Publications by authors named "Concetto Regalbuto"

24 Publications

  • Page 1 of 1

Evidence That Baseline Levels of Low-Density Lipoproteins Cholesterol Affect the Clinical Response of Graves' Ophthalmopathy to Parenteral Corticosteroids.

Front Endocrinol (Lausanne) 2020 22;11:609895. Epub 2020 Dec 22.

Endocrinology, Department of Clinical and Experimental Medicine, University of Catania, Garibaldi-Nesima Medical Center, Catania, Italy.

Background: High dose intravenous glucocorticoid (ivGC) therapy is the first line treatment in moderate to severe Graves' ophthalmopathy (GO) and is associated with a clinical response rate ranging from 50% to 80%. Recently, a positive correlation between total cholesterol and low-density lipoproteins cholesterol (LDLc) with GO presentation and activity has been described.

Objective: We aimed at evaluating whether, in patients with moderate to severe active GO treated with ivGC therapy, cholesterol, and LDLc could represent valuable predictive factors of medium-term GO outcome.

Methods: This single center retrospective study was conducted in a consecutive series of 87 patients undergone ivGC therapy because affected by moderate to severe active GO. Clinical outcome of GO was evaluated at week 6 (W6) and 12 (W12) in respect to baseline conditions (week 0) by the seven points CAS according to EUGOGO recommendations. Univariate analysis and binary logistic regression were performed for the outcome variable W12CAS.

Results: In patients with active GO, an early positive clinical response to ivGC therapy (as evaluated by CAS at 6W) was a strong determinant (OR=13) of the clinical outcome at week 12. Moreover, high levels of LDLc at baseline were positively associated with a reduction in the likelihood of being classified as improved at 12W. Patients with LDLc >193.6 mg/dl were very likely to respond negatively to ivGC therapy independently from the response at 6W. Based on these results, we propose a predictive decision-making model to be tested in future prospective studies.

Discussion: We found that, in patients with active GO, both an early clinical response to ivGC therapy and baseline LDLc levels are significant determinants of GO outcome (W12CAS). These data support the need of a cholesterol-lowering treatment before addressing these patients to ivGC therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fendo.2020.609895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7784376PMC
May 2021

Obesity and Monitoring Iodine Nutritional Status in Schoolchildren: is Body Mass Index a Factor to Consider?

Thyroid 2021 05 27;31(5):829-840. Epub 2021 Jan 27.

Department of Cardiovascular and Endocrine-Metabolic Diseases and Aging, Italian National Institute of Health, Rome, Italy.

The frequency of overweight (OW) and obese (OB) children has increased worldwide, particularly in economically developed countries. No studies have been conducted to verify whether the increasing frequency of OW and obesity in schoolchildren may affect the evaluation of iodine nutritional status in populations. The aim of this study was to verify whether urinary iodine concentration (UIC), thyroid volume (TV), and thyroid hypoechoic pattern may be affected by body mass index (BMI) in schoolchildren. The children included in this study (aged 11-13 years) were a part of the schoolchildren recruited in the second nationwide survey (period 2015-2019) conducted in Italy to monitor by law (Atto di Intesa Stato-Regioni February 26, 2009) the nationwide iodine prophylaxis program. Specifically, 1281 schoolchildren residing in iodine-sufficient areas (IS group) and 384 children residing in a still mildly iodine-deficient area (ID group) were recruited between January and March 2015 in the first-degree secondary state schools. In all the children, spot UIC was measured, thyroid ultrasound was performed to evaluate TV, and hypoechogenicity was assessed to indirectly evaluate iodine-associated thyroid autoimmunity. The frequency of OW, OB, and adequate weight (AW) children was similar in the IS and ID groups at any age. After adjusting for sex and age, the regression analysis showed lower UIC values in OB children than in AW children of the IS group (beta coefficient = -34.09 [95% confidence interval -65.3 to -2.8]), whereas no significant differences were observed in the ID group. In both the IS and ID groups, the distribution of TV in AW children was significantly shifted toward lower values in comparison to the distribution of OB children ( < 0.001 in the IS group;  = 0.012 in the ID group). Furthermore, the frequency of thyroid hypoechogenicity was higher in the ID group than in the IS group (10.9% vs. 6.6%,  = 0.005); however, in both groups, it was significantly lower in AW children than in OB children ( < 0.01). This study for the first time demonstrates that BMI may be a confounding factor in monitoring iodine nutritional status in schoolchildren. Since in Italy as in other Western countries the number of OW and OB children is high, BMI is a factor to consider in monitoring salt iodization programs worldwide.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/thy.2020.0189DOI Listing
May 2021

Thyroidectomy as Treatment of Choice for Differentiated Thyroid Cancer.

Int J Surg Oncol 2019 13;2019:2715260. Epub 2019 Oct 13.

Department of Clinical and Experimental Medicine, Endocrinology Section, University of Catania Medical School, Garibaldi-Nesima Hospital, Via Palermo 636, Catania, Italy.

Background: Despite a large amount of data, the optimal surgical management of differentiated thyroid cancer remains controversial. Current guidelines recommend total thyroidectomy if primary thyroid cancer is >4 cm, while for tumors that are between 1 and 4 cm in size, either a bilateral or a unilateral thyroidectomy may be appropriate as surgical treatment. In general, total thyroidectomy would seem to be preferable because subtotal resection can be correlated with a higher risk of local recurrences and cervical lymph node metastases; on the other hand, total thyroidectomy is associated with more complications.

