Staging of differentiated thyroid carcinoma using diagnostic 131I SPECT/CT.

OBJECTIVE: The purpose of this study was to evaluate the feasibility of staging differentiated thyroid carcinoma (DTC) before initial radioiodine therapy using diagnostic radioiodine-131 ((131)I) scintigraphy with SPECT/CT and to determine the additional value of SPECT/CT. MATERIALS AND METHODS: Forty-eight patients (12 men and 36 women; age range, 17-82 years) with DTC underwent diagnostic (131)I planar imaging and SPECT/CT scintigraphy reinterpreted by two readers, one of whom was not blinded to patients' clinical details. Staging and scoring of carcinomas was done by use of TNM with three levels of sequential information: histopathologic analysis and chest radiograph data, planar images, and SPECT/CT data. Restaging based on the imaging findings was designated as "iTNM." RESULTS: Diagnostic (131)I scintigraphy allowed TNM staging of DTC before initial radioiodine therapy. Planar images detected previously unsuspected distant disease in four (50%) of eight patients with a score of M1. SPECT/CT changed the planar scan interpretation for 19 (40%) of 48 patients, detecting regional nodal metastases in four patients and clarifying equivocal focal neck uptake in 15 patients. Compared with histopathologic analysis and chest radiograph data, planar images and SPECT/CT changed the postsurgical DTC stage for 10 (21%) of 48 patients. SPECT/CT information changed the proposed (131)I therapeutic dose for 28 (58%) of 48 patients, on the basis of our department protocol. CONCLUSION: Diagnostic (131)I scintigraphy, planar images, and SPECT/CT complete the postsurgical staging of DTC. SPECT/CT reduces the number of equivocal diagnoses on planar imaging and improves the interpretation of (131)I scintigraphy. The consequent changes in TNM scores and staging should influence the (131)I dose prescribed at initial therapy.

Radioiodine therapy and Graves' ophthalmopathy.

UNLABELLED: Appearances of and increases in Graves' ophthalmopathy (GO) have been reported after treatment of patients with hyperthyroidism with radioiodine. We sought to determine the rates of appearance or increase in manifestations of GO in American patients treated with radioiodine for hyperthyroidism. METHODS: The study population, which consisted of 76 patients (range, 10.6-72 y), included 61 women and individuals of diverse ethnicity. The patients were followed for 1 y after radioiodine treatment. The clinical activity score (CAS) included 10 items of ophthalmic change that were evaluated at 2 and 6 mo and at 1 y; appearance of a new item scored 1 point. We evaluated interactions of 6 covariates-prolonged hyperthyroidism, prolonged hypothyroidism, smoking, treatment with an antithyroid drug (ATD), and serum levels of thyroid-stimulating immunoglobulin (TSI) and of high free T3 (FT3)--with the numbers of patients with 2 or more CAS points and with exophthalmometer readings increased by at least 2 mm. In addition, patients completed a scored quality-of-life (QOL) questionnaire at baseline and at 1 y to assess eye symptoms. RESULTS: The mean CAS points for all patients at 2 mo was 0.63 and was not significantly different at 1 y. In 9 of 10 CAS items, there were few patients affected at 1 y and for the most part there were fewer patients affected than at baseline. However, exophthalmometer readings increased in 39% of patients by a mean of 2.6 mm. Individual patients frequently exhibited increases and decreases in item manifestations. Exophthalmometer readings decreased by 2 mm or less in 13%. Of the covariates, only hyperthyroidism prolonged by at least 2.5 mo was significantly associated with 2 or more CAS points at 1 y; no covariate was significantly associated with the development of increased exophthalmometer readings. Eye symptoms recorded in the QOL were insignificantly improved over the year; symptoms did not correlate with CAS points or with exophthalmometer readings. CONCLUSION: After radioiodine treatment, no substantial change was seen in manifestations of CAS items except for a modest increase in exophthalmometer readings in 39% of patients. Manifestations of CAS items frequently appeared and disappeared. Prolonged hyperthyroidism is best avoided. Ocular symptoms were insignificantly fewer at 1 y after radioiodine therapy. The observed changes do not warrant prophylactic treatment of patients with steroids.

