy. Effects of rhGH on IGF1 levels, body composition (body fat percentage, BF%), body mass index, lipid profile, and glucose homeostasis (fasting insulin and glucose, insulin sensitivity indexes) were evaluated according to the presence or the absence of the d3GHR variant. The different genotype did not influence basal phenotype of GHD. Short-term rhGH determined normalization of IGF1 levels, decrease in BF%, and worsening of insulin sensitivity, independently from the presence of the d3GHR allele. A significant increase in high-density lipoprotein cholesterol occurred in the d3GHR group. Normalization of IGF1 levels and decrease in BF% were maintained after 5 years. Insulin sensitivity restored to basal values, though in d3GHR patients fasting glucose remained significantly higher than at baseline. After both 1 and 5 years, percentage of subjects with impaired glucose tolerance, similar in the two groups at baseline, decreased in fl/fl while doubled in d3GHR patients. In this last group, a long-term significant reduction in total and low-density lipoprotein cholesterol was also observed. The functional difference of d3GHR may influence some metabolic effects of rhGH on GHD adults.
    European Journal of Endocrinology 09/2010; 163(3):361-8. DOI:10.1530/EJE-10-0317 · 3.69 Impact Factor
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    ABSTRACT: It is unknown whether the metabolic effects of the removal of an adrenal incidentaloma (AI) can be predicted by the assessment of cortisol hypersecretion before surgery. To evaluate the accuracy of several criteria of hypothalamic-pituitary-adrenal axis activity in predicting the metabolic outcome after adrenalectomy. Retrospective longitudinal study. In 55 surgically treated AI patients (Group 1) before surgery and in 53 nontreated AI patients (Group 2) at the baseline, urinary free cortisol (UFC), cortisol after 1 mg overnight dexamethasone-suppression test (1 mg-DST), ACTH, and midnight serum cortisol (MSC) were measured. In Groups 1 and 2, metabolic parameters were evaluated before and 29.6 ± 13.8 months after surgery and at the baseline and after 35.2 ± 10.9 months respectively. The improvement/worsening of weight, blood pressure, glucose, and cholesterol levels (endpoints) was defined by the presence of a >5% weight decrease/increase and following the European Society of Cardiology or the ATP III criteria respectively. The accuracy of UFC, 1 mg-DST, ACTH, and MSC, singularly taken or in combination, in predicting the improvement/worsening of ≥ 2 endpoints was calculated. The presence of ≥ 2 among UFC>70 μg/24 h (193 nmol/l), ACTH<10 pg/ml (2.2 pmol/l), 1 mg-DST>3.0 μg/dl (83 nmol/l) (UFC-ACTH-DST criterion) had the best accuracy in predicting the endpoints' improvement (sensitivity (SN) 65.2%, specificity (SP) 68.8%) after surgery. In the nontreated AI patients, this criterion predicted the worsening of ≥ 2 endpoints (SN 55.6%, SP 82.9%). The UFC-ACTH-DST criterion seems to be the best for predicting the metabolic outcome in surgically treated AI patients.
    European Journal of Endocrinology 09/2010; 163(6):925-35. DOI:10.1530/EJE-10-0602 · 3.69 Impact Factor
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    ABSTRACT: Steroid-producing cell autoantibodies (SCAs) directed against 21-hydroxylase autoantibodies (21OHAbs), 17alpha-hydroxylase autoantibodies (17OHAb), and cholesterol side-chain cleavage enzyme (side-chain cleavage autoantibodies, P450sccAb) characterize autoimmune primary ovarian insufficiency (SCA-POI). The aim of the study was to analyze IgG subclass specificity of autoantibodies related to adrenal and ovarian autoimmunity. We studied 29 women with SCA-POI, 30 women with autoimmune Addison's disease (AAD) without POI, and 14 patients with autoimmune polyendocrine syndrome type 1 (APS1). 21OHAb isotypes were also analyzed in 14 subjects with preclinical AAD. Samples from 30 healthy women served as control group to determine the upper level of normality in the isotype assays. Immunoradiometric assays with IgG subclass-specific secondary antibodies. In 21OHAb-positive sera, IgG1 isotype was detected in 90% SCA-POI and non-POI AAD sera and 67% APS1 patients. IgG1 isotype was found in 69% 17OHAb-positive SCA-POI and 100% 17OHAb-positive APS1 sera, and in 60% P450sccAb-positive SCA-POI and 80% P450sccAb-positive APS1 sera. For 21OHAb, IgG4 isotype was detected in 17% SCA-POI, 7% non-POI AAD, and 8% APS1 sera. None of the 17OHAb-positive sera was positive for IgG4. In P450sccAb-positive sera, 15% POI and 20% APS1 sera were positive for IgG4. Two 21OHAb-positive SCA-POI (7%), one 21OHAb-positive AAD (3%), three P450sccAb-positive SCA-POI (15%), and two P450sccAb-positive APS1 (20%) sera were positive for IgG4, in the absence of IgG1. All preclinical AAD sera resulted as positive for IgG1-21OHAb, but not for IgG4-21OHAb. The autoantibody responses in POI and AAD are IgG1 dominated, which suggests a predominant Th1 response. Selective IgG4 isotype specificity identified a small subset of patients with Th2-oriented response.
    European Journal of Endocrinology 05/2010; 163(2):309-17. DOI:10.1530/EJE-10-0257 · 3.69 Impact Factor

Publication Stats

3k Citations
897.44 Total Impact Points


  • 1970–2013
    • University of Milan
      • • Department of Biomedical Sciences for Health
      • • Department of Medical Sciences
      • • Istituto Di Scienze Endocrine
      Milano, Lombardy, Italy
  • 2001–2008
    • I.R.C.C.S. Policlinico San Donato
      Milano, Lombardy, Italy
  • 2003
    • Università degli Studi di Messina
      • Dipartimento di Medicina Clinica e Sperimentale
      Messina, Sicily, Italy
  • 2000
    • Foundation of the Carlo Besta Neurological Institute
      Milano, Lombardy, Italy
    • Istituto Clinico Humanitas IRCCS
      Rozzano, Lombardy, Italy
  • 1998
    • Istituto Nazionale Tumori "Fondazione Pascale"
      Napoli, Campania, Italy
  • 1996
    • Centro Diagnostico Italiano
      Milano, Lombardy, Italy
  • 1988–1996
    • I.R.C.C.S. Istituto Auxologico Italiano
      Milano, Lombardy, Italy