Methods: This is a retrospective study conducted on 359 patients with differentiated thyroid cancer, subjected to total thyroidectomy. Our aim was to correlate clinical and pathological features (extrathyroid tumor growth, bilaterality, nodal and distant metastasis) with patient (gender and age) and tumor (size and histotype) characteristics. Moreover, we recorded postoperative complications, including hypoparathyroidism and laryngeal nerve damage.

Results: In our study, we found a high occurrence of pathological features indicating cancer aggressiveness (bilaterality, nodal metastases, and extrathyroid invasion). On the other hand, total thyroidectomy was associated with relatively low postsurgical complication rates.

Conclusions: Our data support the view that total thyroidectomy remains the first choice for the routine treatment of differentiated thyroid cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2019/2715260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6815575PMC
February 2020

Differentiated thyroid cancer in children: Heterogeneity of predictive risk factors.

Pediatr Blood Cancer 2018 09 16;65(9):e27226. Epub 2018 May 16.

Endocrinology Division, Department of Clinical and Experimental Medicine, Garibaldi-Nesima Medical Center, University of Catania, Catania, Italy.

Objective: To correlate clinical and pathological characteristics at diagnosis with patient long-term outcomes and to evaluate ongoing risk stratifications in a large series of paediatric differentiated thyroid cancers (DTC).

Study Design: Retrospective analysis of clinical and pathological prognostic factors of 124 paediatric patients with DTC (age at diagnosis <19 years) followed up for 10.4 ± 8.4 years. Patients with a follow-up >3 years (n = 104) were re-classified 18 months after surgery on the basis of their response to therapy (ongoing risk stratification).

Results: Most patients had a papillary histotype (96.0%), were older than 15 years (75.0%) and were diagnosed because of clinical local symptoms (63.7%). Persistent/recurrent disease was present in 31.5% of cases during follow-up, but at the last evaluation, only 12.9% had biochemical or structural disease. The presence of metastases in the lymph nodes of the lateral compartment (OR 3.2, 95% CI, 1.28-7.16, P = 0.01) was the only independent factor associated with recurrent/persistent disease during follow-up. At the last evaluation, biochemical/structural disease was associated with node metastases (N1a, N1b) by univariate but not multivariate analysis. Ongoing risk stratification compared to the initial risk classification method better identified patients with a lower probability of persistent/recurrent disease (NPV = 100%).

Conclusions: In spite of the aggressive presentations at diagnosis, paediatric patients with DTC show an excellent response to treatment and often a favourable outcome. N1b status should be considered a strong predictor of persistent/recurrent disease which, as in adults, is better predicted by ongoing risk stratification.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pbc.27226DOI Listing
September 2018

Outcome of the Diffuse Sclerosing Variant of Papillary Thyroid Cancer: A Meta-Analysis.

Thyroid 2016 09 22;26(9):1285-92. Epub 2016 Jul 22.

1 Endocrinology, Department of Clinical and Experimental Medicine, University of Catania , Garibaldi-Nesima Medical Center, Catania, Italy .

Introduction: The diffuse sclerosing variant (DSV) of papillary thyroid cancer (PTC) is considered an aggressive histotype associated with poor prognosis. However, the available data for both the outcome and best management of this disease are inconsistent.

Methods: This study reviewed the current literature by searching PubMed up to November 30, 2015, using the search terms "diffuse sclerosing variant" and "papillary thyroid cancer (or carcinoma)" and selecting only studies evaluating recurrent/persistent disease and cancer-related mortality in both DSV and classic PTC (cPTC). The association with some features of aggressiveness at diagnosis, the risk of recurrence or persistence, and the risk of cancer-related death were reported as odds ratio (OR) with confidence intervals (CI). Meta-regression analysis was used to assess the effect of covariates across the studies.

Results: Ten studies met the eligibility criteria and contributed 585 DSV and 64,611 cPTC patients. Relative to patients with cPTC, patients with DSV exhibited a higher risk of extrathyroidal extension and lymph node and distant metastases. The risk of persistent/recurrent disease was three times higher in patients with DSV than it was in cPTC patients (OR = 3.19 [CI 1.86-5.49]). This risk was not different when only studies where post-surgical (131)I was routinely administered were considered (OR = 2.07 [CI 0.88-4.90]). The risk of cancer-related mortality was not different between DSV and cPTC (OR = 1.34 [CI 0.76-2.38]).

Conclusions: This meta-analysis confirms the aggressive biological behavior of DSV thyroid cancer. When preoperatively suspected, total thyroidectomy with lymph node excision followed by radioiodine therapy should be the correct management for DSV.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/thy.2016.0168DOI Listing
September 2016

Increased thyroid cancer incidence in a basaltic volcanic area is associated with non-anthropogenic pollution and biocontamination.

Endocrine 2016 Aug 5;53(2):471-9. Epub 2015 Oct 5.

Endocrinology, Department of Clinical and Experimental Medicine, Garibaldi-Nesima Medical Center, University of Catania, via Palermo n. 636, 95122, Catania, Italy.

The increased thyroid cancer incidence in volcanic areas suggests an environmental effect of volcanic-originated carcinogens. To address this problem, we evaluated environmental pollution and biocontamination in a volcanic area of Sicily with increased thyroid cancer incidence. Thyroid cancer epidemiology was obtained from the Sicilian Regional Registry for Thyroid Cancer. Twenty-seven trace elements were measured by quadrupole mass spectrometry in the drinking water and lichens (to characterize environmental pollution) and in the urine of residents (to identify biocontamination) in the Mt. Etna volcanic area and in adjacent control areas. Thyroid cancer incidence was 18.5 and 9.6/10(5) inhabitants in the volcanic and the control areas, respectively. The increase was exclusively due to the papillary histotype. Compared with control areas, in the volcanic area many trace elements were increased in both drinking water and lichens, indicating both water and atmospheric pollution. Differences were greater for water. Additionally, in the urine of the residents of the volcanic area, the average levels of many trace elements were significantly increased, with values higher two-fold or more than in residents of the control area: cadmium (×2.1), mercury (×2.6), manganese (×3.0), palladium (×9.0), thallium (×2.0), uranium (×2.0), vanadium (×8.0), and tungsten (×2.4). Urine concentrations were significantly correlated with values in water but not in lichens. Our findings reveal a complex non-anthropogenic biocontamination with many trace elements in residents of an active volcanic area where thyroid cancer incidence is increased. The possible carcinogenic effect of these chemicals on the thyroid and other tissues cannot be excluded and should be investigated.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12020-015-0761-0DOI Listing
August 2016

Worldwide increasing incidence of thyroid cancer: update on epidemiology and risk factors.

