Sex dimorphism in the thyroid gland. IV. Cytologic aspects of sex dimorphism in the rat thyroid gland

This study was designed to explain whether the sex-dependent differences in the structure of the thyroid gland of adult male and female rats depend on quantitative or qualitative changes in the thyroid follicular cells. Absolute thyroid gland weight was similar in male and female rats, but its relative weight was markedly higher in females however. Volume fractions of epithelium and stroma were higher and that of colloid lower in male than in female rats and the epithelium/colloid ratio was higher in the males. Also absolute the volumes (in mm3) of epithelium and stroma were higher in the males; the thyroid gland of females contained more colloid. The average volume of a thyroid follicular cell, estimated by stereology, was higher in males than in females, although the thyroid gland contained similar numbers of follicular cells in both sexes. Also, thyroid glands from both male and female rats contained a similar DNA quantity. Results of the present study show that the sex dimorphism in the rat thyroid depends upon a difference in the mean volume of thyroid follicular cells, with males having larger cells than females. However, in both sexes the thyroid gland contains a similar quantity of these cells.     

Ultrasonographic thyroid volume as a reliable prognostic index of radioiodine-131 treatment outcome in Graves' disease hyperthyroidism.

OBJECTIVE: We studied the relationship between thyroid volume, thyroid function and immunological markers of Graves' disease (GD) to determine prognostic factors of treatment response to low-dose radioiodine-131 (131I). MATERIAL AND METHODS: A prospective study of 40 patients with GD hyperthyroidism treated with 131I (141 +/- 85MBq) and 10 GD patients who went spontaneously into remission (controls). Free T4, total T3 and basal TSH levels, TSH-receptor antibodies (TRAb) and anti-thyroid peroxidase antibodies (TPOAb) were studied. Thyroid volume was determined by ultrasonography. Logistic regression models were used to predict the probability of final thyroid status. Receiver-operating characteristics (ROC) curves and Hosmer Lemeshow tests were used to evaluate the final statistical models. RESULTS: Of 40 patients treated with 131I, 16 became euthyroid, 12 hyperthyroid and 12 hypothyroid at 12 months. Median thyroid volume was reduced from 24.8 ml before to 8.5 ml at 12 months (p<0.001). In 10 control patients, the median reduction was from 16.6 ml to 11.3 ml (p=0.029). Thyroid volume reduction was lower in the hyperthyroid than in the euthyroid group, but higher in the hypothyroid group. Thyroid volume at baseline and at 3 months predicted hyperthyroidism outcome with a cut-off of 45 ml and 24.4 ml, respectively (odds ratio 1.074, p=0.003, ROC curve 0.78 and odds ratio 1.182, p=0.012, ROC curve 0.86 respectively). Thyroid volume at 6 months differentiated the hyperthyroid group with a cut-off of 17 ml. Thyroid volume at 3 and 6 months with a cut-off of 8.5 ml and 9.3 ml respectively, predicts permanent hypothyroidism outcome (odds ratio 0.768 and 0.685, p=0.012 and p=0.008, ROC curve 0.89 and 0.88, respectively). Changes in thyroid echogenicity and TRAb and TPOAb levels did not show any predictive value in the follow-up after 131I therapeutic outcome. CONCLUSION: The study shows that the ultrasonographic thyroid volume at 3 and 6 months after low-dose 131I treatment for GD hyperthyroidism could be a reliable prognostic factor of thyroid function outcome in the first year after treatment, and also reveals that the changes in the thyroid echogenicity and in the immunological markers of GD have no prognostic value.     

