Anna Ciampolillo

Free triiodothyronine and thyroid stimulating hormone are directly associated with waist circumference, independently of insulin resistance, metabolic parameters and blood pressure in overweight and obese women

Objective  To examine whether obesity, body fat distribution and insulin resistance have an independent effect on serum TSH and free thyroid hormones (FT3 and FT4) in a cohort of euthyroid women, represented by overweight and obese patients.

The IGF-I/IGF-I receptor pathway: Implications in the Pathophysiology of Thyroid Cancer.

The biological actions of the insulin-like growth factor(IGF)-I are mediated by its activation of the IGF-I receptor (IGF-I R), a transmembrane tyrosine kinase linked to the Akt and ras-raf-MAPK cascades. A functional IGF-I R is required for the cell to progress through the cell cycle. Most importantly, cells lacking this receptor cannot be transformed by any of a number of dominant oncogenes, a finding that proves that the presence of the IGF-I R is important for the development of a malignant phenotype. Consistent with this role, it has been well established that IGF-I can protect cells from apoptosis under a variety of circumstances. For example, IGF-I prevents apoptosis induced by overexpression of c-myc in fibroblasts, by interleukin-3 withdrawal in interleukin-3-dependent hemopoietic cells, etoposide, a topoisomerase I inhibitor, anti-cancer drugs, UV-B irradiations, and serum deprivation. While the anti-apoptotic effect of IGF-I has been clearly demonstrated, the molecular mechanisms by which IGF-I inhibits apoptosis induced by these various stimuli remain unknown. We have previously documented increased IGF-I and IGF-I receptor immunoreactivity in human thyroid carcinomas with a corresponding up-regulation of IGF-I mRNA. Immunoreactivity for IGF-I and IGF-I receptor positively correlated with tumor diameter, but not with the occurrence of lymph node metastases. Several recent studies have identified new signaling pathways emanating from the IGF-I receptor that affect cancer cell proliferation, adhesion, migration and apoptosis, which represent critical functions for cancer cell survival and metastasizing capacity. In this review, various aspects of the IGF-I/IGF-I R pathway and its relationship to thyroid cancer are discussed.

Insulin-like growth factor 1 (IGF-1) in multinodular goiters: a possible pathogenetic factor.

In order to support previous in vitro studies which had stressed a possible autocrine role for Insulin-like Growth Factor 1 (IGF-1) in thyroid growth regulation, we have investigated the presence of IGF-1, as detected by means of radioimmuno assay and of immunocytochemistry, in thyrocytes from normal thyroid and from multinodular goiter. Our study revealed that IGF-1 is detectable in thyroid cells from multinodular goiter and, to a lesser extent, from normal thyroid. Both techniques used in this study demonstrated that thyrocytes are the site of accumulation of IGF-1 and that stromal cells contain lower amounts of this growth factor. The findings of the present study seem to suggest that thyrocytes could produce IGF-1 in vivo. This feature gives further support to the hypothesis that IGF-1 may regulate thyroid growth and therefore it might be involved in the pathogenesis of multinodular goiter.

The IGF-I axis in thyroid carcinoma.

Insulin like-growth factor I (IGF-I) has been involved in the pathogenesis of a variety of human neoplasia due to the mitogenic and anti-apoptotic properties of its cognate receptor. In human thyroid carcinomas, we have previously documented an increased immunoreactivity of both IGF-I and the IGF-I receptor (IGF-I R) associated with up regulation of IGF-I mRNA . Immunoreactivity of IGF-I and cognate receptor positively correlated with tumor diameter and wide intrathyroidal extension but not with patients gender and age or with the stage of the tumors and the occurrence of limph node metastases. Most experimental studies indicate that the effects of IGF-I on target cells are regulated in a complex fashion and depend on the simultaneous occurrence of IGF-IR and the binding proteins.