J Cancer Epidemiol 2013 7;2013:965212. Epub 2013 May 7.

Endocrinology, Garibaldi-Nesima Hospital, Via Palermo, 636, 95122 Catania, Italy.

Background. In the last decades, thyroid cancer incidence has continuously and sharply increased all over the world. This review analyzes the possible reasons of this increase. Summary. Many experts believe that the increased incidence of thyroid cancer is apparent, because of the increased detection of small cancers in the preclinical stage. However, a true increase is also possible, as suggested by the observation that large tumors have also increased and gender differences and birth cohort effects are present. Moreover, thyroid cancer mortality, in spite of earlier diagnosis and better treatment, has not decreased but is rather increasing. Therefore, some environmental carcinogens in the industrialized lifestyle may have specifically affected the thyroid. Among potential carcinogens, the increased exposure to medical radiations is the most likely risk factor. Other factors specific for the thyroid like increased iodine intake and increased prevalence of chronic autoimmune thyroiditis cannot be excluded, while other factors like the increasing prevalence of obesity are not specific for the thyroid. Conclusions. The increased incidence of thyroid cancer is most likely due to a combination of an apparent increase due to more sensitive diagnostic procedures and of a true increase, a possible consequence of increased population exposure to radiation and to other still unrecognized carcinogens.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2013/965212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3664492PMC
June 2013

Thyroid cancer cell resistance to gefitinib depends on the constitutive oncogenic activation of the ERK pathway.

J Clin Endocrinol Metab 2013 Jun 4;98(6):2502-12. Epub 2013 Apr 4.

Endocrinology Unit, Department of Clinical and Molecular Bio-Medicine, University of Catania, Garibaldi-Nesima Medical Center, Via Palermo 636, 95122 Catania, Italy.

Context: Poorly differentiated thyroid carcinomas are refractory to common anticancer therapies, and novel inhibitors are being tested in these deadly malignancies. The epidermal growth factor receptor (EGFR) tyrosine kinase represents an attractive target for treatment because it is up-regulated in thyroid cancer and plays a role in cancer progression. However, EGFR inhibitors have provided poor results in thyroid carcinomas.

Objective: We evaluated the possible mechanism underlying the resistance of thyroid cancer cells to EGFR inhibitors.

Design: We tested the effect of the EGFR tyrosine kinase inhibitor gefitinib in a panel of thyroid cancer cell lines.

Results: We found that in most of the cell lines, although gefitinib inhibited EGFR phosphorylation, it was poorly effective in reducing cell viability. gefitinib, however, was able to inhibit epidermal growth factor-induced cell migration and matrix invasion. In most thyroid cancer cell lines, gefitinib significantly inhibited Akt phosphorylation by inhibiting EGFR activation, but it had limited or no effect on ERK phosphorylation. The poor cell response to gefitinib was associated with genetic alterations, leading to constitutive activation of the ERK pathway, including BRAF(V600E) and HRAS(G12A/Q61R) mutations and RET/PTC1 rearrangement. When BRAF(V600E)-positive thyroid cancer cells were incubated with the specific BRAF inhibitor PLX4032, sensitivity to gefitinib was restored. Similar results were obtained with rat sarcoma and RET/papillary thyroid cancer inhibitors.

Conclusions: These results indicate that thyroid cancer resistance to gefitinib is due to the constitutive activation of the mitogenic pathway by either signals downstream of EGFR or other tyrosine kinase receptors. This resistance can be overcome by the combined use of selective inhibitors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1210/jc.2012-3623DOI Listing
June 2013

Papillary thyroid microcarcinomas: a comparative study of the characteristics and risk factors at presentation in two cancer registries.

J Clin Endocrinol Metab 2013 Apr 12;98(4):1427-34. Epub 2013 Mar 12.

Endocrinology, Department of Clinical and Molecular Biomedicine, University of Catania, Garibaldi-Nesima Medical Center, Catania, Italy.

Context: Papillary thyroid microcarcinoma (PTMC) is an indolent neoplasia, often asymptomatic and discovered incidentally. Some PTMCs, however, exhibit a more aggressive behavior, frequently recur, and can even cause cancer-related death.

Objective: The aim of this study was to evaluate the prevalence of PTMCs and the associated risk factors at presentation in 2 thyroid cancer registries from areas with different genetic and environmental characteristics.

Design And Patients: We conducted a retrospective, observational study of all incident cases of PTMCs recorded over a 5-year period in the Sicilian Regional Registry for Thyroid Cancer (SRRTC) and in the Surveillance Epidemiology and End Results (SEER) US registry.

Setting: The study took place at an academic hospital.

