Section of Endocrinology and Diabetology

Rome, Italy

Section of Endocrinology and Diabetology

Rome, Italy

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Trimboli P.,Section of Endocrinology and Diabetology | Guglielmi R.,Ospedale Regina Apostolorum of Albano Laziale | Monti S.,University of Rome La Sapienza | Misischi I.,Ospedale Regina Apostolorum of Albano Laziale | And 8 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2012

Context: Thyroid nodules are selected for biopsy on the basis of clinical and ultrasound (US) findings. Ultrasonography detects nodules at risk of malignancy, but its diagnostic accuracy does not rule out with certainty the possibility of cancer in lesions without suspicious findings. Objective: The objective of the study was to evaluate the diagnostic accuracy of real-time elastography (RTE) in thyroid nodules and to assess the improvement provided by combination of RTE, B-mode US, and color flow Doppler (CFD). Design: This was a prospective multicenter study. Patients: A consecutive series of 498 thyroid nodules was blindly evaluated by US, CFD, and RTE before biopsy or surgery. Nodules were classified at RTE by four-class color scale. Patients with benign cytology underwent follow-up over 12 months, whereas patients with indeterminate, suspicious, or malignant cytology were surgically treated. Results: At follow-up, 126 nodules were malignant and 372 benign. RTE classes III-IV showed 81% sensitivity and 62% specificity. The presence of at least one US risk factor (hypoechogenicity, microcalcifications, irregular margins, intranodular vascularization, and taller than wide shape) had 85% sensitivity and 91% negative predictive value. When RTE was combined with US, the presence of at least one of the six parameters had 97% sensitivity and 97% negative predictive value, with an odds ratio of 15.8 (95% confidence interval 5.7-43.8). Conclusions: RTE is a valuable tool for detecting malignant thyroid lesions with a sensitivity similar to traditional US and CFD features. By adding RTE evaluation, the sensitivity for malignancy of US findings is markedly increased and the selection of nodules that do not need cytology ismademore reliable. Copyright © 2012 by The Endocrine Society.


Giovanella L.,Oncology Institute of Southern Switzerland | Verburg F.A.,RWTH Aachen | Valabrega S.,University of Rome La Sapienza | Trimboli P.,Section of Endocrinology and Diabetology | Ceriani L.,Oncology Institute of Southern Switzerland
Clinical Chemistry and Laboratory Medicine | Year: 2013

Background: To prospectively evaluate the role of procalcitonin (PCT) in detecting or excluding medullary thyroid carcinoma (MTC) among patients with thyroid nodules and increased calcitonin (CT) levels. Methods: Fourteen of 1236 patients referred for thyroid nodules had increased serum CT >10 pg/mL. A stimulation test with pentagastrin was done and both CT and PCT were measured after stimulation. All patients underwent thyroid ultrasound, fine-needle cytology and, if indicated, surgery with histological and immunohistochemical examination of the surgical specimens. Results: After follow-up, two MTCs were found. These two patients had basal CT >100 pg/mL and detectable (>0.1 ng/mL) PCT, with 100% sensitivity. Pentagastrin stimulated CT achieved values above 100 pg/mL in two MTCs and in other two cases with no MTC outcome (50% PPV and 83% NPV). On the contrary, all patients with no MTC had both basal and stimulated undetectable PCT (100% PPV and 100% NPV). Conclusions: The addition of basal PCT measurement in patients with thyroid nodule(s) and increased CT may significantly improve accuracy of CT measurement without needing a PG stimulation test. © 2013 by Walter de Gruyter Berlin Boston 2013.


Giovanella L.,Oncology Institute of Southern Switzerland | Bongiovanni M.,Institute of Pathology | Trimboli P.,Section of Endocrinology and Diabetology
Current Opinion in Oncology | Year: 2013

