A Pinchera

Università di Pisa, Pisa, Tuscany, Italy

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Publications (716)2818.34 Total impact

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    ABSTRACT: Objective: Sulfate conjugation of thyroid hormones is an alternate metabolic pathway that facilitates the biliary and urinary excretion of iodothyronines and enhances their deiodination rate, leading to the generation of inactive metabolites. A de-sulfating pathway reverses this process and thyromimetic effects have been observed following the parenteral administration of 3,5,3'-triiodothyronine sulfate (T3S) in rats. The present study investigated whether T3S is absorbed after oral administration in humans and if it represents a source of 3,5,3'-triiodothyronine (T3).Methods: Twenty-eight hypothyroid patients (7 men and 21 women, mean age ± SD = 44 ± 11 years) who had a thyroidectomy for thyroid carcinoma were enrolled. Replacement thyroid hormone therapy was withdrawn (42 days for thyroxine, 14 days for T3) prior to radioiodine remnant ablation. A single oral dose of 20, 40, 80 (4 patients/group) or 160 μg (16 patients/group) T3S was administered 3 days before the planned administration of 131I. Blood samples for serum T3S and total T3 (TT3) concentrations were obtained at various times up to 48 hours after T3S administration.Results: At all T3S doses, serum T3S concentrations increased reaching a peak at 2-4 hours and progressively returned to basal levels within 8 to 24 h. The T3S Cmax and area under the curve (AUC0-48h) were directly and significantly related to the administered dose.An increase in serum TT3 concentration levels was observed, significant after 1 hour, further increased at 2 and 4 hours, and then remained steady up to 48 hours after T3S administration. There was a significant direct correlation between the TT3 AUC0-48h and the administered dose of T3S. No changes in serum free thyroxine (FT4) concentrations during the entire study period were observed, while serum TSH levels increased slightly at 48 hours not related to the dose of administered T3S. No adverse events were reported.Conclusions: 1) T3S is absorbed following oral administration in hypothyroid humans; 2) the oral administration of a single dose of T3S is converted to T3 in a dose-dependent manner and results in steady state serum T3 concentrations for 48 hours; 3) T3S may represent a new agent in combination with thyroxine (T4) in the therapy of hypothyroidism, if similar conversion of T3S to T3 can be demonstrated in euthyroid patients who are already taking T4.
    Endocrine Practice 02/2014; · 2.49 Impact Factor
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    ABSTRACT: Background: Enhanced reduction of multinodular goiter (MNG) can be achieved by stimulation with recombinant human thyrotropin (rhTSH) before radioiodine (131I) therapy. The objective was to compare the long-term efficacy and safety of two low doses of modified release rhTSH (MRrhTSH) in combination with 131I-therapy. Methods: In this phase II, single-blinded, placebo-controlled study, 95 patients (57.2±9.6 years old, 85% women, 83% Caucasians) with MNG (median size 96.0 ml (31.9 - 242.2 ml)) were randomized to receive placebo (n=32), 0.01 mg MRrhTSH (n=30) or 0.03 mg MRrhTSH (n=33), 24 hours before a calculated 131I activity. Thyroid volume (TV) and smallest cross-sectional area of trachea (SCAT) were measured (by CT-scan) at baseline, month 6 and month 36. Thyroid function and quality of life (QoL) was evaluated at 3 month and yearly intervals, respectively. Results: At 6 months, TV reduction was enhanced in the 0.03 mg MRrhTSH group (32.9% versus 23.1% in the placebo group, p=0.03), but not in the 0.01 mg MRrhTSH group. At month 36 the mean percent TV reduction from baseline was 44 ± 12.7% (SD) in the placebo group, 41 ± 21.0% in the 0.01 mg MRrhTSH-group and 53 ± 18.6% in the 0.03 mg MRrhTSH-group, with no statistically significant differences among the groups, p=0.105. In the 0.03 mg MRrhTSH-group, the subset of patients with basal 131I uptake <20% had at month 36 a 24% greater TV reduction than the corresponding subset of patients in the placebo group, p=0.01. At month 36, the largest relative increase in SCAT was observed in the 0.03 mg MRrhTSH-group (13.4 ± 23.2% (SD)), but this was not statistically different from the increases observed in the placebo or the 0.01 mg MRrhTSH-group, p=0.15. Goiter related symptoms were reduced and QoL improved, without any enhanced benefit from using MRrhTSH. At 3 years, the prevalence of permanent hypothyroidism was 13%, 33% and 45% in the placebo, 0.01 mg and 0.03 mg MRrhTSH-group, respectively. The overall safety profile of the study was favorable. Conclusions: When used as adjuvant to 131I, enhanced MNG reduction could not be demonstrated with MRrhTSH doses at or below 0.03 mg, indicating that the lower threshold for efficacy is around this level.
