Maria Antonia Violi

Iodine Prophylaxis Using Iodized Salt and Risk of Maternal Thyroid Failure in Conditions of Mild Iodine Deficiency

CONTEXT Mild to moderate iodine deficiency during pregnancy can cause transient maternal hypothyroidism and impaired mental development of the progeny. These unfavorable effects are preventable by iodine supplementation. In Europe, however, less than 50% pregnant women receive iodine-containing supplements, thus representing dietary iodized salt the only carrier of iodine for most women in this life stage. OBJECTIVE/DESIGN This longitudinal study is aimed to investigate the effects of long-term iodized salt consumption on maternal thyroid function during gestation. PARTICIPANTS/OUTCOME MEASURES: We prospectively evaluated thyroid function in 100 consecutive thyroperoxidase antibody-negative pregnant women from a mildly iodine-deficient area. Sixty-two women who had regularly used iodized salt for at least 2 yr prior to becoming pregnant and 38 who commenced iodized salt consumption upon becoming pregnant were classified as long-term (LT) and short-term (ST) iodine supplemented, respectively. RESULTS Long-term iodized salt consumption resulted in a very low prevalence of maternal thyroid failure (MTF) in LT women. Conversely, short-term iodine prophylaxis does not seem to protect against the risk of MTF, the prevalence of which was almost 6-fold higher in ST than LT women (36.8% vs. 6.4%; chi(2) 14.7, P < 0.0005; relative risk 5.7, 95% confidence interval 2.03-16.08, P < 0.001). The relative risk reduction amounted to 82.5%, this measure indicating the extent to which long-term iodine prophylaxis using iodized salt would reduce the risk of MTF in ST women. CONCLUSIONS Prolonged iodized salt significantly improves maternal thyroid economy and reduces the risk of maternal thyroid insufficiency during gestation, probably because of a nearly restoring intrathyroidal iodine stores.

Papillary Thyroid Microcarcinomas: A Comparative Study of the Characteristics and Risk Factors at Presentation in Two Cancer Registries

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.

Descriptive Epidemiology of Human Thyroid Cancer: Experience From a Regional Registry and The “Volcanic Factor”

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) = 17.8/105 in females and 3.7/105 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) = 31.7/105 in females and 6.4/105 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.

Changes in both size and cytological features of thyroid nodule after levothyroxine treatment

objective We prospectively evaluated the effects of 12 months thyrotropin suppressive levo‐thyroxine (L‐T4) therapy in terms of changes in both thyroid nodule size and cytological features and considered whether thyroid nodule size changes actually resulted in (or were the result of) cytological changes.

Clinical usefulness of 99mtc-mibi scintigraphy in the postsurgical evaluation of patients with differentiated thyroid cancer

Objective99mTc-methoxyisobutyl isonitrile (MIBI) has been reported to show considerable clinical utility in the study of many neoplastic diseases. The aim of our study was to investigate the possible role of 99mTc-MIBI in the initial follow-up of patients with differentiated thyroid cancer (DTC) for detecting residual thyroid uptake and/or loco-regional/distant metastases. MethodsEighty-two patients with DTC (61 women, 21 men; mean age: 49 years) were studied after total or near-total thyroidectomy (not earlier than 3 months after thyroidectomy but before they underwent radioiodine therapy). About 20 min after the intravenous administration of 370 MBq of 99mTc-MIBI, planar images (and, if necessary, tomographic images, single photon emission tomography) of the cervical and thoracic regions were recorded and compared with posttherapy radioiodine scanning and thyreoglobulin serum levels. ResultsMIBI scans detected thyroid remnants in 53 of 82 patients (65%) and metastatic foci in 10 of 11 (91%) patients, in whom a standard activity of 1110 MBq of 131I administered following MIBI scan had shown the presence of thyroid remnants or metastatic foci, respectively. One metastatic patient was false negative for both MIBI scan and post-131I dose whole body scan. ConclusionOur data indicate that an MIBI scan has a high sensitivity in detecting metastatic lesions from DTC. Therefore, an MIBI scan after thyroidectomy and immediately before radioiodine treatment may be clinically useful for choosing the best therapeutic approach in terms of either ablative or therapeutic 131I activity for both thyroid remnants and/or DTC metastases and for evaluating surgical reappraisal of metastatic lymph nodes.

Thyroid follicular oncogenesis in iodine-deficient and iodine-sufficient areas: Search for alterations of the ras, met and bFGF oncogenes and of the Rb anti-oncogene

