Hyperthyroid Graves' disease after hemithyroidectomy for papillary carcinoma: report of three cases.

Here we report three cases of hyperthyroid Graves' disease that occurred after partial thyroidectomy for papillary carcinoma. In Case 1, the patient first developed hyperthyroidism 2 years after resection of left thyroid lobe, was treated for 2 years with antithyroid drug which was then discontinued, and relapsed with periodic paralysis after 8 years of remission. In Case 2, a hyperfunctioning remnant thyroid was noted 22 years after right hemithyroidectomy. In Case 3, where thyrotoxic symptoms became evident 7 weeks after right hemithyroidectomy, autoantibodies to thyroglobulin and thyroid microsome were positive in preoperative serum, in line with a report by others detecting these antibodies in 2 out of 3 such cases examined. Later bioassay revealed activity of thyroid stimulating antibodies in that serum, with further increase in titer in the sample taken at the clinical manifestation. Hence in Case 3, surgical stress may have altered immunological homeostasis, promoting a preclinical Graves' disease to full-blown hyperthyroidism.

Brain metastasis from differentiated thyroid cancer in patients treated with radioiodine for bone and lung lesions.

Brain metastasis of differentiated thyroid cancer (DTC) often is detected during treatment of other remote lesions. We examined the prevalence, risk factors and treatment outcome of this disease encountered during nuclear medicine practice. Of the 167 patients with metastasis to lung or bone treated 1-14 times with radioactive iodine (RAI), 9 (5.4%) also had lesions in the brain. Five were males and 4 females, aged 49-84, out of the original population of 49 males and 118 females aged 10-84 (mean 54.7) years. Three of them underwent removal of their brain tumors, 5 received conventional external beam irradiation, and 2 had stereotactic radiosurgery with supervoltage X-ray. None of the brain lesions showed significant uptake of RAI despite demonstrable accumulation in most extracerebral lesions. Seven patients died 4-23 (mean 9.4) months after the discovery of cerebral metastasis, brain damage being the primary or at least a contributing cause. The 8th and 9th patients remained relatively well for more than 42 and 3 months, respectively, without any evidence of intracranial recurrence. Our results confirmed that the brain is a major site of secondary metastasis from DTC. No statistically significant demographic risk factor was detected. Any suspicious neurological symptoms in the course of RAI treatment warrant cerebral computed tomography. As for therapy, from our initial experience, radiosurgery seemed promising as an effective and less invasive alternative to surgical removal.

Comparison of short inversion time inversion recovery (STIR) and fat-saturated (chemsat) techniques for background fat intensity suppression in cervical and thoracic MR imaging.

The purpose of this study was to compare short inversion time inversion recovery (STIR) fast spin-echo (FSE), and fat-saturated T2-weighted FSE sequences in terms of uniformity of fat suppression and lesion conspicuity for magnetic resonance (MR) imaging of the neck and thorax. STIR FSE and fat-saturated T2-weighted FSE images were scored for uniformity of fat suppression (n = 40) and lesion conspicuity (n = 35). Five-point rank score analyses were utilized by three experienced radiologists. The mean scores of STIR and fat-saturated FSE techniques for uniformity of fat suppression were 4.3 and 2.3, respectively (P < 0.0001). The mean scores of STIR and fat-saturated FSE techniques for lesion conspicuity were 4.2 and 3.5, respectively (P < 0.0001). Insufficient fat suppression was prominent in the mandible, supraclavicular region, anterior mediastinum, epipericardial fat, and subdiaphragmatic fat. In addition, fat-saturated T2-weighted FSE showed inadvertent water suppression in 25%. The STIR FSE technique was superior to the fat-saturated FSE technique for cervical and thoracic MR imaging.

[Recent progress in radionuclide therapy].