Gender-specific determinants of goiter

Despite the strong implications of differences between females and males in the risk of goiter, gender-specific issues have not been extensively addressed in investigations of goiter prevalence. The objective of our analysis was to investigate the gender-specific determinants of goiter. Between April 2001 and April 2002. A total of 853 healthy employees from 4 institutions in the western part of Germany between 18 and 68 yr of age were examined by ultrasound of the neck to determine the thyroid volume. Information on sex, age, daily use of iodized salt, the history of goiter in the first-degree relatives, type and amount of smoking, oral contraceptives, and number of pregnancies were assessed by standardized questionnaires. Gender-specific predictors of goiter prevalence were assessed by multivariate logistic regression. The overall prevalence of goiter among study subjects was 204/853 (23.9%). Goiter was present in 80 out of 370 females (21.6%) vs 124/483 (25.7%) in males. In general, smoking (p<0.0001), increasing age (p<0.0001), and lack of daily intake of iodized salt (p=0.004) were associated with goiter prevalence, but not sex (p=0.39) and family history of goiter (p=0.16). In 370 females, parity (p=0.004) and lack of daily intake of iodized salt (p=0.01) were the major determinants for goiter, whereas age (p=0.18), oral contraceptives (p=0.82), family history of goiter (p=0.33), and smoking (p=0.09) did not affect goiter prevalence. In 483 males, smoking (p<0.0001) and age (p<0.001) affected goiter prevalence, but not family history of goiter (p=0.39), and the iodine status failed just to reach the significant level (p=0.08) in this analysis. Gender-specific determinants of goiter are parity and iodine status in females and smoking and increasing age in males.     

The treatment of multinodular large non-toxic goiter using repeated doses of radioiodine (preliminary report)

INTRODUCTION: The aim of study was to establish the effectiveness of radioiodine therapy using 131I in the group of patients with multinodular large non-toxic goiter. MATERIAL AND METHODS: Therapy was undertaken in female patients disqualified from surgery due to high risk and these patients who didn't agree to surgery. Studies were performed in 7 women (age range: 62-82 yrs) with large goiters (2nd degree according to WHO classification and goiter volume assessed by USG over 100 cm(3)). Serum TSH, fT4, fT3, antithyroid antibodies (TPOAb, TgAb, TRAb) levels, urinary iodine concentration (UIE) were estimated in all patients parallel with radioiodine uptake test (after 5 and 24 hours), 131I thyroid scintigraphy and fine needle biopsy to exclude neoplasmatic transformation. These studies and therapy with 22 mCi 131I were repeated every 3 months. RESULTS: Before therapy median thyroid volume was approximately 145 cm(3) and during therapy gradually decreased to 76 cm(3) after 6 months and to 65 cm(3) after 12 months. Increase of TRAb can be a inhibiting factor of thyroid volume reduction. Other antithyroid antibodies showed marked tendency to rise but without significant correlation with radioiodine uptake and goiter reduction. After 12 months we found 2 patients with clinical and laboratory hypothyroidism. CONCLUSIONS: In some cases of multinodular large non-toxic goiter, the radioiodine therapy can be the best alternative way for L-thyroxine treatment or surgery therapy. The fractionated radioiodine therapy of multinodular large non-toxic goiter is safe and effective method but continuation of nodules observation is necessary.     

Pituitary-thyroid axis, thyroid volume and leptin in healthy adults.

OBJECTIVE: Patients with thyroid diseases usually have disturbances relating to body weight and thermogenesis. On the other hand, leptin is involved in the regulation of body weight, food intake and thermogenesis. Some studies have investigated the relationship between leptin and dysthyroid states, but the complex interactions between leptin and pituitary-thyroid axis have led to controversial results. DESIGN: The aims of this cross-sectional study were to investigate the relationship among basal TSH, ultrasonographic thyroid volume and leptin in a group of 268 healthy adults randomly selected from our city, L'Hospitalet de Llobregat, Barcelona, an area free of iodine deficiency. In this euthyroid group, we determined basal TSH, thyroid autoantibodies, leptin concentrations, and thyroid volume by ultrasonography, body anthropometry, and body composition. RESULTS: All subjects were free of goitre and were negative for anti-thyroid antibodies. Basal TSH concentrations were 1.49 +/- 0.8 mU/l in males and 1.67 +/- 0.83 mU/l in females (p = 0.6). Anti-thyroid antibodies were negative in all cases; leptin concentrations were 6.1 +/- 4 ng/ml in males and 16.8 +/- 11.7 ng/ml in females (p = 0.0001). Thyroid volume was 9.8 +/- 4.6 ml in males and 6.5 +/- 2 ml in females (p = 0.001). There were significant correlations among leptin concentrations and anthropometric and body composition variables in both sexes, without correlation with TSH concentrations. There was no significant correlation between anthropometric and body composition variables and thyroid volume in males but there was a correlation in females. In females, there was a positive correlation between leptin and thyroid volume (r = 0.181, p = 0.038). In males, there was a negative correlation between TSH concentrations and thyroid volume (r = - 0.271, p = 0.002). CONCLUSIONS: We did not find any correlation between leptin levels and pituitary-thyroid axis in this control population. The correlation between leptin and thyroid volume in females is probably a consequence that leptin and thyroid volume are regulated in parallel by variables relating to anthropometry and body composition.     

