The first Canadian experience with the Afirma® gene expression classifier test.

BACKGROUND: Thyroid nodules are common and often benign, although prove to be malignant upon surgical pathology in 5-15% of cases. When assessed with ultrasound-guided fine-needle aspiration (USFNA), 15-30% of the nodules yield an indeterminate result. The Afirma® gene expression classifier (AGEC) was developed to improve management of indeterminate thyroid nodules (ITNs) by classifying them as "benign" or "suspicious." Objectives were (1) to assess the performance of the AGEC in two Canadian academic medical centres (2), to search for inter-institutional variation and (3) to compare AGEC performance in Canadian versus American institutions. METHODS: We undertook a retrospective cohort study of patients with indeterminate cytopathology (Bethesda Class III or IV) as per USFNA who underwent AGEC testing. We reviewed patient demographics, cytopathological results, AGEC data and, if the patient underwent surgery, results from their final pathology. RESULTS: In total, we included 172 patients with Bethesda Class III or IV thyroid nodules underwent AGEC testing, 109 in Montreal, Quebec and 63 in St. John's, Newfoundland, in this study. Among the nodules sent for testing, 55% (60/109) in Montreal and 46% (29/63) in St. John's returned as "benign." None of these patients underwent surgery. On the other hand, 45% (49/109) nodules in Montreal and 54% (34/63) in St. John's were found to be "suspicious," for a total of 83 specimens. Seventy seven of these patients underwent surgery. Both in Montreal and St. John's, the final pathology yielded malignant thyroid disease in approximately 50% of the specimens categorized as "suspicious." Since 2013, no patient diagnosed with a benign nodule as per AGEC testing was found to harbor a malignant thyroid nodule on follow-up. CONCLUSIONS: Molecular analysis is increasingly used in the management of indeterminate thyroid nodules. This study highlights the experience of two Canadian centres with AGEC testing. We found inter-institutional variability in the rate of nodules returning as "benign," however we found similar rates of confirmed malignancy in nodules returning as "suspicious." According the literature, results for AGEC testing in two Canadian institutions align with results reported in American centres.

Seasonal Difference in Postthyroidectomy Hypocalcemia: A Montreal-Based Study.

OBJECTIVE: Hypocalcemia following thyroidectomy often prolongs hospital stay and is potentially life-threatening. The objective of this study is to determine whether the season when thyroidectomy is performed is associated with postoperative hypocalcemia. STUDY DESIGN: Retrospective case series of patients undergoing thyroid surgery from 2009 to 2015. SETTING: Tertiary care academic institution in Montreal, Canada. SUBJECTS AND METHODS: A consecutive sample of 823 patients undergoing thyroidectomy by a single high-volume otolaryngologist for a suspected or confirmed thyroid malignancy. Patient demographics, procedure type, calcium and vitamin D supplementation, and seasonal rate of hypocalcemia postthyroidectomy were calculated and compared. RESULTS: Average seasonal rates of postthyroidectomy hypocalcemia in the winter, spring, summer, and autumn were, respectively, 8.3% (8 of 216), 7.3% (12 of 165), 1.5% (3 of 201), and 3.5% (8 of 228; P < .005). Patients operated in the winter were 5.6 times more likely to develop hypocalcemia as compared with those in the summer (P < .01; 95% confidence interval: 1.7-18.7). In a multiple regression analysis factoring in season when surgery was performed, procedure type, and preoperative vitamin D/calcium supplementation, surgery occurring in the winter predicted a hypocalcemia event (correlation coefficient [SE]: 0.72 [0.024], P = .026; 0.006 [0.025], P = .81; 0.004 [0.019], P = .82, respectively). CONCLUSION: In this study, patients undergoing thyroidectomy in the winter months were more likely to develop postoperative hypocalcemia when compared with those operated in the summer. Further studies are needed to understand the role of vitamin D in the observed seasonal difference in hypocalcemia rates.

Serum thyroglobulin improves the sensitivity of the McGill Thyroid Nodule Score for well-differentiated thyroid cancer.

