Thyroid function in Japanese adults as assessed by a general health checkup system in relation with thyroid-related antibodies and other clinical parameters.

BACKGROUND: A limited number of epidemiological studies have attempted to assess thyroid function in the general population of iodine-sufficient countries. The aim of the present study was to determine the underlying thyroid diseases responsible for abnormal thyroid function detected by a general health checkup system in Japan, and to characterize the lipid metabolism in subjects found to have thyroid dysfunction. METHODS: Serum thyrotropin (TSH), free thyroxine, anti-thyroglobulin antibodies (TgAb), anti-thyroid peroxidase antibodies (TPOAb), and TSH-binding inhibitor immunoglobulins (TBII) were determined in 1818 Japanese adults (804 men and 1014 women; mean age 51.3 +/- 9.0 years) who undertook a general health checkup. RESULTS: Of the 1818 examinees, 12 (0.7%) had overt hypothyroidism (OH), 105 (5.8%) subclinical hypothyroidism, 13 (0.7%) overt thyrotoxicosis, and 39 (2.1%) subclinical thyrotoxicosis. TgAb or TPOAb tests were positive in 17.7% of men and 31.4% of women. The prevalence of positive tests for TgAb or TPOAb was 14.8% for men and 23.4% for women without palpable goiter. Positive tests for TgAb, TPOAb, TBII, and a palpable goiter were more common in subjects with abnormal thyroid function tests than in subjects with normal thyroid function. At the time that abnormal thyroid function test results were first obtained, the signs of thyrotoxicosis were mild or even absent in all 13 subjects with overt thyrotoxicosis, 8 of whom had Graves' disease and 5 of whom had painless thyroiditis. Of the 12 patients with OH, only 2 patients had a palpable goiter. In the OH group, TgAb tests were positive in eight, TPOAb tests were positive in eight, and TBII tests were positive in two. The prevalence of disturbed lipid metabolism, when adjusted for age, was significantly higher in the subclinical hypothyroidism group than in normal controls (p < 0.001; odds ratio, 1.67; 95% confidence interval, 1.10-2.51). CONCLUSIONS: In Japanese adults who chose to be screened by a general health checkup system, the prevalence of abnormal thyroid function was nearly 10%. In a high percentage of these patients, abnormal thyroid function could not be detected by their history or physical examination. Just a physical examination without thyroid function tests, particularly serum TSH levels, was not adequate even when performed by a thyroid specialist.

[The 29th report on survey of the adverse reaction to radiopharmaceuticals (the 32nd survey in 2006)].

This survey was performed in order to investigate the incidence of adverse reactions to radiopharmaceuticals in FY2006 in Japan. It was based on responses to questionnaires sent to nuclear medicine institutions. The reply was obtained from 975 institutions among 1263 to which the questionnaire had been sent. Thirty-two cases of adverse reactions were reported. A total of 1,189,127 radiopharmaceutical administrations was reported. The incidence of adverse reactions per 100,000 cases was 2.7. Three cases of defect products were reported, and the incidence of defect products per 100,000 cases was 0.3.

[Epidemiology of thyroid tumors: effect of environmental iodine intake].

The incidence of thyroid cancer has been reported to be 0.5-1.3%, when assessed by sonographic examination and 3.7-28.4% by histologic examination at autopsies. These incidences are much higher than those of clinically evident thyroid cancer, which are 2.0/100,000 for males and 7.2/100,000 for females, reported in Japan. In iodine deficient areas, chronic stimulation by TSH causes multinodular autonomous growth and function, leading to hyperthyroidism in middle-aged and elderly subjects. Incidence of Plummer's disease among Japanese with sufficient iodine intake is very low, accounting for 0.5-0.8% of all thyroid nodules and 0.3% of all thyrotoxic patients. The Plummer/Graves ratio was higher than 1 in endemic goiter area before iodine supplementation. Iodine intake affects the type of thyroid carcinoma. Decreased intake of iodine is associated with higher frequency of follicular and anaplastic cancers and lower frequency of papillary cancer. The high prevalence of papillary cancer(>85%) with good prognosis may explain the preferred selection of partial rather than total thyroidectomy in Japan.

[The 28th report on survey of the adverse reaction to radiopharmaceuticals (the 31st survey in 2005)].

