Breast cyst simulating metastases on iodine-131 imaging in thyroid carcinoma

False-positive radioiodine uptake has been reported in many organ systems. We describe a female patient who had mixed papillary and follicular thyroid carcinoma, and on radioiodine total-body imaging demonstrated focal, lower-right chest uptake. Special prone imaging with the right breast dependent proved that the uptake was inside the right breast. Review of a recent breast ultrasound and mammograms showed this uptake to correspond to a large breast cyst. It is known that 131I breast uptake may be functional within the mammary gland. In this patient, it was due to retention within the cyst after the background activity decreased. Knowledge of this phenomenon may improve the interpretation of total-body 131INa studies.     

The comparative value of serum thyroglobulin measurements and iodine 131 total body scans in the follow-up study of patients with treated differentiated thyroid cancer

This study is an attempt to unify the evaluation of patients with well-differentiated thyroid cancer after ablative therapy. As such serum thyroglobulin determinations on and off thyroid hormone (T4) therapy and iodine 131 total body scans were examined in 53 patient studies. No metastases were found in patients whose thyroglobulin value was undetectable (less than 1 ng/ml). Values during T4 therapy that were detectable, even as low as 4.2 ng/ml, were occasionally associated with metastases. After T4 withdrawal, thyroglobulin value and scan were obtained. Neither metastasis nor clinically detectable cancer was found in patients whose thyroglobulin value was less than 10 ng/ml while off T4. Conversely, a value greater than 10 ng/ml was often associated with documented metastases even when the scan was negative. In summary, a thyroglobulin value less than 1 ng/ml during T4 therapy or less than 10 ng/ml off T4 therapy suggests successful therapy and a routine scan could be avoided unless clinically indicated. However, a value greater than 10 ng/ml suggests the presence of metastasis despite a negative scan. Thyroglobulin determination substantially improves the management of these patients.     

Thallium-201, technetium-99m-tetrofosmin and iodine-131 in detecting differentiated thyroid carcinoma metastases

The purpose of this study was to asses the detectability of differentiated thyroid carcinoma (DTC) metastases by 99mTc-tetrofosmin and to compare the results of 99mTc-tetrofosmin with 131I and 201Tl. The reliability of 201Tl and 99mTc-tetrofosmin scanning during suppression therapy also has been studied. METHODS: A prospective study was performed on 41 patients (30 females, 11 males) with DTC (30 papillary, 11 follicular) who had undergone total thyroidectomy and received an average dose of 117 mCi (4329 MBq) of radioiodine for ablation of postsurgical residual thyroid tissue. All patients (n = 41) had 201Tl, 99mTc-tetrofosmin or 131I whole-body imaging after discontinuation of thyroid hormone replacement (thyroxine-off group). Eight of 14 patients with distant metastases also were imaged when they were on thyroxine therapy both with 201Tl and 99mTc-tetrofosmin (thyroxine on-and-off group). Radiologic studies (chest radiography, CT and MRI), serum thyroglobulin assays and histopathologic examinations were performed to clarify the presence of metastases with positive uptake on any of three radionuclide studies. RESULTS: In 26 of 41 patients all three scans were negative. These patients also clinically didn't show any evidence of metastases. Fourteen patients were considered to have distant metastases on the basis of clinical, radiologic and histopathologic findings. The sensitivities of 201Tl, 99mTc-tetrofosmin and 131I in diagnosing distant metastases were comparable (0.85, 0.85 and 0.78, respectively). Iodine-131 was much more sensitive than 201Tl and 99mTc-tetrofosmin for demonstrating residual thyroid tissue after surgery (1.00, 0.33 and 0.33, respectively). The only false-positive case involved radioiodine uptake in a tuberculoma. Thyroxine-on images of 8 patients with distant metastases showed no difference from their thyroxine-off images regarding the site, number and uptake of metastases. CONCLUSION: Technetium-99m-tetrofosmin and 201Tl imaging are highly sensitive for detecting differentiated thyroid carcinoma metastases and do not require prior withdrawal of thyroid hormone suppressive therapy.     