Current approaches to estimating the sizes of the thyroid in neonates and infants from ultrasonographic data

The thyroid was ultrasonographically studied in 384 pre-term babies aged 4-8 days of life. The sizes of thyroid lobes were determined; the echogenicity of the thyroid was compared with that of the parotid salivary gland. The infants were born by apparently healthy mothers and females with iodine deficiency. An original procedure for neonatal ultrasound study was developed. Data statistical processing yielded a formula of the individual standard of a thyroid volume, which allows neonatal goiter and thyroid hypoplasia to be established at early stages of life.     

Congenital goiter sustaining normal level of serum triiodothyronine

We attempted to elucidate the deficient site of thyroid hormone biosynthesis in the thyroid gland and the mechanism of sustaining normal T3 level in sera of a patient with congenital goiter. TY, a 8-yr-old boy, first noted the onset of a diffuse goiter at the age of 2. There was no clinical evidence of hypothyroidism except for the slight impairment of intellectual development and the awkward physical activity. BMR, T3-RSU and T4 showed low values (-13%, 20.8% and 2.2 micrograms/dl), but serum T3 was normal (180 ng/dl). Serum TSH was 18 microU/ml. The intrathyroidal T3 and T4 were slightly low. Thyroidal 131I uptake was high, but KSCN discharge test was negative. Percent distribution of 131I labelled amino acids in the pancreatin digested thyroid homogenate was 17.4% in MIT, 33.4% in DIT and 11.3% in T3 and T4. Thyroid iodide peroxidase activities in mitochondrial and microsomal fractions were slightly low (19.6 and 26.8 (normal: 32 +/- 3.0 and 37.4 +/- 9.5) mumoles/mg protein). The activity was not increased by the addition of hematin. Thyroglobulin was found to be normal. A biological half life of 131I labelled T4 was shorter (3.5 days) than that of the normal. Electron microscopic examination exhibited the increment and expansion of endoplasmic reticulum in the follicular cell. Low iodide peroxidase activity of this patient may correlate to low T3 and T4 level in the thyroid cell. Moreover, shortened biological half life of T4 implies that normal T3 level in serum is sustained by the accelerated conversion of T4 to T3 in peripheral tissues.(ABSTRACT TRUNCATED AT 250 WORDS)     

Characteristics of fresh semen of captive-bred capercaillie Tetrao urogallus L

In Poland Capercaillie (Tetrao urogallus L.) is one of the most seriously endangered grouse species. The ability of semen collection and its utilization for Capercaillie female insemination would allow overcoming some fertility problems observed in captive-bred populations and thus reduce the rate of loss of genetic diversity. The present experiment was carried out on 13 individuals: eight males were kept with females and five alone. From each male, semen was collected four times, every second day, and overall semen appearance (color, viscosity), ejaculate volume, spermatozoa concentration, motility and morphology were examined. Ejaculates suitable for artificial insemination (AI) were obtained from 11 individuals. The volume of ejaculates varied from one drop (noted as 0.010 ml) to 0.180 ml, whereas spermatozoa concentration varied from 100 × 10(6) ml(-1) to 1950 × 10(6) ml(-1). The total amount of live spermatozoa for males kept with females varied from 82.0 to 98.3% (92.9% on average) and among them, from 38.7 to 82.0% were morphologically normal (67.6% on average), whereas for solitary males these values were the following: from 93.7 to 98.7 of total live (96.3% on average) and from 45.0 to 85.3% live normal cells (65.7% on average). No significant group effect was observed for above traits. Semen from males kept with females contained significantly (P<0.01) fewer cells with bulb head (12.2% vs. 21.6%), but higher numbers of bent neck spermatozoa (3.0 vs. 2.1%) and with other deformities (10.0 vs. 6.8%); however, for last two forms existing differences were not significant. Results obtained indicate the possibility of collecting valuable ejaculates from captive-bred Capercaillie, both kept with or without females, which makes possible the application of AI in order to increase the progeny number and gene exchange of this species across time and geographical distance.     

