Francesca Zerbini

A hypoechoic pattern of the thyroid at ultrasound does not indicate autoimmune thyroid diseases in patients with morbid obesity

OBJECTIVE Thyroid ultrasound (US) scan is a valuable tool for diagnosing thyroid diseases. In autoimmune thyroid disease (AITD), an hypoechoic pattern of the thyroid at US is related to circulating thyroid antibodies (Abs). The aim of this study was to evaluate the diagnostic accuracy of thyroid US for the detection of AITD in patients with morbid obesity. DESIGN Thyroid US scans showing an hypoechoic pattern of the thyroid were collected from 105 morbid obese patients (body mass index (BMI) >40 kg/m(2)) and 105 non-obese patients (BMI<or=30 kg/m(2)). RESULTS A thyroid hypoechoic pattern at US was consistent with clinical/biochemical features of AITD in 90/105 (85.7%) non-obese patients and in 22/105 (20.9%) morbid-obese patients (P<0.0001). By performing a complete thyroid work-up, including clinical examination, thyroid morphology, serum hormones, and auto-Ab measurements, the discrepancy between the US pattern and the results of the thyroid Ab tests was justified in 6/15 non-obese patients, and only in 1/83 morbid obese patients. Thus, an unexplained hypoechoic pattern of the thyroid at US, defined as negative tests for thyroid Ab and absence of justifying thyroid disturbances, was found in 2/105 (1.9%) non-obese patients and in 68/105 (64.8%) morbid obese patients (P<0.0001). CONCLUSIONS Our results suggest that i) morbid obesity may affect thyroid morphology, and ii) an hypoechoic pattern of the thyroid at US, a well-established parameter for diagnosing AITD, has a poor diagnostic accuracy when patients with morbid obesity are taken into account.

Comparison of Elastographic Strain Index and Thyroid Fine-Needle Aspiration Cytology in 631 Thyroid Nodules

CONTEXT Ultrasound (US) elastography (USE) was recently been reported as a sensitive, noninvasive tool for identifying thyroid cancer. However, the accuracy of this technique is hampered by the intra- and interoperator variability, some US features of the nodule, and the coexistence of autoimmune thyroid disease (ATD). OBJECTIVES The purpose of this article was to assess the accuracy of USE findings in the differential diagnosis of thyroid nodules compared with other US features to evaluate its feasibility in the presence of ATDs and identify the strain index (SI) cutoff with the highest diagnostic performance. DESIGN We evaluated 528 consecutive patients for a total of 661 thyroid nodules. All nodules underwent fine-needle aspiration cytology (FNAC) and USE evaluation. The SI was calculated as a ratio of the nodule strain divided by the strain of the softest part of the surrounding normal tissue. RESULTS The median SI value was significantly higher in THY4 and THY5 than in THY2 nodules in ATD-positive, ATD-negative, and ATD-unknown patients. The cutoff of SI for malignancy was estimated to be 2.905 by receiver operating characteristic curve analysis in a screening set (379 FNAC results), and then tested in a replication set (252 FNAC results). In all cases, a SI value of ≥ 2.905 conferred to the nodule a significantly greater probability of being malignant. This SI cutoff had the greatest area under the curve, sensitivity, and negative predictive value, compared with the conventional US features of malignancy. CONCLUSION The elastographic SI has a high sensitivity, specificity, and negative predictive value for the diagnosis of thyroid malignancy both in the presence and in the absence of ATD. If our data on USE are also confirmed in THY3 nodules, FNAC could be avoided in a number of thyroid nodules with certain features.

Severe disability in patients with relapsing-remitting multiple sclerosis is associated with profound changes in the regulation of leptin secretion.