    Thyroid: official journal of the American Thyroid Association 12/2013; · 2.60 Impact Factor
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    ABSTRACT: Background: GPR7, the endogenous coupled receptor for neuropeptide B and neuropeptide W, is expressed in several regions of the Central Nervous System (CNS), which are involved in the regulation of feeding behaviour. GPR7 affects the regulation of energy balance through a mechanism independent of leptin and melanocortin pathways. Aim: Aim of this study was to investigate whether GPR7 gene mutations can be detected in human subjects and, in that event, if they are differently distributed among lean and obese subjects. Subjects and Methods: The coding region of GPR7 were sequenced in 150 obese patients and 100 normal-weight unrelated controls. Functional studies of the allelic variants were performed. Results: One genetic GPR7 variant was found (Tyr135Phe - rs33977775) in obese subjects (13,3%) and lean control (25%). Functional studies did not reveal significant differences between the wild type and the Tyr135Phe allelic variants in their NPW mediated capacity to inhibit forskolin-induced cAMP production. Conclusions: Screening of GPR7 gene mutations among lean and obese subjects revealed a Tyr135Phe allelic variant that was fairly common in the study population. As indicated by in vitro and in silico studies, this variant is unlikely to cause a functional derangement of the receptor.
    Journal of endocrinological investigation 04/2013; · 1.65 Impact Factor
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    ABSTRACT: Background:Iodine deficiency is the result of insufficient intake of dietary iodine and as a consequence causes multiple adverse effects. About 2 billion individuals in the world are affected by iodine deficiency. It has been found that the most effective way to control iodine deficiency is through the universal salt iodization. However, salt iodization alone may not be sufficient to assure adequate iodine nutrition. In most industrialized countries, excess consumption of salt has become recognized as a health risk. Therefore, biofortification of vegetables with iodine offers an excellent opportunity to increase iodine intake.Aim and Methods:The aim of this study was to test the efficiency of a new model of iodine prophylaxis in a group of 50 healthy volunteers through the intake of vegetables (potatoes, cherry tomatoes, carrots, and green salad) fortified with iodine. Each serving of vegetables consisted of 100 g of potatoes, carrots, tomatoes, or salad containing 45 mg of iodine (30% of the Recommended Daily Allowance), and the volunteers consumed a single serving of vegetables, as preferred, each day for 2 weeks. Urinary iodine (UI) excretion was measured before and after intake of vegetables.Results:The UI concentration measured in volunteers before the intake of vegetables was 98.3 mg/L (basal value), increasing to 117.5 mg/L during the intake of vegetables. Seven days after the discontinuation of vegetable intake, UI was 85 mg/L. UI concentration increment was 19.6% compared with the basal value; therefore, the difference was statistically significant (P = .035).Conclusions:Biofortification of vegetables with iodine provides a mild but significative increase in UI concentration and, together with the habitual use of iodized salt, may contribute to improve the iodine nutritional status of the population without risks of iodine excess.
    The Journal of clinical endocrinology and metabolism 03/2013; · 6.50 Impact Factor
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    ABSTRACT: Context: Iodine deficiency disorders are a major public health problem, and programs have been implemented to improve iodine nutrition. Objective: The objective of the study was to verify the effects of voluntary iodine prophylaxis in a small rural community (Pescopagano, Italy). Design: The design of the study was the evaluation of the prevalence of thyroid disorders 15 years after a previous survey conducted before iodine prophylaxis. Setting: The setting for this study was a general community survey. Participants: One thousand one hundred forty-eight residents were examined in 2010 and 1411 in 1995. Results: In 2010, 757 of 1148 subjects (65.9%) routinely used iodized salt, urinary iodine excretion being significantly higher than in 1955 (median 98.0 μg/L, vs 55.0 μg/L, P < .0001). The prevalence of goiter was lower in 2010 than in 1995 (25.8% vs 46.1%, P < .0001), mainly due to the reduction of diffuse goiter (10.3% vs 34.0%, P < .0001). In 2010 vs 1995, thyroid autonomy in subjects younger than 45 years old (3 of 579, 0.5% vs 25 of 1010, 2.5% P = .004) and nonautoimmune hyperthyroidism in subjects older than 45 years old (8 of 569, 1.4% vs 18 of 401, 4.5%, P = .03) were less frequent. The prevalence of hypothyroidism was higher in 2010 vs 1995 (5.0% vs 2.8%, P = .005), mainly because of an increased frequency of subclinical hypothyroidism in subjects younger than 15 years old (7 of 83, 8.4% vs 0 of 419, 0.0%, P < .0001). Accordingly, serum thyroid autoantibodies (19.5% vs 12.6%; P < .0001) and Hashimoto's thyroiditis (14.5% vs 3.5%; P < .0001) were more frequent in 2010 than in 1995. Conclusions: In the present work, the role of voluntary iodine prophylaxis was assessed in a small rural community relatively segregated, in which genetic and other environmental factors have not substantially changed between the 2 surveys. Iodine intake strongly affected the pattern of thyroid diseases, but the benefits of correcting iodine deficiency (decreased prevalence of goiter and thyroid autonomy in younger subjects and reduced frequency of nonautoimmune hyperthyroidism in older subjects) far outweighs the risk of development of thyroid autoimmunity and mild hypothyroidism in youngsters.
