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C Pelosini,
M Maffei,
G Ceccarini,
M Marchi,
A Marsili,
G Galli,
G Scartabelli,
A Tamberi,
F Latrofa,
P Fierabracci,
P Vitti, A Pinchera,
F Santini
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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; · 1.57 Impact Factor
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F Aghini Lombardi,
E Fiore,
M Tonacchera,
L Antonangeli,
T Rago,
M Frigeri,
A M Provenzale,
L Montanelli,
L Grasso, A Pinchera,
P Vitti
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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.
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; · 1.57 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. · 1.57 Impact Factor
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ABSTRACT: We analyzed the in vitro effects of celecoxib, a COX-2 inhibitor, and determined if celecoxib can sensitize a human MTC-derived cell line (TT) to chemotherapeutics. We found that celecoxib induced apoptosis in TT cells and decreased drug efflux by reducing the expression of MDR-1 mRNA, which codes for the drug efflux pump P-gp. We also observed that TT cells were 10-fold more resistant to doxorubicin than to vinorelbine, mimicking what can be observed in clinical practice. In addition, we found that the combination of celecoxib and vinorelbine, but not doxorubicin, induced a significant reduction in cell viability and a significant increase in apoptosis. In conclusion, we showed that celecoxib was able to enhance the chemotherapeutic effect of vinorelbine. A clinical trial exploring the in vivo activities of celecoxib in MTC patients who cannot benefit from available treatments would be desirable, taking into account the possible risks of cardiovascular effects of this drug.
Molecular and Cellular Endocrinology 01/2012; 355(1):41-8. · 4.19 Impact Factor
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M Giannetti,
P Piaggi,
G Ceccarini,
S Mazzeo,
G Querci,
P Fierabracci,
G Salvetti,
G Galli,
I Ricco,
S Martinelli,
C Di Salvo,
M Anselmino,
A Landi,
P Vitti, A Pinchera,
F Santini
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ABSTRACT: Nonalcoholic fatty liver disease is a common finding in obese subjects. Increasing evidence has been provided suggesting that it represents the hepatic component of the metabolic syndrome.
Aim of this longitudinal study was to evaluate the relationships between several anthropometric measures, including the hepatic left lobe volume (HLLV), and various indicators of the metabolic syndrome in a cohort of severely obese women before and after laparoscopic adjustable gastric banding (LAGB).
Seventy-five obese women (mean age 45 ± 10 years and body mass index (BMI) 42.5 ± 4.8 kg m(-2)) underwent LAGB and completed an average (± s.d.) post-surgical follow-up of 24 ± 6 months. Determination of HLLV, subcutaneous and intra-abdominal fat (IAF) was based on ultrasound. The principal component statistical analysis applied to pre-operative measurements, highlighted HLLV as a parameter that clustered with serum insulin, IAF, serum glucose and uric acid, along with triglycerides (TGs), alkaline phosphatase and high-density lipoprotein cholesterol. After LAGB, the average reduction of BMI was 23%, 12% for subcutaneous fat (SCF), 42% for HLLV and 40% for visceral fat. Among body weight, BMI, SCF, IAF and HLLV, reduction of the latter was an independent predictor of reduction of serum transaminases and γ-Glutamyltransferase, glucose, insulin and TGs.
In severely obese women: (i) HLLV is a sensitive indicator of ectopic fat deposition, clustering with parameters defining the metabolic syndrome; (ii) weight loss achieved by LAGB is associated with a reduction of liver volume as estimated by HLLV; (iii) among various anthropometric parameters measured, reduction of HLLV that follows LAGB represents the best single predictor of improvement of various cardiometabolic risk factors.
International journal of obesity (2005) 12/2011; 36(3):336-41. · 4.34 Impact Factor
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M Tonacchera,
P Agretti,
T Rago,
G De Marco,
F Niccolai,
A Molinaro,
M Scutari,
A Candelieri,
D Conforti,
R Musmanno,
G Di Coscio,
F Basolo,
P Iacconi,
P Miccoli, A Pinchera,
P Vitti
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ABSTRACT: Fine needle aspiration (FNA) with cytologic evaluation is the most reliable tool for malignancy prediction in thyroid nodules, but cytologic diagnosis remains undetermined for 20% of nodules.
