L Antonangeli

Incidental thyroid carcinoma in a large series of consecutive patients operated on for benign thyroid disease

Background:  The diagnosis of incidental thyroid carcinoma (ITC) in patients operated on for a benign disease is frequent. This study aims to determine both its clinical effect and the possibility of identifying this class of patients preoperatively.

Mild iodine deficiency during fetal/neonatal life and neuropsychological impairment in Tuscany

The neuropsychological performance of schoolchildren living in areas with present and past iodine deficiency in Tuscany was investigated. Children were submitted to: a) block design subtest of the Wechsler Intelligence Scale for Children-Revised (WISC-R) and a modified version of the WISC-R coding subtest which evaluate the general neuropsychological and cognitive performance, independently from familial cultural background; b) simple reaction time (RT) session which evaluates the efficiency of the whole information processing and nervous transmission mechanisms. Neuropsychological performance was tested in 107 children living in Borgo a Mozzano, an area of mild iodine deficiency (IDA) with a median urinary iodine excretion (UIE) of 64 μg/L (mean±SD: 80.1±57). One hundred and six sex and age-matched children living in Marina di Pisa, an iodine sufficient coastal village of Tuscany (ISA) with a median UIE of 142 μg/L (mean±SD: 173±95) were used as controls. Tests for neuropsychological performance were performed in 57 children living in the village of Vagli, an area with past iodine deficiency (PIDA): 30 children born before iodine prophylaxis (Group 1), when the median UIE was 32 μg/L (mean±SD: 47±22), 27 children born after the institution of iodine prophylaxis (Group 2), when the median UIE was 109 μg/L (mean±SD:130±73). Sex and age-matched ISA-children were used as controls for each group. RTs were significantly delayed (p<0.05) in IDA than in ISA children, while block design and coding subtests showed no significant difference. PI-DA children of Group 1, but not those of Group 2 showed significantly delayed RTs when compared to controls, block design and coding tests being unaffected. In conclusion, our data indicate that: i) mild iodine deficiency may impair the rate of motor response to perceptive stimuli, as assessed by measurement of reaction time, in the absence of general cognitive impairment; ii) the effects of exposure to iodine deficiency during fetal/neonatal life, in spite of correction in the early childhood, may persist longer. Our findings also suggest that the measurement of simple RTs is a sensitive test to detect subtle neurological damages in mild iodine deficiency.

The Effect of Voluntary Iodine Prophylaxis in a Small Rural Community: The Pescopagano Survey 15 Years Later

CONTEXT Iodine deficiency disorders are a major public health problem, and programs have been implemented to improve iodine nutrition. OBJECTIVE The objective of the study was to verify the effects of voluntary iodine prophylaxis in a small rural community (Pescopagano, Italy). DESIGN The design of the study was the evaluation of the prevalence of thyroid disorders 15 years after a previous survey conducted before iodine prophylaxis. SETTING The setting for this study was a general community survey. PARTICIPANTS One thousand one hundred forty-eight residents were examined in 2010 and 1411 in 1995. RESULTS In 2010, 757 of 1148 subjects (65.9%) routinely used iodized salt, urinary iodine excretion being significantly higher than in 1955 (median 98.0 μg/L, vs 55.0 μg/L, P < .0001). The prevalence of goiter was lower in 2010 than in 1995 (25.8% vs 46.1%, P < .0001), mainly due to the reduction of diffuse goiter (10.3% vs 34.0%, P < .0001). In 2010 vs 1995, thyroid autonomy in subjects younger than 45 years old (3 of 579, 0.5% vs 25 of 1010, 2.5% P = .004) and nonautoimmune hyperthyroidism in subjects older than 45 years old (8 of 569, 1.4% vs 18 of 401, 4.5%, P = .03) were less frequent. The prevalence of hypothyroidism was higher in 2010 vs 1995 (5.0% vs 2.8%, P = .005), mainly because of an increased frequency of subclinical hypothyroidism in subjects younger than 15 years old (7 of 83, 8.4% vs 0 of 419, 0.0%, P < .0001). Accordingly, serum thyroid autoantibodies (19.5% vs 12.6%; P < .0001) and Hashimotos thyroiditis (14.5% vs 3.5%; P < .0001) were more frequent in 2010 than in 1995. CONCLUSIONS In the present work, the role of voluntary iodine prophylaxis was assessed in a small rural community relatively segregated, in which genetic and other environmental factors have not substantially changed between the 2 surveys. Iodine intake strongly affected the pattern of thyroid diseases, but the benefits of correcting iodine deficiency (decreased prevalence of goiter and thyroid autonomy in younger subjects and reduced frequency of nonautoimmune hyperthyroidism in older subjects) far outweighs the risk of development of thyroid autoimmunity and mild hypothyroidism in youngsters.