This survey was performed in order to investigate the incidence of adverse reactions to radiopharmaceuticals in FY2005 in Japan. It was based on responses to questionnaires sent to nuclear medicine institutions. The reply was obtained from 1,007 institutions among 1,243 to which the questionnaire had been sent. Nineteen cases of adverse reactions were reported. A total of 1,264,098 radiopharmaceutical administrations was reported. The incidence of adverse reactions per 100,000 cases was 1.5. Three cases of defect products were reported, and the incidence of defect products per 100,000 cases was 0.2.

[The 27th Report on Survey of the Adverse Reaction to Radiopharmaceuticals (the 30th survey in 2004)].

This survey was performed in order to investigate the incidence of adverse reactions to radiopharmaceuticals and defect products in FY2004 in Japan. It was based on responses to questionnaires sent to nuclear medicine institutions. The reply was obtained from 968 institutions among 1,220 to which the questionnaire had been sent. Sixteen cases of adverse reactions were reported. A total of 1,277,906 radiopharmaceutical administrations was reported. The incidence of adverse reactions per 100,000 cases was 1.3. Eight cases of defect products were reported, and the incidence of defect products per 100,000 cases was 0.6.

Long-term remission in HIV-negative patients with multicentric Castleman's disease using rituximab.

Multicentric Castleman's disease (MCD) is an indolent lymphoproliferative disorder. The pathogenesis of MCD has not been established, and its treatment remains uncertain. Several authors have described the relationship of human herpes virus type 8 (HHV-8) to MCD in human immunodeficiency virus (HIV)-positive patients. Recently, anti-CD20 monoclonal antibody (rituximab) is increasingly being used to treat HIV-positive MCD; although it is uncertain whether rituximab is effective for HIV-negative patients with MCD. To explore the benefit of rituximab for HIV-negative patients with MCD, we describe the clinical and biologic course in three HIV-negative patients with MCD, and examined the relationship of HHV-8 infection to HIV-negative MCD. Their polymerase chain reaction analyses for the HHV-8 sequence in peripheral blood were negative, and there was no relationship between HHV-8 infection and symptoms of HIV-negative MCD. Two of three patients (66%) achieved a near complete remission with no clinical symptoms due to MCD with a follow-up of 16-40 months after rituximab administration. One of the three patients presented no clinical remission of MCD after rituximab administration, although a significant decrease of inflammatory parameters was observed. These findings suggest that rituximab treatment may be an appropriate first-line therapy for HIV-negative MCD.

Comparison of whole-body 18F-FDG PET, 99mTc-MIBI SPET, and post-therapeutic 131I-Na scintigraphy in the detection of metastatic thyroid cancer.

UNLABELLED: The usefulness of fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) in differentiated thyroid cancer (DTC) has been demonstrated by many investigators, but in only a small number of studies have FDG-PET images been compared with those obtained using other non-iodine tumour-seeking radiopharmaceuticals. In most of the studies, planar imaging was performed for comparison using thallium-201 chloride or technetium-99m 2-methoxyisobutylisonitrile ((99m)Tc-MIBI). Furthermore, FDG-PET studies were not always performed in the hypothyroid state with increased levels of thyroid stimulating hormone (TSH), which are known to increase FDG uptake by DTC. The aim of this study was to compare the ability of FDG-PET to detect metastatic DTC with that of (99m)Tc-MIBI whole-body single-photon emission tomography (SPET) and post-therapeutic iodine-131 scintigraphy, evaluated under TSH stimulation. Nineteen patients (8 men, 11 women; age range, 38-72 years, mean 60 years; 17 thyroidectomised and 2 inoperable patients following (131)I ablation of the remaining thyroid tissue; 16 papillary and 3 follicular carcinomas) with metastatic DTC underwent FDG-PET whole-body scan (WBS) and (99m)Tc-MIBI SPET WBS at an interval of less than 1 week, followed by (131)I therapy. The SPET images were reconstructed using the maximum likelihood expectation maximisation (ML-EM) method. All patients were hypothyroid at the time of each scan. (131)I WBS was performed 3-5 days after oral administration of the therapeutic dose. A total of 32 lesions [10 lymph node (LN), 15 lung, 6 bone, 1 muscle] were diagnosed as metastases, as confirmed by histopathology and/or other imaging modalities (X-ray, US, CT, MRI, bone, (201)Tl and (131)I scans). FDG-PET, (99m)Tc-MIBI SPET and post-therapeutic (131)I scintigraphy respectively revealed a total of 26 (81.3%), 20 (62.5%) and 22 (68.8%) lesions. These techniques respectively demonstrated nine (90.0%), eight (80.0%) and six (60.0%) LN metastases, and eleven (73.3%), seven (46.7%) and ten (66.7%) lung metastases. They each demonstrated five of the six bone metastases (83.3%). FDG-PET and (99m)Tc-MIBI SPET were positive in 17 (78.3%) and 14 (63.6%) of the 22 (131)I-positive lesions, respectively, and also in nine (90.0%) and six (60.0%) of the ten (131)I-negative lesions, respectively. Three of the five (131)I-positive and FDG-PET-negative lesions were miliary type lung metastases with a maximal nodular diameter of less than 10 mm. Comparison of FDG-PET with (99m)Tc-MIBI SPET revealed concordant results in 24 lesions, and discordant results in eight lesions (seven with positive FDG-PET alone and one with positive (99m)Tc-MIBI SPET alone). IN CONCLUSION: (a) even using whole-body SPET, FDG PET is superior to (99m)Tc-MIBI in terms of ability to detect metastases of DTC; (b) the higher sensitivity of FDG-PET compared with the previous studies could partly be due to increased serum TSH.