BACKGROUND: The McGill Thyroid Nodule Score (MTNS) is a scoring system devised to help physicians to assess the preoperative risk that a thyroid nodule is malignant. It uses 22 different known risk factors for thyroid cancer (radiation exposure, microcalcifications on ultrasound, positive HBME-1 stain on biopsy, etc.) and attributes a percentage risk that the nodule is malignant. Recently, preoperative thyroglobulin (Tg) levels have been shown to correlate with the risk of malignancy. The aim of this study was to incorporate Tg levels into the already established MTNS. METHODS: This is a retrospective analysis of 184 thyroidectomy patients at the McGill University Thyroid Cancer Center. Patients with preoperative Tg levels were included in the study, and patients with incidental papillary microcarcinoma without extrathyroidal extent on final pathology were excluded. MTNS scores were calculated for all patients. Preoperative Tg levels of 75 ng/mL added one point to the MTNS, and levels of 187.5 ng/mL added two points. The new system is named MTNS+. RESULTS: Malignancy rates were calculated for each MTNS+ score. Patients with a score of 0-1 were <5% at risk of malignancy. The malignancy rate for scores of 2-3 was 14.29%, followed by 28.95% for scores of 4-6, 32.65% for scores of 7-8, 64.86% for scores of 9-11, 71.43% for scores of 12-14, 78.57% for scores of 15-18, and 92.31% for scores of 19-22. All patients (five of five) with an MTNS+ score of 23 or more had a malignant final pathology result. Patients with scores greater than eight had a relative risk of 2.5 [CI 1.79-3.49] of malignancy compared to patients with lower scores. MTNS+ showed good specificity at higher scores, with 89%, 96%, and 100% at scores above 11, 14, and 20 respectively. Compared to MTNS, adding Tg levels did not improve positive predictive values (PPV) or specificity, but improved sensitivity by 7.89% for scores greater than eight, and by up to 10.48% for scores greater than seven. CONCLUSION: This study shows that adding Tg to the MTNS increases the sensitivity of this scoring system. Moreover, it suggests that a combined scoring system such as the MTNS+ can accurately stratify the risk of well-differentiated malignancy in patients with thyroid nodules.

Selumetinib-enhanced radioiodine uptake in advanced thyroid cancer.

BACKGROUND: Metastatic thyroid cancers that are refractory to radioiodine (iodine-131) are associated with a poor prognosis. In mouse models of thyroid cancer, selective mitogen-activated protein kinase (MAPK) pathway antagonists increase the expression of the sodium-iodide symporter and uptake of iodine. Their effects in humans are not known. METHODS: We conducted a study to determine whether the MAPK kinase (MEK) 1 and MEK2 inhibitor selumetinib (AZD6244, ARRY-142886) could reverse refractoriness to radioiodine in patients with metastatic thyroid cancer. After stimulation with thyrotropin alfa, dosimetry with iodine-124 positron-emission tomography (PET) was performed before and 4 weeks after treatment with selumetinib (75 mg twice daily). If the second iodine-124 PET study indicated that a dose of iodine-131 of 2000 cGy or more could be delivered to the metastatic lesion or lesions, therapeutic radioiodine was administered while the patient was receiving selumetinib. RESULTS: Of 24 patients screened for the study, 20 could be evaluated. The median age was 61 years (range, 44 to 77), and 11 patients were men. Nine patients had tumors with BRAF mutations, and 5 patients had tumors with mutations of NRAS. Selumetinib increased the uptake of iodine-124 in 12 of the 20 patients (4 of 9 patients with BRAF mutations and 5 of 5 patients with NRAS mutations). Eight of these 12 patients reached the dosimetry threshold for radioiodine therapy, including all 5 patients with NRAS mutations. Of the 8 patients treated with radioiodine, 5 had confirmed partial responses and 3 had stable disease; all patients had decreases in serum thyroglobulin levels (mean reduction, 89%). No toxic effects of grade 3 or higher attributable by the investigators to selumetinib were observed. One patient received a diagnosis of myelodysplastic syndrome more than 51 weeks after radioiodine treatment, with progression to acute leukemia. CONCLUSIONS: Selumetinib produces clinically meaningful increases in iodine uptake and retention in a subgroup of patients with thyroid cancer that is refractory to radioiodine; the effectiveness may be greater in patients with RAS-mutant disease. (Funded by the American Thyroid Association and others; ClinicalTrials.gov number, NCT00970359.).