    The Journal of clinical endocrinology and metabolism 03/2013; 98(3):1031-9. · 6.50 Impact Factor
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    ABSTRACT: Background:Short sleep and weight gain are inversely related. Sleep deprivation acutely increases food intake but little is known about eating behavior in chronically sleep-deprived, obese individuals.Objective:To characterize the relationship between sleep, food intake and alcohol consumption under free-living conditions in obese, chronically sleep-deprived individuals.Design:Cross-sectional study of a cohort of obese men and premenopausal women.Subjects:A total of 118 obese subjects (age: 40.3±6.7 years; 91 females/27 males; body mass index 38.7±6.4 kg m(-2)).Measurements:Energy, macronutrient, alcohol and caffeine intake assessed by 3-day food records. Sleep duration estimated by actigraphy. Respiratory disturbance index assessed by a portable device.Results:Subjects slept 360.7±50.2 min per night and had a total energy intake of 2279.1±689 kcal per day. Sleep duration and energy intake were inversely related (r=-0.230, P=0.015). By extrapolation, each 30-min deficit per day in sleep duration would translate to an ∼83 kcal per day increase in energy intake. In addition, sleep apnea was associated with a shift from carbohydrate to fat intake. Alcohol intake in subjects consuming >3.5 g of alcohol per day (N=41) was inversely related to sleep duration (r=-0.472, P=0.002).Conclusions:Shorter sleep duration and obstructive sleep apnea are associated with higher energy, fat and alcohol intakes in obese individuals. The importance of this study relies on the population studied, obese subjects with chronic sleep deprivation. These novel findings apply to the large segment of the US population who are obese and sleep-deprived.
    Nutr Diabetes. 01/2013;
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    ABSTRACT: AIM: The objective of this study was to establish the status of iodine nutrition in Southern Italy. MATERIAL AND METHODS: The survey was carried out on 11-14 yr old children attending primary school and living in urban and non urban areas of 8 regions of Southern Italy. Urinary iodine excretion (UIE) was measured in 23,103 urinary samples randomly collected. RESULTS: Median UIE in the whole studied population was 74 mug/l [interquartile range (IR) 34-139 mug/l]. UIE was significantly higher in chief towns compared to non chief towns (81 mug/l, IR 39-145 mug/l vs 73 mug/l, IR 33-138 mug/l, p<0.0001) and in areas with >500 inhabitants per km(2) (median 87 mug/l, IR 43-154 mug/l) compared to areas with 100-500 per km(2) (median 66 mug/l, IR 29-126 mug/l, p<0.0001) and with <100 per km(2) (median 61 mug/l, IR 25-121 mug/l, p<0.0001). Median UIE was significantly lower in inland mountainous/hilly areas (68 mug/l, IR 30-129 mug/l) compared to coastal mountainous/hilly areas (79 mug/l, IR 37-144 mug/l, p<0.0001) and lowland (79 mug/l, IR 37-146 mug/l, p<0.0001). According to a binary logistic regression model, population density was the only independent parameter significantly associated with UIE >/= 100 mug/l. CONCLUSION: The results of the present survey indicate that: 1) in Southern Italy mild to moderate iodine deficiency is still present; 2) median UIE in non urban areas is lower than in urban areas and is related to the size of the community rather than to its geographical location, being higher in a larger community. This may be due to better diversification of dietary habits and the easier availability of iodized salt and processed food through commercial facilities, more common in larger communities. Future monitoring surveys should take into account these observations.
    J Endocrinol Invest. 01/2013; 36(5):282-6.