Modified-Release Recombinant Human TSH (MRrhTSH) Augments the Effect of 131I Therapy in Benign Multinodular Goiter: Results from a Multicenter International, Randomized, Placebo-Controlled Study

BACKGROUND Recombinant human TSH (rhTSH) can be used to enhance (131)I therapy for shrinkage of multinodular goiter (MG). OBJECTIVE, DESIGN, AND SETTING The objective of the study was to compare the efficacy and safety of 0.01 and 0.03 mg modified-release (MR) rhTSH as an adjuvant to (131)I therapy, vs. (131)I alone, in a randomized, placebo-controlled, international, multicenter study. PATIENTS AND INTERVENTION Ninety-five patients (57.2 ± 9.6 yr old, 85% females, 83% Caucasians) with MG (median size 96.0, range 31.9-242.2 ml) were randomized to receive placebo (group A, n = 32), MRrhTSH 0.01 mg (group B, n = 30), or MRrhTSH 0.03 mg (group C, n = 33) 24 h before a calculated activity of (131)I. MAIN OUTCOME MEASURES The primary end point was a change in thyroid volume (by computerized tomography scan, at 6 months). Secondary end points were the smallest cross-sectional area of the trachea; thyroid function tests; Thyroid Quality of Life Questionnaire; electrocardiogram; and hyperthyroid symptom scale. RESULTS Thyroid volume decreased significantly in all groups. The reduction was comparable in groups A and B (23.1 ± 8.8 and 23.3 ± 16.5%, respectively; P = 0.95). In group C, the reduction (32.9 ± 20.7%) was more pronounced than in groups A (P = 0.03) and B. The smallest cross-sectional area of the trachea increased in all groups: 3.8 ± 2.9% in A, 4.8 ± 3.3% in B, and 10.2 ± 33.2% in C, with no significant difference among the groups. Goiter-related symptoms were effectively reduced and there were no major safety concerns. CONCLUSION In this dose-selection study, 0.03 mg MRrhTSH was the most efficacious dose as an adjuvant to (131)I therapy of MG. It was well tolerated and significantly augmented the effect of (131)I therapy in the short term. Larger studies with long-term follow-up are warranted.

Evaluation of thyroid function in patients with rapid-cycling and non-rapid-cycling bipolar disorder

The problem of whether rapid-cycling (RC) bipolar disorder is more frequently associated than non-rapid-cycling (NRC) bipolar disorders with thyroid dysfunction was investigated in two groups of 11 women matched for age and therapy. Seven patients in each group were under chronic lithium therapy. Both RC and NRC patients, as compared to euthyroid controls, showed a reduction in mean total and free thyroid hormone concentrations, subnormal values of free thyroxine being found in four RC and three NRC patients. No patient had supranormal baseline thyroid stimulating hormone (TSH) values, but an exaggerated TSH response to thyrotropin releasing hormone was found in three RC and two NRC patients: all these patients had been receiving lithium therapy for more than one year. No differences in the prevalence of goiter and thyroid-directed autoantibodies were observed in the two groups. These data confirm that bipolar disorder, especially during treatment with lithium, is associated with at least subclinical hypothyroidism, and suggest that RC patients do not differ from NRC patients in the prevalence of spontaneous or lithium-induced thyroid hypofunction. Lithium-induced hypothyroidism is likely to be related to the length of treatment.