Effect of iodine restriction on thyroid function in patients with primary hypothyroidism.

Dietary iodine intake in Japan varies from as little as 0.1 mg/day to as much as 20 mg/day. The present study was undertaken to assess the frequency of iodine-induced reversible hypothyroidism in patients diagnosed as having primary hypothyroidism, and to clarify the clinical backgrounds responsible for the spontaneous recovery of thyroid functions. Thirty-three consecutive hypothyroid patients (25 women and eight men) with a median age of 52 years (range, 21-77 years) without a history of destructive thyroiditis within 1 year were asked to refrain from taking any iodine-containing drugs and foods such as seaweed products for 1-2 months. The median serum thyrotropin (TSH) level, which was initially 21.9 mU/L (range, 5.4-285 mU/L), was reduced to 5.3 mU/L (range, 0.9-52.3 mU/L) after iodine restriction. Twenty-one patients (63.6%) showed a decrease in serum TSH by >50% and to <10 mU/L. Eleven patients (33.3%) became euthyroid with TSH levels within the normal range (0.3-3.9 mU/L). The ratios of TSH after iodine restriction to TSH before iodine restriction (aTSH/bTSH) did not correlate significantly with titers of anti-thyroid peroxidase antibody and anti-thyroglobulin antibody or echogenicity on ultrasonography, but correlated inversely with (99m)Tc uptake (r = 0.600, p < 0.001). Serum non-hormonal iodine levels, although not correlated significantly with aTSH/bTSH values, were significantly higher in the 21 patients with reversible hypothyroidism than in the remaining 12 patients. TSH binding inhibitor immunoglobulin was negative in all except one weakly positive case. In conclusion, (1) primary hypothyroidism was recovered following iodine restriction in more than half of the patients, and (2) the reversibility of hypothyroidism was not significantly associated with Hashimoto's thyroiditis but with increased (99m)Tc uptake and elevated non-hormonal iodine levels.

Seasonal variation in relapse rate of graves' disease after thionamide drug treatment.

OBJECTIVE: Controversy abounds on the issue of seasonal variation in new onset of Graves' disease, partly due to the difficulty of precisely dating the exact start of symptoms. To address the possible relationship between climatic changes and disease activity from a different perspective, we reviewed time of relapse during regular follow-up after successful drug treatment with thionamides. DESIGN: Retrospective analysis of a case series in a university clinic. PATIENTS AND MEASUREMENTS: We consecutively registered patients who experienced re-emergence of hyperthyroidism between 1992 and 2001 after successful antithyroid drug therapy. Excluded were subjects with superimposing painless thyroiditis, in postpartum, on immunomodulatory drugs, or off thionamides prematurely on their own volition. RESULTS: Fifty-two patients recurred 2 to 36 months after drug cessation. The frequency was higher in spring and summer (March to August) than in autumn and winter (September to February). With a new coated-tube radioreceptor assay, TSH binding inhibitor immunoglobulin activity was detected in sera from 87.5% of the reworsened patients. CONCLUSIONS: Graves' disease tends to relapse more frequently in spring and summer. Further clinical studies are warranted to clarify underlying mechanism (s) for this seasonal variation.

Chemo-radionuclide therapy for thyroid cancer: initial experimental study with cultured cells.