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    ABSTRACT: Background:Short sleep and weight gain are inversely related. Sleep deprivation acutely increases food intake but little is known about eating behavior in chronically sleep-deprived, obese individuals.Objective:To characterize the relationship between sleep, food intake and alcohol consumption under free-living conditions in obese, chronically sleep-deprived individuals.Design:Cross-sectional study of a cohort of obese men and premenopausal women.Subjects:A total of 118 obese subjects (age: 40.3±6.7 years; 91 females/27 males; body mass index 38.7±6.4 kg m(-2)).Measurements:Energy, macronutrient, alcohol and caffeine intake assessed by 3-day food records. Sleep duration estimated by actigraphy. Respiratory disturbance index assessed by a portable device.Results:Subjects slept 360.7±50.2 min per night and had a total energy intake of 2279.1±689 kcal per day. Sleep duration and energy intake were inversely related (r=-0.230, P=0.015). By extrapolation, each 30-min deficit per day in sleep duration would translate to an ∼83 kcal per day increase in energy intake. In addition, sleep apnea was associated with a shift from carbohydrate to fat intake. Alcohol intake in subjects consuming >3.5 g of alcohol per day (N=41) was inversely related to sleep duration (r=-0.472, P=0.002).Conclusions:Shorter sleep duration and obstructive sleep apnea are associated with higher energy, fat and alcohol intakes in obese individuals. The importance of this study relies on the population studied, obese subjects with chronic sleep deprivation. These novel findings apply to the large segment of the US population who are obese and sleep-deprived.
    Nutrition & Diabetes 01/2013; 3:e58.
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    ABSTRACT: Background Iodine deficiency (ID) still now represents one of the major worldwide health problems. ID is the result of insufficient dietary iodine intake. Iodine is an essential micronutrient but scarcely presents in nature. The main strategy for the correction of iodine deficiency is the fortification of table salt with iodide/iodine but Italy is far from reaching an iodized salt use higher 90% of population. Also because of the evidence for the risk on blood pressure, it is recommended to decrease the daily salt intake to less than 5g/d. An opportunity to increase the iodine intake is the possibility to introduce iodine fortification in the industrial processing foods. Aim The aim was to evaluate the effectiveness of a diet containing iodized foods enriched during industry processing with protected iodized salt (Presal®). Subjects and Methods The evaluation of increasing of iodine intake was assessed by measuring the urinary iodine excretion (UIE) in 30 healthy volunteers who added to own alimentary habits a basket of iodine enriched foodstuffs. Results Median UIE at baseline was 105 mcg/L, 156 mcg/L during the enriched diet and 90.5 mcg/L a week after withdrawal of enriched diet. Conclusions Stable iodized salt (Presal®) represent a good way to introduce iodine with the normal diet without increasing the normal consumption of salt for the healthy problems related to the blood pressure. The availability of stable iodized salt (Presal®) allows the preservation of iodine after cooking.
    Journal of endocrinological investigation 11/2012; · 1.65 Impact Factor
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    ABSTRACT: OBJECTIVE: Premature ovarian insufficiency (POI) is defined as a primary ovarian defect characterized by absent menarche (primary amenorrhea) or premature depletion of ovarian follicles before the age of 40 (secondary amenorrhea) with hypergonadotropism and hypoestrogenism. METHODS: We studied the clinical, biological, and genetic data related to 50 POI patients with a mean age of menopause of 29years (94% with secondary amenorrhea, 6% with primary amenorrhea and 15% with a family history of POI). Seventeen patients were affected by endocrine autoimmune diseases, antral follicles were observed in 31 patients by ultrasonography. RESULTS: Karyotype analysis did not show any abnormality of the X chromosome. No mutation in FSH receptor and GDF-9 genes was reported, while in one patient a variant of BMP-15 gene (A180T) was found. Four patients had fragile X mental retardation 1 gene (FMR1) premutation and one an intermediate sized CGG repeats of the same gene. Two patients with FMR1 premutation were sister and developed secondary amenorrhea at the age of 34 and 37years. The other two patients presented with oligoamenorrhea at the age of 39 and 34years. The patient harboured the intermediate sized CGG repeats developed secondary amenorrhea at the age of 33years. CONCLUSIONS: The genetic analysis performed on a cohort of patients with POI revealed that 8% had FMR1 premutation and only one patient a previously known variant of BMP-15 gene. No alteration of the karyotype and FSH receptor and GDF-9 genes was evidenced.
