Massimino D’Armiento

The effects of iodoprophylaxis on thyroid size during pregnancy

Thyroid gland size was ultrasonographically determined in 35 pregnant women who live in an area with moderate iodine deficiency. Iodide salt was administered to group A (n = 17), whereas group B (n = 18) was used as a control. Each group was tested for thyroid-stimulating hormone serum levels, iodine excretion, and thyroid volume. In both groups thyroid-stimulating hormone levels were similar and did not change throughout pregnancy. The iodine excretion at the third trimester in the treated group was significantly (p less than 0.01) higher than that of group B (100.0 +/- 39.0 versus 50.0 +/- 37.0 micrograms iodine per 24 hours, respectively). Initially, thyroid volume did not differ between the two groups. At the end of pregnancy, no difference was found in thyroid size in group A, whereas in the untreated women it increased significantly (p less than 0.0001) with a mean increase of 1.6 +/- 0.6 ml (16.2% +/- 6.0%). These results show that the increased thyroid size in the control group was mainly a result of relative iodine deficiency and that iodoprophylaxis should be warranted even in areas with moderate iodine deficiency to prevent the increase in thyroid size and, probably, to avoid the risk of maternal and fetal hypothyroidism.

Transforming acidic coiled-coil 3 and Aurora-A interact in human thyrocytes and their expression is deregulated in thyroid cancer tissues

Aurora-A kinase has recently been shown to be deregulated in thyroid cancer cells and tissues. Among the Aurora-A substrates identified, transforming acidic coiled-coil (TACC3), a member of the TACC family, plays an important role in cell cycle progression and alterations of its expression occur in different cancer tissues. In this study, we demonstrated the expression of the TACC3 gene in normal human thyroid cells (HTU5), and its modulation at both mRNA and protein levels during cell cycle. Its expression was found, with respect to HTU5 cells, unchanged in cells derived from a benign thyroid follicular tumor (HTU42), and significantly reduced in cell lines derived from follicular (FTC-133), papillary (B-CPAP), and anaplastic thyroid carcinomas (CAL-62 and 8305C). Moreover, in 16 differentiated thyroid cancer tissues, TACC3 mRNA levels were found, with respect to normal matched tissues, reduced by twofold in 56% of cases and increased by twofold in 44% of cases. In the same tissues, a correlation between the expression of the TACC3 and Aurora-A mRNAs was observed. TACC3 and Aurora-A interact in vivo in thyroid cells and both proteins localized onto the mitotic structure of thyroid cells. Finally, TACC3 localization on spindle microtubule was no more observed following the inhibition of Aurora kinase activity by VX-680. We propose that Aurora-A and TACC3 interaction is important to control the mitotic spindle organization required for proper chromosome segregation.

Ontogeny and regulation of variant thyroid hormone receptor isoforms in developing rat testis

High affinity-low capacity nuclear triiodothyronine (T3) receptors (TRs), identified as a product of c-erbAα proto-oncogene, are expressed in prepubertal rat Sertoli cell. At this age, exogenous T3 treatment as well as hypothyroidism affects Sertoli cell functions. We examined the ontogenetic expression pattern of TRs in the rat testis. Northern analysis confirms that TRs are expressed at high level from fetal development until prepubertal period. Rnase protection analysis demonstrates that TRα2, the variant isoform of TRα1, is constitutively expressed at all ages, while TRα3 is absent in the adult gonad. While TRα1 and TRα2 expression declines during development, Rev-erbAα (Rev), the antisense mRNA encoded by the same c-erbAα genomic locus, increases beginning 5 days after birth and maximizing in adulthood. TRα1, TRα2, and Rev mRNAs do not appear to be directly regulated by thyroid hormone in testis; however, short-term neonatal hypothyroidism leads to the expression of TRα1 and its variant in adult testis, which is absent in control coeval animals. Thus, during development of rat testis, the levels of messages of genes encoded in the c-erbAα genomic locus have different ontogenetic control. The ontogenetic profile of TRα1 and its variant isoforms within the seminiferous epithelium suggests that these receptors are involved in the differentiation of the male gonad.

Analysis of clinical, ultrasound and colour flow‐Doppler characteristics in predicting malignancy in follicular thyroid neoplasms

Fine-needle aspiration cytology (FNAC) represents the main diagnostic tool in the evaluation of thyroid nodules because of its high sensitivity, specificity and accuracy. However, while FNAC is very reliable in detecting papillary thyroid carcinomas (PTC) and anaplastic thyroid carcinomas, follicular neoplasms (FN) represent the grey zone in which cytology cannot discriminate malignant from benign tumours. 1 Consequently, in presence of nodules cytologically classified as FN, thyroidectomy is usually required and the histological evaluation reveals that about 80% are benign lesions. Thus, identification of parameters associated with malignancy is needed. In this context, several studies have focused on clinical, ultrasonographic and cytological aspects, with controversial results. 2,3

