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.

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 novel mutation in the thyrotropin (TSH) receptor gene causing loss of TSH binding but constitutive receptor activation in a family with resistance to TSH.

Resistance to TSH is a syndrome due to reduced responsiveness of the thyroid gland to biologically active TSH. Inactivating mutations of the TSH receptor (TSH-R) have been detected in several cases of resistance to TSH, both partial and complete, sporadic and familial. In this study, we describe a family with the presence of resistance to TSH responsible for euthyroid hyperthyrotropinemia in two siblings from consanguineous parents. By direct sequencing of the TSH receptor gene, we identified a new mutation responsible for the substitution of an arginine with a cysteine at position 310, in the extracellular domain of the TSH-R. The mutation was homozygous in two brothers; heterozygous in both parents, an uncle, and an unaffected brother; and absent in the other unaffected brother. When stably transfected in Chinese hamster ovary cells, the Cys310 mutant TSH-R showed loss of response to TSH in terms of cAMP stimulation. However, a constitutive activity in terms of basal cAMP production was detected in the Cys310 mutant, compared with the wild-type TSH-R. Our data suggest that such a Cys310 TSH-R mutant may determine both the TSH resistance and the clinical euthyroidism detected in this family.

Serum thyroglobulin measurements in differentiated thyroid cancer.

In pathological states, the serum thyroglobulin (Tg) concentrations are generally high. Therefore, a serum assay of Tg levels is not useful for the differential diagnosis between benign or malignant disease in the preoperative period. Serum Tg measurements are a suitable marker in the follow-up of patients with differentiated thyroid carcinoma (DTC) during the postoperative period. After total thyroidectomy, serum Tg concentrations were found to be undetectable in subjects without evidence of residual thyroid tissue or metastases; however, detectable serum Tg levels in subjects on and off thyroid hormone suppressive therapy indicate the presence of residual or metastatic thyroid tissue. An increase in serum Tg levels during thyroid stimulating hormone (TSH) suppression indicates that further investigations are necessary.

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.

Germline and somatic mutations of the RET proto-oncogene in apparently sporadic medullary thyroid carcinomas.

Medullary thyroid carcinomas (MTC) occur sporadically or as part of inherited multiple endocrine neoplasia (MEN) type 2 syndromes. To recognize misdiagnosed familial cases and to establish the frequency of somatic mutations, a series of 50 patients, clinically diagnosed with sporadic MTC, were analyzed for mutations in the RET proto-oncogene. The clinical management of the patient and of the family is different in the two cases. Germline mutations were detected in three independent cases, demonstrating that they were associated to familial MTC. The mutations affected exon 11 in two cases and exon 14 in one case. Somatic mutations were detected in eight patients (30%) and they were indicative of sporadic MTC. In seven cases the mutation affected codon 918 of exon 16 and in one case codon 634 in exon 11. No RET mutations were detected in the remaining patients. A different genetic and clinical management is proposed for individuals with a diagnosis of familial or sporadic MTC.

[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.

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.

[Which thyroidectomy in Basedow disease?]. / Quale tiroidectomia per il morbo di Basedow?

One hundred and seventy patients with Graves' disease underwent thyroidectomy between 1987 and 1994 (10.5% of all thyroidectomies performed in the same period). Female/male ratio was 9/1; mean age 55.2 years and average period between diagnosis and surgical treatment 5.3 years. The average thyroid weight was 230 g (range 90-950 g). Thyroidectomy was subtotal in 110 and total in 60 patients, 5 of which had been previously treated elsewhere from 5 to 33 years before. Malignancy was incidentally found in 2.35% of patients. The complication rate resulted higher in total thyroidectomies than in subtotal procedures (bleeding 0.9% vs 5.4%, transient hypoparathyroidism 4.5% vs 12.7%, recurrent nerve lesion 0.45% vs 2.72%) however the differences were not statistically significant; this probably because both the procedures were carried out with the same technique for parathyroid gland and recurrent nerve safety. The need of repeated surgery increased the risk. In opposition to total thyroidectomy, subtotal thyroidectomy does not doom to complete and permanent replacement therapy (96.4% of hypothyroidism at 2 months, 72.6% at 4 years), but in this series it failed to achieve remission in 2 patients who maintained a mild hyperthyroidism and in one more patient who developed a relapse 4 years later. Serum TSI meaning is not clear, but preoperative positivity suggests a wider resection and postoperative persistence a closer follow-up by functional assessment. In conclusion surgical procedures for Graves' disease range from subtotal to total thyroidectomy but for a safe outcome the choice depends more on the intraoperative troubles of each single case than on theoretic advantages.

Natural course of subclinical hypothyroidism in Down's syndrome: prospective study results and therapeutic considerations.