We investigated the diagnostic potential of a set of 6 marker genes to distinguish benign and malignant thyroid nodules.
The prospective study included 153 thyroid samples obtained by FNA of thyroid nodules from 151 patients (56 benign, 43 malignant, and 54 nodules with undetermined cytology). Gene expression was evaluated by quantitative realtime PCR and statistical analysis of data was performed. All samples were analyzed for V600E BRAF mutation.
A decrease in TTF3 and HGD1 expression was observed in malignant nodules with respect to benign ones, while an increase in PLAB expression was demonstrated in these nodules. The decision model was valid for 88 of 99 cases of benign and malignant nodules, with a total of 11 false positive or negative predictions. The obtained malignant/benign phenotype prediction was also valid for 37 of 54 cases of nodules with undetermined cytology with a total of 8 false positive and 9 false negative predictions. V600E BRAF gene mutation was demonstrated in 19/43 malignant nodules, in 0/56 benign nodules, and in 1/54 undetermined nodules.
The expression profiles of genes (TFF3, HGD1, and PLAB) allowed a good prediction for the differentiation of benign thyroid lesions and thyroid cancer starting from cells of FNA; however, this assay showed limitations when applied to discriminate thyroid nodules with undetermined cytology.
Journal of endocrinological investigation 10/2011; 35(8):754-9. · 1.57 Impact Factor
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ABSTRACT: Patients with primary hyperparathyroidism (PHPT) with contraindications to parathyroidectomy (PTx) or persistent PHPT have few non surgical options.
The aim of the study was to investigate the efficacy of cinacalcet in reducing serum calcium in patients with PHPT, for whom PTx would be indicated according to serum calcium levels, but in whom PTx is not clinically appropriate or is contraindicated [European Medicines Agency (EMA) prescription labeling].
The study (open-label prospective, conducted in a single tertiary center) included 12 sporadic and 2 multiple endocrine neoplasia type 1 PHPT patients with serum calcium greater than 11.2 mg/dl. Cinacalcet was administered in increasing doses until normal serum calcium was reached or side effects preventing a further increase occurred. Serum calcium, PTH, phosphate, 25OHD, markers of bone turnover, 24h-urinary calcium and areal bone mineral density (BMD) were measured. Safety biochemical indices and adverse events were monitored.
The maintenance cinacalcet dose [median 30 mg twice daily (range 30 daily-60 mg twice daily)] was maintained constant during follow-up (median 12 months). Mean±SE baseline serum calcium was 12.2±0.3 mg/dl. Serum calcium decreased by at least 1 mg/dl in all patients and normalized in 10. Serum calcium at the last observation was 9.9±0.2 mg/dl (p<0.0001 vs baseline). PTH decreased by 17.1% compared to baseline (p=0.13), and never reached a normal value. BMD was unchanged. Adverse events occurred in 6 patients (43%) and required treatment withdrawal in 2.
Cinacalcet reduced and often normalized serum calcium in PHPT patients who met the EMA labeling.
Journal of endocrinological investigation 09/2011; 35(7):655-60. · 1.57 Impact Factor
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F Belcari,
G Placidi,
A Guzzetta,
M Tonacchera,
M Ciampi,
A Bartoli,
R T Scaramuzzo,
P Frumento,
G Cioni, A Pinchera,
A Boldrini,
P Ghirri
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ABSTRACT: To identify perinatal factors associated with sub-optimal neuromotor outcome in infants without evident central nervous system lesions (intraventricular hemorrhage/ periventricular leukomalacia), with gestational age ≤30 (group I) and of 31-32 weeks (group II).
A total of 102 premature infants admitted to the Neonatal Intensive Care Unit of Pisa, at 26-32 weeks of gestation, were studied. Data about perinatal factors and TSH values at 3-4 days of life were collected. The assessment of neuromotor development was performed at 18 months of corrected age, using the locomotor subscale of the Griffiths Scales of Mental Development.