Therapeutic use of radionuclides includes 131I for thyroid cancer and hyperthyroid Graves' disease, 89SrCl3 for metastatic bone tumors, 131I-MIBG for malignant pheochromocytoma and neuroblastoma, and radioimmunotherapies. 131I is concentrated in 60-70% of metastases from differentiated thyroid cancer following total thyroidectomy. Radioiodine uptake in metastatic lesions is greater in younger patients than in older ones. Hypothyroidism is often mild or even absent in patients with a large amount of tumor tissue, indicating that thyroid hormones produced by highly differentiated tumors compensate partially or even completely for hypothyroidism following total thyroidectomy. Adequate uptake of 131I has been reported to be associated with significant reduction in the size and number of metastases, and with lower recurrence and higher survival rates. Other favorable factors for longer survival are younger age, well-differentiated histological type, small disease extent, and early discovery of metastases. Older patients with extensive metastases and/or bulky tumor masses in the bone have a poor prognosis. Therefore, it is important to discover metastases as early as possible, when patients are still young. Long-term follow-up with periodic thyroglobulin measurements and imaging studies is strongly recommended. In Japan, 131I treatment for Graves' disease is performed only in selected patients in whom antithyroid drugs cannot be used because of side effects or not effective, considering the high prevalence of permanent hypothyroidism. 89SrCl3 is useful for reducing pain due to bone metastases of malignant tumors. 131I-MIBG therapy is effective for improvement of QOL in some patients with metastatic malignant pheochromocytoma. Radioimmuno-therapy using anti-CD20 has been used successfully in clinical application in patients with malignant B cell lymphoma.

Rapid progression of pituitary hyperplasia in humans with primary hypothyroidism: demonstration with MR imaging.

PURPOSE: To use magnetic resonance (MR) imaging to evaluate the morphologic changes of the pituitary gland during the development of hypothyroidism. MATERIALS AND METHODS: Fourteen patients who had undergone thyroidectomy were evaluated before radioactive iodine 131 therapy. In each patient, MR imaging and measurement of serum hormone levels were performed twice: 5 weeks before 131I treatment as the "euthyroid state" with thyroid hormone supplementation and on the day of 131I treatment as the "hypothyroid state" after a 3-week depletion of thyroid hormone supplements. Nine healthy volunteers also underwent MR imaging twice at an interval of 5 weeks. Pituitary volume and the relative signal intensity ratio of the anterior pituitary to the pons were measured. The shape and signal intensity of the pituitary gland were also visually assessed. The paired Student t test was used to evaluate the significance of the data. A P value less than .05 indicated a statistically significant difference. RESULTS: The patients had significantly larger pituitary volume in the hypothyroid state than in the euthyroid state both quantitatively (P < .001) and visually. No significant differences were found in the relative signal intensity ratios of the anterior pituitary to the pons. In healthy volunteers, no significant differences in pituitary volumes or signal intensity were found between the two MR images. CONCLUSION: Rapid progression of hyperplasia of the anterior pituitary may occur with acute development of hypothyroidism.

Goiter associated with acromegaly: sonographic and scintigraphic findings of the thyroid gland.

Elevation in serum human growth hormone (GH) level is known to be a factor that causes goiter development. The present study was designed to analyze sonographic and scintigraphic appearances of the thyroid in patients with acromegaly. The records of 48 consecutive patients with acromegaly were examined. Two patients had a history of operation for thyroid cancer. One had an atrophic thyroid gland after 131I treatment for Graves' disease. Goiter was palpable in 39 of the remaining 45 patients. Neither ultrasonography (US) nor scintigraphy was performed in 17 patients, including 6 with no palpable goiter and 11 with small diffuse goiter (group 1). Of the remaining 28 patients who underwent US, 14 had a moderately or markedly enlarged diffuse goiter (group 2), 13 were diagnosed as having adenomatous goiter (group 3), and 1 had a solitary cystic nodule. Among 11 patients in group 3 who underwent 123I or 99mTc thyroid scintigraphy, 6 showed uneven uptake, and 2 with undetectably reduced levels of thyrotropin (TSH) showed localized functioning areas. The mean serum TSH concentration in group 3 was significantly lower than that in group 1 or 2 (p<0.01). The duration of illness as acromegaly was significantly longer in group 2 and 3 as compared with group 1 (p<0.05). These results suggest that long-term stimulation by GH and insulin-like growth factor-I of thyroid follicular cells might be responsible for thyroid enlargement, presence of functioning lesions, slight overactivity of the thyroid, and the subsequent formation of multiple nodules in acromegalic patients. In conclusion, excluding two patients with thyroid cancer and one with Graves' disease, goiter was palpable in 39 of the 45 patients with acromegaly, among whom 14 (13 adenomatous goiters and 1 solitary cystic nodule) showed nodular enlargement.