Free triiodothyronine is associated with smoking habit, independently of obesity, body fat distribution, insulin, and metabolic parameters

Background: The aim of this study was to examine the relationship between thyroid hormones and smoking and several other parameters like age, gender, insulin, and anthropometric and metabolic parameters in subjects with a wide range of body mass index (BMI). Patients and methods: A total of 931 euthyroid normal weight (BMI<25.0 kg/m2), overweight and obese subjects (BMI>25.0 kg/m2), 663 women and 268 men, aged 18–68 yr, were investigated. Fasting TSH, free T3 (FT3), free T4 (FT4), insulin, glucose, and lipid serum levels were determined. Waist circumference was measured as an indirect parameter of central fat accumulation. Results: Smokers were younger (p<0.001 ) and showed higher FT3 (p<0.01), and triglyceride (p<0.01) levels and lower glucose (p<0.01) and HDL (p<0.001) concentrations than non smoking subjects. FT3 levels were directly associated with BMI (p<0.001), waist circumference (p<0.001), insulin (p<0.001), and triglyceride (p<0.01) levels and negatively correlated with age (p<0.001) and HDL-cholesterol levels (p<0.001). When a multiple regression analysis was performed with FT3 levels as the dependent variable, and smoking, age, gender, and TSH, insulin, triglyceride, and HDL-cholesterol serum concentrations as independent variables, FT3 levels maintained an independent positive association with smoking (p<0.05), age (p<0.001), male sex (p<0.001), waist circumference (p<0.05), and insulin levels (p<0.001). Conclusions: Smoking increases FT3 levels independently of age, gender, obesity, body fat distribution and metabolic parameters.

Assessment of cardiac vagal activity in patients with hyperthyroidism

Previous studies suggested that in patients with hyperthyroidism an autonomic imbalance and in particular a lower than normal vagal activity might be present. To verify this hypothesis we have evaluated the respiratory sinus arrhythmia (RSA, a measure of cardiac vagal activity) in ten hyperthyroid patients and in ten normal subjects. RSA was calculated from the power of the spectral component of the heart rate variability in high frequency band (HF-RR) during both spontaneous (supine and passive head-up tilt) and controlled breathing (supine). During controlled breathing the phase relation between heart rate and respiratory has been computed. The hyperthyroid patients showed a higher heart rate in all three conditions (P<0.001) and higher spontaneous respiratory rate in supine position (centered frequency of HF-RR: 0.342+/-0.015 vs 0.262+/-0.016 Hz; P<0.001). No difference was found in hyperthyroid patients compared to controls in terms of the HF-RR power in normalized units both during spontaneous breathing (supine, 43+/-8.3 vs 39.7+/-6.7%; tilt 18.8+/-5.9 vs 19.3 vs 4.1%; mean+/-SE) and controlled breathing (45.4+/-7.1 vs 48.9+/-6.9%). No difference was found also in terms of the phase relationship between the heart rate and the respiratory signals (77.5+/-32.3 vs 77.5+/-28.1, degrees). Hyperthyroid patients seem not to have an impaired cardiac vagal activity.

High Frequency of Incidental Diagnosis of Extrathyroidal Neoplastic Diseases at the Fine-Needle Aspiration Biopsy of Laterocervical Lymph Nodes in Patients with Thyroid Nodules

This study was undertaken to evaluate the frequency of the incidental diagnosis of extrathyroidal lymph node diseases at ultrasound-guided fine-needle aspiration biopsy/cytology (FNAB/C) being done to check the presence of metastatic thyroid cancer in 30 subjects with thyroid nodule (TN) and enlarged cervical lymph nodes (CLN). The patients in whom cytology suggested the presence of malignancy in the TN or in the CLN underwent surgical removal for histologic diagnosis. The spectrum of diseases revealed by this survey included: (1) 10 benign diseases including 1 case of Piringer-Kuchinka lymphadenitis with benign TN; (2) 10 metastatic thyroid cancers (2 anaplastic and 8 papillary cancers); (3) 3 benign TN associated with metastatic invasion of cervical lymph nodes from lung (2 cases) and breast (1 case) cancer; (4) 1 Hodgkins lymphoma of the cervical lymph nodes with hyperplastic TN; (5) 3 nodal lymphomas with benign thyroid nodule and 2 cases of thyroid lymphoma with nodal invasion; and (6) 1 nodal sarcoidosis with benign TN. The results of this study demonstrate that important neoplastic and hematologic diseases affecting the cervical lymph nodes may frequently be incidentally detected using ultrasonography (US) and FNAB/C in the diagnostic procedure for thyroid nodule.

