Iodine status in schoolchildren living in northeast Italy: the importance of iodized-salt use and milk consumption.

BACKGROUND: The aims of the study were: (i) to determine iodine status of schoolchildren living in northeast Italy; (ii) to assess dietary habits and iodine status and (iii) to investigate the level of knowledge concerning iodine sufficiency and ways to ameliorate iodine status. METHODS: One thousand three hundred seventy-five consecutive 12-13 year-old completed questionnaires collecting demographic data and information about the use of iodized salt and food frequency habits. Iodine concentration in urine samples (UIC) and in commercially available milk samples has been measured. RESULTS: The median UIC was found to be 81 µg/l (95% confidence interval (CI) 74-87); 40% of the subjects had an UIC of ≥ 100 µg/l. Iodine deficiency was prevalent in subjects living in hilly areas. Median iodine concentration in milk was 264 µg/l. Only the combined use of iodized salt plus daily milk normalized UIC, resulting into a median value of 108 µg/l. A logistic regression model confirmed independent associations between low UIC and low intake of milk, use of non-iodized salt and geographical location (P<0.0001). Only 45% of the subjects were aware of the importance of iodine. CONCLUSIONS: Northeast Italy is still characterized by mild iodine deficiency. An adequate iodine status was achieved only when iodized salt was combined with daily milk intake. The national iodine prophylaxis program has led to greater consumption of iodized salt and, it is now used in 60-70% of the Italian households. The low level of awareness highlights the need for public programs to promote knowledge and efforts to improve iodine status.

Selenium and autoimmune thyroiditis.

Selenium (Se) takes part in the activation and deactivation of thyroid hormones as a component of the catalytic site of selenodeiodinases and plays an important role in thyroid protection against oxidative damage. Based on these assumptions, in the last 10 years, several clinical trials have evaluated the effects of Se supplementation in patients with autoimmune thyroid disease (AIT) with not conclusive results. This review aims to analyze the effects of Se supplementation in patients with AIT considering studies published on this subject, so far. The emphasis is especially given on the multifactorial genesis of Hashimoto's thyroiditis (HT), which can affect the action of selenoproteins, and on the poor correlation between thyroid structural damage in HT, measurable by ultrasound examination, and antibody titer, suggesting possible recommendations for future studies.

Effects of selenium supplementation on the natural course of autoimmune thyroiditis: a short review.

Selenium (Se) is an important element that exerts its effects on the selenoproteins. It is an essential component of the glutathione peroxidase enzymes, which have anti-oxidant and anti-inflammatory properties, and a component of iodothyronine selenodeiodinases, which catalyze the extrathyroid production of T3 from T4. Se is important to several aspects of thyroid homeostasis and may influence the natural course of thyroid diseases such as autoimmune thyroiditis (AIT). This review analyzes the effects of Se supplementation in patients with AIT, based on the studies published on this issue to date.

Restricted intraindividual urinary iodine concentration variability in nonfasting subjects.

OBJECTIVE: Individual urinary iodine concentration (UIC) reflects iodine intake over a short time prior to sampling. Since eating habits are relatively constant in single subjects, UIC should be relatively constant in a given individual. The aim of our study was to verify this hypothesis by assessing UIC in repeated single urine samples from a group of healthy subjects. DESIGN AND SETTING: A prospective sequential investigation was performed in 131 volunteer health workers or students recruited in our University hospital. INTERVENTIONS: Single urine samples were taken in a nonfasting state, between 0900 and 1100 hours. Group 1 was composed by 131 subjects who collected one urine sample. Group 2 was composed by 11 subjects of the group 1, who collected multiple repeated urine samples (as a whole 158 urine samples, mean 14 samples each). UIC mean+/-s.d., median and coefficient of variation (CV%) was measured in both groups. RESULTS: Interindividual UIC variation was wide, UIC ranging from 21 to 382 microg/l, mean 136+/-84 microg/l, median 124 microg/l, CV 62%. Also in the 11 subjects repeatedly sampling there were considerable differences among individual UIC average levels (ranging from 37+/-15 to 221+/-91 microg/l). However, in this second group, the intraindividual variation was considerably restricted (CV% 36). CONCLUSIONS: The present study shows that in a nonfasting state in mid-morning UIC is more stable from day to day in a single subject, depending on his eating habits, than in various subjects. Thus, a single urine sample even in nonfasting state may give some rough information about the individual's iodine status.