Estimating risk of recurrence in differentiated thyroid cancer after total thyroidectomy and radioactive iodine remnant ablation: using response to therapy variables to modify the initial risk estimates predicted by the new American Thyroid Association staging system.

BACKGROUND: A risk-adapted approach to management of thyroid cancer requires risk estimates that change over time based on response to therapy and the course of the disease. The objective of this study was to validate the American Thyroid Association (ATA) risk of recurrence staging system and determine if an assessment of response to therapy during the first 2 years of follow-up can modify these initial risk estimates. METHODS: This retrospective review identified 588 adult follicular cell-derived thyroid cancer patients followed for a median of 7 years (range 1-15 years) after total thyroidectomy and radioactive iodine remnant ablation. Patients were stratified according to ATA risk categories (low, intermediate, or high) as part of initial staging. Clinical data obtained during the first 2 years of follow-up (suppressed thyroglobulin [Tg], stimulated Tg, and imaging studies) were used to re-stage each patient based on response to initial therapy (excellent, acceptable, or incomplete). Clinical outcomes predicted by initial ATA risk categories were compared with revised risk estimates obtained after response to therapy variables were used to modify the initial ATA risk estimates. RESULTS: Persistent structural disease or recurrence was identified in 3% of the low-risk, 21% of the intermediate-risk, and 68% of the high-risk patients (p < 0.001). Re-stratification during the first 2 years of follow-up reduced the likelihood of finding persistent structural disease or recurrence to 2% in low-risk, 2% in intermediate-risk, and 14% in high-risk patients, demonstrating an excellent response to therapy (stimulated Tg < 1 ng/mL without structural evidence of disease). Conversely, an incomplete response to initial therapy (suppressed Tg > 1 ng/mL, stimulated Tg > 10 ng/mL, rising Tg values, or structural disease identification within the first 2 years of follow-up) increased the likelihood of persistent structural disease or recurrence to 13% in low-risk, 41% in intermediate-risk, and 79% in high-risk patients. CONCLUSIONS: Our data confirm that the newly proposed ATA recurrence staging system effectively predicts the risk of recurrence and persistent disease. Further, these initial ATA risk estimates can be significantly refined based on the assessment of response to initial therapy, thereby providing a dynamic risk assessment that can be used to more effectively tailor ongoing follow-up recommendations.

Radioactive iodine administered for thyroid remnant ablation following recombinant human thyroid stimulating hormone preparation also has an important adjuvant therapy function.

BACKGROUND: In December 2007, the USFDA approved recombinant human thyroid stimulating hormone (rhTSH) for radioiodine remnant ablation after total thyroidectomy in patients with well-differentiated thyroid cancer without evidence of metastatic disease. Because previously undetected radioactive iodine (RAI)-avid metastatic lesions can be identified during remnant ablation, we sought to determine if rhTSH-stimulated uptake of RAI into these incidentally discovered metastases is associated with a significant therapeutic (tumoricidal) effect. METHODS: This retrospective review describes the clinical outcome of 84 well-differentiated thyroid cancer patients in whom RAI-avid lesions outside the thyroid bed were first identified at the time of RAI remnant ablation (64 rhTSH stimulated, 20 thyroid hormone withdrawal [THW]) on either the diagnostic (63/84, 75%) or posttherapy (21/84, 25%) whole body scan (76 with locoregional metastasis only and 8 with pulmonary uptake). Following ablation, patients were classified as having either no evidence of disease or persistent disease on the basis of subsequent diagnostic whole body RAI scans, stimulated thyroglobulin, and cross-sectional imaging studies. RESULTS: Despite having RAI-avid metastatic disease identified outside the thyroid bed at the time of initial ablation, 70% (45/64) of rhTSH-assisted patients and 55% (11/20) of the THW group had no evidence of disease at a median of 2.7 years following the initial RAI ablation (p = 0.159). THW and rhTSH-stimulated RAI ablation had similar efficacy in eliminating RAI-avid locoregional metastases (42/60, 70% of rhTSH and 10/16, 63% of THW, p = 0.65) and pulmonary metastases (3/4, 75% of rhTSH and 1/4, 25% of THW, p = 0.41). CONCLUSIONS: Preparation with either rhTSH or THW in this retrospective study appears to have similar therapeutic (tumoricidal) effects on small volume RAI-avid metastatic disease incidentally discovered at the time of ablation in both locoregional lymph nodes and pulmonary parenchyma.

