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Aquilina M.,Instituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori IRST | Tartaglia A.,Endocrinology and Metabolism Unit | Serra L.,Morgagni Pierantoni Hospital | Oboldi D.,Radiology Unit | Nizzoli M.,Endocrinology and Metabolism Unit
Oncology Letters | Year: 2015

Hypocalcemia is an uncommon clinical symptom of patients with malignant tumors, and a number of factors may be involved in its development. The present study describes the case of a 67-year-old Caucasian female, presenting with severe refractory hypocalcemia and heart failure. The patient was subsequently diagnosed with breast cancer and bone metastases. The paraneoplastic origin of the syndrome was confirmed by its complete resolution once the tumor responded to specific antineoplastic treatments, comprising weekly paclitaxel and aromatase inhibitor administration. The present case report suggested the need for greater awareness of the possibility of paraneoplastic hypocalcemia in breast cancer patients, and suggested that this condition may also contribute to the occurrence of heart failure. The mechanisms potentially responsible for this event were discussed and a brief review of the literature presented. © 2015, Spandidos Publications. All rights reserved.


Reimondo G.,University of Turin | Bondanelli M.,University of Ferrara | Ambrosio M.R.,University of Ferrara | Grimaldi F.,Endocrinology and Metabolism Unit | And 10 more authors.
Endocrine | Year: 2014

The optimal method of assessing GH status in acromegalic patients receiving medical therapy with somatostatin analogs (SSA) has been matter of debate. The aim of the study has been to investigate whether OGTT may add information in patients with discordant random GH (GHr) and IGF values. Moreover, we evaluated the association of GH nadir with the prevalence of co-morbidities observed in acromegalic patients on SSA therapy. We evaluated 130 patients with proven diagnosis of acromegaly on SSA. The patients were subdivided in three groups: patients with controlled disease (both safe random GH and normal IGF-I, group A, 20.0 %), patients with uncontrolled disease (both high random GH and IGF-I, group B, 34.6 %), and patients with discordant random GH and IGF-I values (group C, 35.4 %). A high concordance rate for GH nadir with random GH and IGF-I was observed in group B, while a significant reduced concordance rate has been observed in group A (100 % sensitivity, 64.5 % specificity). By contrast, in group C, we observed concordant results between GH nadir and IGF-I only in 14/59 patients. In group A, the prevalence of diabetes was lower than in group B or C. Safe random GH was the only single criteria associated with a lower prevalence of diabetes. Discrepant IGF-I and either GH nadir or random GH values are frequently observed in acromegalic patients treated with SSA. Concordant IGF-I and random GH may influence the prevalence of metabolic complications. GH nadir measurement may help to interpret discrepancies between random GH and IGF-I data only in few cases. © 2013 Springer Science+Business Media New York.


Bernardi S.,Baker IDI Heart and Diabetes Research Institute | Grimaldi F.,Endocrinology and Metabolism Unit | Sabato N.,DMTTS and UCO Medicina Clinica | Bertolotto M.,Ospedale di Cattinara | Fabris B.,DMTTS and UCO Medicina Clinica
American Journal of the Medical Sciences | Year: 2011

Pheochromocytoma (PCC) is a challenging and life-threatening neoplasm. Herein, the authors report an interesting and unexpected solution for a clinical case concerning a patient with a PCC, who developed delayed ectopic adrenocorticotropic hormone Cushing syndrome originating from the PCC. In addition, after a misleading I-labeled metaiodobenzylguanidine single-photon emission computed tomography/computed tomography, an F-fluorodeoxyglucose positron emission tomography/computed tomography, executed to confirm the diagnosis of PCC, showed a silent pulmonary nodule that unexpectedly turned out to be a lung nocardiasis. © 2011 Lippincott Williams & Wilkins.