Thyroid dysfunction in adult long-term survivors after hemapoeitic stem-cell transplantation (HSCT).

Thyroid function was evaluated in 72 adult survivors (41 females and 31 males) at 16 to 56 years of age, 1.5 years mean time (range 0.2 - 9.8) after hemapoeitic stem cell transplantation (HSCT) with no known prior history of thyroid dysfunction. Thyroid stimulating hormone (TSH) and free thyroxin levels (FT4) were determined before and after stimulation with thyrotropin releasing hormone (TRH). Conditioning regimens for HSCT did not include TBI. Overt hypothyroidism (basal TSH > 8 microIU/ml, FT4 < 0.8 ng/dl) was observed in 6% of male patients and 5% of female patients; subclinical hypothyroidism (basal TSH 4 - 8 microIU/ml, low normal FT4 0.8 - 1.9 ng/dl) was observed in 13% of males and 5% of females. A significant number of euthyroid patients (40% males and 54% females) with normal basal TSH and FT4 levels overresponded to TRH stimulation; the finding being statistically significant (p < 0.005). A heavy TSH response after TRH stimulation indicates compensated subclinical dysfunction of the thyroid gland. Chemotherapy-only conditioning regimens may have an adverse effect on thyroid gland function not always detected by determination of basal TSH and FT4 levels. This finding warrants long-term evaluation of thyroid function in HSCT patients.     

Results of epidemiologic studies performed after the disaster in Czernobyl among the adult part of the population in the region of Krakow]

Epidemiologic studies following the Czernobyl accident were performed in region Kraków, including Kraków, Nowy Sacz and Kielce district. 1426 males and 2495 females were selected according to the random sample on the whole population of Kraków and Nowy Sacz, as well as in some selected areas in Swietokrzyski Mountains, and in Kielcecity. The aim of the study was to assess the results of the prophylaxis with Kalium iodine after the radiation and the incidence of the goiter in the population. It was stated, that 19.2% of the population in Kraków district, 16.9% in Nowy Sacz and 20% in Kielce received the prophylactic dosis of K.J. 80% took mainly the Lugol solution, between May, the 1st and 5th, 1986. Among 18 of person showing side effects like gastrointestinal disturbances, 16 were of female sex. Goiter incidence according to WHO classification was 50.7%, 67.3% and 49.9% in Kraków, Nowy Sacz and Kielce respectively. The difference between the incidence of goiter in males and females was 1:3. In women it was rather Ist and IInd degree of goiter, in men OB and Ist. Nodules of thyroid gland in the rural region of Kraków, Nowy Sacz and Kielce were seen in women in 10.8%, 1.7%, add 12.3% consecutively. Hormonal studies i.e T3, T4, TSH serum concentration showed normal results in all groups studied. TSH concentration was the highest in the group OB. The microsomal and antithyroglobulin antibodies level was the same independently on the prophylactic dosis of Lugol solution. The high incidence of thyroid diseases not related to the accident was observed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Reference values of thyroid volume in a healthy, non-iodine-deficient Spanish population.

Our aim was to assess reference values of thyroid volume by ultrasonography in healthy adult subjects. We conducted an epidemiological cross-sectional study where 880 subjects were randomly selected from the town census of L'Hospitalet de Llobregat after being invited to participate in our study directly by mail and phone call. We made a clinical history of each subject and determined serum thyrotropin, antiperoxidase antibodies, urinary iodine excretion and thyroid volume by ultrasonography. Subjects with thyroid disease were excluded. We finally studied 268 representative subjects. The reference thyroid volume was median 7.31 ml, mean 8.22 ml (Confidence Interval: 7.75 - 8.69 ml). In men: median 9.19 ml, mean 9.87 ml (CI: 9.09 - 10.65 ml); in women: median 6.19 ml, mean 6.57 ml (CI: 6.22 - 9.92 ml) (p < 0.0001). We grouped the subjects into decades, and found that thyroid volume was different (p = 0.0034) in males because the younger group had lower volume. We did not find any differences among age groups in women. The mean of the urinary iodine excretion was 154.23 microg/l. We have determined reference values of thyroid volume measured by ultrasonography in our iodine non-deficient population and prepared tables that distribute thyroid volume by sex and age.     