Pathogenesis, natural course and therapeutic management of subclinical hypothyroidism (SH) in Down's syndrome (DS) remain object of debate in literature. In the present study thyroid function, antithyroid antibody (ATA) prevalence and serum lipid concentrations were investigated in a group of 344 Down patients (DP) and data were compared with those obtained from a control group of 257 age and sex matched healthy subjects. Thyroid function and ATA prevalence were also studied in 120 parents of DP. SH prevalence was clearly higher in DP (32.5% of cases) than in controls (1.1%) and parents (0%). Similarly, ATA prevalence was higher in DP (18% of cases) than in controls (5.8%) and parents (6.6%). In spite of this, no correlation was found in DP between SH and ATA prevalences, since ATA were detected in 18.7% of SH-DP and in 15.8% of euthyroid DP. Thus, circulating ATA were not detected in the majority of SH-DP. No significant differences regarding T4, FT4, T3 and serum lipid levels among SH and euthyroid DP and controls were found. Moreover, TSH levels were only slightly increased, generally less than 10 microU/ml, in most cases of SH-DP. Follow-up was longer than 24 months (range 2-7 years, mean 3.1) in a group of 201 DP: two different patterns of SH course were observed, mainly depending on the presence or the absence of circulating ATA. In particular, 35.7% of ATA-positive SH-DP developed a clinically evident thyroid disease (overt hypothyroidism or hyperthyroidism), while no similar case was recorded among ATA-negative SH-DP.(ABSTRACT TRUNCATED AT 250 WORDS)

The extent of surgery for thyroid medullary cancer.

AIMS: Evaluation of the impact of the extent of primary surgery and reintervention on the outcome of patients with medullary thyroid carcinoma. METHODS: Seventy-two patients with medullary thyroid carcinoma (MTC) were surgically treated between 1967 and 1992. RESULTS: Fifty-five cases were sporadic, 5 patients had MEN 2A, 4 MEN 2B syndrome and 8 familial non-MEN MTC; 1 patient had stage I disease, 30 patients stage II, 36 stage III and 5 stage IV. Sixty-four had their initial treatment at our center, and 8 came for subsequent treatment. At first treatment, 8 patients were subjected to partial thyroidectomy, 10 to total thyroidectomy, 53 to total thyroidectomy with neck dissection, and 1 to only radical neck dissection; postoperative serum calcitonin (Ct) levels returned to normal in 3, 6 and 27 patients, respectively. In the patient with only radical neck dissection, Ct levels remained elevated. No patient with Ct normalization after surgery became responsive to pentagastrin in the follow-up. Thirteen patients had a reoperation due to nodal relapse. At a mean follow-up of 5.7 years (6-252 months), the 10-year survival rate was 84.5% with a significant difference between patients under and over 40 years of age (96.4 vs 57%), between stage I-II (100%) and stage III, IV (83.8%, 0% respectively). At the last follow-up, 36 (50%) patients were alive and disease free and 26 were alive with disease (15 with distant metastases). Of the 10 deaths, 7 were due to tumor recurrence, 3 to 120 months after surgery. CONCLUSIONS: Data suggest that an earlier diagnosis rather than more extensive surgery could improve survival and reduce recurrences. However, the least treatment required is total thyroidectomy plus central neck and upper mediastinum clearance and in addition, according to the extent of nodal involvement, mono- or bilateral neck dissection. To avoid ineffective reoperation due to distant (mainly liver) micrometastases, persistent residual microscopic disease requires a more aggressive restaging.

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.

Different features of pulmonary metastases in differentiated thyroid cancer: natural history and multivariate statistical analysis of prognostic variables.

We studied 134 patients with differentiated thyroid cancer and pulmonary metastases. All were treated with total or near total thyroidectomy, radioiodine and L-thyroxine. The prognostic value of the following variables in three groups of patients were evaluated by univariate and multivariate analysis: age at diagnosis, sex, histologic type, tumor extension, cervical lymph node metastases, mediastinic metastases, presence of metastases in distant sites other than lungs (multiple distant metastases) and morphological (chest x-rays) and functional (131I uptake) features of lung metastases. Univariate analysis identified patient age (p < 0.0001), morphological and functional features of lung metastases (p < 0.0001), presence of multiple distant metastases (p < 0.0001) and histologic type (p = 0.04) as significant prognostic factors. Multivariate analysis showed only morphological (p = 0.0014) and functional (p < 0.0001) features of lung metastases and the presence of multiple distant metastases (p = 0.01) as significant and independent variables. The data show that early (pre-radiological) scintigraphic diagnosis and 131I therapy of lung metastases appear to be the most important elements in obtaining both a significant improvement in survival rate and a prolonged disease-free time interval in these patients.