Radioimmunotherapy of medullary thyroid cancer with iodine-131-labeled anti-CEA antibodies

This study evaluates the pharmacokinetics, dosimetry, toxicity and therapeutic potential of radiolabeled NP-4 and MN-14 anti-CEA antibodies in medullary thyroid cancer (MTC). METHODS: Eighteen patients with advanced MTC entered exploratory clinical studies with therapeutic doses of 131I-labeled NP-4 and MN-14 murine monoclonal antibodies (MAbs) reactive with carcinoembryonic antigen (CEA). Doses administered ranged from 46 mCi for 131I-MN-14 lgG to 195 mCi for 131I-MN-14 F(ab)2 in patients negative for human anti-mouse antibodies (HAMA). RESULTS: The radioconjugate blood half-life (T1/2) for the whole lgG was 42.5+/-5.0 hr compared to 18.8+/- 4.1 hr for the bivalent fragments. Tumor doses of 17.5+/-11.0 and 11.4+/-6.3 cGy/mCi were estimated for 131I-MN-14 lgG and F(ab)2, respectively. Tumor/red marrow dose ratios exceeded 3:1 for most lesions. Red marrow doses of up to 350 cGy generally could be delivered with < grade 4 toxicity. Seven of 14 evaluable patients showed evidence of anti-tumor effects lasting up to 26 months, based on physical exam, tumor markers or computed tomography. CONCLUSION: This study demonstrates that anti-CEA MAbs may be suitable for radioimmunotherapy of metastatic or recurrent MTC.     

Thallium-201 scintigraphy to predict therapeutic outcome of iodine-131 therapy of metastatic thyroid carcinoma

We studied the relationship between 201Tl uptake and the efficacy of radioiodine therapy in thyroid carcinoma. METHODS: Forty-four patients with metastases of well-differentiated thyroid carcinoma received 201Tl scintigraphy within the 2 mo before their initial 131I therapy. Patients were classified into two groups according to the tumor-to-background (T/B) ratio on the late 201Tl scan: high 201Tl uptake (T/B > or = 2.1) and low 201Tl uptake (T/B < 2.1). The therapeutic outcome was judged by the percent reduction in the tumor diameter at 6 mo after the treatment. The treatment was defined as effective when the tumor showed more than 50% reduction in the tumor diameter. The patients in whom radioiodine was ineffective were followed up to determine if the tumor showed further growth. RESULTS: Of the 44 patients, 25 had high 201Tl uptake and 19 had low 201Tl uptake. The therapy was effective in 15 patients and was ineffective in 29. All the patients in whom radioiodine was effective had low 201Tl uptake. On the other hand, 25 of 29 patients in whom radioiodine was ineffective had high 201Tl uptake. Eight patients, in whom radioiodine was ineffective despite good 131I uptake, had high 201Tl uptake. There were no significant differences in the positive predictive value and the negative predictive value for effective treatment between 201Tl scintigraphy and therapeutic dose 131I scintigraphy. Among the 25 patients in whom radioiodine was ineffective and who had high 201Tl uptake, the tumor diameter increased in 7 (28%). However, none of the tumors with low 201Tl uptake increased in size during the follow-up period. CONCLUSION: Thallium-201 scintigraphy has a high predictive value for the efficacy of radioiodine therapy in metastatic thyroid carcinoma. Thus, it is helpful in determining the indication for radioiodine therapy and it seems to be an adjunct to tracer dose 131I scintigraphy.     

The role of iodine-131 and thallium-201 imaging and serum thyroglobulin in the management of differentiated thyroid carcinoma

BACKGROUND: A prospective study was conducted to evaluate the use of iodine-131 sodium scintigraphy, thallium-201 chloride scintigraphy, and quantitative serum thyroglobulin estimation in the detection of differentiated thyroid carcinoma after thyroidectomy and iodine-131 sodium ablative therapy. METHODS: Thirty-one patients with a median age of 45.6 years (range, 20-73 years) were included in the study. After optimal endogenous thyroid-stimulating hormone stimulation (> 50 mU/ml), 53 pairs of iodine-131 and thallium-201 scans were performed. Concomitant serum thyroglobulin levels were available for 32 pairs of scans. The presence or absence of thyroid cancer was established by clinical, radiologic, and/or biopsy findings. RESULTS: The concordance between iodine-131 and thallium-201 scan findings in the presence of disease (25 scan sets) was 36%. The concordance in the absence of disease (28 scan sets) was 82%. Iodine-131 scanning was found to be significantly better (P < 0.05) than thallium-201 scanning, in terms of sensitivity (0.8 versus 0.6), specificity (0.96 versus 0.82), accuracy (0.89 versus 0.72), and the predictive value of a positive test (0.95 versus 0.75). The measurement of serum thyroglobulin had a low sensitivity (0.3) in the study but had a specificity of 1.0. CONCLUSION: It was concluded that iodine-131 sodium scintigraphy is superior to thallium-201 scintigraphy and serum thyroglobulin estimation for the detection of residual or metastatic differentiated thyroid carcinoma. However, the use of combined modalities provides a higher diagnostic yield. Thallium-201 scintigraphy was especially useful in cases in which iodine-131 scintigraphy was negative and quantitative thyroglobulin levels were elevated.     