Mild decreases in white blood cell and platelet counts are present one year after radioactive iodine remnant ablation.

BACKGROUND: Bone marrow suppression after multiple, high-dose radioactive iodine (RAI) therapies is well described. However, changes in the peripheral complete blood count (CBC) that may occur after a single treatment of RAI such as that commonly used for routine remnant ablation is much less well studied. In this retrospective trial, we examined the rate of persistent anemia, leukopenia, and thrombocytopenia 1 year after a single RAI administration. METHODS: Peripheral blood counts at baseline were compared to those obtained 1 year after RAI remnant ablation in 206 consecutive thyroid cancer patients. Analyses were performed to determine the potential impact of both the method of preparation (recombinant human thyroid stimulating hormone [rhTSH] vs. thyroid hormone withdrawal) and administered activity of (131)I on hemoglobin, white blood cell (WBC), and platelet counts. RESULTS: Comparison of the baseline CBC before RAI ablation (median administered activity of approximately 3700 MBq or 100 mCi) with the follow-up CBC done 1 year later demonstrated a statistically significant decline in total WBC (6.7 +/- 2.1 x 10(9) vs. 6.0 +/- 1.8 x 10(9)/L, p < 0.001; 9.7% below the reference range at 1-year follow-up) and platelet (272 +/- 67 vs. 250 +/- 65 x 10(9)/L, p < 0.001; 5.8% below the reference range at 1-year follow-up) with no significant change in hemoglobin (1.40 +/- 0.14 vs. 1.40 +/- 0.14 g/L or 14.0 +/- 1.4 vs. 14.0 +/- 1.4 g/dL; 1.5% below the reference range at 1-year follow-up). There were no significant clinical complications observed during the 1-year follow-up period. The changes in total WBC and platelets were not related to the method of preparation or the administered activity of RAI. CONCLUSION: A single RAI treatment of approximately 3700 MBq (100 mCi) after thyroidectomy is associated with a statistically significant, mild decline in WBC and platelet counts that persists for at least 1 year after ablation. Given the small magnitude of the changes and the lack of clinically significant adverse events, these observations should not decrease the use of RAI ablation in moderate to high-risk patients in whom the benefits of ablation are likely to outweigh these minor risks.

Follow up approaches in thyroid cancer: a risk adapted paradigm.

The primary goal in the follow up of thyroid cancer patients is to identify and treat persistent and recurrent disease at a time that minimizes morbidity and disease specific mortality. This article presents a risk-adapted follow-up paradigm to guide both intensity and methodology of follow-up testing based on initial risk stratification, ongoing risk stratification, and secondary risk stratification that incorporates each of the well-known risk factors for recurrence and death from thyroid cancer, with a response to therapy variable as well as duration of disease-free survival. With a proper understanding of the biology of the disease and with accurate assessments of response to therapy, clinicians are better able to tailor a risk-appropriate follow-up approach to individual patients, minimizing excessive testing while still providing adequate testing to detect clinically significant disease recurrence in a timely fashion.

Medical management of thyroid cancer: a risk adapted approach.

Risk adapted treatment recommendations are dependent on accurate predictions of the risk of recurrence, risk of death, and likely sites of recurrence. When combined with response to therapy assessments and secondary risk stratification during follow-up, this risk adapted approach will allow the clinician to tailor the aggressiveness of therapy and follow up to the risk of recurrence and death in individual patients.

BRAFV600E mutation is associated with preferential sensitivity to mitogen-activated protein kinase kinase inhibition in thyroid cancer cell lines.