First description of parathyroid disease in multiple endocrine neoplasia 2A syndrome.

Hyperparathyroidism and/or parathyroid hyperplasia, medullary thyroid carcinoma (MTC), and pheochromocytomas compose the hallmarks of the multiple endocrine neoplasia type 2A (MEN 2A) syndrome. Revisiting a report in 1939 of a patient with hyperparathyroidism and parathyroid hyperplasia led to a search for evidence of MEN 2A. From medical records and discussion with family members, longitudinal follow-up of the patient and her descendants was obtained. Molecular diagnostics were integrated in the care of subsequent generations. The literature on hyperparathyroidism and MEN 2A was reviewed. Children of the proband exhibited all components of MEN 2A and the RET mutation of 634 TGC>CGC. The pedigree was typical for this mutation. Papers on anthropologic studies demonstrate skeletal evidence of hyperparathyroidism in humans centuries ago. The initial report of the proband preceded the publications defining both MTC and MEN 2A. The values of in-depth family histories and genetic analyses are exemplified.

The so-called stunning of thyroid tissue.

UNLABELLED: When thyroid tissues exhibited concentrations of therapeutic (131)I that appeared to be less than that predicted by data from the preceding diagnostic (131)I, the phenomenon was called stunning. We hypothesized that stunning arose from the early effects of the therapeutic dose of (131)I and that the initial uptake of (131)I, observed within the first day, was not impaired by the diagnostic dose. METHODS: The hypothesis was tested by 2 types of studies. In each type, the fractional concentrations of (131)I in residual neck thyroid tissues of patients with papillary thyroid carcinoma were quantified. In the first study, fractional concentrations of diagnostic and therapeutic (131)I were measured at 2 d, a time when stunning has been observed, and expressed as ratios of radioactivity: therapeutic/diagnostic (Rx/Dx). Three different doses of diagnostic (131)I were prescribed to assess a dose response. In the second study, patients were prospectively recruited and tested to record disappearances of radioactivity from thyroid tissues. Diagnostic doses were 1.0 mCi (37 MBq) in all; therapeutic doses were 150 and 30 mCi (5,550 and 1,110 MBq), each to half of the patients. The disappearance curves were extrapolated to the period between 0 and 1 d, an interval when maximum uptake of ingested (131)I would be expected. The fractional concentrations of (131)I at 2 d and at 0-1 d were compared in terms of Rx/Dx ratios to assess changes at each time point. RESULTS: In the first study, after diagnostic doses of 2, 1, and 0.5 mCi (74, 37, and 18.5 MBq), mean 2-d Rx/Dx values in 24, 29, and 17 patients were 0.35, 0.50, and 0.46 (P = 0.087). Of all patients, 74% exhibited Rx/Dx <0.6. In the second study, 6 of 10 patients exhibited disappearance curves of (131)I in which Rx/Dx was <0.6 at 2 d; 5 of the 6 had Rx/Dx values >0.97 at the 0- to 1-d point. In 1 patient the Rx/Dx was 0.54 at 2 d and 0.66 at the earlier time point. The other 4 patients had disappearance curves in which Rx/Dx values were >1.0 throughout or were above 0.6 and did not greatly change. CONCLUSION: Two days after the administration of (131)I, the mean fractional concentration of radioactivity in thyroid tissues after a therapeutic dose is <60% of the diagnostic dose in most patients, but no correlation of Rx/Dx with the mCi in the diagnostic dose was seen. In 5 of 6 patients in whom the Rx/Dx at 2 d was <0.6, the maximum fractional concentrations of therapeutic and diagnostic (131)I (i.e., the tissue uptakes during the first day) were similar; this pattern was most apparent after therapies with 150 mCi. These results support the hypothesis that "stunning" of thyroid tissues, often observable by 2 d, is primarily the consequence of early destructive effects from therapeutic (131)I.

Courses of malignant pheochromocytoma: implications for therapy.