UNLABELLED: Radioiodine therapy has long been used for distant metastases of thyroid cancer. Although partially effective in most cases, it can render a complete cure only in a limited number of patients. One way to enhance its efficacy would be to combine it with antineoplastic agents. Here we describe an initial in vitro evaluation with 4 thyroid cancer cell lines. METHODS: Cells were sparsely seeded in microtiter plates and allowed to grow for 2 days; then they were exposed to sublethal concentrations of cisplatin (CDDP), doxorubicin (Dox), or 5-fluorouracil (5-FU), followed by treatment with I-131 for 48 hr. Cell survival was measured with a commercial kit based on the colorimetry of succinate dehydrogenase activity. RESULTS: Chemotherapeutic drugs exerted similar concentration-dependent cytotoxic effects in all 4 cell lines. The doses necessary to reduce the surviving fraction to half of the control were about 3 microg/ml for CDDP, 0.3 microg/ml for Dox, and 3 microg/ml for 5-FU (when used continuously for 48 hours). On the other hand, sensitivity to I-131 irradiation differed among the lines; same doses (7.4-14.8 MBq/ml) caused the greatest damage in FRO cells, a modest effect in NPA and WRO, and only minimal change in B-CPAP. The combined effect was most demonstrable in wells treated with Dox and radioiodine, whereas the addition of CDDP or 5-FU had marginal or insignificant merit, respectively. In FRO cells, half-lethal doses of the above mentioned CDDP, Dox, and 5-FU, when used together with 14.8 MBq/ml I-131, reduced cell survival to 54.5%, 29.4% and 33.4%, respectively, vs. 60.2% with radioiodine alone. CONCLUSION: In vitro, clinical concentrations of Dox can accelerate the killing of thyroid cancer cells by radioiodine. These favorable experimental results warrant future studies to evaluate whether this new bidisciplinary approach is clinically relevant and feasible.

A patient with two thyroid papillary carcinomas demonstrating hot and cold lesions on 113I thyroid scintigraphy.

A 44-year-old euthyroid woman had two palpable nodules in the thyroid gland. 123I thyroid scintigraphy showed a hot nodule in the right lobe and a cold one in the left lobe. Total thyroidectomy was performed, and histopathologic examination revealed that both tumors contained papillary carcinoma. Thus, hot nodules on a thyroid scintigram with 123I do not necessarily preclude malignancy.

Causes of appearance of scintigraphic hot areas on thyroid scintigraphy analyzed with clinical features and comparative ultrasonographic findings.

This study was done retrospectively to analyze the ultrasonographic (US) findings in thyroid scintigraphic hot areas (HA). Three-thousand, eight-hundred and thirty-nine consecutive patients who underwent 99mTc-pertechnetate (n = 3435) or 123I (n = 457) scintigraphy were analyzed. HA were regarded as present when the tracer concentration was greater than the remaining thyroid tissue, or when hemilobar uptake was observed. High-resolution US examinations were performed with a real-time electronic linear scanner with a 7.5 or 10 MHz transducer. One hundred and four (2.7%) were found to be scintigraphic HA (n = 120). US revealed a nodular lesion or well-demarcated thyroid tissue corresponding to the HA in 94 areas (78.4%, Category 1), an ill-defined region with different echogenicity in 13 areas (10.8%, Category 2), and no correlating lesion in 13 areas (10.8%, Category 3). These 104 patients included 43 with adenomatous goiter (59 areas), 33 with adenoma, 11 with Hashimoto's thyroiditis, 5 with primary thyroid cancer, 4 with euthyroid ophthalmic Graves' disease (EOG), 3 with hemilobar atrophy or hypogenesis, 2 with hemilobar agenesis, 2 with hypothyroidism with blocking-type TSH-receptor antibodies (TSHRAb), I with acute suppurative thyroiditis. Among the 59 adenomatous nodules and 33 adenomas, 51 (86.4%) and 32 (97.0%), respectively, belonged to Category 1. A solitary toxic nodule was significantly larger and occurs more often in older patients than in younger patients. On the other hand, all 17 patients with known autoimmune thyroid diseases including Hashimoto's thyroiditis, EOG and hypothyroidism with blocking TSHRAb belonged to Category 2 or 3. Possible underlying mechanisms are 1) hyperfunctioning tumors or nodules, 2) localized functioning thyroid tissue freed from autoimmune destruction, inflammation or tumor invasion, 3) congenital abnormality, 4) clusters of hyperactive follicular cells caused by long-term TSH and/or TSHRAb stimulation, 5) asymmetry, etc. Scintigraphic HA are observed in patients with various thyroid diseases and high-resolution US appears to be helpful clinically for the differential diagnosis of the above mentioned disorders.