CONTEXT: Mutually exclusive mutations of RET, RAS, or BRAF are present in about 70% of papillary thyroid carcinomas, whereas only the latter two are seen in poorly differentiated and anaplastic cancers. Although the signal output common to these oncoproteins is ERK, a recent report showed that only BRAF mutations consistently predicted responsiveness to MAPK kinase (MEK) inhibitors. OBJECTIVES: Here we investigated whether sensitivity to MEK inhibition was determined by oncogene status in 13 human thyroid cancer cell lines: four with BRAF mutations, four RAS, one RET/PTC1, and four wild type. RESULTS: Growth of BRAF (+) cells was inhibited by the MEK antagonist PD0325901 with an IC(50) of less than 5 nm. By contrast, RAS, RET/PTC1, or wild-type cells had IC(50) of 4 nm to greater than 1000 nm. Sensitivity was not predicted by coexisting mutations in PIK3CA or by PTEN status. Similar effects were obtained with the MEK inhibitor AZD6244. PD0325901 induced a sustained G1/S arrest in BRAF (+) but not BRAF (-) lines. PD0325901 was equipotent at inhibiting pERK1/2 after 2 h, regardless of genetic background, but pERK rebounded at 24 h in most lines. MEK inhibitor resistance was associated with partial refractoriness of pERK to further inhibition by the compounds. AZD6244 was more potent at inhibiting growth of NPA (BRAF +) than Cal62 (KRAS +) xenografts. CONCLUSION: Thyroid cancers with BRAF mutation are preferentially sensitive to MEK inhibitors, whereas tumors with other MEK-ERK effector pathway gene mutations have variable responses, either because they are only partially dependent on ERK and/or because feedback responses elicit partial refractoriness to MEK inhibition.

Tall cell variant of papillary thyroid carcinoma without extrathyroid extension: biologic behavior and clinical implications.

BACKGROUND: The tall cell variant (TCV) is a histologic subtype of papillary thyroid carcinoma (PTC) that is more aggressive than "classical" PTC. Most authors believe that TCV's worse prognosis is related to older age at presentation, larger tumor size, and high frequency of extrathyroid tumor extension (ETE). To assess the biologic and clinical behavior of TCV without ETE, we performed a detailed comparative clinicopathologic analysis of classical PTC and TCV without ETE. METHODS: TCV was defined as a PTC harboring >50% tall cells, while classical PTC was restricted to those tumors containing >1% papillae and <30% tall cells. Microscopic analysis and chart review identified 62 cases of TCV and 83 classical PTC without ETE. These patients were analyzed for various pathologic, imaging, and clinical parameters including outcome. RESULTS: There was no statistical difference between TCV and classical PTC in relation to age, gender, tumor size, risk stratification, type of therapy, and length of follow-up. TCV displayed more invasion of the tumor capsule and more often infiltrated into the thyroid capsule (p = 0.047 and 0.0004, respectively). Among patients with microscopically assessable regional lymph node (LN), 33 of 49 (67.3%) patients with TCV had LN metastasis at presentation, while only 24 of 60 (40%) classical PTC had positive nodes (p = 0.004). In multivariate analysis, histologic subtype (TCV vs. classical PTC) was the only independent factor associated with LN metastases (p = 0.007). In patients with adequate follow-up, 4 of 62 (6.5%) classical PTC and 7 of the 47 (14.9%) TCV had thyroid cancer recurrence (p = 0.202). TCV recurred at a distant site (3 of 47, 6.4%) while none of the 62 classical PTC developed distant metastases (p = 0.077). CONCLUSION: TCV without ETE is biologically a more aggressive tumor than classical PTC without ETE independent of age, gender, and tumor size.

Papillary thyroid cancer: monitoring and therapy.

The last 10 years have seen a major paradigm shift in the management of thyroid cancer, with greater reliance on serum thyroglobulin and neck ultrasonography, and less emphasis on routine diagnostic whole-body radioactive iodine scanning for detection of recurrent disease. As our follow-up tests become more sensitive for detection of recurrent disease, we are finding many asymptomatic patients who have low-level persistent disease many years after initial therapy that may or may not benefit from additional testing and therapy. These difficult issues have been addressed by at least five different sets of guidelines published recently by various thyroid specialty organizations around the world. In this article, the authors compare and contrast the recommendations from the various guidelines in an attempt to define areas of consensus and explore possible reasons for differing recommendations.

