Publications by authors named "Claudia Scollo"

14 Publications

  • Page 1 of 1

Prognostic Factors for Adrenocortical Carcinoma Outcomes.

Front Endocrinol (Lausanne) 2016 25;7:99. Epub 2016 Jul 25.

Endocrinology, Department of Clinical and Experimental Medicine, University of Catania , Catania , Italy.

Purpose: Adrenocortical carcinoma (ACC) is an aggressive tumor characterized by a high recurrence rate and poor response to treatment. This study analyzes a consecutive series of ACC patients to evaluate the prognostic value of various clinical and pathological characteristics.

Methods: We retrospectively evaluated 32 ACC patients followed at our Medical Center from 1997 to 2015 and evaluated the prognostic value of age at diagnosis, gender, tumor functional status, stage, and type of treatment with respect to overall survival (OS) and disease-free survival (DFS), as determined by Kaplan-Meier curves.

Results: ACC was associated with hormonal overproduction in 50% of cases, and patients with isolated hyperandrogenism had a better prognosis. Recurrence was observed in 12/26 (46.2%) patients with no evidence of disease after surgery. Tumor size [hazard ratio (HR) 1.32, 95% confidential intervals (CI) 1.12-1.64; p = 0.007], ki-67 (HR 1.06, 95% CI 1.02-1.11; p = 0.009) and advanced stage at diagnosis (III-IV) (HR 6.51, 95% CI 1.65-24.68; p = 0.006) were associated with recurrence in the 26 R0 patients in the univariate analysis. Advanced stage was an independent risk factor for recurrence in the multivariate analysis (HR 8.10, 95% CI 1.55-41.35; p = 0.01). Five-year survival was 40.0%. Positive resection margins (HR 10.61, 95% CI 3.02-38.31; p = < 0.001), ki-67 (HR 1.04, 95% CI 1.01-1.07; p = 0.01) and advanced stage (HR 11.31, 95% CI 1.45-87.76; p = 0.02) were associated with poor survival in all 32 patients, but only positive resection margins were an independent predictor of mortality in the multivariate analysis (HR 6.22, 95% CI 1.44-26.05; p = 0.01).

Conclusion: ACC has a poor prognosis with a high recurrence rate. Tumor stage at diagnosis and the completeness of surgical excision are the most relevant prognostic factors.
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August 2016

A novel RET gene mutation in a patient with apparently sporadic pheochromocytoma.

Endocr J 2016 24;63(1):87-91. Epub 2015 Oct 24.

Endocrinology, Garibaldi Nesima Hospital, Catania, Italy.

Pheochromocytoma (Pheo) is a chromaffin tumor arising from the adrenal medulla. The recent discovery of new germline mutations in RET, SDHA, SDHB, SDHC, SDHD, VHL, NF1, TMEM127, MAX genes, increased the rate of genetic disease from 10% to 28% in patients with apparently sporadic tumor. RET germline mutations cause multiple endocrine neoplasia type 2 syndrome (MEN 2A) characterized by complete penetrance of medullary thyroid cancer (MTC), and lower prevalence of Pheo and hyperparathyroidism. We describe the genetic etiology of an apparently sporadic case of monolateral Pheo in a 42-year-old male patient. A new (not previously reported) MEN 2A-associated germline RET mutation located in exon 11 (Glu632Gly, caused by an A>G point mutation at position 1895 of the RET cDNA) was found in the patient but not in his living first-degree relatives. This observation increases the number of possible germline RET mutations. Genotype-phenotype correlation of this new genetic alteration is unknown, but this rare mutation is probably associated with a low risk for MTC (usually the first tumor diagnosed in MEN 2A syndrome) and with the development of Pheo before the onset of MTC. Since we expect MTC to occur in our patient, strict follow-up is mandatory. Our findings emphasize the relevance of genetic testing in patients with Pheo, especially when the clinical presentation (family history, young age at diagnosis, multiple locations, malignant lesions, and bilateralism) is suggestive.
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November 2016

Familial Non-Medullary Thyroid Cancer Represents an Independent Risk Factor for Increased Cancer Aggressiveness: A Retrospective Analysis of 74 Families.

Front Endocrinol (Lausanne) 2015 3;6:117. Epub 2015 Aug 3.

Endocrinology, Garibaldi Nesima Hospital , Catania , Italy.

Objectives: To assess whether familial non-medullary thyroid cancer (FNMTC) represents an independent risk factor for increased aggressiveness of the tumor, as concern as the clinical presentation and the long-term follow-up in respect of sporadic differentiated thyroid cancer (SDTC).

Design: Retrospective study; 1976-2014.