Milk represents an important source of iodine in schoolchildren of the Veneto region, Italy.

The aim of the present study is to evaluate the relationships between urinary iodine concentration (UIC) and the intake of milk and other foods, in a group of school children of the Veneto region, in North East Italy. A questionnaire, concerning the daily intake of milk, yoghurt, cheese and other animal foodstuffs, was distributed to 233 schoolchildren aged between 11 and 15 yr. The use of iodized salt was also investigated. UIC was measured in a casual urine sample of all children investigated. The iodine content of 28 samples of milk and of 13 samples of yoghurt, bought during the summer in shops of the same area, was measured. UIC values ranged between 25 and 436 microg/l, median value was 140 microg/l, mean value 149+/-78 microg/l. The median iodine content of milk and yoghurt were 278 microg/l and 216 microg/l, respectively. With regard to dietary habits, about 70% of the children took 200 ml of milk or more per day, which corresponds to a daily intake of iodine ranging between 50 and 100 microg a day. About 30% of schoolchildren used iodized salt. A highly significant correlation between UIC and milk intake was observed (p=0.0005), while the relationship was poor or absent in the case of both intake of other foodstuffs and use of iodized salt (p=0.38). In conclusion, the results of the study document the very important role of cows' milk as a source of iodine in childhood in the Veneto region, Italy.

Normal values for thyroid ultrasonography, goiter prevalence and urinary iodine concentration in schoolchildren of the Veneto Region, Italy.

Goiter prevalence in school-age children and median urinary iodine concentration (UIC) are the main indicators of iodine deficiency in a population. In areas of mild iodine deficiency, where goiters are small, ultrasound is preferable to physical examination to estimate goiter prevalence. The World Health Organization (WHO) has adopted thyroid volume ultrasonography results from a survey of European schoolchildren as an international reference, but these values have recently been questioned. The aims of the study were: a) to determine regional normal echographic reference values of thyroid volume in children aged between 11 and 14 yr in the Veneto Region, in North-East Italy; b) to determine goiter prevalence by physical and ultrasonographic examination; c) to determine UIC in this section of the population. A cross-sectional study was carried out on 1730 schoolchildren, aged between 11 and 14, living in towns in low-lying areas, in the valleys of the pre-Alps and in the mountains between 600 and 1200 m. Thyroid volume was evaluated by inspection and palpation using the WHO criteria. In 560 children thyroid volume was determined by ultrasound. UIC was measured in 1368 children. On physical examination a grade I goiter was found in 7.5% of children. No goiter grade II or grade III was found. The regional thyroid volume reference values by ultrasonography were similar, or slightly lower (5-20%), to the corresponding WHO reference values. Mean UIC was 148 +/- 110 microg/l, with no difference between lowlands and uplands; UIC values less than 100 microg/l were found in about 30-35% of the children. UIC was higher in children using iodized salt than in non-users. No correlation was found between thyroid volume by ultrasonography and UIC. Thyroid volume was found to be bigger in upland children than in those in low-lying areas, probably because of low iodine intake in people living in the mountains in previous generations. This data show that Veneto is not a iodine-deficient area, with no presence of endemic goiter. However, the great number of children with a UIC of less than 100 microg/l also suggests the use of iodized salt in the Veneto Region.

A multimodality therapeutic approach in anaplastic thyroid carcinoma: study on 39 patients.