Association of different pathologic processes of the thyroid gland in fine needle aspiration samples

OBJECTIVE: To evaluate the possible significant association between different pathologic processes of the thyroid gland. STUDY DESIGN: From a series of 10,039 fine needle aspiration biopsies of the thyroid gland, a total of 1,330 cases were aspirated involving two or more palpable nodules. In 103 (1%) cases, two different pathologic processes were cytologically diagnosed. Statistical analysis was performed through four two-tailed chi 2 tests to evaluate the following events: (1) mononodularity and multinodularity vs. neoplasms, (2) colloid goiter and neoplasms, and (3) all neoplasms vs. colloid goiter and lymphocytic thyroiditis. All tests were performed using < .05 as the probability level. RESULTS: Simultaneous pathologic processes observed were: goiter and chronic lymphocytic thyroiditis (32), goiter and Hashimoto's thyroiditis (21), goiter and subacute granulomatous thyroiditis (8), goiter and follicular neoplasm (9), and goiter and papillary carcinoma (14). In 12 cases we found goiter and Hürthle cell tumor, goiter and medullary thyroid carcinoma (2), papillary thyroid carcinoma and Hashimoto's thyroiditis (2), Graves' disease and lymphocytic thyroiditis (2), and follicular neoplasm and lymphocytic thyroiditis (1). Statistical analysis showed significant association between multinodularity and neoplasms (P < .001), while the association between goiter and any type of neoplasia was not statistically significant. All the neoplasms taken together were associated with lymphocytic thyroiditis and goiter (P < .005). CONCLUSION: While there may be no statistically significant associations between the individual pathologies, it seems that having one pathology increases the risk of developing another. All the palpable nodules in the same gland should be investigated by fine needle aspiration in order to improve diagnostic sensitivity and to identify occult neoplasms.     

Amiodarone: a common source of iodine-induced thyrotoxicosis

Amiodarone, a iodine-rich drug widely used in the treatment of tachyarrhythmias, represents one of the most common sources of iodine-induced thyrotoxicosis. The data concerning 58 patients with amiodarone-iodine-induced thyrotoxicosis (AIIT) were analyzed in the present study. Prevalence of AIIT was higher in males than in females (M/F = 1.23/l). Thyrotoxicosis occurred either during treatment with or at various intervals after withdrawal of amiodarone. AIIT developed not only in patients with underlying thyroid disorders, but also in subjects with apparently normal thyroid gland. Classical symptoms of thyrotoxicosis were often lacking, the main clinical feature being a worsening of cardiac disorders. Biochemical diagnosis of AIIT was established by the finding of elevated serum total and free triiodothyronine levels, since elevated serum total and free thyroxine could be found also in euthyroid amiodarone-treated subjects. Twenty-four-hour thyroid radioiodine uptake was very low or undetectable in AIIT patients with apparently normal thyroid glands, while it was inappropriately elevated in patients with underlying thyroid disorders, despite iodine contamination. The role of autoimmune phenomena in the pathogenesis of AIIT appeared to be limited, because circulating thyroid autoantibodies were undetectable in AIIT patients without underlying thyroid disorders or with nodular goiter. Conversely, humoral features of thyroid autoimmunity were mostly found in AIIT patients with diffuse goiter. Treatment of AIIT appeared to be a difficult challenge. Among the 11 patients given no treatment, thyrotoxicosis spontaneously subsided in the 5 patients with apparently normal thyroid gland, whereas the 6 patients with nodular or diffuse goiter were still hyperthyroid 6-9 months after discontinuation of the drug. The administration of high doses (40 mg/day) of methimazole alone proved to be ineffective in most (14/16) patients given this treatment. Twenty-seven patients were treated by methimazole combined with potassium perchlorate (1 g/day). With one exception, euthyroidism was restored within 15-90 days in all cases with underlying thyroid abnormalities, and within 6-55 days in subjects with apparently normal thyroid gland. Thus, the combined treatment appears to be the most effective one, but, due to the potential toxicity of potassium perchlorate, it should be reserved to patients with severe thyrotoxicosis and should be carefully monitored.     

Structure of the thyroid gland, serum thyroid hormones, and the reproductive cycle of the Atlantic stingray, Dasyatis sabina.