Impact of pregnancy on serum thyroglobulin and detection of recurrent disease shortly after delivery in thyroid cancer survivors.

OBJECTIVE: Since pregnancy can stimulate thyroid growth, we examined the effect of pregnancy on recurrence and serum thyroglobulin (Tg) shortly after delivery in thyroid cancer survivors. DESIGN: Retrospective analysis of thyroid cancer survivors who became pregnant after completing initial therapy. MAIN OUTCOME: 36 women (age 34 +/- 4 years) who became pregnant a median of 4.3 years after initial therapy for differentiated thyroid cancer were evaluated a median of 4 months after delivery. As part of their initial therapy, 23 women underwent total thyroidectomy with radioactive iodine remnant ablation (RRA), six had total thyroidectomy without RRA, and seven underwent lobectomy without RRA. Following total thyroidectomy with or without RRA, no evidence of recurrence was detected in the early postpartum period in women with negative prepregnancy ultrasound and either undetectable or low suppressed Tg levels. However, disease progression was documented as enlargement of a previously stable cervical lymph node in one of three patients and a marked rise in serum Tg without evidence of structural disease progression in a patient with previously stable distant metastases. When analyzed based on initial therapy, the mean suppressed Tg after delivery was not significantly different than the prepartum value. However, eight women had Tg values after delivery more than 20% higher than the baseline Tg before pregnancy (three with known disease, five with no clinical evidence of disease). CONCLUSION: In thyroid cancer survivors, pregnancy is unlikely to cause clinically significant disease recurrence in the early postpartum period when structural imaging studies confirm the absence of residual disease but can occasionally be associated with progression of known metastatic lesions. Even though the serum Tg did not differ significantly before and after pregnancy, the long-term implications of minor rise in serum Tg seen in some individual patients cannot be assessed without longer studies in larger cohorts.

L-T3 preparation for whole-body scintigraphy: a randomized-controlled trial.

BACKGROUND: Patients with thyroid cancer often need whole-body scintigraphy (WBS) under TSH stimulation after 4-6 weeks withdrawal from levothyroxine (L-T(4)). Patients often become severely hypothyroid with impaired quality of life. Liothyronine (L-T(3)) substitution is used empirically to prepare patients; however, no data exist to prove its benefit. Objectives To compare the hypothyroid state in patients receiving either placebo or L-T(3) following L-T(4) withdrawal and to evaluate the time needed for adequate TSH elevation in preparation for WBS. METHODS: At the time of L-T(4) withdrawal, patients were randomized to receive L-T(3 )(50 microg qd) or placebo for 3 weeks, after which treatment was stopped. A validated evaluation of hypothyroidism (Billewicz score) was administered in a double-blind fashion every 2 weeks until the WBS. TSH, fT(4) and fT(3) were measured weekly. RESULTS: A total of 20 patients were randomized between September 2003 and May 2005. There was no difference in the Billewicz score at any time between the two groups. Before WBS, both groups were profoundly hypothyroid. TSH at time of WBS was similar in both groups. The time needed to reach a TSH level of more than 30 mUI/l was longer in L-T(3) group (mean +/- SD: 32 +/- 4 days vs. 17 +/- 9 days in placebo group, P = 0.006). CONCLUSION: Preparation for WBS with L-T(3) does not prevent profound hypothyroidism and delays TSH elevation required for WBS. L-T(4) withdrawal alone for 2-3 weeks is simpler and sufficient to allow TSH to reach a level of more than 30 mUI/l in the majority of patients without increasing morbidity from hypothyroidism.

Empiric radioactive iodine dosing regimens frequently exceed maximum tolerated activity levels in elderly patients with thyroid cancer.