Risk factors supposed to be predictive of sub-optimal neuromotor outcome (odds ratio >1) were at ≤30 weeks: male sex, small for gestational age, patent duct arterious, respiratory distress syndrome, and at 31-32 weeks: Apgar at 5 min <7, respiratory distress syndrome, patent duct arterious and birth weight <1500 g. A strong correlation was also found between TSH screening values >4,3 mU/l and suboptimal neuromotor outcome in both groups.
Several perinatal factors, acting on an immature and more vulnerable nervous system, such as the pre-term one, different for different gestational ages, are associated with a sub-optimal neuromotor outcome. Higher, but within the normal range, TSH values at screening seem to be a strong risk factor for neuromotor outcome in preterm infants without intraventricular hemorrhage or periventricular leukomalacia.
Journal of endocrinological investigation 06/2011; 34(10):e308-13. · 1.57 Impact Factor
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ABSTRACT: In patients with breast cancer (BC) a high prevalence of benign thyroid diseases (BTD) has been described, Hashimoto's thyroiditis accounting to a large extent for this association. The aim of this study was to evaluate the prevalence of BC in a large group of patients with BTD.
Clinical records of 622 consecutive patients with BTD were examined. BC prevalence in BTD patients was compared with BC frequency in general population living in the same country.
BC prevalence in patients with BTD (38/622; 6.11%) was significantly higher (p=0.0002) compared to BC frequency in general population (2.07%). When patients were divided according to the age of menopause, in females older than 49 yr BC frequency in BTD was significantly higher than in age-matched population (7.6 vs 3.3%; p=0.006), while in females aged 30-49 yr BC frequency in BTD was higher, but not statistically significantly, than in agematched population (3.7 vs 0.5%; p=0.06). No significant difference in BC prevalence was found when patients were grouped according to the diagnosis of thyroid disorders: Graves' disease, Hashimoto's thyroiditis, nodular goiter associated or not associated with serum thyroid autoantibodies (TAb). No significant difference in BC frequency was observed between TAb+ (26/377; 6.9%) and TAb- (12/245; 4.9%) patients. The distribution of known risk factors for breast malignancies was similar in patients with or without BC.
In patients with BTD the prevalence of BC is significantly higher than the expected, showing the usefulness of screening for breast malignancy of patients with BTD.
Journal of endocrinological investigation 05/2011; 34(5):349-52. · 1.57 Impact Factor
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A Dimida,
E Ferrarini,
P Agretti,
G De Marco,
L Grasso,
M Martinelli,
I Longo,
D Giulietti,
A Ricci,
M Galimberti,
B Siervo,
G Licitra,
F Francia, A Pinchera,
P Vitti,
M Tonacchera
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ABSTRACT: Electric and magnetic fields (EMF) might be involved in human disease and numerous research and scientific reviews have been conducted to address this question. In particular thyroid structural and functional alterations caused by various forms of non-ionizing radiation have been described.
The aim of this study was to analyze the possible effects of EMF on thyroid, in particular we analyzed the effects caused by a GSM (Global System for Mobile Communications) signal (900 MHz) on cultured thyroid cells (FRTL- 5).
The experimental setup was designed in order to expose samples to a radiofrequency wave in well-controlled conditions. We used the FRTL-5 cell line, an epithelial monoclonal continuous cell line derived from Fisher rat thyroid tissue growing as monolayer, expressing the TSH receptor and the sodium-iodide symporter (NIS). FRTL-5 were subsequently irradiate for 24, 48, and 96 h with EMF (800-900 MHz, power-frequency of mobile communication systems) and iodide uptake and cAMP production were measured.
The irradiation of cells with EMF at 900 Mhz for 24, 48, and 96 h did not influence the level of cAMP production and was not able to modify iodide accumulation in FRTL- 5 cells with respect to basal conditions.
In conclusion, EMF do not seem to be able to interfere with the biochemical properties of FRTL-5 cells in vitro.