PURPOSE OF REVIEW: Differentiated thyroid cancers (DTCs) have generally an indolent behavior. However, in a minority of these patients cervical metastasis at diagnosis or recurrence during follow-up may occur. Then, in suspicious neck lymph nodes fine-needle aspiration (FNA) is warranted. Thyroglobulin measurement in needle washout fluids (FNA-Tg) since its first description has been reported to increase the diagnostic accuracy of cytology in neck lymph nodes suspicious for metastatic DTC. RECENT FINDINGS: Recent literature suggests that FNA-Tg can substitute conventional cytology and, in turn, simplifies clinical management of DTC patients. However, because of the large difference between these clinical studies, the data are sparse. Thus, neither procedures nor assay method for FNA-Tg have been standardized. SUMMARY: FNA-Tg measurement is the more accurate tool to detect neck recurrences and metastases from DTC. Providing strict standardization of preanalytical and analytical phase, FNA-Tg may suffice to confirm or exclude neck DTC recurrence in patients with concurrent well differentiated papillary cancer type, suspicious neck ultrasound findings and increased serum thyroglobulin after thyroidectomy. On the contrary, FNA-Tg accuracy increases by adding cytological examination when FNA is performed before thyroidectomy, in patients with more aggressive histological types, and if low-undetectable serum thyroglobulin and/or positive serum antithyroglobulin antibodies occur. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Giovanella L.,Oncology Institute of Southern Switzerland | Trimboli P.,Section of Endocrinology and Diabetology | Verburg F.A.,RWTH Aachen | Treglia G.,Oncology Institute of Southern Switzerland | And 3 more authors.
European Journal of Nuclear Medicine and Molecular Imaging | Year: 2013

Purpose To assess the relationship between serum thyroglobulin (Tg) levels, Tg doubling time (Tg-DT) and the diagnostic performance of 18F-FDG PET/CT in detecting recurrences of 131I-negative differentiated thyroid carcinoma (DTC). Methods Included in the present study were 102 patients with DTC. All patients were treated by thyroid ablation (e.g. thyroidectomy and 131I), and underwent 18F-FDG PET/CT due to detectable Tg levels and negative conventional imaging. Consecutive serum Tg measurements performed before the 18FFDG PET/CT examination were used for Tg-DT calculation. The 18F-FDG PET/CT results were assessed as true or false after histological and/or clinical follow-up. Results Serum Tg levels were higher in patients with a positive 18F-FDG PET/CT scan (median 6.7 ng/mL, range 0.7-73.6 ng/mL) than in patients with a negative scan (median 1.8 ng/mL, range 0.5-4.9 ng/mL; P<0.001). In 43 (88 %) of 49 patients with a true-positive 18F-FDG PET/CT scan, the Tg levels were >5.5 ng/mL, and in 31 (74 %) of 42 patients with a true-negative 18F-FDG PET/CT scan, the Tg levels were ≤5.5 ng/mL. A Tg-DT of <1 year was found in 46 of 49 patients (94 %) with a true-positive 18F-FDG PET/CT scan, and 40 of 42 patients (95 %) with a truenegative scan had a stable or increased Tg-DT. Moreover, combining Tg levels and Tg-DT as selection criteria correctly distinguished between patients with a positive and a negative scan (P<0.0001). Conclusion The accuracy of 18F-FDG PET/CT significantly improves when the serum Tg level is above 5.5 ng/mL during levothyroxine treatment or when the Tg-DT is less than 1 year, independent of the absolute value. © 2013 Springer-Verlag Berlin Heidelberg.


Trimboli P.,Section of Endocrinology and Diabetology | Trimboli P.,Oncology Institute of Southern Switzerland | Giovanella L.,Oncology Institute of Southern Switzerland
Clinical Chemistry and Laboratory Medicine | Year: 2015

Generally, calcitonin (CT) values below the upper reference limit rule-out medullary thyroid carcinoma (MTC) with very high accuracy. However, sparse cases of serum-calcitonin-negative MTC (CT-NEG-MTC) have been reported. Here we reviewed CT-NEG-MTC reported in literature, discussed the potential causes and proposed a practical laboratory and clinical approach. A comprehensive literature search was conducted by using the terms "medullary thyroid carcinoma" AND "non-secreting calcitonin" OR "undetectable calcitonin". The search was updated until December 2014. Original articles that described CT-NEG-MTC were eligible for inclusion. Only MTC cases with preoperative CT below the upper reference limit were included in the present review. Eleven papers with 18 CT-NEG-MTC cases (age 50 years, size 26 mm) were retrieved. Four patients with poorly differentiated MTC died within 3 years. Different CT assays were employed and different reference values were adopted. Preoperative serum CT values were below the institution cut-off levels in all cases, and undetectable in four patients. In some papers negative CT results were confirmed by additional tests. Further laboratory investigations were performed in some of the included studies. In patients with well founded suspicious of MTC and within the reference limits/undetectable CT other laboratory investigations [carcinoembryonic antigen (CEA), procalcitonin, CT stimulation, CT in washout of nodule's aspiration] have to be performed. Surgical approach to CT-NEG-MTC does not differ from those secreting CT. Postoperative follow-up of these rare cases should include periodical imaging and measurement of all potential markers. Patients with poorly differentiated MTC are at higher risk of disease-related death, and require more aggressive follow-up strategy. © 2015 by De Gruyter.