Results: The incidence of PTMCs was much higher in Sicily (1777 PTMC diagnosed in 2002-2006; age-standardized incidence rate for the world population [ASRw] = 5.8 per 100 000) than in the United States (14 423 PTMC in the period 2004-2008; ASRw = 2.9 per 100 000). Within the SRRTC, a significantly higher incidence was observed in the volcanic area (ASRw = 10.4 vs 4.6 in the rest of Sicily). In Sicily, the female to male ratio was higher, and PTMC patients were younger. In both registries, a significant inverse correlation was observed between age and tumor size. Young patients (≤45 y) exhibited a higher frequency of nodal metastases.

Conclusions: PTMC incidence is twice as high in Sicily compared with the United States, and within Sicily, the incidence is twice as high in the volcanic area. In young patients, PTMCs are larger at presentation and exhibit more risk factors. In both registries, more than 35% of PTMCs exhibited 2 or more risk factors, suggesting that they may require surgery and follow-up similar to that of larger carcinomas.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1210/jc.2012-3728DOI Listing
April 2013

Thyroid cancer in thyroglossal duct cysts requires a specific approach due to its unpredictable extension.

J Clin Endocrinol Metab 2013 Feb 4;98(2):458-65. Epub 2013 Jan 4.

Endocrinology, Department of Clinical and Molecular Bio-Medicine, Garibaldi-Nesima Hospital, University of Catania, Via Palermo 636, 95122 Catania, Italy.

Context: Differentiated thyroid cancer (DTC) in thyroglossal duct cysts is uncommon. The requirement of total thyroidectomy and lymph node dissection is still controversial.

Setting: The study was performed in a referral thyroid cancer center at an academic hospital.

Patients: We conducted a single center retrospective study of a consecutive series of 26 patients with DTC in thyroglossal duct cyst, all having undergone cyst resection and total thyroidectomy.

Main Outcome Measures: Diagnostic modalities, surgical treatment, histopathological features, and clinical outcome were included in the study.

Results: Thyroglossal duct cyst cancer histotype was papillary in 23 of 26 patients (88.5%) and follicular-Hurthle in 3 of 26 cases (11.5%). A concomitant papillary DTC in the thyroid gland was found in 16 of 26 cases (61.5%), and it was multifocal in 8 of 16 cases (50%). At presentation, the patients with cancer in both the thyroglossal duct cyst and the thyroid were older than the patients who only had cancer in the thyroglossal duct cyst (44.9 ± 7.6 vs 32.0 ± 12.7; P = .006). Lymph node dissection, performed in 17 of 26 patients (65.4%), indicated that the central compartment was involved in 6 patients (35.3%, all having cancer also in the thyroid), the laterocervical compartments in 10 patients (58.8%), and the submental in 4 (23.5%). Six patients (23.1%) had persistent disease at 6-year median follow-up.

Conclusions: DTC in thyroglossal duct cysts occurs at a younger age and with more aggressive features at presentation. Concomitant cancer in the thyroid and lymph node metastases is present in most cases. Lymph node compartment involvement is different from that of cancers in the thyroid gland. Therefore, surgical treatment should include both thyroglossal duct cyst resection and total thyroidectomy, with individualized surgical nodal dissection. Subsequent management should follow current DTC guidelines.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1210/jc.2012-1952DOI Listing
February 2013

Update on thyroid cancer treatment.

Future Oncol 2012 Oct;8(10):1331-48

Endocrinology, Department of Clinical & Molecular Biomedicine of the University of Catania, Garibaldi-Nesima Hospital, Catania, Italy.

Surgery and radioiodine therapy are usually effective for most patients with differentiated thyroid cancer. However, poorly differentiated and anaplastic thyroid carcinomas represent a challenge to physicians on the basis of the current cancer treatment modalities. These cancer subtypes are often lethal and refractory to radioiodine therapy as well as most of the common chemotherapy drugs. Several kinase inhibitors are promising targeted therapies for these malignancies; however, clinical trials involving these drugs have provided controversial results and their clinical use is still under debate. Advanced medullary thyroid carcinomas may also be refractory to conventional therapies and novel kinase inhibitors may also be useful to control tumor progression in certain patients. Novel evidence is emerging that thyroid cancer is a stem cell disease, thereby implying that the driving force of thyroid cancers is a subset of undifferentiated cells (thyroid cancer stem cells) with unlimited growth potential and resistance to conventional therapeutic regimens. Thyroid cancer stem cells have been proposed as responsible for tumor invasiveness, metastasis, relapse and differentiation. Therefore, drugs that selectively target these cells could serve as a cornerstone in the treatment of poorly differentiated thyroid cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2217/fon.12.123DOI Listing
October 2012

Severe Graves' ophthalmopathy after percutaneous ethanol injection in a nontoxic thyroid nodule.

Thyroid 2012 Feb 23;22(2):210-3. Epub 2011 Dec 23.

Endocrinology Unit, Department of Clinical and Molecular Bio-Medicine, University of Catania Medical School, Garibaldi-Nesima Hospital, Catania, Italy.

Background: Percutaneous ethanol injection (PEI) is used to treat cystic or mixed benign thyroid nodules. This treatment can result in rare complications, and three cases of Graves' disease (GD) without Graves' ophthalmopathy (GO) have been reported after PEI treatment of toxic thyroid adenomas. Here we present a 55-year-old male patient who developed GD and severe GO after PEI treatment of a mixed cystic-solid, nontoxic thyroid nodule.

Patient Findings: Six months after PEI, the nodule volume had decreased from 8.9 to 3.0 mL, but we observed severe hyperthyroidism with elevated serum free triiodothyronine, free thyroxine, and thyrotropin receptor antibody levels. We also observed ophthalmopathy with symmetrical orbit and soft tissue involvement (grade b/c) and a clinical activity score of 4/7. The diagnosis of GO was confirmed by bilateral corneal damage, increased intraocular pressure on upgaze, and inconstant diplopia. A computed tomography scan showed that the inferior, medial, and superior extraocular muscles were bilaterally enlarged, the perineural space at the orbital cone was slightly reduced and the ophthalmic vein was congested.