UNLABELLED: Although 131I-iodine (RAI) therapy is a mainstay in the treatment of metastatic thyroid cancer, there is controversy regarding the maximum activity that can safely be administered without dosimetric determination of the maximum tolerable activity (MTA). At most institutions, a fixed empiric dosing strategy is often used, with administered activities ranging from 5.55 to 9.25 GBq (150-250 mCi). In our experience with dosimetry, we have observed that this empiric dosing strategy often results in administered RAI activities exceeding the MTA safety limit of 200 cGy (rads) to the blood or bone marrow in many patients with metastatic thyroid cancer. METHODS: We retrospectively analyzed 535 hypothyroid dosimetry studies performed as part of routine clinical care in 328 patients with apparently normal renal function. RESULTS: The MTA was less than 5.18 GBq (140 mCi) in 3%, less than 7.4 GBq (200 mCi) in 8%, and less than 9.25 GBq (250 mCi) in 19%. Analysis of MTA values by age at the time of dosimetry revealed little change in the MTA until the age of 70 y, when a significant decrease occurred. An empiric administered activity of 7.4 GBq (200 mCi) would exceed the MTA in 8%-15% of patients less than 70 y old and 22%-38% of patients 70 y old or older. However, administration of 9.25 GBq (250 mCi) would exceed the MTA in 22% of patients less than 70 y old and 50% of patients 70 y old or older. Factors associated with a lowering of MTA to less than 9.25 GBq (250 mCi) were age at dosimetry greater than 45 y, the female sex, subtotal thyroidectomy, and RAI-avid diffuse bilateral pulmonary metastases. CONCLUSION: Administered RAI activities of less than 5.18 GBq (140 mCi) rarely exposed blood to more than 200 cGy except in the very elderly. However, administered activities of 7.4-9.25 GBq (200-250 mCi) frequently exceeded the calculated MTA in patients 70 y old or older. Therefore, dosimetry-guided RAI therapy may be preferable to fixed-dose RAI treatment strategies in older patients with thyroid cancer and in patients with RAI-avid diffuse bilateral pulmonary metastases, even when renal function is normal.

Thyroid cancer presenting as a PET incidentaloma in a patient with concomitant breast cancer metastases to the thyroid.

INTRODUCTION: Metastases to the thyroid gland are considered a rare cause of thyroid tumor. Furthermore, a relationship between breast and thyroid carcinoma has been previously proposed. CASE DESCRIPTION: We describe the case of a 59-year-old woman who presented with simultaneous papillary and breast carcinoma within the thyroid gland. F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) done for the evaluation of her metastatic breast cancer revealed a thyroid incidentaloma with a high metabolic rate (standardized uptake value [SUV] of 13). She underwent thyroidectomy and the pathology revealed papillary thyroid carcinoma corresponding to the lesion visualized on FDG PET. However, small metastatic implants of breast carcinoma were seen within the opposite thyroid lobe. CONCLUSION: This is a rare description of a concomitant papillary thyroid carcinoma presenting as an FDG PET incidentaloma alongside breast cancer metastases to the thyroid gland. Thyroid and breast cancer sometimes occur in the same patient. However, no explanation has been found to link these 2 cancers. Although uncommon, FDG PET thyroid incidentalomas seem to harbor a higher rate of malignancy than incidentalomas found on conventional imaging. In the appropriate clinical setting, it is therefore suggested to investigate these lesions thoroughly.

"Hook effect" in calcitonin immunoradiometric assay in patients with metastatic medullary thyroid carcinoma: case report and review of the literature.

CONTEXT: Calcitonin is a well-established tumor marker for medullary thyroid carcinoma (MTC). Because surgery is the only effective treatment for patients with MTC, the postoperative level of serum calcitonin will dictate whether residual disease was left behind and whether reintervention is necessary. RESULTS: We describe here the case of a 41-yr-old man with metastatic MTC. Despite extensive disease in the neck as well as metastatic lesions in the liver, his serum calcitonin, measured with a commercial one-step immunoradiometric assay, was only minimally elevated (244 ng/liter). After serial dilutions, a nonlinear relationship became evident, suggesting the presence of a "hook effect." Treatment of the serum with heterophilic blocking reagent revealed no change. Calcitonin was then measured with a different immunoradiometric assay and revealed a much higher level. Similar discrepancies were found in different samples from various patients when analyzed with different calcitonin immunoassays. CONCLUSION: To our knowledge, this is the first reported case of a phenomenon such as the hook effect in a calcitonin immunoradiometric assay in patients with MTC. Being aware of this phenomenon is important, because a low calcitonin result could give false reassurance to both the patient and the clinician and could dramatically change the prognosis of the patient.