Iodine supplementation restores fertility of sheep exposed to iodine deficiency

The aims of the study were to monitor sheep iodine intake in different sheep breeding farms in Abruzzo and to evaluate the effects of iodine supplementation on ovine fertility. The urinary iodine concentrations (UIC) in animals of 8 out of the 11 breeding farms analyzed were borderline (UIC 100–150 μg/l) or very low (UICФ50 μg/l). Only animals bred in 3 farms showed an adequate iodine intake with a mean UICГ300 μg/l. Animals with very low iodine intake had lower T4 and T3 (plt;0.01) serum levels, compared to those with adequate iodine intake. To investigate the effects of iodine supplementation on ovine fertility, 32 ewes and 20 rams, characterized by low UIC, were randomly divided into 2 groups. One group (16 ewes and 10 rams) received a sc injection of 1 ml of Lipiodol, containing 480 mg of iodine, while the remaining animals were employed as control. This treatment was able to maintain UIC above 300 μg/l for 3 months and to increase T4 and T3 serum levels (plt;0.01). After 9 months, the fertility of control and treated animals was assessed by monitoring the rate of successful matings by ultrasonography. The results showed that 100% of treated ewes mated with treated rams were pregnant vs 37% of the control ewes mated with control rams (p=0.007). The iodine content was 4-fold higher in milk from treated ewes (2393±453 μg/l), compared to controls (675±154 μg/l).The results demonstrated that iodine supplementation restores fertility of sheep living in iodine deficient areas and may represent a means to achieve a silent iodine prophylaxis of local populations.

Deregulated expression of aurora kinases is not a prognostic biomarker in papillary thyroid cancer patients

A number of reports indicated that Aurora-A or Aurora-B overexpression represented a negative prognostic factor in several human malignancies. In thyroid cancer tissues a deregulated expression of Aurora kinases has been also demonstrated, butno information regarding its possible prognostic role in differentiated thyroid cancer is available. Here, weevaluated Aurora-A and Aurora-B mRNA expression and its prognostic relevance in a series of 87 papillary thyroid cancers (PTC), with a median follow-up of 63 months. The analysis of Aurora-A and Aurora-B mRNA levels in PTC tissues, compared to normal matched tissues, revealed that their expression was either up- or down-regulatedin the majority of cancer tissues. In particular, Aurora-A and Aurora-B mRNA levels were altered, respectively, in 55 (63.2%) and 79 (90.8%) out of the 87 PTC analyzed.A significant positive correlation between Aurora-A and Aurora-B mRNAswas observed (p=0.001). The expression of both Aurora genes was not affected by the BRAFV600E mutation. Univariate, multivariate and Kaplan-Mayer analyses documented the lack of association between Aurora-A or Aurora-B expression and clinicopathological parameterssuch as gender, age, tumor size, histology, TNM stage, lymph node metastasis and BRAF status as well asdisease recurrences or disease-free interval. Only Aurora-B mRNA was significantly higher in T(3-4) tissues, with respect to T(1-2) PTC tissues. The data reported here demonstrate that the expression of Aurora kinases is deregulated in the majority of PTC tissues, likely contributing to PTC progression. However, differently from other human solid cancers, detection of Aurora-A or Aurora-B mRNAs is not a prognostic biomarker inPTC patients.

Is Minimally Invasive Surgery Appropriate for Small Differentiated Thyroid Carcinomas

PurposeTo retrospectively evaluate the surgical completeness of minimally invasive total thyroidectomy for small (<20 mm) differentiated thyroid carcinoma (DTC).MethodsThe subjects of this study were 30 patients who underwent minimally invasive total thyroidectomy as a single procedure. We registered the following postoperative measurements in the LT4 withdrawal period: serum thyroglobulin level, 6-h radioiodine uptake diagnostic test results, and neck ultrasound (US) findings.ResultsThe mean serum thyroglobulin level was 4.99 ± 4.67 ng/ml, the mean radioiodine uptake diagnostic test after 6 h was 3.11% ± 2.90%, and US showed no thyroid remnant.ConclusionsThe short-term outcome measures showed adequate resection of thyroid tissue, comparable with that reported after conventional surgery. Our findings suggest that small nodules with suspicious or malignant cytology are one of the best indications for minimally invasive surgery.