Comparison of serum thyrotrophin concentrations determined by a third generation assay in patients with various types of overt and subclinical thyrotoxicosis.

OBJECTIVE: Recent increases in the sensitivity of methods used to measure TSH, especially third generation assays, have enabled separation of partial from complete pituitary suppression in patients with thyrotoxicosis. We have investigated the use of a sensitive chemiluminescent enzymeimmunoassay in the differential diagnosis of thyrotoxicosis. DESIGN AND PATIENTS: Serum TSH concentrations were determined by chemiluminescent enzymeimmunoassay in patients with various types of overt and subclinical thyrotoxicosis. RESULTS: The assay was highly sensitive with an analytical sensitivity of 0.0016 mU/l. Among 45 hyperthyroid patients with untreated Graves' disease, 37 (82.2%) showed undetectably low levels (< 0.002 mU/l). Serum TSH in the remaining 8 patients (17.8%) was 0.003-0.005 mU/l. In contrast, TSH was undetectably low in only 5 (20.0%) of 20 patients with painless thyroiditis and in 2 (12.5%) of 16 patients with subacute thyroiditis. Eleven (55.0%) with painless thyroiditis and 12 (75.0%) with subacute thyroiditis had TSH values greater than 0.005 mU/l (0.006-0.032 and 0.006-0.228 mU/l, respectively; normal range 0.5-5.0 mU/l). Serum TSH levels were subnormal in 10 of 12 patients with euthyroid ophthalmic Graves' disease, including 4 with undetectably low levels. Among 11 patients with an autonomously functioning thyroid nodule 6, including 1 with normal free T4 and free T3 and 2 with normal free T3, showed TSH values less than 0.002 mU/l. No significant correlation was observed between serum free T4 or free T3 and TSH concentrations in thyrotoxic patients. Together with the incomplete suppression of TSH observed in those with destructive thyroiditis, this suggests that the grade of TSH suppression was influenced by the duration of illness at the time of blood sampling. CONCLUSION: The third-generation TSH assay is useful for the differential diagnosis of various types of thyrotoxicosis, especially between Graves' disease and destructive thyroiditis.

Thyroxine (T4) metabolism in an athyreotic patient who had taken a large amount of T4 at one time.

As we had an opportunity to take blood samples from a totally thyroidectomized patient who had attempted suicide by taking 2,000 microg of Levothyroxine (L-T4), the serum levels of thyroid hormones were sequentially measured to investigate the metabolism of circulating thyroid hormones in an athyreotic human. The serum concentrations of most thyroid hormones reached a peak on the second day, but the serum T3 level showed a peak one day later. The maximum concentrations of T4 (315 microg/l), FT4 (48.8 ng/l) and rT3 (0.80 microg/l) were very high, while the peak T3 level (1.92 microg/l) did not exceed the upper limit of the normal range. The serum T4 and rT3 levels returned to their normal range 13-17 days after the suicide attempt. The TSH level was suppressed rapidly and reached its nadir (0.044 mU/l) on the 6th day. During this period, the T1/2 and MCR of serum T4 were 10.4 days and 0.64 l/day, respectively, which values were almost equivalent to those observed during 15 days after discontinuation of the maintenance L-T4 therapy. In summary, the oral intake of a large amount of L-T4 at one time does not induce a proportional increase in the T3 level in an athyreotic person. The MCR of serum T4 is decreased and the T1/2 of serum T4 is prolonged, probably due to the lack of intrathyroidal deiodination. These findings support the conclusion that the D1 activity in the thyroid is one of the major determinants in the metabolic clearance of serum T4.