Cervical lymph node metastasis of thyroid papillary carcinoma imaged with fluorine-18-FDG, technetium-99m-pertechnetate and iodine-131-sodium iodide

A 49-yr-old white woman with diffuse sclerosing variant of papillary carcinoma of the thyroid revealed abnormal [18F]FDG accumulation within cervical lymph node metastases prior to thyroidectomy. The abnormal cervical foci of glucose metabolism corresponded to similar areas of abnormal [99mTc]pertechnetate and radioiodine accumulation on presurgical scans. The primary thyroid tumor within the thyroid gland was not delineated as a focal defect on any of the three imaging studies. The relative thyroid-to-background soft-tissue ratio in the [18F]FDG study, however, appeared higher than usual. As with 131I and [99mTc]pertechnetate, this case demonstrates that [18F]FDG PET can detect cervical lymph node metastases in the preoperative thyroid cancer patient.     

Percent 131I uptake and post-therapy 131I scans: their role in the management of thyroid cancer

Renal disease in patients infected with human immunodeficiency virus (HIV) often presents with significant proteinuria and progressive renal failure; focal glomerulosclerosis is the most common renal pathology identified. To our knowledge, we report the first case of nephrotic-range proteinuria and preserved renal function in an HIV-infected patient in association with disseminated histoplasmosis. The initial level of proteinuria was 12.5 g/24 h. The patient developed a concomitant lesion on his neck, which was biopsied and identified as Histoplasma capsulatum by fungal stains and culture. The serum CF titer of antibody against yeast antigens of H. capsulatum was 1:8. The level of serum albumin decreased to 2.0 g/dL, and the level of serum cholesterol increased to 284 mg/dL. Immunohistochemical staining of renal biopsy tissue demonstrated immune complexes within the mesangium; H. capsulatum antigen was also demonstrated in the mesangium. Therapy with oral itraconazole resulted in marked clinical improvement. The findings in this case emphasize the need to rule out treatable causes of the nephrotic syndrome in AIDS, especially in cases of immune-complex glomerulonephritis.     

Cost minimization analysis of various treatment options for surgical stage I endometrial carcinoma

A rapid bioluminometric technique for real-time detection of known single-base changes is presented. The concept relies on the measurement of the difference in primer extension efficiency by a DNA polymerase of a matched over a mismatched 3' terminal. The rate of the DNA polymerase-catalyzed primer extension is measured by an enzymatic luminometric inorganic pyrophosphate (PPi) detection assay (ELIDA) (P. Nyrén (1987) Anal. Biochem. 167, 235-238). The PPi formed in the polymerization reaction is converted to ATP by ATP sulfurylase and the ATP production is continuously monitored by the firefly luciferase. In the single-base detection assay, immobilized single-stranded DNA fragments are used as template. Two detection primers differing with one base at the 3' end are designed, one precisely complementary to the nonmutated DNA sequence and the other precisely complementary to the mutated DNA sequence. The primers are hybridized with the 3'-termini over the base of interest and the primer extension rates are, after incubation with DNA polymerase and deoxynucleotides, measured with the ELIDA. We show that the relative mismatch extension efficiency is strongly decreased by substituting the alpha-thiotriphosphate analog for the next correct natural deoxynucleotide after the 3'-mismatch termini. The possibility of using the technique for studies of mismatch extension kinetics for two polymerases lacking exonucleolytic activity is shown.     

131I treatment of 131I negative whole body scan, and positive thyroglobulin in differentiated thyroid carcinoma: what is being treated?