The aim of this study was to investigate the role of multimodality treatment in patients with anaplastic thyroid carcinoma. From 1992 to 1999, 39 consecutive patients with a histologically or cytologically proven anaplastic thyroid carcinoma were referred to the Thyroid Center of Padua General Hospital. There were 28 females and 11 males with a median age of 69 years (range 39-88 years). About one-third of patients had a history of preceeding nodular goiter. Two patients had areas of differentiated thyroid carcinoma at histological examination. Local disease was present in 26 patients while distant metastases, mainly to the lung, were present in 22 at diagnosis or quickly developed during the observation period in all the others except one. Thirty-two patients were previously untreated: 9 of them were in good general condition, 1 had limited lung metastases, and the tumor mass was considered resectable by the surgeon. These 9 patients were treated with cisplatin once a week and radiotherapy (RT) 36Gy in 18 fractions over three weeks, followed by total thyroidectomy (TT) and by further chemotherapy (CHT) with adriamycin and bleomycin in 4 patients. Seven patients, 3 with lung metastases at diagnosis, had undergone TT, followed by RT in 5, in another hospital and were subsequently referred to our center due to the presence of distant metastases. Therefore, a total of 16 patients (Group 1) was treated with TT, RT and CHT in various order. Nine patients with distant metastases at diagnosis (Group 2) received CHT; one of them had a disappearance of lung metastases and was then treated by TT and further CHT. Group 3 consisted of 14 elderly patients in poor general conditions; 4 of these received local RT, while the remaining did not receive any treatment. Four complete responses were seen in patients from Group 1, and 1 from Group 2. One patient without distant metastases at diagnosis is alive and free of disease 6 months after TT and adjuvant CHT, and 12 months after diagnosis. Three had long-term survival (14, 24, 27 months) with a disease-free interval of 6-8-10 months. The patient from Group 2 who was treated in a second time by TT is alive without disease after 60 months. Median survival rate was 11 months for Group 1, 5.7 months for Group 2 and 4 months for Group 3. In some patients multimodality treatment (TT, RT and CHT) is associated with increased survival. Nine out of 16 patients, who underwent surgery and complementary treatment, had no local progression. In all but one distant metastases developed, mainly in the lung, during or after post-surgical CHT. The best results were obtained in younger patients with less advanced disease. Early diagnosis is mandatory. Only a few patients responded to CHT, confirming that anaplastic thyroid carcinoma is often resistant to anticancer drugs. Our experience with combination modalities suggests that aggressive and appropriate combinations of RT, TT and CHT may provide some benefit in patients with anaplastic thyroid carcinoma. Preoperative CHT and RT may enhance surgical resectability of the primary tumor.

Medullary thyroid carcinoma: clinical features and long-term follow-up of seventy-eight patients treated between 1969 and 1986.

This article describes the findings of a retrospective analysis of data obtained on 78 patients with medullary thyroid carcinoma (MTC), recorded between 1969 and 1986, and then followed at the Thyroid Center of Padua (Italy). The ages of the patients ranged between 15 and 89 years, with a median age of 45. The female to male (F:M) ratio was 2.9:1. All patients except 2 had total thyroidectomy. In 70 cases the tumor was of sporadic type; there were 3 familial non-multiple endocrine neoplasia (MEN) MTC; 3 MEN IIa; and 2 MEN IIb. The median duration of follow-up was 15.9 years (13 patients were followed up between 15 and 20 years, and 9 longer than 20). At diagnosis, the tumor was intrathyroid (stage I and II) in 31 patients, with local lymphnodes involved (stage III) in 41 patients, and with distant metastases (stage IV) in 6 patients. A total of 34 patients died (4 were at stage II at diagnosis, 26 at stage III, and 4 at stage IV); 4 of them died of unrelated causes, the others with tumor. The median survival rate of the deceased patients was 6 years (41% of these patients died within 3 years and 24% after more than 10 years); 76% of the deceased patients were older than 45 years at diagnosis. A total of 44 patients are still alive, 22 are alive free of disease (with follow-up between 10 and 24 years, median 14.2 years) and 22 are alive with disease (median follow-up 12.2 years). Only 30% of the patients of both these groups was older than 45 years at diagnosis. Survival is strongly related to tumor stage and to age at diagnosis, because only 8 of the 34 deceased patients were younger than 45 years (and 2 of them died of unrelated causes); moreover, patients who were treated at earlier stages of the disease had better prognosis. Survival rate at 10 and 20 years was 95% for patients with tumor limited to the thyroid, whereas it was 55% and 28.6%, respectively, for patients at stage III and IV. Bone metastases were correlated with worse prognosis than distant metastases only to soft tissues. The sex did not affect survival. None of the patients who had postoperative low serum calcitonin (CT) levels and no response to pentagastrin stimulation showed recurrences in the follow-up. In patients with postoperative elevated serum CT levels, recurrences of the tumor increased over time. However, 30% of these patients continued to show only elevated CT levels without evidence of the disease, even after 15 years.