Objectives: Experimental evidences indicate that leptin is involved in the neuroinflammatory process sustaining multiple sclerosis (MS). However, the relationship between leptin and body fat, as assessed by body mass index (BMI), in MS was not previously evaluated. It was the aim of this study to compare serum leptin levels between patients with MS and healthy controls and to evaluate the possible relationship between circulating leptin levels and disease severity. Patients and Methods: Eighty-four MS patients and 57 sex-matched healthy volunteers were enrolled. Serum leptin levels were measured in all patients and controls. MS patients were stratified in 3 groups according to their degree of disability as assessed by the Expanded Disability Status Scale (EDSS). Patients were classified as having low (33 patients with an EDSS score <1.5), intermediate (28 patients with an EDSS score from 2 to 3) and high disability (23 patients with an EDSS score ≥3.5). Results: No significant differences in serum leptin levels and BMI were observed between patients and controls. In patients with MS, serum leptin levels were significantly correlated with BMI in those patients with low (R2 = 0.363; p < 0.001) and intermediate disability (R2 = 0.408; p < 0.001), but not in patients with a higher disability score (R2 = 0.064; p = 0.256). Conclusion: BMI, the major determinant of leptin level in physiological conditions, has a minor role in determining the serum levels of leptin in MS patients with a high EDSS score. Future longitudinal studies will be required in order to provide further insights into the regulation of leptin secretion in patients with MS.

Interferon-β but not Glatiramer acetate stimulates CXCL10 secretion in primary cultures of thyrocytes: A clue for understanding the different risks of thyroid dysfunctions in patients with multiple sclerosis treated with either of the two drugs

Autoimmune thyroid disease (AITD) has been reported in patients with multiple sclerosis (MS) receiving interferon-beta (IFN-β), but not in those receiving Glatiramer acetate (GA). CXCL10 is a chemokine playing a pathogenetic role in AITD and MS. Our aim was to evaluate the effects on CXCL10 secretion of IFN-β and GA, alone and in combination with TNF-α, in primary cultures of thyrocytes (PCT). Significant and dose-dependent secretions of CXCL10 were induced by IFN-β but not GA. TNF-α synergistically increased IFN-β induced CXCL10 secretion. These results may provide an explanation for the occurrence of AITD during IFN-β, but not during GA, treatment for MS.

Migration flows affect women’s dietary iodine intake and jeopardize their iodine sufficiency: a pilot study

In Latin American countries iodine deficiency was recognized as a public health problem since the early years of the twentieth Century. Due to effective salt iodization programs, since 2004 the successful elimination of iodine deficiency by iodized salt was reported in Latin America [1]. On the contrary, Italy is still classified as a mild iodine deficiency country [2]. Several studies provide evidence that migration impacts the individual’s life, being a strong determinant of health [3–5]. Migrants live in a new environment, which significantly differs from the one of origin [4–7]. Thus, Latin American immigrants migrating to Italy might experience a lower iodine intake due to both different food habits and different amounts of iodine content in foods. The aim of this pilot study was to investigate the iodine intake of native Latin American women migrating to Italy.

MAXIMAL STIFFNESS EVALUATION BY REAL-TIME ULTRASOUND ELASTOGRAPHY, AN IMPROVED TOOL FOR THE DIFFERENTIAL DIAGNOSIS OF THYROID NODULES

OBJECTIVE The aim of the study was to evaluate the diagnostic performance of a new ultrasound elastography (USE) parameter based on the measurement of the percentage of maximal stiffness within a nodule as compared with the already established elastographic strain index (SI) and to investigate their diagnostic performance according to nodule size. METHODS The study included 218 nodules. Each nodule underwent conventional ultrasound (US), USE evaluation, and fine-needle aspiration cytology (FNAC). Thyroid nodules were further stratified into 4 subgroups (G) according to their size (G1, <1 cm; G2, 1-2 cm; G3, >3 cm). USE evaluation comprised the measurement of the percentage of the areas included in the region of interest corresponding to the maximal stiffness (% Index) and of the SI. RESULTS The % Index and of the SI were significantly higher in malignant than in benign thyroid nodules, and both measurements displayed a good diagnostic performance (SI sensitivity and specificity, 0.66 and 0.90, respectively; % Index sensitivity and specificity, 0.76 and 0.89, respectively). Compared with SI, the % Index was more informative, both in the whole group of thyroid nodules (odds ratio [OR], 18.68; 95% confidence interval [CI], 6.06 to 63.49; P<.0001 versus OR, 26.15; 95% CI, 8.01 to 102.87; P<.0001, respectively) and in the G1 and G2 subgroups. CONCLUSION The % Index is a stronger predictor of nodule malignancy than both the SI and the conventional US signs. This is particularly true in nodules smaller than 1 cm, which are more difficult to explore both by conventional US and FNAC.

GENDER INFLUENCES THE CLINICAL PRESENTATION AND LONG-TERM OUTCOME OF GRAVES' DISEASE.