Grimaldi F.,Endocrinology and Metabolism Unit | Verrienti A.,University Rome | Tamburrano G.,University Rome | Durante C.,University Rome | And 4 more authors.
Clinical Endocrinology | Year: 2013

Context Germline mutations in four genes (RET, VHL, SDHB and SDHD) are detected in about 17% of patients with apparently sporadic pheochromocytoma. Thus, genetic screening of all patients with this disease is suggested for a rational diagnostic approach and management. Objective To report the clinical, biochemical and genetic analysis of three unrelated patients affected by pheochromocytoma. Design and patients All the coding regions and exon-intron boundaries of RET, VHL, SDHB and SDHD genes were sequenced in three unrelated patients with intra-adrenal pheochromocytoma: a 17-year-old girl, a 15-year-old boy and a 73-year-old man. The family history of all three cases was negative for von Hippel-Lindau lesions or other types of endocrine tumours. Structural modelling of the VHL protein was then performed. Results We identified a novel germline VHL gene point mutation, a G to A nucleotide substitution in exon 3, leading to an aspartate to asparagine amino acid change in codon 197 (D197N). No mutations were found in RET, SDHB and SDHD genes. Structural modelling of the VHL protein suggests that the D197N mutation could have a functional role. Conclusions Our study expands the number of VHL gene known mutations and indicates the usefulness of performing the genetic analysis in all patients with apparently sporadic pheochromocytoma. © 2012 Blackwell Publishing Ltd.


Grimaldi F.,Endocrinology and Metabolism Unit | Muser D.,Cardiothoracic Surgery | Beltrami C.A.,Azienda Ospedaliero Universitaria Santa Maria della Misericordia di Udine | Machin P.,Azienda Ospedaliero Universitaria Santa Maria della Misericordia di Udine | And 8 more authors.
Frontiers in Endocrinology | Year: 2010

Introduction: Histological distinction between typical and atypical bronchopulmonary car- cinoids is based on mitotic activity and necrosis. Regardless of these two parameters, outcome after surgery is often unpredictable. In this study the prognostic value of different clinico-pathological factors was retrospectively analyzed in a large series of patients with bronchopulmonary carcinoid. Materials and Methods: The long-term post-surgical out- come of 106 radically treated patients affected by bronchopulmonary carcinoid from two Italian centers was correlated with tumor characteristics assessed by combining conven- tional histology with a panel of immunohistochemical markers of neuroendocrine differen- tiation (chromogranin-A, NSE) and proliferation activity (Ki-67 score). Results: Carcinoids were assessed as typical (TC = 75; 70.8%) and atypical (AC = 31; 29.2%). Mean follow-up was 8.3 years (range: 0-20; median: 8.0). All cases expressed neuroendocrine markers. At univariate analysis, tumor recurrence [14/75 TC (18.7%), 15/31 AC (48.4%)] correlated with carcinoid histotype (P = 0.003), tumor size (P = 0.012), mitotic index (P = 0.044), Ki-67 score (P < 0.0001), and synchronous node metastasis (P = 0.037). Of these, Cox multivari- ate analysis confirmed only Ki-67 score as independent predictor of disease recurrence (P = 0.009). The best cut-off for Ki-67 score (calculated by ROC curves) discriminating recurrent vs non-recurrent disease was 4% (sensitivity 79.3%; specificity 83.8%; area under the curve 0.85). By stratifying patients according to this cut-off, a significantly dif- ferent disease-free survival was found (log-rank test P < 0.0001). Conclusion: Ki-67 score accurately separates bronchopulmonary carcinoids in two well-distinct histo-prognostic categories. Ki-67 score predicts the patients outcome better than mitotic count, histotype, and tumor stage and it is therefore helpful in establishing the appropriate follow-up. © 2011 Grimaldi, Muser, Beltrami, Machin, Morelli, Pizzolitto, Talmassons, Marciello, Colao, Monaco, Monaco and Faggiano.


Koren R.,Assaf Harofeh Medical Center | Koren R.,Tel Aviv University | Lerner A.,Endocrinology and Metabolism Unit | Tirosh A.,Tel Aviv University | And 7 more authors.
Journal of Alternative and Complementary Medicine | Year: 2015

Introduction: The use of complementary and alternative medicine (CAM) has been on the rise in recent years in the general population, as well as among patients with chronic diseases such as diabetes mellitus. The aim of this study was to add information regarding the use of CAM in patients with type 2 diabetes mellitus (DM2) in Israel and explore possible interactions between CAM and prescription medication (PM). Methods: This is a cross-sectional study based on questionnaires. The study included type 2 diabetic patients who were hospitalized in an internal medicine department at Assaf Harofeh Medical Center, Zerifin, Israel, between December 2013 and December 2014. Possible interactions between CAM and PM were evaluated by a clinical pharmacist and a clinical pharmacologist. Results: Out of 111 diabetic patients, 23.4% used CAM. There was no significant difference between the consumers and nonconsumers in terms of age, education, income, smoking, or alcohol habits. Only 11 of the 26 CAM consumers informed their physician regarding the use. We found possible drug-herb interactions in 19 of the 26 CAM consumers. A major interaction was found between omega-3 and antiaggregants and was encountered in 7 (26.9%) of the CAM consumers. Other minor and major interactions were found with vitamin E, ginkgo-biloba, co-enzyme Q10, green tea, fenugreek seeds, pyridoxine, and dandelion. Conclusions: Since CAM consumption is on the rise, it is desirable to improve our knowledge concerning their potential effects and adverse effects, especially in conjunction with PM. Given the complexity of pharmaceutics in patients with chronic diseases, among them patients with DM, the use of supplementary medicine cannot be ignored. © Copyright 2015, Mary Ann Liebert, Inc. 2015.