Occult papillary thyroid carcinoma in Hashimoto's thyroiditis presenting as a metastatic bone tumor.

Some occult thyroid carcinomas are hypothesized to regress and be eventually obliterated. We report here a patient whose condition supports this hypothesis. A 51-year-old male with primary hypothyroidism due to Hashimoto's thyroiditis suffered from a rib bone tumor. He had a diffuse goiter with no nodular lesion. Serum FT4 and TSH concentrations were 0.8 ng/dl and 36.4 microU/ml on taking 100 microg/day of T4. Anti-Tg- and -TPO-Ab were strongly positive (99 and 1380 U/ml). The iodine 123 scintigraphy demonstrated clear accumulation in the rib tumor, whereas the thyroid was scarcely visible. Biopsy of the rib tumor showed papillary proliferation of large atypical cells, which were immunohistochemically positive for thyroglobulin. Metastatic bone tumor of papillary thyroid carcinoma was therefore strongly suspected. He underwent a total thyroidectomy and the thyroid was stepwise sectioned completely at 3 mm intervals. The thyroid condition was diagnosed as Hashimoto's thyroiditis demonstrating diffuse and dense fibrosis, lymphocyte infiltration with lymphoid follicles and flattened atrophied follicles, but no carcinomatous foci were found. He was treated with I-131 and scintigraphy after the ingestion showed distinct accumulation in the rib tumors similar to that before thyroidectomy. No other abnormal uptake was observed. It is suggested that the primary occult thyroid papillary carcinoma regressed and was obliterated possibly by some immunologic or other host-resistance factors after it metastasized to the distant bone.

Diffuse bony uptake of thallium-201-chloride in the granulocyte colony-stimulating factor-producing lung carcinoma.

Diffuse uptake of 201TI in the axial bone is reported in a patient with large cell carcinoma of the lung who showed leukocytosis and an increased concentration of granulocyte colony-stimulating factor (G-CSF) in plasma. The abnormal bony uptake of 201TI disappeared in association with normalization of the elevated plasma G-CSF level after complete tumor resection. The production of G-CSF was confirmed by immunoperoxidase staining of the tumor tissue.

Diagnostic value of technetium-99m methoxyisobutyl isonitrile (99mTc-MIBI) scintigraphy in detecting thyroid cancer metastases: a critical evaluation.

Technetium-99m methoxyisobutyl isonitrile (99mTc-MIBI) scintigraphy has recently been used in clinical application for detecting thyroid cancer metastases, its role being considered supplementary to serum thyroglobulin (Tg) measurements and radioactive iodine (131I) whole-body scans (WBS). The present retrospective study was designed to elucidate the role of 99mTc-MIBI scans in localizing metastatic lesions by assessing sensitivity and specificity of the scan results obtained in a group of 68 thyroidectomized thyroid cancer patients. Presence or absence of thyroid cancer was judged with other diagnostic modes including serum Tg measurements, 131I WBS, bone scans, chest x-rays, computed tomography (CT), ultrasonography, histopathology, and evolution of disease during follow-up. All scans were read on lesion basis for detecting neck, lung, and bone metastases and also on region basis, namely head-neck, chest, and abdomen-pelvis-extremities (ab-p-ex) areas. The sensitivity of detection was 94.4% (17/18) for neck, 78.4% (40/51) for lung, and 92.8% (64/69) for skeletal lesions. Positive predictive value (PPV) and negative predictive value (NPV) were 96.3% (26/27) and 97.7% (43/44) for head-neck; 94.7% (71/75) and 50.0% (12/24) for chest; 100.0% (25/25) and 93.1% (54/58) for ab-p-ex regions, respectively. For all scan sites taken together, PPV and NPV were 96.1% (122/127) and 86.5% (109/126), respectively. In conclusion, the present study reveals that 99mTc-MIBI can be proposed as a first-line diagnostic agent for the follow-up protocol of thyroid cancer patients, although the ability to detect small lung metastases is somewhat limited.