To gain insights into the role of iodine deficiency in favoring thyroid tumorigenesis (particularly of the follicular histotype), 22 Sicilian patients with thyroid tumors were selected for having lived permanently in either one of two areas of different iodine availability. Eleven patients (age 46.1 ±14.6 years, mean±SD; 10 females and 1 male) were from the iodine-deficient (ID) areas of the provinces of Messina and Catania (mean urinary excretion of iodine=48.1 µg/2A hours). Thyroid tumors were follicular or Hürthle cell adenomas (no.=3), follicular carcinomas (FC, no.=4), papillary carcinomas (PC, no.=2) and anaplastic carcinomas (no.=2). Eleven patients (age 47.1±15.2 years; 10 females and 1 male) were from the metropolitan area of Messina, an area of relative iodine-sufficiency (IS) (urinary excretion of iodine=95.2 µg/24 hours). These 11 patients had serum levels of TSH that were significantly lower than the corresponding values of the 11 patients from the ID area (0.76±0.33 vs 1.80±1.22 mU/l, p=0.01) The tumors of the 11 patients from the IS area were: follicular or Hürthle cell adenomas (no.=6), Hürthle cell carcinoma (no.=1), FC (no.=2), PC (no.=2). Molecular biology studies revealed that both the normal as well as the tumor tissue of all 22 patients did not harbor any of the three classical activating mutations (codons 12, 13 and 61) in any of the three ras oncogenes. Similar negative results were obtained as far as loss of heterozygosity of the retinoblastoma (Rb) anti-oncogene is concerned. Immunohistochemistry studies were performed to investigate expression of c-met and basic fibroblast growth factor (bFGF) proto-oncogenes. Only one Hürthle cell carcinoma and the two PC from the IS group, and one FC and the two PC from the ID group stained for the c-met oncogene. Expression of c-met was greater (3+) in the four PC (concerning 70–80% of the tumor cells) than in the other two cancers (1+; <5% of the tumor cells). In the IS group, positivity for bFGF was detected in 3/6 adenomas, 1/2 FC, the Hürthle cell carcinoma and the two PC. In the ID group, positivity for bFGF was observed in 2/3 adenomas, 2/4 FC, the two PC and the two anaplastic carcinomas. The 8 positive cases from the ID group had a greater level of bFGF expression than the 7 positive cases from the IS group (intensity of staining = 2.0+ vs 1.57+). Interestingly, the greatest expression of bFGF was seen in the cases with peri-tumoral lymphocytic infiltration from either group. In the ID group correlations between (i.) pre-intervention serum TSH and intensity of tumoral staining for bFGF, (ii.) serum TSH and per cent of tumoral cells reactive with anti-bFGF and (iii.) between intensity of staining for bFGF and per cent of tumoral cells bFGF +ve were higher than in the IS group. We conclude that activating mutations of ras, loss of DNA from the Rb locus and over-expression of both c-met and bFGF are of no pathogenetic relevance in driving thyroid tumorigenesis of iodine-deficient areas.

Thyroid remnant ablation in differentiated thyroid cancer: searching for the most effective radioiodine activity and stimulation strategy in a real-life scenario.

ObjectiveDifferentiated thyroid cancer is rare, but the incidence has been increasing in the last few decades. Early treatment is based on surgery and thyroid remnant ablation (TRA) by means of radioiodine therapy. Despite radioiodine being widely used for decades, the choice of ablative activity is generally empirical and no consensus has been reached to date. The aim of our study was to compare the efficacy and safety of different radioiodine activities. In addition, we compared the ablation rate in patients treated in the hypothyroid state or after recombinant human thyroid-stimulating hormone (rhTSH) administration, retrospectively reviewing the records of 471 patients affected by differentiated thyroid cancer. Patients and methodsPatients were subdivided into three groups on the basis of the different activities of radioiodine administered and taking into account the different approaches used to perform the therapy: thyroid hormonal withdrawal or rhTSH stimulation. ResultsThe success of TRA was evaluated 12 months later. TRA was obtained in 62/79 (78.5%) in group A (1110 MBq in the hypothyroid state), 183/190 (96.3%) in group B [2220 MBq in the hypothyroid state or after rhTSH administration: 87/90 (97%) and 96/100 (96%) patients, respectively], 199/202 (98.5%) in group C [3700 MBq in hypothyroid state or after rhTSH administration: 98/100 (98%) and 101/102 (99%) patients, respectively]. ConclusionOur data demonstrate that 2220 and 3700 MBq radioiodine are more effective compared with 1110 MBq in TRA, without significant differences between 2220 and 3700 MBq or between hypothyroidism and euthyroidism. We suggest rhTSH-aided TRA with 2220 MBq iodine-131, as this approach permits efficacious treatment, thereby reducing side effects, absorbed dose to body and hospital stay.

Prevalence of Thyroglossal Duct Cyst Carcinoma in Adults Having Surgery for Thyroglossal Duct Cysts