[Goiter and iodine deficiency in Veneto: study on 6285 elementary and media school children]. / Gozzo e carenza iodica nel Veneto: studio su 6285 ragazzi delle scuole elementari e medie.

The aim of this paper was to determine goiter prevalence and urinary iodine excretion in the Veneto region. An extensive epidemiological survey was carried out in school-aged children visiting 6285 students and testing 1861 urinary samples. A goiter prevalence of 8.8% was found: 7.7% of grade 1A and 1.1% 1B; in the pre-mountainous area the prevalence was higher than 10% (11.7% in the Treviso and 12.7% in the Vicenza area). Urinary iodine excretion was less than 100 micrograms/Cr in about 45% of all examined children with a peak of 20% under 50 micrograms/Cr in the Vicenza district. According to the WHO criteria, the goiter prevalence in the Veneto can be considered under the limits of the epidemic standards. However the use of iodized salt seems advisable also in this area.

Hyperosmolar nonketotic coma at the onset of type I diabetes in a child.

A 12 yr-old child without any past medical history of diseases was admitted to hospital for sopor and polyuria. At admission he was markedly dehydrated. Blood glucose was 72 mmol/l, sodium 154 mmol/l, osmolarity 381 mOsm/Kg, urinary ketons were negative. He was rehydrated with hypotonic saline and treated with insulin. The osmolality and sodium initially increased to 176 mmol/l and 408 mOsm/Kg respectively and progressively decreased to normal levels. Serum transaminases increased to GOT 336 and GPT 209 U/l in the first days of treatment and normalized after 15 days. The anti-islet antibodies were positive. The non ketotic hyperosmolar coma and Type I diabetes is rare in children but this possibility must be kept in mind especially when some familial or psychological problems are present as in our case.

Epidemiological survey of goiter and iodine deficiency in Veneto region.

The aim of this paper was to determine goiter prevalence and urinary iodine excretion in the Veneto region. It is known since ancient times that goiter prevalence has affected mainly the mountainous areas in Italy. An extensive epidemiological survey was carried out in school-aged children, visiting 5,439 students and testing 1,883 urinary samples. A goiter prevalence of 8.8% was found in the Region; 7.7% of grade 1A and 1.1% of grade 1B respectively; in the pre-mountainous area the prevalence was higher than 10% (11.7% in the Treviso area and 12.7% in the Vicenza area). Urinary iodine excretion was less than 100 mcg/cr in about 45% of all examined children, with a peak of 20% under 50 mcg/cr in the Vicenza district. According to the WHO criteria, the goiter prevalence in the Veneto area can be considered under the limits of epidemic standards. Nevertheless we feel that in light of the urinary data a prophylaxis with iodine added salt should be recommended in any case.

[Treatment of hot thyroid nodule with percutaneous ethanol injection: indications, complications, and prognostic factors]. / La cura del nodulo caldo della tiroide con alcolizzazione percutanea: indicazioni, complicanze e fattori prognostici.

Percutaneous ethanol injection (PEI) has recently been proposed as an alternative therapy for toxic thyroid adenomas, instead of conventional treatments (pharmacological, surgical and radiometabolic therapies). The aim of this study was to investigate efficacy, complications and prognostic factors of PEI treatment in a group of 74 patients, 14 men and 60 women, treated from May, 1991, to December, 1994. Twenty-seven patients had nontoxic (pre-toxic) nodules (normal T3 and T4 and undetectable TSH serum levels) and 47 toxic nodules (high serum levels of thyroid hormones). A mean of 1.6 ml ethanol/cc of nodule volume was injected in 3-14 sessions (mean = 6). Ten subjects were treated twice, and 2 patients three times. Results were defined as: 1) complete cure: normalization of T3, T4 and TSH levels and appearance of extranodular thyroid tissue at scintigraphy; 2) partial cure: reduction in thyroid hormones within the normal range but still undetectable TSH levels and still suppressed extranodular thyroid tissue at scintigraphy; 3) failure. Complete cure was obtained in 96% of nontoxic (pretoxic) nodules and 65% of toxic ones. Moreover, partial cure was seen in 27.5% more toxic nodules and failure in 7.5%. The most significant complications were a case of transient dysphonia and two cases of common jugular vein thrombosis, both resolved spontaneously. The most important prognostic factor was the degree of hyperthyroidism (as FT4 and T3 serum levels), while nodule volume was rather useless to predict the final result. In conclusion, PEI can be an alternative, effective and low-cost treatment for autonomous thyroid nodules, without any severe complication and well tolerated by the patients.