Journal of endocrinological investigation 03/2011; 34(3):185-9. · 1.57 Impact Factor
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R Negro,
P Beck-Peccoz,
L Chiovato,
P Garofalo,
R Guglielmi,
E Papini,
M Tonacchera,
F Vermiglio,
P Vitti,
M Zini, A Pinchera
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ABSTRACT: Hyperthyroidism in pregnancy is an uncommon disease, involving less than 1% of pregnancies. The recognition of hyperthyroidism may be elusive as some sign and symptoms may be attributed to the state of pregnancy itself. Furthermore, the diagnosis of hyperthyroidism is sometimes challenging and treatment must take into account not only the mother but also the fetus' health. A carefully tailored treatment is necessary to avoid or reduce the risks of complications associated with uncontrolled disease which are represented by spontaneous abortion, congenital abnormalities, preeclampsia, preterm birth, low birth weight, placental abruption, neonatal thyroid dysfunction, and perinatal mortality. The Italian Thyroid Association (AIT) and Italian Association of Clinical Endocrinologists (AME) constituted an ad hoc committee that developed clinical practice recommendations for diagnosis and treatment of hyperthyroidism in pregnancy. The review and recommendations have been based on a comprehensive analysis of the current literature and from the consensus of experts.
Journal of endocrinological investigation 03/2011; 34(3):225-31. · 1.57 Impact Factor
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ABSTRACT: Thyroid gland is highly dependent on dietary intake of iodine for normal function, so it is particularly subjected to "endocrine disruptor" action. The human sodium/iodide symporter (hNIS) is an integral plasma membrane glycoprotein mediating the active transport of iodide into thyroid follicular cells, a crucial step for thyroid hormone biosynthesis. Beyond to perchlorate and thyocianate ions a few other inhibitors of iodide uptake have been described.
The aim of this study was to investigate if 10 substances usually used as drugs in clinical practice were able to inhibit NIS-mediated iodide uptake in vitro.
A CHO cell line stably expressing hNIS was used to test any inhibition of NIS-mediated iodide uptake exerted by drugs. Perchlorate and thyocianate ions were used as positive controls.
None of the analyzed substances was able to significantly inhibit iodide uptake in our system. As we expected, perchlorate and thyocianate ions were able to inhibit iodide uptake in a dose-dependent manner.
In conclusion, we carried out an in vitro assay to evaluate the potential inhibitory effect of common drugs on NISmediated iodide uptake by using CHO-hNIS cells. None of the analyzed substances was able to inhibit iodide uptake; only perchlorate and thyocianate were able to inhibit iodide uptake in a dose-dependent manner.
Journal of endocrinological investigation 03/2011; 34(3):170-4. · 1.57 Impact Factor
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H. Graf,
S. Fast,
F. Pacini, A. Pinchera,
A. Leung,
M. Vaisman,
C. Reiners,
J.L. Wemeau,
D. Huysmans,
W. Harper, [......],
R. Corbo,
C. Duren,
E. Proust-Lemoine,
M.A. Edelbroek,
C. Marriott,
I. Rachinsky,
P. Grupe,
T. Watt,
J. Magner,
L. Hegedüs
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ABSTRACT: Background: Recombinant human TSH (rhTSH) can be used to enhance (131)I therapy for shrinkage of multinodular goiter (MG). Objective, Design, and Setting: The objective of the study was to compare the efficacy and safety of 0.01 and 0.03 mg modified-release (MR) rhTSH as an adjuvant to (131)I therapy, vs. (131)I alone, in a randomized, placebo-controlled, international, multicenter study. Patients and Intervention: Ninety-five patients (57.2 +/- 9.6 yr old, 85% females, 83% Caucasians) with MG (median size 96.0, range 31.9-242.2 ml) were randomized to receive placebo (group A, n = 32), MRrhTSH 0.01 mg (group B, n = 30), or MRrhTSH 0.03 mg (group C, n = 33) 24 h before