Survival of patients with metastatic pheochromocytoma that have exceeded 30 years without therapy to reduce tumors have been reported. We reviewed the records of 38 patients with malignant pheochromocytoma who had received 131I-metaiodiobenzylguanidine (131I-MIBG) treatments between 1981 and 1996 to evaluate longevity. Survival from diagnosis to last follow-up exceeded 5 years in 21 of 38 (55%) and >or=10 years in 50%. In 17 of 21, the interval from diagnosis to 131I-MIBG therapy was greater than 5 years. Survival following 131I-MIBG was >or=5 years in 12 of 17 and >or=10 years in 7 of 17 patients despite continued evidence of excessive circulating catecholamines. Objective responses to 131I-MIBG therapy were seen in about 30% and were usually of a few years, duration, but one individual exhibited marked reductions in volume and function of tumors that have persisted for 21 years. No feature, including a remission of >5 years following surgical excision, was found to predict prolonged survival. In summary, many patients with malignant pheochromocytoma will follow a course extending over many years. The role of 131I-MIBG therapy in longevity is uncertain, but this radiopharmaceutical reduces evidence of tumors in some patients. Criteria for selecting patients who will benefit from treatment remain to be determined.

Current trends in functional imaging of pheochromocytomas and paragangliomas.

Most pheochromocytomas/paragangliomas should be evaluated with anatomical imaging (computed tomography or magnetic resonance imaging) followed by functional imaging (nuclear medicine modalities). Functional imaging assures that the tumor is indeed a pheochromocytoma/paraganglioma and enables more thorough localization, especially detecting as many lesions as possible (in particular for metastatic disease). Functional imaging for pheochromocytomas/paragangliomas, can use radiolabeled ligands specific for pathways of synthesis, metabolism, and inactivation of catecholamines or nonspecific ligands. In an overview of the available nuclear medicine modalities, we summarize the accumulated experience and recommend when functional imaging should be applied to patients with pheochromocytoma/paraganglioma.

Biochemical diagnosis and localization of pheochromocytoma: can we reach a consensus?

Pheochromocytomas can have a highly variable presentation, making diagnosis challenging. To think of the tumor represents the crucial initial step, but establishing the diagnosis requires biochemical evidence of excessive catecholamine production and imaging studies to localize the source. Currently, however, there exist no generally agreed upon guidelines based on which tests and testing algorithms should be used to confirm and locate or exclude a suspected pheochromocytoma. Choice of biochemical tests and imaging studies instead usually depends on institutional experience. At the First International Symposium on Pheochromocytoma (ISP2005), held in Bethesda in October 2005, a panel of experts and patient representatives discussed current problems and available options for tumor diagnosis and localization and formulated recommendations, which were subsequently agreed upon by those in attendance at the meeting. This article summarizes the discussion and recommendations derived from that session.

Radiation-induced osteosarcoma and papillary carcinoma of the thyroid.

PURPOSE: This article describes a patient with dual radiation-induced malignancies after treatment of neuroblastoma. MATERIALS AND METHODS: A 12-year-old boy with a history of neuroblastoma was treated with chemotherapy, I-131 MIBG, and radiotherapy at age 4. He was disease-free for 8 years, but then developed left shoulder pain resulting from osteosarcoma. A thyroid malignancy was discovered during the evaluation. RESULTS: The patient was treated with thyroidectomy and then chemotherapy according to a Children's Cancer Group Study protocol. CONCLUSION: Radiation-induced sarcoma should be suspected whenever a patient who has received radiation several years previously presents with pain or swelling in the irradiated area.

Pilot study of iodine-131-metaiodobenzylguanidine in combination with myeloablative chemotherapy and autologous stem-cell support for the treatment of neuroblastoma.