Several aspects of the management of differentiated thyroid cancer cause considerable controversy. Among these is the role of 131I therapy in patients after thyroidectomy. There is no controlled study to demonstrate whether this treatment reduces the recurrence rate or improves mortality. Because of the overall excellent prognosis, it is unlikely that a controlled study will ever be conducted. Most frequently, patients have a diagnostic scan with 131I to determine whether radioiodine would be an appropriate therapy and to judge much to be prescribed, based on the extent of abnormalities seen on the scintiscan. Serum thyroglobulin (Tg) has been found to be a valuable tumor marker, with very good sensitivity and specificity. In most patients, the result of whole-body 131I scintiscan and Tg measurement give concordant results. However, in some patients, Tg is measurable, but the diagnostic scan with 131 is normal. There has been data published about treatment of these patients with therapeutic doses of 131I. The author questions whether this treatment is appropriate, prompted by seeing and hearing of patients who were treated with therapeutic doses of 131I, but had no abnormal uptake of the therapeutic doses and who had no improvement in serum Tg level. These patients have no clinical evidence of disease, and the only abnormality is measurable Tg. Since large doses of radioiodine are not without problems, a controlled clinical trial should be developed to evaluate efficacy in this situation.     

Phase I/II radioimmunotherapy trial with iodine-131-labeled monoclonal antibody G250 in metastatic renal cell carcinoma

This Phase I/II radioimmunotherapy study was carried out to determine the maximum tolerated dose (MTD) and therapeutic potential of 131I-G250. Thirty-three patients with measurable metastatic renal cell carcinoma were treated. Groups of at least three patients received escalating amounts of 1311I (30, 45, 60, 75, and 90 mCi/m2) labeled to 10 mg of mouse monoclonal antibody G250, administered as a single i.v. infusion. Fifteen patients were studied at the MTD of activity. No patient had received prior significant radiotherapy; one had received prior G250. Whole-body scintigrams and single-photon emission computed tomography images were obtained in all patients. There was targeting of radioactivity to all known tumor sites that were > or =2 cm. Reversible liver function test abnormalities were observed in the majority of patients (27 of 33 patients). There was no correlation between the amount of 131I administered or hepatic absorbed radiation dose (median, 0.073 Gy/mCi) and the extent or nature of hepatic toxicity. Two of the first six patients at 90 mCi/m2 had grade > or =3 thrombocytopenia; the MTD was determined to be 90 mCi/m2 131I. Hematological toxicity was correlated with whole-body absorbed radiation dose. All patients developed human antimouse antibodies within 4 weeks posttherapy; retreatment was, therefore, not possible. Seventeen of 33 evaluable patients had stable disease. There were no major responses. On the basis of external imaging, 131I-labeled mouse monoclonal antibody G250 showed excellent localization to all tumors that were > or =2 cm. Seventeen of 33 patients had stable disease, with tumor shrinkage observed in two patients. Antibody immunogenicity restricted therapy to a single infusion. Studies with a nonimmunogenic G250 antibody are warranted.     

Brain metastases in patients with differentiated thyroid carcinoma

We present a retrospective review of six patients who developed brain metastases in our series of 649 with differentiated thyroid carcinoma seen at the Royal Marsden Hospital between 1936 and 1991. Prognosis was poor, with survival 1-19 months from the diagnosis of brain metastases in five patients. One patient remains alive at 18 months. A dosimetric approach may help to individualize and optimize treatment.     

An analysis of lymphocyte subsets in the regional lymph nodes of patients with papillary thyroid carcinoma

Lymphocyte subsets in the lymph nodes regional to papillary thyroid carcinoma were determined using flow cytometry to ascertain the differences in local immunological responses between elderly and young patients. Lymph nodes from age-matched patients with benign thyroid tumors were used as controls. No significant alterations in lymphocyte subsets were observed in the lymph nodes from the young patients regardless of whether metastasis was present, whereas those from the elderly patients showed significant decreases in pan T cell (CD2+, CD3+) and cytotoxic T cell (CD8+, CD8+CD11b-) populations, and a significant increase in B cells (CD19+) compared with those from both the young patients and the age-matched controls. These results indicate that local immunological alterations occur in elderly patients with papillary thyroid carcinoma, and we believe that immunological changes are one of the clinical characteristics of this tumor.     

Unilateral total lobectomy: is it sufficient surgical treatment for patients with AMES low-risk papillary thyroid carcinoma?