Thyroglossal duct cyst (TGDcyst) is the most common developmental abnormality of the thyroid gland (1). It usually presents as an asymptomatic, soft swelling in the midline and has characteristic ultrasound features. TGDcysts are usually benign lesions but a few cases of TGDcyst carcinoma (TGDcyst-Ca), approximately 250, have been reported (2). The data regarding the prevalence of TGDcyst-Ca in adults with clinically evident TGDcysts is sparse (3). In an attempt to estimate this, at least for patients with TGDcysts that demanded intervention, we carried out a retrospective review of the patients in our hospital who underwent surgical excision of TGDcysts between 2001 and 2011. Overall there were 23 patients who were surgically treated for TGDcysts and these were either large or rapidly increasing in size TGDcysts. Among them, there were three patients with TGDcyst-Ca. The first patient was a 37-year-old woman who in October 2001 was diagnosed with a 20-mm papillary thyroid carcinoma (PTC) within a TGDcyst (pT3N0Mx). The diagnosis was based on histopathology following surgical excision of the cyst by Sistrunk procedure. A total thyroidectomy (tTx) was subsequently performed and the thyroid itself was free of PTC. Following thyroid removal, because of persistently elevated recombinant human thyrotropin (rhTSH)-stimulated serum thyroglobulin (Tg), she received five treatments with I (RAI) for a cumulative dose of 15.91 GBq, between 2002 and 2009. She was prepared for these treatments with rhTSH. PostRAI whole body scans (WBS) revealed persistent low uptake in the left hemithorax. She declined further RAI treatments. The second patient was a 42-year-old man who underwent Sistrunk surgical excision of a cystic lesion of the neck in November 2001. Histological examination revealed a 14-mm PTC within a TGDcyst. It infiltrated surrounding tissues (pT3N0Mx). In March 2002, following tTx, a 3-mm PTC was found in the left thyroid lobe, and a second 1-mm PTC focus in the contralateral lobe (pT1bN0Mx). Six months after tTx, 3.7 GBq of RAI with rhTSH preparation was administered. The post-RAI WBS was negative and serum Tg concentrations after rhTSH administration were undetectable. The third patient was a 21-year-old woman underwent surgical excision of a TGDcyst by Sistrunk procedure in March of 2010. Histopathology showed a follicular variant of PTC within the TGDcyst (pT1N0Mx). A tTx was subsequently performed and no malignancies were noted in the thyroid gland. She was treated with 4.5 GBq RAI and serum Tg concentrations after rhTSH stimulation were consistently undetectable. In our series of 23 patients who had surgery for TGDcyst, the prevalence of TGDcyst-Ca was 13%. A similar study by Patel et al. (3) of patients who had surgery for TGDcyst at a large cancer center obtained a prevalence of 14%. In our small series of three patients with TGDcyst-Ca, the thyroid gland was free of PTC in two patients. This supports the hypothesis that PTC can arise from ectopic thyroid tissue, but can remain confined to its site of origin. None of the patients with TGDcyst-Ca in our series had follicular thyroid carcinoma, squamous cell carcinoma, Hurthle cell carcinoma, or anaplastic carcinoma. This is consistent with other reports indicating that PTC is the most common cancer to occur in TGDcysts but these other tumors have also been reported (1). There is considerable controversy regarding the role of thyroidectomy in the management of TGDcyst-Ca (4). We believe that tTx should be performed on all patients in whom TGDcyst-Ca is confirmed by histopathology of the TGDcyst specimen in order to rule out occult thyroid carcinomas that might have metastasized to the TGDC, even though it is evident that not all TGDcyst-Ca are associated with carcinoma within the thyroid gland itself. Moreover, the prognosis of TGDcyst-Ca is generally good. A very large prospective study would be needed to adequately address this issue. Although all three of our patients received radioactive iodine ablation the value of this treatment is unclear; future guidelines should address this issue. In summary, most patients who present with a large or clearly growing TGDcyst have a good prognosis, not only because most such lesions do not harbor cancer, but also because in many of them who do harbor cancer, this is confined to the TGDcyst. Nevertheless, we advocate that such lesions have prompt surgical treatment.

Anaplastic Thyroid Cancer in Sicily: The Role of Environmental Characteristics

Background Anaplastic thyroid cancer (ATC) is a rare but extremely aggressive cancer of the thyroid, contributing up to 30–40% of thyroid cancer-specific mortality. We analyzed ATC characteristics and survival rates in Sicily to evaluate the possible influence of environmental factors. With this aim, data regarding ATC incidences in urban/rural and industrial, iodine-deficient, and volcanic vs control areas were compared in Sicily as well as ATC data from Sicily and USA. Methods Using the Sicilian Register of Thyroid Cancer (SRTC) database incidence, age, gender, tumor size and histotype, extrathyroidal extension, stage, and coexistence with pre-existing differentiated thyroid cancer (DTC) were evaluated in different areas of Sicily and also compared with Surveillance Epidemiology and End Results data in USA. Results Forty-three ATCs were identified in Sicily in the period 2002–2009. In our series only age <70 years at diagnosis (p = 0.01), coexistence with DTC (p = 0.027) and tumor size ≤6 cm (p = 0.012) were significant factors for increased survival at univariate analysis (only age at multivariate analysis). No difference in ATC incidence was found in urban vs rural areas and in iodine-deficient and industrial vs control areas. By contrast, in the volcanic area of Sicily, where DTC incidence is doubled relative to the rest of the island, also ATC incidence was increased. ATC data in Sicily were similar to those reported in the same period in the USA where overall survival rate at 6 and 12 months, however, was smaller. Conclusion The similar ATC data observed in Sicily and USA (having different genetic background and lifestyle) and the increased ATC incidence in the volcanic area of Sicily paralleling the increased incidence of papillary thyroid cancer are compatible with the possibility that casual additional mutations, more frequent in a background of increased cell replication like DCT, are the major causes of ATC rather than genetic background and/or direct environmental influences.