a calculated activity of (131)I. Main Outcome Measures: The primary end point was a change in thyroid volume (by computerized tomography scan, at 6 months). Secondary end points were the smallest cross-sectional area of the trachea; thyroid function tests; Thyroid Quality of Life Questionnaire; electrocardiogram; and hyperthyroid symptom scale. Results: Thyroid volume decreased significantly in all groups. The reduction was comparable in groups A and B (23.1 +/- 8.8 and 23.3 +/- 16.5%, respectively; P = 0.95). In group C, the reduction (32.9 +/- 20.7%) was more pronounced than in groups A (P = 0.03) and B. The smallest cross-sectional area of the trachea increased in all groups: 3.8 +/- 2.9% in A, 4.8 +/- 3.3% in B, and 10.2 +/- 33.2% in C, with no significant difference among the groups. Goiter-related symptoms were effectively reduced and there were no major safety concerns. Conclusion: In this dose-selection study, 0.03 mg MRrhTSH was the most efficacious dose as an adjuvant to (131)I therapy of MG. It was well tolerated and significantly augmented the effect of (131)I therapy in the short term. Larger studies with long-term follow-up are warranted
The Journal of clinical endocrinology and metabolism 02/2011; 96(5). · 6.50 Impact Factor
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ABSTRACT: Indeterminate and nondiagnostic patterns represent the main limitation of fine-needle aspiration (FNA) cytology of thyroid nodules, clinical and echographic features being poorly predictive of malignancy. The newly developed real-time ultrasound elastography (USE) has been previously applied to differentiate malignant from benign lesions. The aim of this study was to get further insights into the role of USE in the presurgical diagnosis of nodules with indeterminate or nondiagnostic cytology.
The study included 176 patients who had one (n=138) or multiple (n=38) nodules with indeterminate or nondiagnostic cytology on FNA, for whom histology was available after thyroidectomy. A total of 195 nodules (142 indeterminate, 53 nondiagnostic) were submitted to USE, and elasticity was scored as 1 (high), 2 (intermediate), or 3 (low).
In indeterminate lesions, the score 1, describing high elasticity, was strongly predictive of benignity, being found in 102 of 111 benign nodules and in only one of 31 carcinomas (P<0.0001). By combining the scores 2 and 3, USE had a sensitivity of 96.8% and a specificity of 91.8%. In nodules with nondiagnostic cytology, score 1 was found in 39 of 45 benign nodules and in only one of eight carcinomas (P<0.0001). By combining the scores 2 and 3, USE had a sensitivity of 87.5% and a specificity of 86.7%.
USE may represent an important tool for the diagnosis of thyroid cancer in nodules with indeterminate or nondiagnostic cytology and may prove useful in selecting patients who are candidates for surgery.
The Journal of clinical endocrinology and metabolism 12/2010; 95(12):5274-80. · 6.50 Impact Factor
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C Romei,
B Cosci,
G Renzini,
V Bottici,
E Molinaro,
L Agate,
P Passannanti,
D Viola,
A Biagini,
F Basolo,
C Ugolini,
G Materazzi, A Pinchera,
P Vitti,
R Elisei
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ABSTRACT: This study was aimed to demonstrate the clinical benefits of rearranged during transfection (RET) genetic screening in patients with apparently sporadic medullary thyroid cancer (MTC) not only to identify the hereditary nature of the disease in the index case but also to discover family members harbouring the same germline mutations (i.e. gene carriers) who are unaware of their condition.
RET genetic screening allowed the identification of germline RET mutations in apparently sporadic MTC resulting in their re-classification as hereditary forms.
RET genetic screening was performed in 729 apparently sporadic MTC patients by direct sequencing RET exons 5, 8, 10, 11 and 13-16. Clinical and biochemical evaluation of gene carriers was also performed.