Summary: A cause-effect relationship between PEI and GD/GO was likely in this patient because of the temporal sequence. Although the mechanism was unknown, we speculated that the thyroid tissue damage caused by PEI released a large amount of antigenic materials from follicular thyroid cells, including thyrotropin receptor protein, which triggered the autoimmune inflammatory response against the thyroid itself and the orbital soft tissues. The patient did not have any risk factors for either GD or GO.

Conclusions: This observation raises the concern, therefore, that unpredictable and severe complications, such as GD and GO, may occur in a few patients treated with PEI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/thy.2011.0315DOI Listing
February 2012

Graves' orbitopathy: extraocular muscle/total orbit area ratio is positively related to the Clinical Activity Score.

Eur J Ophthalmol 2012 May-Jun;22(3):301-8

Department of Internal Medicine, Endocrinology, University of Catania, Garibaldi-Nesima Hospital, Catania, Italy.

Background And Objective: Both extraocular muscle (EOM) and orbital fat are involved in Graves' orbitopathy (GO) but their enlargement might occur with a different temporal pattern. Two GO subtypes have been described, one with predominant EOM enlargement and the other with prevalent fat tissue involvement. We longitudinally investigated the EOM in patients with GO and their relationship with clinical activity.

Patients And Methods: By using commercial software with a segmentation technique, we calculated from computed tomography (CT) scan EOM coronal area (CA) and total orbit coronal area (TOA) in 23 control subjects and in 32 patients with GO. The latter were studied both at presentation and 18 months later. Superior, lateral, inferior, and medial EOM areas and TOA were selected by 3 different contiguous CT slices: A, B, and C, chosen at globe pole tangent and 2 and 4 mm backward. The Clinical Activity Score (CAS) was also measured.

Results: Orbital EOM CA/TOA ratio (OM/TOA ratio) after 18 months decreased in most patients with GO, indicating that EOM area decrement contributed significantly to OM/TOA ratio reduction. Clinical Activity Score decrease was significantly correlated to the OM/TOA ratio decrease.

Conclusions: An easy method to measure CA of EOM and orbit allowed us to observe that in most patients with GO the OM/TOA ratio decreases with time, suggesting that macroscopic EOM involvement occurs initially and resolves as the other clinical signs and symptoms of the disease resolve, as indicated by the significant OM/TOA ratio correlation with CAS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5301/ejo.5000018DOI Listing
July 2012

Risk-adapted management of differentiated thyroid cancer assessed by a sensitive measurement of basal serum thyroglobulin.

J Clin Endocrinol Metab 2011 Jun 30;96(6):1703-9. Epub 2011 Mar 30.

Endocrinology, Department of Clinical and Molecular Medicine, University of Catania, Garibaldi-Nesima Hospital, via Palermo n.636, 95122 Catania, Italy.

Context: Treatment and follow-up of patients thyroidectomized for differentiated thyroid carcinoma (DTC) mainly depends on the identification of the patient's risk of recurrence. Thyroglobulin (Tg) is the most important marker of persistent/recurrent disease. The recent introduction of a new, more sensitive Tg measurement allows for the early detection of the disease by measuring the basal (under L-T(4) therapy) serum Tg level without TSH stimulation.

Objective: The goal of this study is to identify the basal serum Tg threshold value that indicates recurrent disease by using a second-generation Tg assay.

Design And Patients: A continuous series of 425 DTC patients, all thyroidectomized and treated with (131)I after surgery and having basal Tg of no more than 1.0 ng/ml, negative anti-Tg antibodies, and a recombinant human TSH-stimulated Tg measurement was retrospectively analyzed.

Setting: The study took place at an academic hospital.

Results: The most accurate basal Tg value for predicting the presence of recurrent/residual disease was more than 0.15 ng/ml (sensitivity 87%, specificity 91%, negative predictive value 98.6%, and positive predictive value 47.8%). When the basal Tg level was no more than 0.15 ng/ml, the risk of disease presence was very low, even in patients classified at an intermediate or high risk. In contrast, when the basal Tg level was more than 0.15 ng/ml, the percentage of recurrent disease was relatively high (12.5% or one in eight cases) in low-risk patients.

Conclusions: Basal Tg, measured using a second-generation Tg assay allows for the identification of DTC patients who are likely to remain disease free with great accuracy. This simple measurement, therefore, may be sufficient to assess the risk-adapted management of DTC patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1210/jc.2010-2695DOI Listing
June 2011

A diffuse sclerosing variant of papillary thyroid carcinoma: clinical and pathologic features and outcomes of 34 consecutive cases.

Thyroid 2011 Apr;21(4):383-9

Endocrinology, Department of Clinical and Molecular Medicine of the University of Catania, Garibaldi-Nesima Hospital, Catania, Italy.

Background: The diffuse sclerosing variant of papillary thyroid carcinoma (DSPC) is a relatively rare variant of papillary thyroid cancer. Large studies of patients with DSPC have been infrequently performed, and controversy still exists concerning some DSPC features and outcomes. The aim of the present study was to retrospectively evaluate the clinicopathologic features and outcomes in a series of 34 consecutive patients with DSPC and to compare them with a larger group of 245 consecutive patients with the classic variant of papillary thyroid carcinoma (cPTC) that were evaluated in the same period.