BACKGROUND: Controversy continues regarding the optimal extent of primary thyroid resection in most patients with papillary thyroid carcinoma (PTC), who are at minimal risk of cause-specific mortality (CSM). This study was designed to compare CSM and recurrence rates after either unilateral lobectomy (UL) or bilateral lobar resection (BLR) in patients with PTC considered low risk by AMES criteria. METHODS: Outcome was studied in 1685 patients initially treated during 1940 through 1991 and followed for up to 54 postoperative years (mean, 18 years). One thousand six hundred fifty-six patients (98%) had complete primary tumor resection; 634 (38%) had involvement of regional nodes. One hundred ninety-five patients (12%) had UL; BLR accounted for 1468 (near-total 60%; total thyroidectomy 18%). RESULTS: Thirty-year rates for CSM and distant metastasis were 2% and 3%, respectively. Twenty-year rates for local recurrence and nodal metastasis were 4% and 8%, respectively. There were no significant differences in CSM or distant metastasis rates between UL and BLR (P > .2). After UL, 20-year rates for local recurrence and nodal metastasis were 14% and 19%, significantly higher (P = .0001) than the 2% and 6% rates seen after BLR. CONCLUSIONS: UL was not associated with higher CSM rates, but it was associated with a significantly higher risk of locoregional recurrence. Thus BLR probably represents a preferable initial surgical approach to patients with low-risk PTC.     

Bronchogenic carcinoma: utility of CT in the evaluation of patients with suspected lesions

PURPOSE: To assess the utility of computed tomography (CT) in the evaluation of suspected bronchogenic carcinoma. MATERIALS AND METHODS: CT scans were reviewed of 362 patients who had undergone CT for suspected bronchogenic carcinoma. RESULTS: CT findings of 275 patients were consistent with bronchogenic carcinoma. Sixty-five tumors were deemed unresectable on the basis of CT findings, 21 were deemed unresectable on the basis of CT findings and poor surgical risk, 26 proved to be benign, six were metastatic disease from an extrathoracic primary tumor, and 157 were potentially resectable bronchogenic carcinoma. Surgical mediastinal nodal sampling enabled documentation of metastases in 60 of 159 patients. According to nodal station, the sensitivity of CT for metastases was 67% for nodes measured in the long axis and 58% for nodes measured in the short axis; specificity was 56% and 86%, respectively. CONCLUSION: CT can be used to confirm or exclude the presence of bronchogenic carcinoma and to obviate thoracotomy. The specificity of CT is limited, and a histologic diagnosis or follow-up evaluation is necessary. CT has limited value in staging mediastinal lymph nodes.     

Prognostic factors in differentiated thyroid carcinoma: a multivariate analysis of 234 consecutive patients

The role of prostaglandin E2 (PGE2) and prostaglandin F2alpha (PGF2alpha) in the pathogenesis of hypertension and altered renal functions, which are the main symptoms of preeclampsia, has gained importance. Serum and urine samples of 59 women (24 preeclamptic pregnant (PEP), 20 normotensive pregnant (NTP) and 15 nonpregnant) were investigated by means of prostaglandin levels and urea, creatinine and creatinine clearance values. PEP patients, when compared with NTP patients, show a significant decrease in PGE2 and PGF2alpha levels (p < 0.01 and p < 0.05, respectively) accompanied by changes in some parameters of renal function such as serum urea, creatinine and creatinine clearance. Although disorders in prostaglandin levels may be responsible for some renal pathologic changes, renal functional and morphologic alterations may also result in abnormal prostaglandin activity.     

Elevated CEA in breast cancer patients with overlooked medullary thyroid carcinoma

After mastectomy and radiation for breast cancer, two patients were found to have persistent elevated CEA in their serum. This finding was erroneously attributed to occult metastases for the first patient and to local recurrence for the second. Overlooked medullary thyroid carcinoma (MTC) was the causal disease in both patients. A review of the literature stresses the frequency of CEA elevation in serum of MTC patients. A thorough search for any possible cause of elevated levels of CEA is advocated, particularly by thyroid sonogram with a needle aspiration biopsy when a nodule is discovered and by calcitonin assay in the serum.     

Effect of postoperative 131I treatment on thyroglobulin measurements in the follow-up of patients with thyroid cancer

Correlation of serum thyroglobulin (Tg) levels with recurrent cancer was performed in 200 patients who had undergone a subtotal thyroidectomy for well-differentiated thyroid carcinoma. Patients were divided into three groups: (1) those not treated postoperatively with radioactive iodine, (2) those treated with low dose (30 mCi) radioactive iodine, and (3) those treated with high dose (50-250 mCi) radioactive iodine. Tg levels proved to be reliable in detecting recurrent thyroid cancer regardless of the dose of radioactive iodine given postoperatively. These results reinforce the recommendation of using the Tg assay as the primary method of following these patients postoperatively, even when there was less than a total thyroidectomy and ablation with radioactive iodine.