Iodine Contributes to Thyroid Autoimmunity in Humans by Unmasking a Cryptic Epitope on Thyroglobulin

CONTEXT The mechanisms linking thyroid autoimmunity and iodine use in humans are unknown. OBJECTIVE Our aim was to correlate iodine intake, thyroid autoimmunity, and recognition of thyroglobulin (Tg) epitopes after implementation of iodine prophylaxis. SETTING The general community living in an Italian village was evaluated. MAIN OUTCOME MEASURES Thyroglobulin autoantibodies (TgAb), thyroperoxidase autoantibodies (TPOAb), and urinary iodine excretion were assessed in 906 iodized salt users (IS-users) and 389 nonusers (IS-nonusers). Ultrasound (US) was performed to identify thyroid hypoechogenicity, suggestive of Hashimoto thyroiditis (HT). TgAb epitope pattern in 16 IS-users and 17 IS-nonusers was evaluated by an inhibition binding assay to Tg, using human monoclonal TgAb-Fab directed to A, B, C, and D epitopes on Tg. RESULTS Median urinary iodine excretion was slightly higher in IS-users than in IS-nonusers (112.0 μg/L vs 86.5 μg/L; P < .01). TgAb, and not TPOAb, was more frequent in IS-users (18.9% vs 13.6%, P = .02). HT-US was found in 87 subjects, among whom both positive TgAb (58.4% vs 31.8%, P = .03) and TPOAb (61.5% vs 45.4%. P = .04) were more frequent in IS-users. In this group significantly higher serum levels of TgAb (median 108 U/mL vs 30 U/mL; P = .02), but not of TPOAb, were present. Iodized salt use had no effect on the 1208 non HT-US subjects. TgAb directed to the epitope B of Tg were more frequent in IS-users than in IS-nonusers (27.5% vs 3.0%, P = .047). CONCLUSIONS Iodine-induced thyroid autoimmunity is related to TgAb and the unmasking of a cryptic epitope on Tg contributes to this relationship in humans.

Endemic goiter and thyroid function in Central-Southern Sardinia: Report on an extensive epidemiological survey

Although the existence of endemic goiter and cretinism in Sardinia is known since to ancient time, scanty information collected according to WHO criteria is available. In the present paper the results of an extensive epidemiological survey carried out in juvenile population living in some rural and/or hilly villages in the provinces of Nuoro and Oristano in Central-Southern Sardinia and in urban area of Cagliari, are reported. In the majority of the villages the mean urinary iodine excretion was lower than 60 μg/L; the goiter prevalence ranged between 39% and 61% in the district of Nuoro and between 21% and 56% in the district of Oristano. In the control area the urinary iodine excretion was 105 μg/L with a goiter prevalence of 12%. Goiter prevalence was not always inversely related to urinary iodine excretion. No relevant thyroid function alterations were found. In conclusion: 1) in extraurban areas of Central-Southern Sardinia mild to moderate iodine deficiency and endemic goiter are still a widespread problems; 2) also in urban area endemic goiter prevalence is still higher than 10%; 3) extemporary urinary samples are inadequate for assessing the severity of goiter endemia in mild to moderate iodine deficiency; 4) in mildly affected districts palpation is inaccurate for assessing the prevalence of goiter; 5) no relevant alterations of thyroid function were documented in juvenile population.

Early abnormalities of left ventricular myocardial characteristics associated with subclinical hyperthyroidism

The aim of the present study was to analyze heart function in subclinical hyperthyroidism (sHT) in otherwise healthy subjects by new methods using intramyocardial ultrasonic techniques. Twenty-four newly diagnosed and untreated sHT patients (20 women, 4 men; mean age: 42±4 yr) and 24 sex- and age-matched healthy volunteers were studied. All subjects were submitted to conventional 2D color-Doppler echocardiography, pulsed wave tissue Doppler imaging (PWTDI) for the analysis of diastolic function, color Doppler myocardial imaging (CDMI) for the analysis of regional strain and strain rate (SR) expression of regional myocardial deformability, and to integrated backscatter (IBS) for the evaluation of intrinsic contractility and tissue characterization. Regional myocardial systolic strain findings were significantly higher in sHT patients when compared with controls (p<0.001). Considering diastolic SR, the early phase of diastolic SR was compromised in sHT subjects as compared with controls (p<0.001). Cyclic variation index (CVI), expression of intrinsic contractility, was significantly higher in sHT subjects in comparison with controls (p<0.0001). IBS values were comparable between the 2 study groups. In conclusion, the present study suggests that in patients with sHT early systolic hyperdeformability and hypercontractility are present, together with impairment of both active and passive phases of diastole. On the contrary, no left ventricular hypertrophy or other structural alterations are documented.