    Maturitas 10/2012; · 2.84 Impact Factor
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    ABSTRACT: Background Graves' Orbitopathy (GO) is thought to be related to one or more autoantigens present in the thyroid and in orbital tissues. Although this may not imply a quantitative relation between thyroid antigens and degree of GO, which in turn is a risk factor for a more pronounced GO, we postulated that the severity of GO may parallel the amount of thyroid tissue, namely the size of the thyroid gland. This hypothesis is also based on the observation that patients with Graves' disease presenting with large goiters tend to have more severe hyperthyroidism, Thus, we evaluated retrospectively whether there is a correlation between the degree of GO at its first observation and, among other parameters, the thyroid volume. Methods Eighty-six consecutive patients with untreated GO lasting for no longer than 24 months underwent an endocrinological and an ophthalmological evaluation, the latter including: exophthalmometry, eyelid width, clinical activity score (CAS), diplopia and visual acuity. The overall degree of GO was ranked using the NO SPECS score as well as a modification of the NO SPECS score. The following parameters were considered for correlations: time since GO appearance, time since detection of hyperthyroidism, FT3, anti-TSH receptor antibodies, thyroid volume and cigarette-years. Results Thyroid volume, but not the other parameters, correlated significantly by simple regression with exophthalmometry (P=0.02) and CAS (P=0.02). The standard NO SPECS score correlated with FT3 (P=0.05), thyroid volume (P=0.02), and cigarette-years (P=0.03), by simple, but not by multiple regression analysis. The modified NO SPECS score correlated with thyroid volume (P=0.007) and cigarette-years (P=0.04) by simple regression, and with thyroid volume also by multiple regression analysis (P=0.05). Conclusions Thyroid volume correlates with the severity of GO at its first observation, especially with exophthalmometry and CAS. The finding is in line with a possible pathogenetic role of antigens shared by the thyroid and orbital tissues. Nevertheless, other mechanisms may explain this observation, including an overall more reactive immune system in patients with a large goiter, resulting in more severe thyroid and eye disease, regardless of the nature of the autoantigen, or whether it is shared by the thyroid and the orbit.
    Thyroid: official journal of the American Thyroid Association 10/2012; · 2.60 Impact Factor
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    ABSTRACT: Background: Patients with moderate to severe Graves' orbitopathy (GO) rather frequently require rehabilitative surgery after medical therapy. Diplopia is the most common side effect of orbital decompression (OD). The aim of this study was to evaluate the occurrence of postoperative diplopia in primary gaze after OD, and the influence of the surgical approach on this outcome. Moreover, we investigated the results in terms of proptosis reduction, and the long-term subjective satisfaction of patients treated with OD with regard to their appearance and ocular function. Methods: A retrospective evaluation of 247 patients with GO treated with medial and lateral decompression (MLD) or lateral decompression (LD) OD between January 2002 and December 2009 was performed. Results: The overall prevalence of postoperative diplopia in primary gaze was 55/247 (22.3%), with a statistically significant difference (p<0.001) between patients with (36/113, 31.2%) and those without (19/134, 14.2%) preoperative diplopia in secondary gaze. The surgical procedure influenced the outcome in patients without preoperative diplopia (17.8% after MLD and 0% after LD, p=0.02), but not in patients with preoperative diplopia in secondary gaze (33.3% after MLD and 26.1% after LD, p=0.5). Overall, proptosis reduction was 5.7±2.2 mm (1-11 mm), after MLD and 4.0±1.6 mm (1-8 mm) after LD (p<0.001). Fifty-one/fifty-five patients with constant, postoperative diplopia in primary gaze after OD underwent squint surgery, which was successful in all but two. Four patients refused squint surgery. Patients were also interviewed for satisfaction in terms of recovery of their appearance and ocular function after a mean of 6 years from surgery (range 2-9 years): More than 85% of patients reported a good to excellent postoperative satisfaction for both items. Conclusions: Preoperative diplopia in secondary gaze is a risk factor for the development of diplopia in primary gaze after OD, independently of the surgical approach (MLD vs. LD). In absence of diplopia, MLD, but not LD, seems to be associated with its development in primary gaze. The reduction in proptosis after MLD is greater than that after LD. Most patients were satisfied with the results of both appearance and ocular function after OD.
    Thyroid: official journal of the American Thyroid Association 10/2012; · 2.60 Impact Factor
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    ABSTRACT: Background:The BRAF(V600E) mutation, the most frequent genetic alteration in papillary thyroid carcinoma (PTC), was demonstrated to be a poor prognostic factor. The aim of this study was to evaluate its prognostic significance in a large cohort of low-risk intrathyroid PTC.Methods:Among the 431 consecutive PTC patients, we selected 319 patients with an intrathyroid tumor and no metastases (T1-T2, N0, M0). The BRAF(V600E) mutation was analyzed by PCR-single-strand conformation polymorphism analysis and direct genomic sequencing. The correlation between the presence/absence of the mutation, the clinical-pathological features, and the outcome of the PTC patients was investigated.Results:The BRAF(V600E) mutation was present in 106 of 319 PTC patients (33.2%). Its prevalence was also the same in subgroups identified according to the level of risk. The BRAF(V600E) mutation correlated with multifocality, aggressive variant, absence, or infiltration of the tumoral capsule. BRAF(V600E)-mutated PTC also required a higher number of radioiodine courses to obtain disease-free status. The BRAF(V600E) mutation was the only prognostic factor predicting the persistence of the disease in these patients after 5 yr of follow-up.Conclusions:The BRAF(V600E) mutation was demonstrated to be a poor prognostic factor for the persistence of the disease independent from other clinical-pathological features in low-risk intrathyroid PTC patients. It could be useful to search for the BRAF(V600E) mutation in the workup of low-risk PTC patients to distinguish those who require less or more aggressive treatments. In particular, the high negative predictive value of the BRAF(V600E) mutation could be useful to identify, among low-risk PTC patients, those who could avoid 131-I treatment.