PURPOSE: The survival for children with relapsed or metastatic neuroblastoma remains poor. More effective regimens with acceptable toxicity are required to improve prognosis. Iodine-131-metaiodobenzylguanidine ((131)I-MIBG) selectively targets radiation to catecholamine-producing cells, including neuroblastoma cells. A pilot study was performed to examine the feasibility of a novel regimen combining (131)I-MIBG and myeloablative chemotherapy with autologous stem-cell rescue. PATIENTS AND METHODS: Twelve patients with neuroblastoma were treated after relapse (five patients) or after induction therapy (seven patients). Eight patients had metastatic and four had localized disease at the time of therapy. All patients received (131)I-MIBG 12 mCi/kg on day -21, followed by carboplatin (1,500 mg/m(2)), etoposide (800 mg/m(2)), and melphalan (210 mg/m(2)) administered from day -7 to day -4. Autologous peripheral-blood stem cells or bone marrow were infused on day 0. Engraftment, toxicity, and response rates were evaluated. RESULTS: The (131)I-MIBG infusion and myeloablative chemotherapy were both well tolerated. Grade 2 to 3 oral mucositis was the predominant nonhematopoietic toxicity, occurring in all patients. The median times to neutrophil (> or = 0.5 x 10(3)/microL) and platelet (> or = 20 x 10(3)/microL) engraftment were 10 and 28 days, respectively. For the eight patients treated with metastatic disease, three achieved complete response and two had partial responses by day 100 after transplantation. CONCLUSION: Treatment with (131)I-MIBG in combination with myeloablative chemotherapy and hematopoietic stem-cell rescue is feasible with acceptable toxicity. Future study is warranted to examine the efficacy of this novel therapy.

Choroidal and skin metastases from papillary thyroid cancer: case and a review of the literature.

A patient with widely metastatic papillary thyroid cancer who had been previously treated with (131)I and external beam radiation presented with purple nodular lesions on his face and scalp. On biopsy, the nodules were papillary carcinoma with cells that stained for thyroglobulin. Subsequently he developed decreased left eye visual acuity, and fundoscopy revealed lesions typical of choroidal metastases. Dermal and choroidal metastases of papillary thyroid carcinoma are both rare. However, the significance of these clinical manifestations may be overlooked and ignored unless the diagnosis is considered. New skin nodules or visual acuity decline in a patient with papillary thyroid cancer may represent manifestations of distant metastatic disease and should prompt thorough evaluation with dermatological examination and fundoscopy. Choroidal and skin metastases have almost always occurred in patients with advanced disease, but initial presentation with these lesions is possible, and in such instances a thorough search for additional sites of metastatic disease is recommended. Occasionally such metastases may respond to (131)I therapy or external beam radiation.

Increasing efficacy and safety of treatments of patients with well-differentiated thyroid carcinoma by measuring body retentions of 131I.

UNLABELLED: There is no consensus on the amount of (131)I for treatment of patients with well-differentiated thyroid carcinoma; usual amounts vary widely. Body retention of (131)I has been shown to be a valuable index of radiation toxicity. If a broad range of body retentions occurs among patients, then high and low retentions will be a basis for modifying the usual prescriptions for (131)I to ensure safety and increase efficacy. METHODS: After withdrawal of thyroid hormone in 87 patients, the fractional retention of diagnostic (131)I in each body was measured at 2 d by a scintillation probe. In 43 patients, the retention was measured 2 d after therapeutic (131)I. RESULTS: Diagnostic retention varied from 0.01 to 0.51, with a median of 0.15. These retentions did not correlate with any index of health, thyroid hormone, or carcinoma status. Seventeen patients, previously treated with (131)I, exhibited a significantly lower mean retention. In 43 patients, retention of diagnostic (131)I was highly correlated with retention of therapeutic (131)I: diagnostic predicted therapeutic retention with a mean error of 0.04. In 10 patients receiving thyroxine, the mean retention of diagnostic (131)I after recombinant human TSH (rhTSH) was strikingly lower, 0.06, with a range of 0.016-0.16. CONCLUSION: Body retentions of (131)I are easily measured and vary considerably among patients. Because increased therapeutic (131)I will impart greater irradiation of tumor, and body retention has been accepted as an index of toxicity from (131)I, the use of body retention could enable prescriptions of therapeutic (131)I that enable increased efficacy while ensuring safety. If tumor retention is not proportionally decreased with the body retention of (131)I after rhTSH, then rhTSH may enable increased therapeutic efficacy.

Radiopharmaceutical treatment of pheochromocytomas.