Patients And Methods: Seventy-four FNMTC families (151 affected individuals): family relationship and number of affected family members were evaluated. Clinical and histopathological features and outcome were compared to that of 643 SDTC patients followed in the same period according to the same institutional protocols. Median follow-up was 57.7 months (range 12-136) in FNMTC and 59.7 (range 15-94.6) in SDTC patients.

Results: Three cases occurred in 3 families and 2 cases in the other 71. F:M was 3.7:1 in FNMTC and 4.3:1 in SDTC (NS). The family relationship was siblings in 62.2%. Mean age at diagnosis was lower in FNMTC than in SDTC (p < 0.005). Papillary/follicular histotype distribution was similar (86%). Papillary tumors were more frequently multifocal in FNMTC (p = 0.004) and with lymph-node metastases (p = 0.016). Disease-free survival (DFS) was shorter in FNMTC vs. SDTC (p < 0.0001) with 74.8 vs. 90.8% patients free of disease at the last control (p < 0.005). Three patients died in FNMTC group vs. 1 in SDTC (p = 0.02).

Conclusion: Familial non-medullary thyroid cancer displays distinct characteristics as earlier age of onset and increased aggressiveness at diagnosis and a higher rate of persistent/recurrent disease and mortality with a shorter DFS in respect with SDTC. FNMTC patients, therefore, should be followed accurately. As the specific gene (or genes) responsible for susceptibility for FNMTC has not yet been identified, a low frequency periodic screening of relatives DTC patients may be useful to identify FNMTC patients at early stage of disease.
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August 2015

Mitotane treatment in patients with adrenocortical cancer causes central hypothyroidism.

Clin Endocrinol (Oxf) 2016 Apr 18;84(4):614-9. Epub 2015 Aug 18.

Department of Experimental and Clinical Medicine, Endocrinology Unit, University of Catania, Garibaldi-Nesima Hospital, Catania, Italy.

Introduction: Mitotane, a steroidogenesis inhibitor with adrenolytic properties used to treat adrenocortical cancer (ACC), can affect thyroid function. A reduction of FT4 levels with normal FT3 and TSH has been described in these patients. Using an in vitro murine model, the secretory capacity of thyrotrophic cells has been shown to be inhibited by mitotane.

Objective: To investigate the pathogenesis of thyroid abnormalities in mitotane-treated patients with ACC.

Patients And Methods: In five female patients with ACC (median age 47; range 31-65) treated with mitotane (dosage 1·5 g/day; 1·0-3·0), we analysed the pattern of TSH and thyroid function index (FT4, FT3 and FT3/FT4 ratio) compared to an age- and gender-matched control group. The in vivo secretory activity of the thyrotrophic cells was evaluated using a standard TRH test (200 μg), and the response was compared to both a group of age-matched female controls (n = 10) and central hypothyroid patients (n = 10).

Results: Basal TSH (median 1·54 mU/l; range 1·20-2·17) was normal and scattered around our median reference value, FT3 levels (median 3·80 pmol/l; 3·30-4·29) were normal but below the median reference value of 4·37 pmol/l and FT4 levels were below the normal range in all patients (median 8·40 pmol/l; 7·6-9·9). FT3/FT4 ratio was in the upper range in 4 patients and higher than normal in one patient. A blunted TSH response to TRH was observed in mitotane-treated patients. ΔTSH (absolute TSH response, peak TSH minus basal TSH) was 3·65 (range 3·53-5·26), 12·37 (range 7·55-19·97) and 1·32 mU/l (range 0·52-4·66) in mitotane-treated patients, controls and central hypothyroid patients, respectively. PRL secretion was normal.

Conclusions: Mitotane-treated patients with ACC showed low FT4, normal FT3 and TSH and impaired TSH response to TRH, characteristic of central hypothyroidism. Furthermore, the elevated FT3/FT4 ratio of these subjects reflects an enhanced T4 to T3 conversion rate, a compensatory mechanism characteristic of thyroid function changes observed in hypothyroid conditions. This finding thus confirms in vitro studies and may have a therapeutic implication for treatment with thyroid hormones, as suggested by current guidelines for this specific condition.
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April 2016

Cardiac arrest after intravenous calcium administration for calcitonin stimulation test.

Thyroid 2014 Mar 14;24(3):606-7. Epub 2013 Nov 14.

Department of Endocrinology, Garibaldi-Nesima Hospital , Catania, Italy .

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March 2014

Descriptive epidemiology of human thyroid cancer: experience from a regional registry and the "volcanic factor".

Front Endocrinol (Lausanne) 2013 4;4:65. Epub 2013 Jun 4.