Prevalence of thyroid nodules in an occupationally radiation exposed group: a cross sectional study in an area with mild iodine deficiency

BackgroundThyroid nodules and thyroid cancer occur more frequently in people exposed to radiation for therapeutic purposes, and to nuclear fallout. Furthermore, it is known that a moderate degree of iodine deficiency may be responsible for an increased prevalence of thyroid nodules, while it is suspected that radiation exposure could induce changes in thyroid autoimmunity. The iodine intake of people resident in Bari, S. Italy, is mildly deficient, which could be presumed to cause a higher prevalence of thyroid pathology. This study was conducted to evaluate the prevalence of thyroid nodules in a population occupationally exposed to radiation, in an area of mild iodine deficiency.MethodsA cross-sectional study was designed to evaluate the prevalence of thyroid nodules in radiation exposed workers, compared with a stratified sample of non exposed workers. After giving written consent to participate in the study, all the recruited subjects (304 exposed and 419 non exposed volunteers) were interviewed to fill in an anamnestic questionnaire, and underwent a physical examination, ultrasound thyroid scan, serum determinations of fT3, fT4 and TSH, fine needle aspiration biopsy. The sample was subdivided into one group exposed to a determined quantity of radiation (detected by counter), one group exposed to an undetectable quantity of radiation, and the non exposed control group.ResultsThe prevalence of thyroid nodules <1 cm in diameter, defined as incidentalomas, in the exposed group with detected doses, was 11.28% in males and 9.68% in females, while in the exposed group with undetectable dose the prevalence was 10.39% in males and 16.67% in females. In the non exposed group the prevalence of incidentalomas was 9.34% in males and 13.20% in females. These prevalences were not statistically different when analysed by a multiple test comparison with the bootstrap method and stratification for sex.Instead, the prevalence of thyroid nodules > 1 cm in diameter resulted statistically different in exposed and non exposed health staff: 18.68% in non exposed males vs exposed: 3.76% (determined dose) and 9.09% (undetectable dose) in males, and 20.30% in non exposed females versus 3.23% (detected dose) and 9.52% (undetectable dose) in exposed females.There was a higher proportion of healthy staff in the exposed group than in the non exposed: (80.45% vs 68.68% in males; 80.65% vs 57.87% in females).ConclusionIn our study, occupational exposure to radiation combined with mild iodine deficiency did not increase the risk of developing thyroid nodules. The statistically significant higher prevalence of thyroid nodules in the non exposed group could be explained by the high percentage (22%) of people with a familial history of, and hence a greater predisposition to, thyroid disease.The endemic condition of mild iodine deficiency, demonstrated in other studies, played a major role in determining the thyroid pathology in our study groups.

Pulmonary hypertension in thyroid diseases.

The influence of thyroid hormones on cardiovascular system is well established. Thyroid diseases can effectively enhance the alteration on cardiovascular system by influencing chronotropic and inotropic actions of the heart; altering the strength and the speed of contraction, the speed of relaxation, the duration of the potential of action, and the duration of the refractory period and atrio-ventricular conduction time; modulating circulation and peripheral vascular beds. One of the more intriguing insights in the connection between thyroid diseases and cardiovascular alterations is related to the evaluation of the influence of thyroid hormones on pulmonary vascular beds. Literature reported several studies regarding the association between both hypothyroidism and hyperthyroidism and the occurrence of increased vascular pulmonary arterial pressure. Nevertheless, the pathogenetic mechanisms able to explain such relationship are not fully understood. Many doubts still persist in the comprehension of the mechanisms of pulmonary hypertension in thyroid diseases. The aim of this review was to provide possible explanation about the possible interaction between pulmonary vascular beds and thyroid function in order to evaluate the possibility of novel perspectives in the general management of patients suffering from thyroid and cardiovascular diseases.

Clusterin transcript variants expression in thyroid tumor: a potential marker of malignancy?

BackgroundClusterin (CLU) is a ubiquitous multifunctional factor involved in neoplastic transformation. The CLU transcript variants and protein forms play a crucial role in balancing cells proliferation and death.MethodsWe investigated the regulation of CLU transcript variants expression in an in vivo model system consisting of both neoplastic tissues and fine needle aspiration biopsy (FNAB) samples isolated from patients undergoing thyroidectomy.ResultsThe immunohistochemical analyses showed an overall CLU up-regulation in papillary carcinoma. A specific CLU2 transcript variant increase was registered using qPCR in papillary carcinomas while CLU1 decreased. In addition, the analysis of CLU transcripts expression level showed an increase of the CLU2 transcript in the TIR 3 patients with histologically confirmed thyroid cancer.ConclusionsOur results suggest the existence of a specific alteration of CLU2:CLU1 ratio towards CLU2, thus providing the first circumstantial evidence for the potential use of CLU transcript variants as effective biomarkers for a more accurate assessment of the so called “indeterminate” thyroid nodules.