Malignant pheochromocytomas, a group of tumors that include metastatic paragangliomas, often produce hypertension and episodic symptoms from secretion of norepinephrine and sometimes epinephrine. In addition, the tumors usually manifest progressive metastases. Blockade of alpha and beta adrenergic receptors will control blood pressure and symptoms, but reduction of the malignancy has been difficult to achieve. Meta-iodobenzylguanidine (MIBG) follows the pathways of norepinephrine and, when labeled with 131-I, will concentrate sufficiently in the pheochromocytoma to impart therapeutic radiation. More than 100 patients have received treatment with 131-I-labeled MIBG at multiple medical centers. Individual doses were 3.7 to 18.5 GBq (100 to >500 mCi), and many patients received several doses separated by a few months. Partial remissions, recorded as decreased tumor presence and tumor function, have been observed in one-third or more of the treated patients. However, complete remissions are rare, and recurrence/progression within two years is the rule. Toxicity was generally modest and temporary. Subsequent chemotherapy increased the benefits attained by 131-I MIBG, but, in a small series of patients, this combination did not further change the outcome. Nevertheless, selective radiation from 131-I MIBG or a similar radiopharmaceutical could play a valuable role in treatments that combine several types of attacks on this recalcitrant malignancy.

Is preoperative iodine 123 meta-iodobenzylguanidine scintigraphy routinely necessary before initial adrenalectomy for pheochromocytoma?

BACKGROUND: Iodine 123 meta-iodobenzylguanidine (MIBG) scintigraphy has been used in patients with clinical suspicion of pheochromocytoma to confirm the nature of an adrenal or extraadrenal mass or to identify occult disease. Additionally, it may be used to identify unsuspected bilaterality or metastases in the setting of a known unilateral adrenal mass before operation. We sought to determine the role of (123)I MIBG scintigraphy in this apparently routine preoperative setting. Our hypothesis was that (123)I MIBG would provide additional preoperative information that could modify operative intervention. METHODS: All patients undergoing (123)I MIBG scintigraphy at our institution between 1992 and 2002 were identified. MIBG results, operative procedures and findings, and pathologic findings were retrospectively reviewed and compared. RESULTS: The (123)I MIBG scintigraphy was performed in a total of 315 patients. Of these, 48 were patients with an initial biochemical diagnosis of pheochromocytoma and a unilateral adrenal mass. 47 of the 48 (98%) primary scans were positive for a single focus of activity concordant with anatomic imaging data from computed tomography or magnetic resonance imaging and operative findings. The (123)I MIBG did not reveal unsuspected metastatic or bilateral disease in any patient. CONCLUSION: In this large series of patients undergoing (123)I MIBG scintigraphy, the test served only to confirm diagnostic impressions and corroborate anatomic imaging. The (123)I MIBG did not alter the operative management of any patient with a solitary adrenal lesion in the clinical context of biochemically-proven catecholamine excess.

Appearance of ectopic undescended inferior parathyroid adenomas on technetium Tc 99m sestamibi scintigraphy: a lesson from reoperative parathyroidectomy.

HYPOTHESIS: Critical postoperative review of technetium Tc 99m sestamibi scintigraphy can identify an undescended parathyroid adenoma on scans initially interpreted as nondiagnostic or negative. DESIGN: Case series. SETTING: A single, tertiary care academic medical center. PATIENTS: Three patients with persistent hyperparathyroidism. INTERVENTION: Technetium Tc 99m sestamibi scanning. OUTCOME MEASURE: Medical records, operative reports, selective venous sampling results, and sestamibi scans were reviewed to identify scintigraphic findings diagnostic of an undescended parathyroid adenoma. RESULTS: All patients were cured of their persistent or recurrent hyperparathyroidism during reoperation by resection of an undescended inferior parathyroid adenoma. Subsequent review of the preoperative sestamibi scans demonstrated scintigraphic evidence of the undescended adenoma. In each case there was asymmetry in the physiologic activity attributed to the ipsilateral submandibular gland that, in fact, corresponded to an ectopic parathyroid adenoma at the level of the carotid bifurcation. CONCLUSIONS: Careful attention to the contour of radioactivity in the region of the submandibular salivary gland may alert surgeons to the presence of an undescended inferior adenoma. After corroboration, this finding may facilitate a targeted operation.