Patients And Methods: Clinical and histological features (sex, age, tumor size,multifocality, bilaterality, extra thyroid extension, and local and distant metastases) were recorded in all patients, as well as any persistent or recurrent disease and the patients' disease status at last observation. Patients with cPTC were classified as either low (122) or high risk (123). DSPC and high-risk patients were all treated with the same protocol, including ¹³¹I treatment. All patients were included in a Cox regression model analysis to investigate the effect of each variable on the hazard ratio.

Results: As expected, multifocality, bilaterality, and extra thyroid extension were more frequently noted at presentation, and the pT1 category of TNM classification was less frequently noted in DSPC and high-risk patients with cPTC compared with low-risk patients with cPTC. No significant difference was found between patients with DSPC and those with high-risk cPTC, except that extra thyroid extension was found more frequently in the patients with DSPC. Using multivariate analysis, diffuse sclerosing variant was an independent variable for predicting a high risk of persistent and recurrent disease during initial follow-up. However, at a later time, and after further treatment, the disease status was not different between patients with DSPC and those with high-risk cPTC, and only the presence of distant metastases affected the final outcome.

Conclusions: DSPC is a thyroid papillary carcinoma variant characterized by high aggressiveness. In patients with DSPC, the outcome is worse than in patients with low-risk cPTC; and, at presentation, characteristics are somewhat worse than for patients with high-risk cPTC.At medium term, the outcome is similar to that observed in patients with high-risk cPTC, provided aggressive treatment is used (additional surgical intervention, when required, and/or ¹³¹I radiotherapy).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/thy.2010.0331DOI Listing
April 2011

Effects of either LT4 monotherapy or LT4/LT3 combined therapy in patients totally thyroidectomized for thyroid cancer.

Thyroid 2007 Apr;17(4):323-31

Division of Endocrinology, Department of Internal and Specialistic Medicine, University of Catania, Italy.

After total thyroidectomy all thyroid cancer patients require lifelong treatment with thyroid hormones; the treatment of choice is synthetic levothyroxine (LT4). The question of whether these patients might benefit from the combined LT4 and liothyronine (LT3) treatment has been addressed with conflicting conclusions. The aim of the present study was to compare the effects of combined low LT4/LT3 molar ratio therapy versus LT4 monotherapy on various target organs and tissues in patients thyroidectomized for thyroid cancer. Urine collection (24 hour), a fasting blood sample for laboratory examinations, thyroid function clinical score, and cardiovascular, neurological, and neuropsychological evaluations were obtained. Clinical parameters and peripheral markers of thyroid function were measured during the two different treatment regimens in 20 patients. Mean serum aspartate aminotransferase, alanine aminotransferase, sex hormone binding globulin, and osteocalcin values were significantly higher during the combined treatment. No significant differences in the clinical score, the systolic and diastolic performance, and the neurological and neuropsychological evaluations were observed between the two treatment regimens. Moreover, no alteration due to subclinical hyperthyroidism or to the fluctuations in serum T3 concentrations during the combined therapy was observed. In conclusion, we found no evidence that combined therapy with a low LT4/LT3 molar ratio resulted in improved well-being and cognitive function or in increased thyroid hormone action on peripheral tissues in respect to LT4 monotherapy. Until future large, blind, randomized, and controlled trials prove otherwise, LT4 should remain the standard treatment for thyroid cancer patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/thy.2006.0084DOI Listing
April 2007

Left ventricular function in acute hypothyroidism: a Doppler echocardiography study.

Ital Heart J 2004 Nov;5(11):857-63

Operative Unit of Cardiology, Department of Internal and Specialistic Medicine, "Garibaldi" Hospital, Catania, Italy.

Background: Acute changes in cardiac parameters may occur after L-thyroxine withdrawal in patients totally thyroidectomized for thyroid cancer. The literature data regarding cardiac function in acute hypothyroidism are limited and discordant.

Methods: In order to evaluate the effects of acute hypothyroidism on cardiac function, 20 athyreotic patients (3 males, 17 females, mean age 46.4 +/- 8.6 years, range 18-58 years) underwent Doppler echocardiography during L-thyroxine therapy (euthyroid phase) and 5 weeks after hormone therapy withdrawal (hypothyroid phase).

Results: Significant changes in the left ventricular mass (83 +/- 12 vs 93 +/- 17 g/m2, p = 0.004) and end-diastolic volume (56 +/- 9 vs 50 +/- 9 ml/m2, p = 0.01) were found. Among systolic function parameters, the pre-ejection period/left ventricular ejection time (PEP/LVET) ratio (0.33 +/- 0.07 vs 0.40 +/- 0.08, p = 0.0002), aortic peak flow velocity corrected for heart rate (3.9 +/- 0.7 vs 3.5 +/- 0.5 cm/s, p = 0.02) and mean aortic acceleration corrected for heart rate (45 +/- 15 vs 38 +/- 9 cm/s2, p = 0.007) showed significant variations, whereas the left ventricular fractional shortening (39 +/- 5 vs 40 +/- 6%, p = NS) and ejection fraction (69 +/- 6 vs 68 +/- 7%, p = NS) did not change. Among diastolic function parameters, only the E-wave velocity decreased (73 +/- 17 vs 65 +/- 12 cm/s, p = 0.01); no significant modification was found in the A-wave velocity (62 +/- 19 vs 58 +/- 14 cm/s, p = NS), E/A ratio (1.2 +/- 0.5 vs 1.1 +/- 0.3, p = NS), isovolumic relaxation time (93 +/- 16 vs 95 +/- 37 ms, p = NS) and E-wave deceleration time (233 +/- 48 vs 235 +/- 45 ms, p = NS). The pattern of left ventricular filling remained unchanged, except in 2 patients. The Suga-Sagawa's index, a known parameter of myocardial contractility, was unchanged (5.6 +/- 2 vs 6.1 +/- 2 mmHg/ml, p = NS). The systemic vascular resistance increased (1511 +/- 599 vs 2216 +/- 408 dynes-s-cm(-5), p = 0.002), while the stroke index (39 +/- 8 vs 33 +/- 7 ml/m2, p = 0.001) and cardiac index (2.74 +/- 0.6 vs 2.07 +/- 0.5 l/min/m2, p = 0.0001) significantly decreased.