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

Thyroid cancer (TC), the most common endocrine tumor, has steadily increased worldwide due to the increase of the papillary histotype. The reasons for this spread have not been established. In addition to more sensitive thyroid nodule screening, the effect of environmental factors cannot be excluded. Because high incidences of TC were found in volcanic areas (Hawaii and Iceland), a volcanic environment may play a role in the pathogenesis of TC. In January 2002, the Regional Register for TC was instituted in Sicily. With a population of approximately five million inhabitants with similar genetic and lifestyle features, the coexistence in Sicily of rural, urban, industrial, moderate-to-low iodine intake, and volcanic areas provides a conducive setting for assessing the environmental influences on the etiology of TC. In Sicily, between 2002 and 2004, 1,950 new cases of TC were identified, with an age-standardized rate (world) ASR(w) = 17.8/10(5) in females and 3.7/10(5) in males and a high female/male ratio (4.3:1.0). The incidence of TC was heterogeneous within Sicily. There were 2.3 times more cases in the Catania province (where most of the inhabitants live in the volcanic area of Mt. Etna): ASR(w) = 31.7/10(5) in females and 6.4/10(5) in males vs. 14.1 in females and 3.0 in males in the rest of Sicily. Multivariate analysis documented that residents in the volcanic area of Mt. Etna had a higher risk of TC, compared to the residents in urban, industrial, and iodine deficient areas of Sicily. An abnormally high concentration of several chemicals was found in the drinking water of the Mt. Etna aquifer, which provides water to most of the residents in the Catania province. Our data suggest that environmental carcinogen(s) of volcanic origin may promote papillary TC. Additional analyses, including cancer biological and molecular features, will allow a better understanding of risk factors and etiopathogenetic mechanisms.
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June 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.
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February 2013

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.
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June 2011

Papillary thyroid cancer incidence in the volcanic area of Sicily.

J Natl Cancer Inst 2009 Nov 5;101(22):1575-83. Epub 2009 Nov 5.

Endocrinology Division, Department of Internal and Specialistic Medicine, University of Catania Medical School, Garibaldi-Nesima Hospital, Catania, Italy.

Background: The steadily increasing incidence of thyroid cancer has been attributed mostly to more sensitive thyroid nodule screening. However, various environmental factors, such as those associated with volcanic areas, cannot be excluded as risk factors. We evaluated thyroid cancer incidence in Sicily, which has a homogenous population and a province (Catania) that includes the Mt Etna volcanic area.

Methods: In a register-based epidemiological survey, we collected all incident thyroid cancers in Sicily from January 1, 2002, through December 31, 2004. The age-standardized incidence rate for the world population (ASR(w)) was calculated and expressed as the number of thyroid cancer diagnoses per 100 000 residents per year. The association of thyroid cancer incidence rate with sex, age, tumor histotype, and various environmental factors was evaluated by modeling the variation of the ASR(w). All statistical tests were two-sided.

Results: In 2002-2004, 1950 incident thyroid cancers were identified in Sicily (among women, ASR(w) = 17.8, 95% confidence interval [CI] = 16.9 to 18.7; and among men, ASR(w) = 3.7, 95% CI = 3.3 to 4.1). Although the percentage of thyroid cancers that were microcarcinomas (ie, < or = 10 mm) and ratio of men to women with thyroid cancer were similar in all nine Sicilian provinces, thyroid cancer incidence was statistically significantly higher in the province of Catania (among women, ASR(w) = 31.7, 95% CI = 29.1 to 34.3; and among men, ASR(w) = 6.4, 95% CI = 5.2 to 7.5) than in the rest of Sicily (among women, ASR(w) = 14.1, 95% CI = 13.2 to 15.0; and among men, ASR(w) = 3.0, 95% CI = 2.6 to 3.4) (all P values < .001). Incidence of papillary, but not follicular or medullary, cancers was statistically significantly increased in Catania province, and papillary tumors from patients in Catania more frequently carried the BRAF V600E gene mutation (55 [52%] of 106 tumors) than tumors from patients elsewhere in Sicily (68 [33%] of 205 tumors) (relative risk = 1.7, 95% CI = 1.0 to 2.8, P = .02). Cancer incidence was statistically significantly lower in rural areas than in urban areas of Sicily (P = .003). No association with mild iodine deficiency or industrial installations was found. Levels of many elements (including boron, iron, manganese, and vanadium) in the drinking water of Catania province often exceeded maximum admissible concentrations, in contrast to water in the rest of Sicily.