Prognostic value of early postoperative calcitonin level in medullary thyroid carcinoma.

AIMS: Serum calcitonin (CT) assay is commonly used in the diagnosis and follow-up of medullary thyroid carcinoma (MTC). The aim of this study was to ascertain whether serum CT levels, measured in the first few days after surgery, could be used to evaluate the efficacy of treatment. METHODS: A group of 33 patients was studied. In all patients the follow-up was more than 20 months. RESULTS: Preoperatively basal CT serum levels were high in all patients. Twenty-four hours after surgery CT serum levels dropped to within the normal range in 8 patients and 72 hours after operation in 7 others. In this group 1 patient was at stage I, 11 at stage II and 3 at stage III. Basal and pentagastrin stimulated CT levels continued to be in the normal range in these 15 patients 6 and 12 months after surgery and at the subsequent year by follow-up visits. No clinical or radiological evidence of disease was found during the follow-up in this group. In the other 18 patients CT was reduced but still high 72 hours after surgery; 6 months later basal serum CT levels continued to be elevated or responsive to pentagastrin stimulation. In this group restaging showed tumor relapse in the thyroid bed in 2 patients, cervical lymphadenopathy in 11, and distant metastases (bone, liver) in 3. CONCLUSIONS: Immediate postoperative CT serum levels seem to be the most useful index to evaluate the efficacy of surgical treatment and the presence of residual neoplastic tissue.

[Undifferentiated carcinoma of the thyroid gland]. / Il carcinoma indifferenziato della tiroide.

Anaplastic carcinoma of the thyroid is a tumour of advanced age, with a female/male ratio of 2/1. Its incidence is of 1-2 cases/million/year. The tumour is one of the most aggressive neoplasms affecting humans. It spreads very rapidly to the regional lymph nodes and causes distant metastases, in particular in the lungs and bone. Surgery, external radiation or chemotherapy are usually ineffective when used alone. Better results are obtained by combinations of these modalities, in particular by a combination of radiotherapy and chemotherapy followed by surgery. In our Centre we have, since 1991, adopted a multimodal treatment based on radiotherapy preceded by Cisplatin administration, followed by surgery and then by adjuvant chemotherapy with Adriamycin and Bleomycin. The initial results on a limited number of cases seem encouraging.

[Medullary thyroid carcinoma: prognostic factors]. / Carcinoma midollare della tiroide: fattori prognostici.

Fifty-one patients treated by total thyroidectomy plus nodal neck dissection of necessity for medullary thyroid carcinoma (MTC) with a minimum follow-up of 10 years (mean 14.5, max 22 years) were divided into three groups according to the outcome (alive disease-free; alive with disease; dead) and were compared in order to analyze the prognostic factors of MTC. Twenty years actuarial survival rate for age at diagnosis less than 50 years versus age over 50 (90% vs 45%) as well as for stage II versus stage III (85% vs 55%) was statistically different (p < 0.005 and p < 0.05 respectively). About 60% of recurrences were observed within 5 years after surgical treatment. Recurrence rate for stage III (70%) versus stage II (20%) was statistically different, but it was not for the age. Survival rate for patients with bony metastases (50% at 1 and 30% at 3 years) versus patients with other than bony metastases (100% at 10 years) was statistically different.

Combined chemotherapy with bleomycin, adriamycin, and platinum in advanced thyroid cancer.