Conclusions: Acute hypothyroidism was associated with left ventricular systolic dysfunction, probably due to pre- and afterload alterations rather than to an impaired myocardial contractility. The diastolic function was not significantly modified. An increase in cardiac mass was also found, possibly a consequence of early interstitial myxedema. Unlike the PEP/LVET ratio, both the fractional shortening and ejection fraction may be unreliable indicators of left ventricular systolic dysfunction in patients with acute hypothyroidism.
View Article and Find Full Text PDF

Download full-text PDF

Source
November 2004

Clinical behavior and outcome of papillary thyroid cancers smaller than 1.5 cm in diameter: study of 299 cases.

J Clin Endocrinol Metab 2004 Aug;89(8):3713-20

Istituto di Medicina Interna e Malattie Endocrine e Metaboliche, Cattedra di Endocrinologia, University of Catania, Ospedale Garibaldi, 95123 Catania, Italy.

To investigate predictors of relapse in small (
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1210/jc.2003-031982DOI Listing
August 2004

Effects of thyroidectomy alone or followed by radioiodine ablation of thyroid remnants on the outcome of graves' ophthalmopathy.

Thyroid 2003 Jul;13(7):653-8

Dipartimento Clinico-Sperimentale di Medicina e Farmacologia, Sezione di Endocrinologia, University of Messina, Messina, Italy.

Fifty-five patients with Graves' disease (GD) and mild to moderate Graves' ophthalmopathy (GO) underwent near-total thyroidectomy (Tx). In 16 patients this was followed by a standard ablative dose of (131)I because of the hystologic evidence of differentiated thyroid carcinoma. We retrospectively evaluated whether or not GO activity could be affected by thyroid surgery alone or followed by complete ablation of thyroid tissue. Accordingly, on the basis of clinical activity score (CAS) values prior to thyroidectomy, we identified two groups: group A with active GO (CAS > or = 3; n = 31) and group B with inactive GO (CAS < or = 2; n = 24). CAS values were then recorded at 6, 12, and 24 months after surgery/(131)I ablation. Over the course of the follow-up period, GO became inactive in approximately 70% of group A patients (CAS 4.2 +/- 0.8 at baseline, 2.1 +/- 2.0 at 24 months, p < 0.0001) and became active in 37.5% patients from group B. When we examined GO activity according to the type of treatment used (Tx or Tx and (131)I), the prevalence of inactive GO both short- and long-term, was significantly higher in the group of patients who underwent Tx and (131)I ablation. Therefore, this seems to be a more effective means of inducing and maintaining inactive GO.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/105072503322240004DOI Listing
July 2003

The diagnostic use of the rhTSH/thyroglobulin test in differentiated thyroid cancer patients with persistent disease and low thyroglobulin levels.

Clin Endocrinol (Oxf) 2003 May;58(5):556-61

Dipartimento di Medicina Interna e Medicina Specialistica, University of Catania Medical School, Catania, Italy.

Background: Serum thyroglobulin (Tg) measurement after TSH stimulation, by either thyroid hormone withdrawal or recombinant human TSH (rhTSH) administration, is the most sensitive method for early detection of patients with persistent or recurrent differentiated thyroid cancer (DTC) after total thyroidectomy and 131I ablation. The use of rhTSH is now increasing because it avoids thyroid hormone suppressive therapy (THST) withdrawal and the consequent symptoms of severe hypothyroidism. Current guidelines suggest measurement of serum Tg 4 days after starting a 2-day course of rhTSH injections, and assumes that Tg reaches maximum serum levels at that time.

Objective: The present study was carried out to evaluate the accuracy of rhTSH/thyroglobulin test in DTC patients with persistent disease and low thyroglobulin levels.

Patients And Measurements: A series of 13 DTC patients was selected because they had proven persistent disease associated with low Tg levels (< 2.0 micro g/l) under l-thyroxine treatment. In all of them, serum Tg was > 5.0 micro g/l at the last THST withdrawal. We measured serum Tg and TSH levels on days 0.5, 1, 1.5, 2, 4, 7, 10 and 15 after the first of a 2-day course of intramuscular rhTSH injections.

Results: Serum Tg values were variable in terms of both peak and time-course. Detectable serum Tg levels were recorded on day 4 in all patients. However, among these 13 patients, the peak Tg value was reached earlier than day 4 in three patients and later in two others. In one patient, Tg level at day 2 was higher (3.0 micro g/l) than at day 4 (1.8 micro g/l). In six of the 13 patients studied we compared Tg values after rhTSH to those subsequently obtained after THST withdrawal: in five of them Tg values were two to three times higher after the latter stimulation. Serum Tg value variability after rhTSH was partially accounted for by variability of serum TSH levels, which were inversely related to patient body surface.

Conclusions: In DTC patients with persistent disease and low Tg levels, optimization of the diagnostic use of Tg measurement after rhTSH may require rhTSH dose adjustment to the patient body surface area and repeated blood sampling, in order to improve diagnostic accuracy. In these patients not even a TSH-stimulated serum Tg cut-off of 2.0 micro g/l on day 4 provides 100% accuracy, whereas a cut-off of 1.0 micro g/l seems more appropriate. Therefore, in this subset of patients, if any detectable Tg level >or= 1.0 micro g/l is found after rhTSH, re-evaluation after THST should be advised.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1046/j.1365-2265.2003.01744.xDOI Listing
May 2003

Genetics of specific phenotypes of congenital hypothyroidism: a population-based approach.