Association of Thyroid Diseases with Primary Extra-Thyroidal Malignancies in Women: Results of a Cross-Sectional Study of 6,386 Patients

We here analyzed the prevalence of extra-thyroidal malignancies (EM) in 6,386 female patients affected by different thyroid disease (TD). At first, an age-matched analysis of EM in all patients was performed. We then evaluated EM prevalence in four TD diagnostic categories: non-nodular TD (n = 2,159); solitary nodule (n = 905); multinodular TD (n = 2,871); differentiated thyroid cancers (n = 451). Finally, patients were grouped based on the absence (n = 3,820) or presence of anti-thyroglobulin (TgAb) and/or anti-thyroperoxidase (TPOAb) (n = 2,369), or anti-Thyroid Stmulating Hormone (TSH) receptor autoantibodies (n = 197). A total of 673 EM were recorded. EM prevalence in TD patients was higher compared to the general population (Odds Ratio, OR 3.21) and the most frequent EM was breast cancer (OR 3.94), followed by colorectal (OR 2.18), melanoma (OR 6.71), hematological (OR 8.57), uterus (OR 2.52), kidney (OR 3.40) and ovary (OR 2.62) neoplasms. Age-matched analysis demonstrated that the risk of EM was maximal at age 0–44 yr (OR 11.28), remaining lower, but significantly higher that in the general population, in the 45–59 and 60–74 year age range. Breast and hematological malignancies showed an increased OR in all TD, while other cancers associated with specific TD. An increased OR for melanoma, breast and hematological malignancies was observed in both TPOAb and/or TgAb autoantibody negative and positive patients, while colorectal, uterus, kidney and ovary cancers showed an increased OR only in thyroid autoantibody negative patients. In conclusions, women affected by both benign and malignant TD, especially at a younger age and in absence of thyroid autoimmunity, have an increased risk of developing primary EM, thus requiring a careful follow-up and surveillance.

Overexpression of the Components of the Plasminogen Activating System as Prognostic Factors in Human Thyroid Carcinoma

The plasminogen activating system (PAS) is an ensemble of proteins involved in the extracellular conversion of the ubiquitous inactive plasminogen to the broad spectrum serine protease plasmin, which is implicated in fibrin homeostasis and in numerous physiological and pathological processes requiring the remodelling of extracellular matrix (ECM) and basement membranes (BM). The PAS consists of two serine proteases, the urokinase (uPA) and the tissue-type (tPA) plasminogen activators, the cell membrane receptor for uPA (uPAR) and two main inhibitors belonging to the serine proteinase inhibitors (serpin) superfamily, the plasminogen activator inhibitor 1 (PAI-1), and 2 (PAI-2). The uPA is first synthesized as a single-chain zymogen (pro-uPA or sc-uPA); once secreted in extracellular environs, the sc-uPA is converted to the active disulfide-linked two-chain form (tc-uPA) by a number of proteases such as plasmin, plasma kallikrein, and cathepsin B and L (Choong and Nadesapillai 2003). Plasmin is the primary activator of sc-uPA and is in turn activated by tc-uPA, thus enhancing its own production. Such phenomenon, referred as “reciprocal zymogen activation”, occurs much more efficiently when the sc-uPA is associated with its receptor uPAR, a glycoprotein anchored to the plasma membrane through a glycosyl-phosphatidylinositol moiety (Plesner et al. 1997; Blasi and Carmeliet 2002). As a consequence, the active uPA generation is concentrated in the pericellular area, where it represents an effective and rapid source of plasmin during cell migration and invasion under physiological or pathological conditions. Moreover, in numerous cell types the expression of plasma membrane plasminogen receptors, which colocalize with uPAR, improves the local concentrations of reactants (Castellino and Ploplis 2005).

Subclinical hyperthyroidism and sport eligibility: an exploratory study on cardiovascular pre-participation screening in subjects treated with levothyroxine for multinodular goiter.

Background: Subclinical hyperthyroidism (sHT) affects cardiovascular (CV) morphology and function; whether such changes can impact on sport eligibility is unclear. Aim: This exploratory study evaluated the CV system and sport eligibility in athletes with levothyroxine-induced sHT, in the setting of mandatory pre-participation screening. Subjects and methods: A full, non-invasive CV screening (history and physical examination, 12-lead ECG, echocardiography, 24-hour Holter ECG, exercise stress test) was performed in two groups of untrained female athletes affected by non-toxic multinodular goiter. One group was taking levothyroxine at mildly suppressive doses (TG) whereas the other was untreated (UG). There was also a group of healthy controls (HC). Results: In TG the following characteristics were observed: a) a higher resting heart rate (HR; p<0.01and p<0.05, vs HC and UG respectively), b) a thicker left ventricular posterior wall (p<0.05 vs HC, and p<0.05 vs HC and UG, respectively), c) a higher mean HR during the 24-hour Holter ECG (p<0.01 and p<0.05, vs HC and UG respectively), and d) a lower achieved maximum work load (p<0.05, vs HC). No differences in the prevalence of cardiac arrhythmias among groups were observed. Sport eligibility was granted to all except one subject in the TG. Conclusions: Although some alterations were found in athletes with levothyroxine-induced mild sHT, these are probably of limited clinical relevance and they did not contraindicate sport participation in the majority of cases. Future research to address both health risks and the need for specific evaluations (e.g. free thyroxine, TSH, echocardiography) during the preparticipation screening of athletes with sHT is warranted.