Grossman A.,Endocrinology and Metabolism Unit | Grossman A.,Tel Aviv University | Koren R.,Endocrinology and Metabolism Unit | Koren R.,Tel Aviv University | And 13 more authors.
Endocrine Research | Year: 2015

Background: The prevalence of adrenal incidentalomas (AIs) in asymptomatic individuals is unknown. This study evaluated the prevalence of AIs in healthy kidney donors in whom pre-operative computed tomography (CT) is performed routinely. Methods: All potential kidney donors evaluated at the Rabin Medical Center who had routine abdominal CT were identified and their medical records were retrospectively reviewed. Subjects who had normal CT scans were compared with those with a finding of an AI, evaluating demographic (age, body mass index, systolic and diastolic blood pressure) and laboratory variables (glucose, sodium, potassium, calcium, phosphorus, albumin and creatinine). In addition, prevalence of hypertension, rate of donation and surgical mortality were compared between the two groups. Results: CT was performed in 673 potential kidney donors. Of these, 645 had a normal CT and 28 (4.2%) had evidence of an AI. Those with AIs had a similar prevalence of hypertension, kidney donation and surgical mortality as those with a normal CT. Those with AIs were older (50.93 ± 11.1 versus 43.76 ± 11.1 years) but other demographic variables were similar; laboratory variables were also similar except for slightly lower albumin and creatinine in those with AIs. Conclusions: The prevalence of AIs is high even in healthy asymptomatic individuals. © 2015 Taylor & Francis.


Kebede D.,Endocrinology and Metabolism Unit | Abay Z.,Endocrinology and Metabolism Unit | Feleke Y.,Endocrinology and Metabolism Unit
Ethiopian Medical Journal | Year: 2012

Background: Thyroid diseases are common endocrine abnormalities affecting the cellular metabolism of the body. There are limited recent studies addressing the different aspects of thyroid diseases in Ethiopia. Objectives: To assess the pattern, clinical presentations, management and associated illnesses of thyroid diseases in endocrine referral clinics of Tikur Anbessa Specialized Tertiary Hospital (TASH). Methods: A cross-sectional study was conducted on consecutive thyroid patient attending endocrine referral clinics of TASH from Nov 2009 to March 2010. Patients with thyroid diseases, 14 years of age and above, thyroid patients with other endocrine diseases were included in the study. Data were collected by trained nurses and physicians using pre-constructed questionnaires. Review of charts for patients, presenting manifestations, date of diagnosis, laboratory investigation results, treatment and other pertinent information was conducted. Results: Among 376patients with thyroid diseases, females were 337(90%) and males were 39 (10.4%). The mean (SD) age of female participants was 43.1 ± 15.2 males was 37.3 ±17.3. Age 40 and above accounted for 59%. The prevalence of Hyperthyroidism and hypothyroidism in 376 patients were 233(61.7%) and 129(34.3%) respectively. Toxic Multinodular Goiter occurred in 135(35.9%), Toxic nodules in 32(8.5%) and of Graves' disease in 65 (17.3%), Seven patients progressed from Graves' disease to Hashimoto's thyroiditis. Subclinical hypothyroidism occurred in 5(1.32%), and secondary' hypothyroidism in 4 patients. Palpitation (96%), goiter (99%) and hot intolerance (81.9%) were the commonest presentations of thyrotoxicosis, whereas hypothyroidism patients presented mostly with cold intolerance (50.4%) and goiter (38%). Autoimmune polyglandular syndrome occurred in 16 (4.3%) patients. 26 (7.0%) had history of pregnancy, 82 (22.2%) had family history of thyroid diseases and seven patients had history of alcohol intake. Thyrotoxicosis was treated with Propylthiouracil (96.8%) with or with out beta blockers, thyroidectomy was done in 16 (6.8%), few received radioiodine therapy. Hypothyroidism patients were treated with thyroxin. Conclusion: Thyroid diseases were more common infernales and more prevalent in age group of 40-49. Toxic Multinodular Goiter, Graves ' disease and Toxic Nodular Goiter were causes of thyrotoxicosis. The most common presenting feature of thyrotoxicosis was palpitation, and hypothyroidism was cold intolerance. A few Graves ' disease cases were progressed to hypothyroidism. Autoimmune Polyglandular Syndrome was an important associated disease. There was limited access for radioiodine treatment. Recommendation: To conduct further studies in different aspects of thyroid disease, strengthening access for radioiodine therapy and introduce anti thyroid antibody tests.