Thyroid 2002 Nov;12(11):945-51

Istituto di Medicina Interna, Malattie Endocrine e del Metabolismo dell'Università di Catania, Ospedale Garibaldi, Catania, Italy.

Congenital hypothyroidism (CH) may cause severe and irreversible neurologic and developmental abnormalities when not recognized early. Many millions of newborns have now been screened and many thousands of patients with CH have been identified. Approximately 80%-85% have defects of thyroid gland development, while 15%-20% have congenital errors of thyroid hormone biosynthesis. An entire population screened for CH over a long period of time, was studied in the present report, using a population-based approach. In particular, two CH phenotypes, both presenting with in situ thyroid gland (patients with either goiter or with thyroid gland volume ranging from normal to hypoplasic) were analyzed. Mutations were searched in some of the most likely candidate genes: thyroperoxidase (TPO) in patients with CH goiter, Pax8 and thyrotropin receptor (TSHR) in the other group. In the former group (n = 8), four TPO gene mutations were identified in three patients. One patient was a compound heterozygous. In two cases an already described mutation (1277(insGGCC)) was present; in two other cases mutations not previously described (1996(G-->T) and 2295(G-->A)), which induced aminoacid variations with a Glu --> Stop and Val --> Ile changes, respectively, were identified. In all patients mutations were inherited from one of the parents. In the case of the compound heterozygous patient, one mutation was inherited from the mother (1277(insGGCC)) and the other from the father (1996(G-->T), Glu --> Stop). In the latter group (n = 8), a patient with a 16-base pair C(T)(13)CC deletion in TSHR gene intron 8, 42-bp distal to exon/intron 8 splice junction, was identified. No mutation was identified in Pax8 gene.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/105072502320908277DOI Listing
November 2002

Long-term outcome of patients with insular carcinoma of the thyroid: the insular histotype is an independent predictor of poor prognosis.

Cancer 2002 Nov;95(10):2076-85

Istituto di Medicina Interna e Malattie Endocrine e Metaboliche, Cattedra di Endocrinologia, University of Catania, Ospedale Garibaldi, Catania, Italy.

Background: Insular thyroid carcinoma was described originally as a tumor with aggressive behavior. However, whether a predominant insular component is an independent factor for poor prognosis is unclear.

Methods: The authors compared the clinical behavior of tumors in three groups of patients with thyroid carcinoma--13 patients with insular thyroid carcinoma, 18 patients with follicular thyroid carcinoma, and 26 patients with papillary thyroid carcinoma--who were selected based on similar tumor size and similar age. Disease free survival and disease specific deaths were assessed in the three groups with a Kaplan-Meier analysis and were compared using the log-rank test. Cox regression analysis was used to evaluate the influence of histotype and other prognostic factors on the occurrence of distant metastases and disease specific death.

Results: Patient follow-up ranged from 5.2 months to 190.0 months. At last follow-up, only 1 of 13 patients (7.7%) with insular carcinoma, compared with 8 of 18 patients (44.4%) with follicular carcinoma and 12 of 26 patients (46.1%) with papillary carcinoma, were disease free. The disease specific death rate was 61.5% among patients in the insular carcinoma group compared with 16.7% and 15.4% among patients in the follicular carcinoma group (P = 0.006) and the papillary carcinoma group (P = 0.025), respectively. At multivariate analysis, the insular histotype was the only variable that was related independently to disease specific death (hazard ratio = 4.27; P = 0.005). Distant metastases occurred in 84.6% of patients in the insular carcinoma group compared with 50% and 19.2% of patients in the follicular carcinoma group (P = 0.039) and the papillary carcinoma group (P = 0.0003), respectively. All metastases from patients with insular carcinomas (n = 11 patients) showed radioiodine uptake, but a clinical benefit from this treatment was observed only in 1 patient.

Conclusions: Patients with insular thyroid carcinoma have a poorer outcome compared with patients of similar age who have differentiated types of thyroid carcinoma with tumors of a similar size. Because radioiodine rarely is effective in the treatment of patients with metastatic insular thyroid carcinoma, novel and possible multimodal therapies should be explored for the treatment of patients with these aggressive tumors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cncr.10947DOI Listing
November 2002

False-positive findings on (131)I whole-body scans because of posttraumatic superficial scabs.

J Nucl Med 2002 Feb;43(2):207-9

Department of Internal Medicine, Garibaldi Hospital, University of Catania, Catania, Italy.

Unlabelled: Nonspecific (131)I uptake may affect both the specificity and the accuracy of whole-body scanning (WBS) performed after (131)I administration in the follow-up of thyroid carcinoma after thyroidectomy. We report a newly identified cause of false-positive WBS findings: posttraumatic superficial scabs.

Methods: Four patients who underwent thyroidectomy for differentiated thyroid carcinoma were studied after therapeutic administration of 3,700 MBq (131)I.

Results: WBS revealed an area of uptake in the lower limbs, in a site corresponding to a slight abrasion of the skin that had incidentally occurred between a few hours before and 24 h after radioiodine administration. In 2 patients, a radioiodine concentration in the scab was shown by the disappearance of the radioactivity in the leg after removal of the scab and by detection of radioactivity in the collected material.

Conclusion: Posttraumatic superficial scabs may be a cause of false-positive WBS findings. High (131)I doses, although providing increased sensitivity, may also increase the number of false-positive results.
View Article and Find Full Text PDF

Download full-text PDF

Source
February 2002
-->