This study examines the role of the thyroid gland in the control of reproduction in the viviparous Atlantic stingray, Dasyatis sabina. Thyroid activity in individuals in different reproductive stages was assessed both by microscopic examination of the gland, and by analysis of circulating levels of thyroid hormones from the same individuals. The thyroid gland is a cylindric organ, embedded in a connective tissue capsule, and composed of follicles, i.e., monolayer spheres of thyroid epithelial cells. Stingray follicular cells possess several characteristic features, namely apical cilia and a well-developed endoplasmic reticulum. Cells vary in size and shape, according to the activity of the gland. No structural differences were observed between the thyroid glands of the two sexes. Both thyroid hormones, triiodothyronine, [T(3)], and thyroxine, [T(4)], were detected in the serum of all animals examined. Levels ranged from 1.3-2.6 microg/100 ml for total T(4), and from 1.2-2.6 ng/ml for total T(3). The T(4) levels did not vary significantly in any group. Immature individuals and females undergoing oogenesis had the lowest levels of circulating T(3) and mature females from ovulation throughout gestation had high thyroid gland activity and high levels of circulating T(3). J. Exp. Zool. 284:505-516, 1999.     

Physiological and Morphological Specific Features of the Formation of the Thyroid Status in the Aboriginal and Migrant Populations of Magadan Oblast

Ultrasonographic determinations of the thyroid gland volumes and measurement of the blood plasma content of thyroxin and triiodothyronine were carried out in 1176 apparently healthy residents of the Magadan oblast, all those examined being divided by sex, age, and the adaptation time in the North. Special attention was given to the thyroid system parameters of the aborigines 17 to 40 years old living in the urban area and not involved in the traditional life style. The indigenous population of the Extreme North and migrants were shown to have marked functional adaptive hyperplasia of the thyroid gland and diffuse goiter in 15% of cases. The size of the thyroid gland and the level of the thyroid hormones in the aboriginal population are within the average European range. Diffuse goiter manifestations in males virtually do not occur; in women, the incidence does not exceed 5%. The assumption is advanced as to the formation in aborigines of the northern hypothyroid phenotype providing for the sustained optimal level of the thyroid system functioning without an increase in the thyroid volume.     

Irradiation and second cancers. The thyroid as a case in point

The thyroid gland is highly sensitive to radiation during childhood: the risk of thyroid tumours is increased for mean doses as low as 100 mGy and for higher doses, the risk increases linearly with the dose. Excess relative risk is important, being 7.7 for 1 Gy delivered to the thyroid gland during childhood. The risk of thyroid tumours is modified by several factors: a) age at exposure: in childhood, the risk decreases with increasing age at exposure and is not significant after 20 years; b) gender: females are two times more likely than males to develop thyroid tumours; c) genetic predisposition due to a defect in DNA repair mechanisms, and dietary and hormonal factors may modify the risk; d) the influence of fractionation and dose rate is not well established. Radioiodine 131 (1311) used for medical purposes has almost no tumourigenic effect on the adult thyroid gland. The consequences of the Chernobyl accident have clearly shown that the risk of thyroid cancer after exposure to 1311 in childhood is important, and that such exposure should be prevented by potassium iodine prophylaxis. RET/PTC rearrangements are found in 60-80% of papillary carcinomas and in 45% of adenomas occurring after radiation exposure. They are found in 5-15% of papillary carcinoma and in no follicular adenomas that occurred in the absence of radiation exposure.     

Prevalence of hyperthyroidism after exposure during childhood or adolescence to radioiodines from the chornobyl nuclear accident: dose-response results from the Ukrainian-American Cohort Study