Cryptococcal thyroiditis and hyperthyroidism.

We report a case of cryptococcal thyroiditis presenting with hyperthyroidism that evolved through a transient euthyroid phase to hypothyroidism and finally recovered to normal function. This four-phase clinical presentation is similar to that of subacute thyroiditis, and it is unusual in the setting of infectious nonviral thyroiditis. Cryptococcal thyroiditis is rare; only three cases have been reported. Our patient is the first who survived the disseminated cryptococcal infection with thyroid involvement, thus enabling longitudinal clinical and endocrinologic follow-up.

Practical dosimetry of 131I in patients with thyroid carcinoma.

Radioiodine treatments of patients with well-differentiated thyroid carcinoma have generally been safe and beneficial. Safety can be ensured while efficacy is increased through practical methods of dosimetry that measure body retention of 131I. Prescriptions for therapeutic 131I can be decreased when the retention level is high and increased when the level is low. Assays of serum free T4 will alert the physician to possible increased radiation to blood and bone marrow, and appreciable concentrations of free T4 are indications to reduce the therapeutic 131I. Carcinomas > or = 1 cm in diameter that are not visible on diagnostic scintigraphy are unlikely to respond to the commonly prescribed mCi of 131I. Biologic responses to commonly prescribed levels of therapeutic 131I, as seen in toxic changes of normal tissues and in indices of tumor size, will be the final dosimeters. With lower levels of prescribed diagnostic 131I, stunning should not impair dosimetry. Thus, readily obtained measurements make dosimetry a practical method for improving carcinoma therapy with 131I.

Factors that influence radioactive iodine use for thyroid cancer.

BACKGROUND: There is variation in the use of radioactive iodine (RAI) as treatment for well-differentiated thyroid cancer. The factors involved in physician decision-making for RAI remain unknown. METHODS: We surveyed physicians involved in postsurgical management of patients with thyroid cancer from 251 hospitals. Respondents were asked to rate the factors important in influencing whether a thyroid cancer patient receives RAI. Multivariable analyses controlling for physician age, gender, specialty, case volume, and whether they personally administer RAI, were performed to determine correlates of importance placed on patients' and physicians' worry about death from cancer and differences between low- versus higher-case-volume physicians. RESULTS: The survey response rate was 63% (534/853). Extent of disease, adequacy of surgical resection, patients' willingness to receive RAI, and patients' age were the factors physicians were most likely to report as quite or very important in influencing recommendations for RAI to patients with thyroid cancer. Interestingly, both physicians' and patients' worry about death from thyroid cancer were also important in determining RAI use. Physicians with less thyroid cancer cases per year were more likely than higher-volume physicians to report patients' (p<0.001) and physicians' worry about death (p=0.016) as quite or very important in decision-making. Other factors more likely to be of greater importance in determining RAI use for physicians with lower thyroid cancer patient volume versus higher include the accepted standard at the affiliated hospital (p=0.020), beliefs about RAI expressed by colleagues comanaging patients (p=0.003), and patient distance from the nearest facility administering RAI (p=0.012). CONCLUSION: In addition to the extent of disease and adequacy of surgical resection, physicians place importance on physician and patient worry about death from thyroid cancer when deciding whether to treat a patient with RAI. The factors important to physician decision-making differ based on physician thyroid-cancer case-volume, with worry about death being more influential for low-case-volume physicians. As the mortality from thyroid cancer is low, the importance placed on death in decision making may be unwarranted.

Referral patterns for patients with high-risk thyroid cancer.