    The Journal of clinical endocrinology and metabolism 10/2012; · 6.50 Impact Factor
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    ABSTRACT: Background Orbital fibroblast proliferation and hyaluronic acid (HA) release are responsible for some of the clinical features of Graves' Ophthalmopathy (GO). Thus, inhibition of these processes may be a possible therapeutic approach to this syndrome. Enalapril, a widely used anti-hypertensive drug, was found to have some inhibitory actions on fibroblast proliferation in cheloid scars in vivo, based on which here we investigated its effects in primary cultures of orbital fibroblasts from GO patients and control subjects. Methods Primary cultures of GO and control fibroblasts were treated with enalapril or with a control compound (lisinopril). Cell proliferation assays, lactate dehydrogenase release assays (as a measure of cell necrosis), apoptosis assays and measurement of HA in the cell media were performed. Results Enalapril reduced significantly cell proliferation in both GO and control fibroblasts. Because enalapril did not affect cell necrosis and apoptosis, we concluded that its effects on proliferation reflected an inhibition of cell growth and/or a delay in cell cycle. Enalapril reduced significantly HA concentrations in the media from both GO and control fibroblasts. Conclusions Enalapril has anti-proliferative and HA suppressing actions in both GO and control fibroblasts. Clinical studies are needed to investigate whether enalapril has any effects in vivo in patients with GO.
    Thyroid: official journal of the American Thyroid Association 10/2012; · 2.60 Impact Factor
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    ABSTRACT: Context:Thyroglobulin autoantibodies (TgAb) have been proposed as a surrogate marker of thyroglobulin in the follow-up of differentiated thyroid carcinoma. Commercially available TgAb assays are often discordant. We investigated the causes of discrepancy.Design:TgAb were measured by three noncompetitive immunometric assays and three competitive RIA in 72 patients with papillary thyroid carcinoma and associated lymphocytic thyroiditis (PTC-T), 105 with papillary thyroid carcinoma and no lymphocytic thyroiditis (PTC), 160 with Hashimoto's thyroiditis, and in 150 normal subjects. The results of the six assays were correlated. TgAb epitope pattern, evaluated by inhibition of serum TgAb binding to thyroglobulin by TgAb-Fab regions A, B, C, and D, were compared in sera which were positive in all six assays (concordant sera) and positive in only one to five assays (discordant sera) were compared. TgAb International Reference Preparation (IRP) was measured in 2007 and 2009.Results:The correlations of the six assays ranged from -0.01 to 0.93 and were higher in PTC-T and Hashimoto's thyroiditis than in PTC and normal subjects. Two uncorrelated components, one including the three immunometric assays, the other the three RIA, explained 40 and 37% of the total variance of the results of the six assays. The levels of inhibition were higher in concordant sera than in discordant sera by TgAb-Fab region B (27.0%, 21.2-34.0 vs. 6.0%, and 2.7-12.7%) and region C (30.5%, 21.3-37.7 vs. 4.0%, and 1.0-6.5%); thus, the epitope pattern was more homogeneous in concordant sera than in discordant sera. TgAb IRP ranged from 157 to 1088 (expected 1000) IU/ml in 2009; results in 2007 were similar in all but two assays.Conclusions:TgAb assays are highly discordant. Discrepancy is lower when comparing assays with similar methodology. Results of TgAb from PTC-T are more concordant than those from PTC because their epitope pattern is more restricted. The internal standardization of TgAb is generally, but not completely, satisfactory.