Relatively few data are available on the prevalence of hyperthyroidism (TSH concentrations of <0.3 mIU/liter, with normal or elevated concentrations of free T4) in individuals exposed to radioiodines at low levels. The accident at the Chornobyl (Chernobyl) nuclear plant in Ukraine on April 26, 1986 exposed large numbers of residents to radioactive fallout, principally to iodine-131 ((131)I) (mean and median doses = 0.6 Gy and 0.2 Gy). We investigated the relationship between (131)I and prevalent hyperthyroidism among 11,853 individuals exposed as children or adolescents in Ukraine who underwent an in-depth, standardized thyroid gland screening examination 12-14 years later. Radioactivity measurements taken shortly after the accident were available for all subjects and were used to estimate individual thyroid doses. We identified 76 cases of hyperthyroidism (11 overt, 65 subclinical). Using logistic regression, we tested a variety of continuous risk models and conducted categorical analyses for all subjects combined and for females (53 cases, n = 5,767) and males (23 cases, n = 6,086) separately but found no convincing evidence of a dose-response relationship between (131)I and hyperthyroidism. There was some suggestion of elevated risk among females in an analysis based on a dichotomous dose model with a threshold of 0.5 Gy chosen empirically (OR = 1.86, P = 0.06), but the statistical significance level was reduced (P = 0.13) in a formal analysis with an estimated threshold. In summary, after a thorough exploration of the data, we found no statistically significant dose-response relationship between individual (131)I thyroid doses and prevalent hyperthyroidism.     

Les métastases pulmonaires micronodulaires de type miliaire dans le cancer thyroïdien bien différencié (médullaires exclus) à propos de dix cas

Thyroid cancer is relatively a rare cancer; about 1% from all cancers; between 10 and 15% of patients with differentiated thyroid cancer develop micro or macronodular pulmonary metastases. In this study we examined the characteristics and evolution after treatment of 10 patients with micronodular or miliary metastases of well-differentiated thyroid carcinoma. Total body scintigraphy with 131 iodine, chest X-ray or CT scan, and thyroglobulin assay were performed for all patients. The treatment was iodine 131 (3, 7 GBq), therapeutic 131 iodine scan was done for all patients seven days after the 131 administration. The effect of 131 iodine treatment was evaluated by means of changes in the number and size of lung metastases on the total body scintigraphy with 131 iodine and by serum thyroglobulin levels six months after 131 iodine ablation, they all received L-thyroxin (2,4 μg/kg/j). The minimum duration of follow-up was 12 months. There were six females and four males within a range of 13–70 years old. Eight had papillary and two follicular thyroid cancer. These 10 patients benefited 131 iodine therapy. The effect of 131 iodine treatment and the prognostic values of the following variables were examined: age at the time of 131 iodine, treatment and histological findings. The miliary was rarely diagnosed on the initial investigation, only in two cases by 131 iodine scan after surgery, two cases by chest X-ray, and two cases by CT scan, the initial thyroglobulin levels was very high in seven cases, between 10 and 40 ng/ml in one case and less than 10 ng/ml in two cases. These results indicate that age, 131 iodine uptake, histological findings and the presence of other metastases are important factors in predicting the effects of 131 treatment for pulmonary metastases of well-differentiated thyroid carcinoma. Among all the variables studied, the best prognosis for survival was demonstrated by increased 131 uptake in pulmonary metastases and by early diagnosis during post surgery 131 iodine scanning of radiologicaly inapparent metastases.     

Low Iodine in the Follicular Lumen Caused by Cytoplasm Mis-localization of Sodium Iodide Symporter may Induce Nodular Goiter

Iodine is a key ingredient in the synthesis of thyroid hormones and also a major factor in the regulation of thyroid function. A local reduction of iodine content in follicular lumen leads to overexpression of local thyroid-stimulating hormone receptor (TSHr), which in turn excessively stimulates the regional thyroid tissue, and result in the formation of nodular goiter. In this study, we investigated the relationship between iodine content and sodium iodide symporter (NIS) expression by using the clinical specimens from patients with nodular goiter and explored the pathogenesis triggered by iodine deficiency in nodular goiter. In total, 28 patients were clinically histopathologically confirmed to have nodular goiter and the corresponding adjacent normal thyroid specimens were harvested simultaneously. Western blot and immunohistochemistry were performed to assay NIS expression and localization in thyrocytes of both nodular goiter and adjacent normal thyroid tissues. NIS expression mediated by iodine in follicular lumen was confirmed by follicular model in vitro. Meanwhile, radioscan with iodine-131were conducted on both nodular goiter and adjacent normal thyroid. Our data showed that NIS expression in nodular goiter was significantly higher than that in adjacent normal tissues, which was associated with low iodine in the follicular lumen. Abnormal localization of NIS and lower amount of radioactive iodine-131 were also found in nodular goiter. Our data implied that low iodine in the follicular lumen caused by cytoplasm mis-localization of NIS may induce nodular goiter.