Twenty-two advanced consecutive thyroid cancer patients with varying histologies were treated with the so called BAP regime which consisted of bleomycin (B) 30 mg a day for three days, adriamycin (A) 60 mg/m2 iv in day 5, and cisplatinum (P) 60 to mg/m2 iv in day 5. Patients with progressive, symptomatic recurrent or disseminated disease unresponsive to hormonal and/or isotopic treatment were eligible. Nine patients had an objective response: two long-lasting complete and seven partial responses were observed out of 21 evaluable patients. Stable disease was observed in four additional patients. The median duration of response was 12 months (range, 6-29). The total series experienced a median survival of 11 months (range, 1 to 57), with 2 patients actually disease free. Several histologic types of thyroid carcinoma responded, but the best responses were observed in medullary and anaplastic giant-cell carcinomas. Toxicity was reversible in all but one patient. Of the patients failing on BAP chemotherapy three responded to a four drug second line combination containing vincristine, fluorouracil, BCNU and methotrexate. BAP regime can achieve reasonable palliation, and probably increases survival, in poor-prognosis thyroid cancers.

Favorable long term results in patients with small differentiated thyroid cancer not treated with radioiodine.

Data on a group of 110 patients with differentiated thyroid cancer not treated by radioiodine are reported. Most of them had intrathyroid (stage I) papillary or capsuled follicular cancer of less than 3 cm diameters. They all received thyroxine at TSH suppressive doses. The follow-up ranged between 4 and 25 years, mean 8.7. No patient died of tumor. Two very old patients died free of disease. Four recurrences occurred, within 8 years, all in patients over 45 years, all local or nodal, all papillary, 3 out of 4 after total thyroidectomy. This study shows that radioiodine therapy may be avoided and that lobectomy may be sufficient in patients under 45 years with small papillary or capsuled follicular cancer.

Effects of thyroid hormones on the biochemical specialization of human muscle fibers.

The effects of thyrotoxicosis and of hypothyroidism on human muscle have been studied on single fiber preparations. In thyrotoxic muscle, the ratio between fibers showing the fast type of myofibrillar protein isoforms (fast fibers) and fibers showing the slow type (slow fibers) is increased, as is the percentage of fibers with incomplete segregation of fast and slow myosin (intermediate fibers). Furthermore, in fast fibers, the volume and, to a greater extent, the rate of Ca transport of sarcoplasmic reticulum (SR) are increased, without changes in the affinity for Ca2+ of the Ca-pump or in its sensitivity to the cyclic adenosine monophosphate (cAMP) dependent protein kinase system. These effects are completely reversed by the removal of thyroid hormones, as demonstrated by hypothyroid muscles. It is suggested that in human muscle cells thyroid hormones are critical for the expression of fast genes and for SR Ca transport.

Nonparallel patterns of calcitonin and carcinoembryonic antigen levels in the follow-up of medullary thyroid carcinoma.

Serum levels of calcitonin (CT) and carcinoembryonic antigen (CEA) were evaluated in a group of 41 patients with histologically proven medullary thyroid carcinoma (MCT) before and sequentially after treatment for a period up to 7 years. Before thyroidectomy, CT levels were high in all patients, and significantly more elevated when metastases were present. On the other hand, CEA levels were high in most but not all the patients, and they also were found more frequently to be elevated in patients with metastases. After treatment, most of the patients without metastases showed persistently normal basal and pentagastrin stimulated CT and CEA levels. In some patients either without or with local metastases, postoperative CT levels, although considerably reduced, remained persistently above normal limits, whereas CEA levels became completely normal. This pattern may be due to the persistence of minute occult foci of the tumor, not sufficient to produce measurable amounts of CEA, which is not synthesized by all tumor cells. Most of the patients with metastases at diagnosis, showed still elevated CT and CEA levels after treatment. In the nonprogressive cases both markers decreased after adjunctive treatment or remained unchanged. In patients with progressive disease, an increase of CEA levels in the absence of a parallel increase of CT levels, which even decreased, was often observed. In one patient with progressive disease high CEA levels were seen for the first time when liver metastases had occurred. These data seem to suggest that, even though CEA production is not recognizable in all patients with MCT, in the CEA positive cases CEA levels may follow a nonparallel pattern and may have a distinct diagnostic meaning with respect to CT levels. In some cases, particularly in advanced disease, CEA may be a more useful marker of poor prognosis.