OBJECTIVE: Knowledge of referral patterns for specialty cancer care is sparse. Information on both the need and reasons for referral of high-risk, well-differentiated thyroid cancer patients should provide a foundation for eliminating obstacles to appropriate patient referrals and improving patient care. METHODS: We surveyed 370 endocrinologists involved in thyroid cancer management. From information in a clinical vignette, respondents were asked to identify the reasons they would need to refer a high-risk patient to a more specialized facility for care. We performed multivariable analysis controlling for hospital and physician characteristics. RESULTS: Thirty-two percent of respondents reported never referring thyroid cancer patients to another facility. Of those that would refer a high-risk patient to another facility, the opportunity for a patient to enter a clinical trial was the most common reason reported (44%), followed by high-dose radioactive iodine (RAI) with or without dosimetry (33%), lateral neck dissection (24%), and external beam radiation (15%). In multivariable analysis, endocrinologists with a higher percentage of their practice devoted to thyroid cancer care were significantly less likely to refer patients to another facility (P = .003). CONCLUSION: The majority of endocrinologists treating thyroid cancer patients report referring a high-risk patient to another facility for some or all of their care. Knowledge of the patterns of physician referrals and the likelihood of need for referral are key to understanding discrepancies in referral rates and obstacles in the referral process.

Variation in the management of thyroid cancer.

CONTEXT: Little is known about practice patterns in thyroid cancer, a cancer that is increasing in incidence. OBJECTIVE: We sought to identify aspects of thyroid cancer management that have the greatest variation. DESIGN/SETTING/PARTICIPANTS: We surveyed 944 physicians involved in thyroid cancer care from 251 hospitals affiliated with the US National Cancer Database. Physicians were asked questions in the following four domains: thyroid surgery, radioactive iodine use, thyroid hormone replacement postsurgery, and long-term thyroid cancer management. We calculated the ratio of observed variation to hypothetical maximum variation under the assumed distribution of the response. Ratios closer to 1 indicate greater variation. RESULTS: We had a 66% response rate. We found variation in multiple aspects of thyroid cancer management, including the role of central lymph node dissections (variation, 0.99; 95% confidence interval [CI], 0.98-1.00), the role of pretreatment scans before radioactive iodine treatment (variation, 1.00; 95% CI, 0.98-1.00), and all aspects of long-term thyroid cancer management, including applications of ultrasound (variation, 0.97; 95% CI, 0.93-0.99) and radioactive iodine scans (variation, 0.99; 95% CI, 0.97-1.00). For the management of small thyroid cancers, variation exists in all domains, including optimal extent of surgery (variation, 0.91; 95% CI, 0.88-0.94) and the role of both radioactive iodine treatment (variation, 0.91; 95% CI, 0.89-0.93) and suppressive doses of thyroid hormone replacement (variation, 1.00; 95% CI, 0.99-1.00). CONCLUSION: We identified areas of variation in thyroid cancer management. To reduce the variation and improve the management of thyroid cancer, there is a need for more research and more research dissemination.

Theranostics: evolution of the radiopharmaceutical meta-iodobenzylguanidine in endocrine tumors.

Since 1981, meta-iodobenzylguanidine (MIBG), labeled with (131)I and later (123)I, has become a valuable agent in the diagnosis and therapy of a number of endocrine tumors. Initially, the agent located pheochromocytomas and paragangliomas (PGLs), both sporadic and familial, in multiple anatomic sites; surgeons were thereby guided to excisional therapies, which were previously difficult and sometimes impossible. The specificity in diagnosis has remained above 95%, but sensitivity has varied with the nature of the tumor: close to 90% for intra-adrenal pheochromocytomas but 70% or less for PGLs. For patients with neuroblastoma, carcinoid tumors, and medullary thyroid carcinoma, imaging with radiolabeled MIBG portrays important diagnostic evidence, but for these neoplasms, use has been primarily as an adjunct to therapy. Although diagnosis by radiolabeled MIBG has been supplemented and sometimes surpassed by newer scintigraphic agents, searches by this radiopharmaceutical remain indispensable for optimal care of some patients. The radiation imparted by concentrations of (131)I-MIBG in malignant pheochromocytomas, PGLs, carcinoid tumors, and medullary thyroid carcinoma has reduced tumor volumes and lessened excretions of symptom-inflicting hormones, but its value as a therapeutic agent is being fulfilled primarily in attacks on neuroblastomas, which are scourges of children. Much promise has been found in tumor disappearance and prolonged survival of treated patients. The experiences with therapeutic (131)I-MIBG have led to development of new tactics and strategies and to well-founded hopes for elimination of cancers. Radiolabeled MIBG is an exemplar of theranostics and remains a worthy agent for both diagnosis and therapy of endocrine tumors.