    The Journal of clinical endocrinology and metabolism 09/2012; · 6.50 Impact Factor
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    ABSTRACT: Thyroglobulin autoantibodies (TgAb) can develop in patients with subacute thyroiditis (SAT). Comparison of the epitope pattern of TgAb of patients with SAT, Hashimoto's thyroiditis (HT) [autoimmune thyroid disease (AITD)] and non-toxic multinodular goiter (NTMG) (non-AITD). Serum TgAb from 10 patients with SAT, 45 with HT, and 19 with NTMG were evaluated. Serum TgAb binding to Tg was inhibited by 4 recombinant human TgAb-Fab, recognizing Tg epitope regions A, B, C, and D. The ability of single TgAb-Fab to inhibit the binding of serum TgAb to Tg was evaluated in enzymelinked immunosorbent assay. Levels of inhibition were different for all TgAb-Fab in the 3 groups of patients. Inhibition by region A TgAb-Fab in SAT [50.5 (30.3-62.5)%] (median and 25th to 75th percentiles) was similar to HT [49.0 (38.0-69.5)%] and significantly higher than in NTMG [25.0 (14.0-37.0)%]; by region B TgAb-Fab in SAT [0.0 (0.0-12.5)%] was significantly lower than in HT [28.0 (9.5-48.0)%] and similar to NTMG [9.0 (4.8-20.5)%]; by region C TgAb-Fab in SAT [9.5 (0.0-25.8)%] were similar to HT [23.0 (9.5-41)%] and NTMG [6.5 (1.7-21.5)%]; and by region D TgAb-Fab in SAT [0.0 (0.0-8.0)%] were lower than in HT [12.0 (1.0-28.5)%] and similar to NTMG [1.0 (0.0-5.0)%]. The epitope pattern of TgAb of SAT is restricted to the A region that is immunodominant in AITD and non-AITD. In the majority of patients with SAT, the autoimmune phenomena represent a non-specific and transient response to the release of thyroid antigens, rather than the expression of thyroid autoimmunity.
    Journal of endocrinological investigation 09/2012; 35(8):712-4. · 1.65 Impact Factor
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    ABSTRACT: Background: Approximately 60% of sporadic Medullary Thyroid Carcinomas (sMTC) remain orphan of a recognized genetic cause. Recently, a high percentage of RAS point mutations have been described in RET-negative sMTC. The aim of this study was to assess the prevalence of RAS point mutations in a large series of MTC collected in four Italian centers. Methods: For this purpose, we studied codons 12, 13 and 61 of H-, K- and N-RAS genes in 188 hereditaty and sporadic MTC samples by direct sequencing. Correlations between the RAS mutational status and the clinical-pathological features of MTC patients were performed as well as a meta-analysis of all published data. Results: The prevalence of RAS mutations in the present series of sMTC was 10.1%, and 17.6% when considering only RET-negative cases. RAS mutations were found in MTC tumoral tissue, but not in peripheral blood indicating their somatic origin. A novel mutation in codon 72 (M72I) was found, but with a low or null transforming potential. No association was found between the presence of RAS mutations and the clinical-pathological features of the patients. Although not statistically significant, a positive association between the presence of RAS mutations and a better outcome was observed. The meta-analysis of all published studies confirmed a prevalence of 11.3% for RAS mutations in sMTC. Conclusions: The prevalence of RAS mutations in our MTC series was relatively low and consistent with the meta-analysis data. Only somatic RAS mutations were found and only in RET-negative sMTC. Likely, MTC that harbour a RAS mutation identify a subgroup of tumors with a less aggressive behavior. To our knowledge, this is the largest series of MTC studied for the presence of mutations in the RAS genes and the first meta-analysis on this specific topic.
    Thyroid: official journal of the American Thyroid Association 08/2012; · 2.60 Impact Factor
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    ABSTRACT: Background. Patients with moderate to severe Graves' orbitopathy (GO) rather frequently require rehabilitative surgery after medical therapy. Diplopia is the most common side effect of orbital decompression (OD). The aim of this study was to evaluate the occurrence of post-operative diplopia in primary gaze after OD, and the influence of the surgical approach on this outcome. Moreover, we investigated the results in terms of proptosis reduction, and the long term subjective satisfaction of patients treated with OD with regards to their appearance and ocular function. Methods. Retrospective evaluation of 247 patients with GO treated with medial and lateral (MLD) or lateral (LD) OD between January 2002 and December 2009. Results. The overall prevalence of post-operative diplopia in primary gaze was 55/247 (22.3%), with a statistically significant difference (p<0.001) between patients with (36/113, 31.2%) and without (19/134, 14.2%) pre-operative diplopia in secondary gaze. The surgical procedure influenced the outcome in patients without pre-operative diplopia (17.8% after MLD and 0% after LD, p=0.02), but not in patients with preoperative diplopia in secondary gaze (33.3% after MLD and 26.1% after LD, p=0.5). Overall, proptosis reduction was 5.7±2.2 mm (1-11 mm), after MLD and 4.0±1.6 mm (1-8 mm) after LD (p<0.001). Fifty-one/55 patients with constant, post-operative diplopia in primary gaze after OD underwent squint surgery, which was successful in all but two. Four patients refused squint surgery. Patients were also interviewed for satisfaction in terms of recovery of their appearance and ocular function after a mean of 6 years from surgery (range 2-9 years): more than 85% of patients reported a good to excellent post-operative satisfaction for both items. Conclusions. Pre-operative diplopia in secondary gaze is a risk factor for the development of diplopia in primary gaze after OD, independently of the surgical approach (MDL versus LD). In absence of diplopia, MLD but not LD, seems to be associated with its development in primary gaze. Reduction in proptosis after MLD is greater than that after LD. Most patients were satisfied for the results of both appearance and ocular function after OD.