We discovered an unsuspected germline RET mutation in 47 of 729 (6·5%) apparently sporadic MTC who were re-classified as hereditary. We found 60 of 146 (41·1%) gene carriers, 35 of whom had biochemical or clinical evidence of MTC. Thirty gene carriers underwent total thyroidectomy and 27 of 30 (90%) were persistently cured after a mean follow-up of 6·0 years. As a further result of RET genetic screening, we observed a significantly higher prevalence of familial medullary thyroid cancer (FMTC) in our series with respect to the largest series of the International RET Consortium (P = 0·0002).
RET genetic screening of patients with apparently sporadic MTC represents a major tool for the preclinical diagnosis and early treatment of unsuspected affected family members and allows the identification of a relevant percentage of hidden FMTC.
Clinical Endocrinology 11/2010; 74(2):241-7. · 3.17 Impact Factor
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E Papini,
R Negro, A Pinchera,
R Guglielmi,
A Baroli,
P Beck-Peccoz,
P Garofalo,
M P Pisoni,
M Zini,
R Elisei,
L Chiovato
Journal of endocrinological investigation 09/2010; 33(8):579-86. · 1.57 Impact Factor
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T Rago,
E Fiore,
M Scutari,
F Santini,
G Di Coscio,
R Romani,
P Piaggi,
C Ugolini,
F Basolo,
P Miccoli, A Pinchera,
P Vitti
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ABSTRACT: To evaluate the risk of papillary thyroid carcinoma (PTC) at fine-needle aspiration (FNA) cytology in 34 120 patients.
False positive and false negative rates of FNA cytology were 1.2 and 1.8% in comparison with the histology in 3406 nodules from 3004 patients who underwent surgery. PTC (901 cases) was more frequent in solitary nodule (SN; 446/13 549, 3.3%) than in multinodular goiter (MNG; 411/19 923, 2%, chi(2)=48.8; P<0.0001), and in males (209/6382, 3.3%) than in females (648/26 945, 2.40%, chi(2)=15.58; P<0.0001). PTC prevalence in Graves' disease (GD; 13/286, 4.5%) and Hashimoto's thyroiditis (HT; 31/508, 6.1%) was higher than in SN, this difference being significant in HT (chi(2)=8.7; P=0.003), but not in GD (chi(2)=1.6; P=0.2). Using the multiple logistic regression analysis, independent risk predictors of PTC were determined, which were younger age (odds ratio (OR)=0.97, confidence interval (CI) 0.964-0.974; P<0.0001), male gender (OR=1.44, CI 1.231-1.683; P<0.0001), and SN versus MNG (OR=0.63, CI 0.547-0.717; P<0.0001). The individual risk predictivity was highly improved by including serum TSH in the prediction model, which was measured at FNA in 11 919 patients.
A cytology suspicious or indicative of PTC was associated with younger age, male gender, and solitary versus multiple nodularity. These clinical parameters, together with serum TSH, may allow formulation of an algorithm that could be usefully applied to predict the risk of PTC in individual patients when cytology does not give a diagnostic result.
European Journal of Endocrinology 04/2010; 162(4):763-70. · 3.42 Impact Factor
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ABSTRACT: Cooperations between engineers and physicians are crucial for studying and solving complex medical-biological problems. The study of obesity - unanimously regarded as a multi-factorial disease - is a typical example where specialists from various areas of medical research may be supported by engineers expert in system theory and software development. The effectiveness and the risk-benefit profile of medical intervention in this field (i.e., bariatric surgery and gastric banding) may require advanced data analysis to classify patient typologies and to predict the effects of therapies. In this paper the experience gained by a team of engineers joining a team of physicians is described: as a first step a specific software for data analysis was developed in the case of obese patients. The software toolbox implemented standard statistical models for classification of subjects according to their psychological profile. Afterwards, the analysis was extended using artificial neural networks for modeling and predicting the outcome of gastric banding in term of excess weight loss after 2 years, based on the preliminary knowledge of the psychological profile of patients involved. Obtained results demonstrate that the cooperation led to the development of a reliable tool for physicians, as an aid to forecasting the outcome of the therapy and to predict the patients candidate to get better benefits from a gastric banding treatment.
Health Care Management (WHCM), 2010 IEEE Workshop on; 03/2010