Conclusion: Residents of Catania province with its volcanic region appear to have a higher incidence of papillary thyroid cancer than elsewhere in Sicily.
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November 2009

High prevalence of differentiated thyroid carcinoma in acromegaly.

Clin Endocrinol (Oxf) 2005 Aug;63(2):161-7

Divisione Clinicizzata di Endocrinologia, Ospedale Garibaldi, Catania, Italy.

Objective: Acromegaly is a chronic disease caused by increased GH secretion and associated with a greater risk of developing both benign and malignant tumours. In the present study we evaluated the prevalence of thyroid disorders and thyroid malignancies in a series of acromegalic subjects.

Design And Patients: We studied, retrospectively, a continuous series of 125 acromegalic patients referred to the Endocrinology Centres at the University Hospitals of Catania and Ferrara, Italy, over a 22-year period.

Measurements: Diagnosis and management of acromegaly were based on standardized criteria. In all patients thyroid function and morphology were evaluated by serum free T4, free T3, TSH measurements and ultrasound scanning, respectively. Fine-needle aspiration biopsy (FNAB) was performed in all solid-mixed thyroid nodules of diameter greater than 1 cm. IGF-1 expression was assessed by semiquantitative immunohistochemical analysis in some patients with differentiated thyroid cancer.

Results: Abnormal thyroid function was found in eight cases (6%). A diffuse or nodular goitre was present in 102 cases (82%). Thyroidectomy was performed in 17 patients. Histological examination revealed a differentiated thyroid cancer in seven of the patients. No significant association of thyroid cancer with GH or IGF-1 levels was found. Semiquantitative assessment of IGF-1 expression by immunohistochemistry revealed a more intense staining in thyroid cancer from acromegalic subjects than in papillary thyroid cancer from nonacromegalic subjects.

Conclusions: The frequency of thyroid disorders in our series of acromegalic subjects was similar to that previously observed in these patients. However, the prevalence of thyroid cancer was not only strikingly elevated (5.6%) in comparison to the estimated prevalence in the general population (0.093%), but it was even higher than that reported for acromegalic subjects. Sustained exposure to high serum IGF-1 levels is likely to play a role in the development of thyroid cancer in this disease. An additive role for the autocrine/paracrine action of locally produced IGF-1 is also possible. Our results suggest that thyroid function and morphology should be carefully monitored in all acromegalic patients.
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August 2005

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 (
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August 2004

Rationale for central and bilateral lymph node dissection in sporadic and hereditary medullary thyroid cancer.

J Clin Endocrinol Metab 2003 May;88(5):2070-5

Nuclear Medicine, Institut Gustave-Roussy, 94805 Villejuif cedex, France.

Unlabelled: A retrospective study was performed on 101 consecutive medullary thyroid cancer (MTC) patients who underwent at Institut Gustave-Roussy (IGR) total thyroidectomy with central and bilateral lymph node dissection. At histology, lymph node metastases were found in 55% of patients. In sporadic MTC, lymph node metastases were observed in the central compartment in 50% of patients, in the ipsilateral jugulocarotid chain in 57%, and in the contralateral jugulocarotid chain in 28%. In hereditary MTC, lymph node metastases were identified in the central compartment in 45% of patients, in the ipsilateral jugulocarotid chain in 36%, and in the contralateral jugulocarotid chain in 19%. Contralateral lymph nodes were found in 37% of metastatic patients with an unilateral tumoral involvement of the thyroid gland. A strong association was observed between tumor size and lymph node involvement for both hereditary and sporadic MTC (P < 0.02). Permanent hypoparathyroidism occurred in 4% of patients and laryngeal nerve palsy in 5%. An undetectable calcitonin level was obtained after surgery in 61% of patients, in 95% of patients without lymph node metastases, and in 32% of patients with lymph node metastases. Among patients with lymph node involvement, undetectable calcitonin level was obtained in 57% of patients with less than or with 10 lymph node metastases and in 4% of patients with more than 10 (P < 0.01).

In Conclusion: 1) lymph node metastases occur early in the course of MTC; 2) the pattern of lymph node metastatic distribution in neck areas varied between patients and was not related to the thyroid tumor size; 3) contralateral lymph node metastases were observed even in patients with small thyroid tumor; 4) total thyroidectomy with central and complete bilateral neck dissection should be performed routinely in all patients with sporadic and hereditary MTC, even in those with small thyroid tumors-a contralateral neck dissection may be avoided only in sporadic MTC patients with unilateral involvement of the thyroid gland in the absence of central and ipsilateral neck involvement; and 5) the number of lymph node metastases was predictive of biological cure after surgery.
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May 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.
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May 2003

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.
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November 2002