PubMed | Endocrinology and Metabolism Unit
Type: | Journal: Frontiers in endocrinology | Year: 2012

Histological distinction between typical and atypical bronchopulmonary carcinoids is based on mitotic activity and necrosis. Regardless of these two parameters, outcome after surgery is often unpredictable. In this study the prognostic value of different clinico-pathological factors was retrospectively analyzed in a large series of patients with bronchopulmonary carcinoid.The long-term post-surgical outcome of 106 radically treated patients affected by bronchopulmonary carcinoid from two Italian centers was correlated with tumor characteristics assessed by combining conventional histology with a panel of immunohistochemical markers of neuroendocrine differentiation (chromogranin-A, NSE) and proliferation activity (Ki-67 score).Carcinoids were assessed as typical (TC=75; 70.8%) and atypical (AC=31; 29.2%). Mean follow-up was 8.3years (range: 0-20; median: 8.0). All cases expressed neuroendocrine markers. At univariate analysis, tumor recurrence [14/75 TC (18.7%), 15/31 AC (48.4%)] correlated with carcinoid histotype (P=0.003), tumor size (P=0.012), mitotic index (P=0.044), Ki-67 score (P<0.0001), and synchronous node metastasis (P=0.037). Of these, Cox multivariate analysis confirmed only Ki-67 score as independent predictor of disease recurrence (P=0.009). The best cut-off for Ki-67 score (calculated by ROC curves) discriminating recurrent vs non-recurrent disease was 4% (sensitivity 79.3%; specificity 83.8%; area under the curve 0.85). By stratifying patients according to this cut-off, a significantly different disease-free survival was found (log-rank test P<0.0001).Ki-67 score accurately separates bronchopulmonary carcinoids in two well-distinct histo-prognostic categories. Ki-67 score predicts the patients outcome better than mitotic count, histotype, and tumor stage and it is therefore helpful in establishing the appropriate follow-up.


PubMed | Endocrinology and Metabolism Unit
Type: Journal Article | Journal: Endocrinology | Year: 2010

Adiponectin (ApN) exhibits metabolic and antiinflammatory properties. This hormone is exclusively secreted by adipocytes under normal conditions. We have shown that ApN was induced in tibialis anterior muscle of mice injected with lipopolysaccharide (LPS) and in C2C12 myotubes cultured with proinflammatory cytokines. We hypothesized that muscle ApN could be a local protective mechanism to counteract excessive inflammatory reaction and oxidative damage. To test this paradigm, we examined whether muscles of ApN-knockout (KO) mice exhibit a higher degree of oxidative stress and apoptosis than wild-type mice when challenged by ip LPS and whether these abnormalities may be corrected by local administration of ApN. Eventually we investigated the effects of ApN in vitro. When compared with wild-type mice, ApN-KO mice exhibited myocyte degenerescence, especially after LPS. Myocytes of ApN-KO mice also displayed much stronger immunolabeling for markers of oxidative stress (peroxiredoxin-3/5 and heme oxygenase-1) as well as for a lipid peroxidation product (hydroxynonenal). Expression of TNF-, caspase-6, a marker of apoptosis, and nuclear factor-B was enhanced as well. Eventually muscle electrotransfer of the ApN gene, which did not induce any rise of systemic ApN, corrected all these abnormalities in LPS-injected ApN-KO mice. Likewise, ApN attenuated LPS-induced production of proinflammatory cytokines and activation of nuclear factor-B in C2C12 cells. Thus, induction of ApN into skeletal muscle in response to an inflammatory aggression appears to be a crucial mechanism to counteract in an autocrine or paracrine fashion excessive inflammatory damage, oxidative stress, and subsequent apoptosis.

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