OBJECTIVE The outcome of antithyroid drug (ATD) treatment for Graves disease (GD) is difficult to predict. In this study, we investigated whether male gender, besides other factors usually associated with a poor outcome of ATD treatment, may affect disease presentation and predict the response to medical treatment in subjects with GD. METHODS We studied 294 patients with a first diagnosis of GD. In all patients, ATD treatment was started. Clinical features, thyroid volume, and eye involvement were recorded at baseline. Serum levels of free thyroxine (FT4), free triiodothyronine (FT3), thyroid-stimulating hormone (TSH), and TSH-receptor antibodies (TRAb) were measured at baseline and during the follow-up. Treatment outcome (FT4, FT3, and TSH serum levels and further treatments for GD after ATD withdrawal) was evaluated. RESULTS When compared to women, men showed a significantly larger thyroid volume and a higher family positivity for autoimmune diseases. During ATD, the mean serum levels of TSH, FT4, FT3, and TRAb did not differ between groups. Within 1 year after ATD discontinuation, relapse of hyperthyroidism was significantly more frequent in men than in women. Within the 5-year follow-up period, the prevalence of men suffering a late relapse was higher compared with that of women. The outcome at the end of the 5-year follow-up period was significantly associated with gender and TRAb levels at disease onset. CONCLUSION Male patients with GD have a poorer prognosis when submitted to medical treatment with ATDs. A larger goiter at presentation and a stronger genetic autoimmune background might explain this gender difference in patients with GD. ABBREVIATIONS ATD = antithyroid drug FT3 = free triiodothyronine FT4 = free thyroxine GD = Graves disease GO = Graves orbitopathy RAI = radioiodine TRAb = thyroid-stimulating hormone-receptor antibody TSH = thyroid-stimulating hormone.

Poverty and immigration as a barrier to iodine intake and maternal adherence to iodine supplementation

PurposeIodine deficiency still remains a significant health issue worldwide. Pregnant and lactating women are at risk for iodine deficiency when living in mild iodine-deficient areas such as Italy. This study aims at evaluating the consumption of iodized salt, iodine-rich-foods and maternal micronutrient supplements in a group of women with limited access to the Italian National Health System.MethodsA cross-sectional survey was conducted among immigrant and Italian women living in poverty and referring to 40 Non-Governmental Organization throughout Italy for their health needs. 3483 women answered the ad hoc questionnaire between January 2017 and February 2018.ResultsThe consumption of iodized salt was very low, and even lower among immigrant women. Determinants of iodized salt consumption were the period spent in Italy for immigrant women and living in a family-type setting, parity and, particularly, the degree of education for Italian ones. 17.5% of immigrant women and 8.6% of the Italian ones reported a diagnosis of thyroid disease. 521 women, 75.4% of whom were immigrants, were pregnant or breast-feeding. The majority (57.3%) had no specific maternal supplementation.ConclusionsBoth Italian and immigrating women with a low income or without access to the public health system have a poor adherence both to the salt iodization policy and to folic acid and iodine supplements in preconception and pregnancy. They also referred a low-frequency intake of iodine-rich-foods. The identification of barriers to health care access could be useful to promote specific health interventions in this target population.

Äthiopathogenese des morbus basedow: Trends und aktuelles

Basedows disease (BD) owes its name to the German physician Karl Adolph von Basedow, who described in 1840 the clinical picture of exophthalmic toxic goitre. More than one century after the seminal paper of Karl von Basedow, the ultimate cause of BD remains to be fully elucidated. In the last years, evidence was accumulated indicating that BD is a polygenic and multifactorial disease that develops as a result of a complex interplay between genetic susceptibility and environmental and endogenous factors, which leads to the loss of immune tolerance to thyroid antigens and in particular to the TSH receptor. Our aim is to review the current knowledge on the pathogenesis of BD. To this purpose, we will firstly focus our attention on the role of genetic factors (the HLA complex, the genes encoding for thyroglobulin, the TSH receptor, CD40, CTLA-4 and PTPN22), and of environmental factors (iodine, infections, psychological stress, gender, smoking, thyroid damage, vitamin D, selenium, immune modulating agents) as possible causes of BD. Taking advantage of the experimental animal models of BD, we will then focus on the immunological mechanisms leading to the loss of tolerance in BD. The pathogenic role played by the chemokine system will be also reviewed.