    Thyroid: official journal of the American Thyroid Association 08/2012; · 2.60 Impact Factor
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    ABSTRACT: Haptoglobin (Hp) is an inflammatory and adiposity marker, its expression during obesity being specifically induced in the white adipose tissue (WAT). We previously reported that when challenged with a high fat diet (HFD) Hp(-/-) mice are partially protected from the onset of insulin resistance and hepatosteatosis. The aim of the present study was to get further insights into Hp function in WAT. To this end, we performed histological and gene expression analysis of the Hp(-/-) WAT, both in standard and obesity conditions, and investigated how Hp deficiency impacts adipogenesis and WAT development. The average size and percentage of very large adipocytes were respectively smaller and reduced in HFD Hp(-/-) mice as compared with HFD WT. The expression of perilipin, HSL and angiogenesis related markers were increased in HFD Hp(-/-) mice. Lean adult Hp(-/-) showed significantly larger adipocytes and lower subcutaneous WAT expression of aP2 and LPL with respect to WT. Hp(-/-) young mice (P30) were characterized by larger adipocyte size and lower expression of adipocyte and adipogenesis markers. Comparison of adipocyte size distribution between young and adult mice revealed attenuated changes in Hp(-/-) mice compared with WT. Mouse embryonic fibroblasts from Hp(-/-) mice were less capable of accumulating triglycerides and exhibited lower expression of PPARγ, aP2, FAS, LPL and Leptin. In conclusion, Hp deficiency tends to blunt the effect of age and diet on the size of adipocytes, which show less susceptibility to develop hypertrophy during obesity and a reduced adipogenic/hyperplastic potential during youth. In addition, Hp deficiency impacts negatively on adipogenesis.
    Adipocyte. 07/2012; 1(3):142-183.

Publication Stats

16k Citations
2,818.34 Total Impact Points

Institutions

  • 1978–2012
    • Università di Pisa
      • • Department of Clinical and Experimental Medicine
      • • Department of Chemistry and Industrial Chemistry
      Pisa, Tuscany, Italy
  • 2011
    • Ospedali Vito Fazzi
      Lecce, Apulia, Italy
  • 2009–2011
    • Dulbecco Telethon Institute
      Dublin, California, United States
  • 2010
    • Scuola Normale Superiore di Pisa
      • Neurobiology Laboratory
      Pisa, Tuscany, Italy
    • Regina Apostolorum Hospital
      Albano, Latium, Italy
  • 2008
    • Academisch Medisch Centrum Universiteit van Amsterdam
      • Department of Ophthalmology
      Amsterdam, North Holland, Netherlands
  • 2002–2008
    • University of Insubria
      Varese, Lombardy, Italy
  • 2007
    • University of Naples Federico II
      Napoli, Campania, Italy
    • University of Wales
      Cardiff, Wales, United Kingdom
  • 2006
    • University of Hamburg
      Hamburg, Hamburg, Germany
    • Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico
      Milano, Lombardy, Italy
    • Academic Medical Center (AMC)
      Amsterdamo, North Holland, Netherlands
  • 2001
    • Università degli studi di Parma
      Parma, Emilia-Romagna, Italy
  • 1999–2000
    • Massachusetts General Hospital
      • Department of Pathology
      Boston, MA, United States
  • 1995–1998
    • Università degli studi di Cagliari
      Cagliari, Sardinia, Italy
    • University of Cambridge
      Cambridge, England, United Kingdom
  • 1991–1998
    • Università degli Studi del Sannio
      Benevento, Campania, Italy
  • 1997
    • Università degli Studi di Genova
      • Dipartimento di Medicina sperimentale (DIMES)
      Genova, Liguria, Italy
  • 1994–1995
    • Johns Hopkins University
      • Department of Molecular Microbiology and Immunology
      Baltimore, MD, United States
  • 1990
    • University of Milan
      • Istituto Di Scienze Endocrine
      Milano, Lombardy, Italy
  • 1985–1989
    • University of Florence
      • Dipartimento di Medicina Sperimentale e Clinica
      Florence, Tuscany, Italy