Long-Term Efficacy of Modified-Release Recombinant Human Thyrotropin Augmented Radioiodine Therapy for Benign Multinodular Goiter: Results from a Multicenter, International, Randomized, Placebo-Controlled, Dose-Selection Study

BACKGROUND Enhanced reduction of multinodular goiter (MNG) can be achieved by stimulation with recombinant human thyrotropin (rhTSH) before radioiodine ((131)I) therapy. The objective was to compare the long-term efficacy and safety of two low doses of modified release rhTSH (MRrhTSH) in combination with (131)I therapy. METHODS In this phase II, single-blinded, placebo-controlled study, 95 patients (57.2 ± 9.6 years old, 85% women, 83% Caucasians) with MNG (median size 96.0 mL; range 31.9-242.2 mL) were randomized to receive placebo (n=32), 0.01 mg MRrhTSH (n=30), or 0.03 mg MRrhTSH (n=33) 24 hours before a calculated (131)I activity. Thyroid volume (TV) and smallest cross-sectional area of trachea (SCAT) were measured (by computed tomography scan) at baseline, six months, and 36 months. Thyroid function and quality of life (QoL) was evaluated at three-month and yearly intervals respectively. RESULTS At six months, TV reduction was enhanced in the 0.03 mg MRrhTSH group (32.9% vs. 23.1% in the placebo group; p=0.03) but not in the 0.01 mg MRrhTSH group. At 36 months, the mean percent TV reduction from baseline was 44 ± 12.7% (SD) in the placebo group, 41 ± 21.0% in the 0.01 mg MRrhTSH group, and 53 ± 18.6% in the 0.03 mg MRrhTSH group, with no statistically significant differences among the groups, p=0.105. In the 0.03 mg MRrhTSH group, the subset of patients with basal (131)I uptake <20% had a 24% greater TV reduction at 36 months than the corresponding subset of patients in the placebo group (p=0.01). At 36 months, the largest relative increase in SCAT was observed in the 0.03 mg MRrhTSH group (13.4 ± 23.2%), but this was not statistically different from the increases observed in the placebo or the 0.01 mg MRrhTSH group (p=0.15). Goiter-related symptoms were reduced and QoL improved, without any enhanced benefit from using MRrhTSH. At three years, the prevalence of permanent hypothyroidism was 13%, 33%, and 45% in the placebo, 0.01 mg, and 0.03 mg MRrhTSH groups respectively. The overall safety profile of the study was favorable. CONCLUSIONS When used as adjuvant to (131)I, enhanced MNG reduction could not be demonstrated with MRrhTSH doses ≤ 0.03 mg, indicating that the lower threshold for efficacy is around this level.

The size of the community rather than its geographical location better defines the risk of iodine deficiency: Results of an extensive survey in Southern Italy

Aim: The objective of this study was to establish the status of iodine nutrition in Southern Italy. Material and methods: The survey was carried out on 11–14 yr old children attending primary school and living in urban and non urban areas of 8 regions of Southern Italy. Urinary iodine excretion (UIE) was measured in 23,103 urinary samples randomly collected. Results: Median UIE in the whole studied population was 74 µg/l [interquartile range (IR) 34–139 µg/l]. UIE was significantly higher in chief towns compared to non chief towns (81 µg/l, IR 39–145 µg/l vs 73 µg/l, IR 33–138 µg/l, p<0.0001) and in areas with >500 inhabitants per km2 (median 87 µg/l, IR 43–154 µg/l) compared to areas with 100–500 per km2 (median 66 µg/l, IR 29–126 µg/l, p<0.0001) and with <100 per km2 (median 61 µg/l, IR 25–121 µg/l, p<0.0001). Median UIE was significantly lower in inland mountainous/hilly areas (68 µg/l, IR 30–129 µg/l) compared to coastal mountainous/hilly areas (79 µg/l, IR 37–144 µg/l, p<0.0001) and lowland (79 µg/l, IR 37–146 µg/l, p<0.0001). According to a binary logistic regression model, population density was the only independent parameter significantly associated with UIE≥100 µg/l. Conclusion: The results of the present survey indicate that: 1) in Southern Italy mild to moderate iodine deficiency is still present; 2) median UIE in non urban areas is lower than in urban areas and is related to the size of the community rather than to its geographical location, being higher in a larger community. This may be due to better diversification of dietary habits and the easier availability of iodized salt and processed food through commercial facilities, more common in larger communities. Future monitoring surveys should take into account these observations.