Trimboli P.,Section of Endocrinology and Diabetology | Treglia G.,Oncology Institute of Southern Switzerland | Guidobaldi L.,Section of Pathology | Romanelli F.,University of Rome La Sapienza | And 7 more authors.
Clinical Endocrinology | Year: 2015

Background The early detection of medullary thyroid carcinoma (MTC) can improve patient prognosis, because histological stage and patient age at diagnosis are highly relevant prognostic factors. As a consequence, delay in the diagnosis and/or incomplete surgical treatment should correlate with a poorer prognosis for patients. Few papers have evaluated the specific capability of fine-needle aspiration cytology (FNAC) to detect MTC, and small series have been reported. This study conducts a meta-analysis of published data on the diagnostic performance of FNAC in MTC to provide more robust estimates. Research Design and Methods A comprehensive computer literature search of the PubMed/MEDLINE, Embase and Scopus databases was conducted by searching for the terms 'medullary thyroid' AND 'cytology', 'FNA', 'FNAB', 'FNAC', 'fine needle' or 'fine-needle'. The search was updated until 21 March 2014, and no language restrictions were used. Results Fifteen relevant studies and 641 MTC lesions that had undergone FNAC were included. The detection rate (DR) of FNAC in patients with MTC (diagnosed as 'MTC' or 'suspicious for MTC') on a per lesion-based analysis ranged from 12·5% to 88·2%, with a pooled estimate of 56·4% (95% CI: 52·6-60·1%). The included studies were statistically heterogeneous in their estimates of DR (I-square >50%). Egger's regression intercept for DR pooling was 0·03 (95% CI: -3·1 to 3·2, P = 0·9). The study that reported the largest MTC series had a DR of 45%. Data on immunohistochemistry for calcitonin in diagnosing MTC were inconsistent for the meta-analysis. Conclusions The presented meta-analysis demonstrates that FNAC is able to detect approximately one-half of MTC lesions. These findings suggest that other techniques may be needed in combination with FNAC to diagnose MTC and avoid false negative results. © 2014 John Wiley & Sons Ltd.


Trimboli P.,Section of Endocrinology and Diabetology | Crescenzi A.,Biomedical University of Rome
Endocrine | Year: 2015

Recently, the microhistologic evaluation by core needle biopsy (CNB) has been reported as high accurate to diagnose thyroid nodules with previous indeterminate or not adequate fine-needle aspiration cytology. In addition, sparse data have been reported regarding the use of CNB in other conditions. Aim of this review was to furnish the state of the art of this topic by summarizing published data about the diagnostic performance of CNB in thyroid lesions, and provide an easy to use reference for clinical practice. Sources encompass studies published through May 2014. Original articles were investigated and following specific aspects were discussed: 1. The “large” needle biopsy in 90’s; 2. Complications by and patient’s comfort with thyroid CNB; 3. Advantages provided by examination of a microhistologic sample of thyroid nodule; 4. Use of CNB in thyroid nodules with previous not adequate (Thy 1/Class 1/Category I) cytology; 5. Use of CNB in thyroid neoplasms (Thy 3/Class 3/Category III–IV) cytology; 6. Use of CNB in specific ultrasonographic presentations of thyroid nodules or in patients with peculiar clinical contexts; 7. First-line approach by CNB in thyroid nodules; 8. Immunohistochemistry and molecular tests on CNB samples; and 9. Future perspective. © 2014, Springer Science+Business Media New York.


Abbouda A.,University of Rome La Sapienza | Trimboli P.,Section of Endocrinology and Diabetology | Bruscolini A.,University of Rome La Sapienza
Seminars in Ophthalmology | Year: 2014

Introduction: Thyroid ophthalmopathy is a complication most commonly associated with Grave's disease. The disease course ranges from mild to severe, with severe cases resulting in major visual impairment. Methods: A complete ophthalmic examination in a 35-year-old secundigravida to 14 weeks of gestation presented to the hospital for a routine ophthalmological examination with eyelid retraction in the right eye was made. We studied the course of ocular disease through the gestation with orbit ecography and a 3T MRI. Results: A diagnosis of Grave's Ophthalmopathy was made. Conclusion: This case presents an unusual course of the GD during pregnancy and a normal post-partum relapse, according to the Th1/Th2 balance. The frequent follow-up and the use of MRI allowed a prompt identification and complete control of the disease. © 2014 Informa Healthcare USA, Inc.