Assessment of thyroid growth stimulating activity of immunoglobulins from patients with autoimmune thyroid disease by cytokinesis arrest assay.

OBJECTIVE: To develop a novel bioassay for the assessment of thyroid cell growth stimulating activity using cytochalasin B (CB) and to test immunoglobulins (IgGs) from patients with autoimmune thyroid diseases. DESIGN: The assay is based on the principle that growing cells during incubation with CB show an increased number of nuclei in a cell (N/C index), since CB, at appropriate concentrations, is known to inhibit cytoplasmic cleavage without affecting nuclear mitosis. The N/C index represents potential DNA production while cells are incubated with CB. METHODS: FRTL-5 thyroid cells were incubated with various thyroid stimulators in TSH-free medium containing 2 mg/J CB for 3 days. After the incubation, the cells were harvested in trypsin/EDTA to obtain single cell suspension, fixed, dropped onto a glass slide, stained and observed under a microscope to determine the N/C index. RESULTS: Bovine TSH at 10(-3)-1.0 U/I, forskolin at 1x10(-7)-10(-5) mol/l, cholera toxin at 10x10(-5)-10(-3) mg/l, or (Bu)2cAMP at 1 x 10(-5)-10(-3) mol/l increased the N/C index up to approximately 2.0 in a dose-dependent manner. IgGs not only from 27 patients with untreated goitrous Graves' disease but also from 14 patients with goitrous Hashimoto's thyroiditis elicited an increase in the N/C index, which exceeded the mean + 2 S.D. of the values for 17 normal subjects (mean +/- S.D., 1.063 +/- 0.014). Four patients with primary myxedema displayed a normal N/C index. In Graves' disease, the N/C index did not correlate significantly with thyroid stimulating antibodies (TSAb) activities but did correlate significantly with estimated goiter size (P < 0.05). IgGs containing blocking-type TSH-receptor antibodies inhibited the TSH- or Graves IgG-stimulated increase in N/C index almost completely, but did not influence the stimulatory effect of IgG from two patients with Hashimoto's thyroiditis. CONCLUSIONS: We have developed a sensitive and simple assay for thyroid growth stimulating activity by using CB, and found that all tested patients with goitrous Graves' disease and goitrous Hashimoto's thyroiditis have thyroid growth stimulating immunoglobulins whose activity does not correlate with TSAb.

Binding of a human monoclonal antithyroglobulin antibody to cultured human thyroid cancer cells.

To develop a new method of radioimmunodetection for thyroid cancer, we tested the binding ability of a human antithyroglobulin monoclonal antibody, VB5, to primary culture of human thyroid cancer cells. VB5 was able to immunostain cytoplasmic thyroglobulin (Tg) in the acetone-fixed cancer cells when used in a labeled streptavidin-biotin method but not in a conventional indirect immunoperoxidase technique. The antibody was readily labeled with I-125 in the standard chloramin-T method, and showed specific binding to the antigen on cultured malignant thyrocytes displaceable with non-labeled VB5 or with excess Tg antigen. Although these initial results in vitro are encouraging, the observed low specific binding (about 1% at room temperature) to intact cells with a single monoclonal antibody seems insufficient to conduct any in vivo immunolocalization experiments in animals. To obtain more binding, we would need a cocktail of several monoclonal antibodies to different epitopes, and also fragmentation of antibody molecules to penetrate into cytoplasm.

Subclinical Graves' disease as a cause of subnormal TSH levels in euthyroid subjects.

In order to elucidate causes of subclinical thyrotoxicosis, we reviewed records of thyroid function tests obtained in our hospital between 1990 and 1992 showing normal thyroid hormones and subnormal TSH levels, and analyzed underlying clinical conditions of the patients. Of 186 patients with normal T4 and/or free T4 and normal T3 and/or free T3 but subnormal TSH (< 0.1 mU/l) levels in serum, 150 were under treatment with antithyroid drugs for hyperthyroid Graves' disease or with thyroid hormones for hypothyroidism. Twelve were in remission after treatment for Graves' disease, and 4 had destructive thyroiditis. Of the remaining 20 patients, 4 had autonomously functioning thyroid nodule (AFTN), 9 had euthyroid ophthalmic Graves' disease (EOG), and 7 had diffuse goiter without apparent ophthalmopathy (DG). When thyroid stimulating antibodies (TSAb) were measured in the last 3 groups of the patients, they were detected in none with AFTN but in all patients with EOG and DG. These 7 DG patients without ophthalmopathy had a clinical feature showing unstable thyroid functions, changeable to euthyroidism, overt hyperthyroidism and even hypothyroidism during follow-up. In conclusion, TSAb measurement is useful for detection of subclinical Graves' disease in euthyroid subjects with subnormal TSH levels in serum.

Evaluation of technetium-99m-MIBI scintigraphy in metastatic differentiated thyroid carcinoma.

UNLABELLED: Technetium-99m-methoxyisobutyl isonitrile (99mTc-MIBI) was evaluated for its ability to detect metastases from thyroid carcinoma. METHODS: Twenty-seven thyroidectomized patients with metastatic differentiated thyroid carcinoma, of whom 20, 9 and 12 had lung, lymph node and bone metastases, respectively, were examined with 99mTc-MIBI. The scan results were compared with those of 201TI and 131I whole-body scans. RESULTS: Increased accumulation of 99mTc-MIBI was observed in lung metastases of 15 patients (75.0%), 12 lymph node metastases (100.0%) and 29 of 31 bone metastases (93.5%). Increased accumulations of 201TI and 131I scans were seen in, respectively, 16 (80.0%) and 17 (85.0%) of the 20 patients with lung metastases, 12 (100.0%) and 5 (41.7%) of the 12 lymph node metastases and 28 (90.3%) and 27 (85.1%) bone metastases. Because of its better image quality, 99mTc-MIBI detected more lesions in the lung (n = 38) than 201TI did (n = 17). CONCLUSION: Technetium-99m-MIBI is clinically useful for detecting metastases from differentiated thyroid carcinoma and deserves clinical application in the postoperative follow-up of such patients.

Value of combined technetium-99m hydroxy methylene diphosphonate and thallium-201 imaging in detecting bone metastases from thyroid carcinoma.

Detectability of bone metastases from differentiated thyroid carcinoma by technetium-99m hydroxymethylene diphosphonate ([99m]Tc-HMDP) bone scan is considered to be poor. Thallium-201 (201Tl) is also widely used for detecting metastatic lesions. Our present study was aimed at the evaluation of the combined use of (99m)Tc-HMDP and 201Tl imaging in successful detection of bone metastases from differentiated thyroid carcinoma. Twenty-seven thyroidectomized thyroid cancer patients (19 females, 8 males; 12 papillary type, 15 follicular type) with 77 bone lesions were included in this retrospective study. All of these patients received ablative doses of radioiodine. Thyroidal origin of the lesions was proved by positive iodine-131 (131I) uptake. In 131I-negative lesions, histological proof or absence of tumor markers other than thyroglobulin was considered when computed tomography (CT) and/or magnetic resonance imaging (MRI) suggested metastatic nature of the lesions. Of the 77 lesions, 58 (75.3%) were positive and 19 were negative in the (99m)Tc-HMDP bone scintigraphy, whereas 53 lesions (68.9%) could be detected by 201Tl scintigraphy. However, within the 19 (99m)Tc-HMDP-negative lesions, 14 showed abnormal accumulation of 201Tl, and within the 24 201Tl negative lesions, 19 were positive in (99m)Tc-HMDP scan. This resulted in a combined sensitivity of 93.5%. Our present study concludes that combined (99m)Tc-HMDP and 201Tl imaging is a sensitive and effective method for detecting bone metastases from thyroid carcinoma.