Trimboli P.,Section of Endocrinology and Diabetology | Trimboli P.,Oncology Institute of Southern Switzerland | Treglia G.,Oncology Institute of Southern Switzerland | Sadeghi R.,Mashhad University of Medical Sciences | And 2 more authors.
Endocrine | Year: 2015

The main limit of thyroid fine-needle aspiration cytology (FNAC) is represented by indeterminate report. Recently, real-time elastography (RTE) has been described in the management of these cases. Here, we performed a meta-analysis of published studies specifically focused on the use of RTE in indeterminate thyroid nodules. A comprehensive literature search of PubMed/MEDLINE and Google Scholar databases was conducted by using the combination of the terms “thyroid” and “indeterminate” and “elastography.” Pooled sensitivity, specificity, accuracy, PPV and NPV of RTE as predictor of malignancy in thyroid nodules with indeterminate FNAC were calculated, including 95 % confidence intervals (95 % CI). The area under the summary ROC curve (AUC) was also assessed. Databases found 572 papers, and eight were included in the meta-analysis. Of these, six studies had prospective design and two were retrospective. Pooled malignancy rate was 31 %. As common denominator, all studies set the prevalence of hardness within the nodule as risk factor for malignancy of the lesion. Sensitivity of RTE ranged from 11 to 89 % (pooled estimate of 69 %; 95 % CI 55–82 %), specificity varied from 6 to 100 % (pooled estimate of 75 %; 95 % CI 42–96 %), and accuracy was comprised between 35 and 94 % (pooled estimate of 73 %; 95 % CI 54–89 %). The AUC was 0.77. RTE has suboptimal diagnostic accuracy to diagnose thyroid nodules previously classified as indeterminate. Then, RTE alone should not be used for selecting these patients for surgery or not. We advice for further studies using other elastographic approaches and combined RTE and B-mode ultrasonography. © 2014, Springer Science+Business Media New York.


Giovanella L.,Oncology Institute of Southern Switzerland | Treglia G.,Oncology Institute of Southern Switzerland | Sadeghi R.,Mashhad University of Medical Sciences | Trimboli P.,Section of Endocrinology and Diabetology | And 2 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2014

Context: Serum thyroglobulin (Tg) is an indicator of differentiated thyroid cancer (DTC) relapse. Objective: Our objective was to conduct a meta-analysis of published data about the diagnostic performance of highly sensitive serum Tg (hsTg) during levothyroxine therapy in DTC follow-up. Data Sources: We performed a comprehensive literature search of PubMed/MEDLINE and Scopus for studies published until July 2013. Study Selection: Studies investigating the diagnostic performance of basal hsTg in monitoring DTC were eligible. Exclusion criteria were 1) articles not within the field of interest; 2) reviews, letters, or conference proceedings; 3) articles evaluating serum Tg measurement with a functional sensitivity >0.1 ng/mL; 4) overlap in patient data; and 5) insufficient data to reassess diagnostic performance of basal serum hsTg. Data Extraction: Information was collected concerning basic study data, patient characteristics, and technical aspects. For each study, the number of true-positive, false-positive, true-negative, and false-negative findings for basal hsTg, considering stimulated Tg measurement as a reference standard, were recorded. Data Synthesis: Pooled data demonstrated that the negative predictive value of hsTg was97%and 99% considering a stimulated Tg measurement >1 ng/mL and >2 ng/mL as cutoffs for positivity, respectively. Despite the high pooled sensitivity of basal hsTg, the pooled specificity, accuracy, and positive predictive value were insufficient to completely substitute for a stimulated Tg measurement. Conclusions: Basal hsTg measurement has a very high negative predictive value but an insufficient positive predictive value for monitoring DTC patients. Therefore, a Tg stimulation test can be avoided in patients with an undetectable basal hsTg, whereas a stimulated Tg measurement should be considered when hsTg levels are detectable. Copyright © 2014 by the Endocrine Society.

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