Response to Beasley CW, Moore WH, and Wagner LK

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90468/1/thy-2E2011-2E0181-2Ers.pd

Response to Hennessey et al.

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98489/1/thy%2E2011%2E0378%2Ers.pd

Courses of Malignant Pheochromocytoma

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 131 I-metaiodiobenzylguanidine ( 131 I-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 ≥10 years in 50%. In 17 of 21, the interval from diagnosis to 131 I-MIBG therapy was greater than 5 years. Survival following 131 I-MIBG was ≥5 years in 12 of 17 and ≥10 years in 7 of 17 patients despite continued evidence of excessive circulating catecholamines. Objective responses to 131 I-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 131 I-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.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73567/1/annals.1353.053.pd

Three Endocrine Neoplasms: An Unusual Combination of Pheochromocytoma, Pituitary Adenoma, and Papillary Thyroid Carcinoma

Background: Three endocrine neoplasms?bilateral pheochromocytomas, somatotrophic pituitary adenoma inducing acromegaly, and papillary carcinoma of the thyroid?occurred concurrently in a patient. A genetic mutation was hypothesized. Possible previously described genetic mutations were explored. Methods: Clinical assessments, laboratory data, images of tumors, histopathology, and immunohistochemistry of excised tissues documented the three neoplasms. Clinical assessment of the patient, family history, and a review of the literature sought a familial basis for the disorders. Results: The methods confirmed the presence of three endocrine neoplasms. Each neoplasm was surgically excised and histologically verified. Surgical and 131I treatments reduced the papillary carcinoma, but eventually this tumor progressed to a lethal degree. History, including that of nine siblings, uncovered no familial neoplasms. No similar case was found in the literature, but possible associations with germline mutations were considered. Conclusions: The concurrent development of pheochromocytomas, pituitary somatotrophic adenoma, and papillary thyroid carcinoma appears to be unique. Nevertheless, such tumors, particularly bilateral pheochromocytomas, strongly suggest a de novo germline mutation in a gene not previously associated with multiple endocrine neoplasia syndromes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98488/1/thy%2E2011%2E0345.pd

Familial Medullary Thyroid Carcinoma Associated with Cutaneous Lichen Amyloidosis

Background: This is a report of a patient with a novel genotype phenotype relationship of a c804 mutation of the RET proto-oncogene manifesting as medullary thyroid carcinoma (MTC) and cutaneous lichen amyloidosis (CLA). Summary: Clinical data were obtained for patient appearance and laboratory results. Analyzed were histopathology of the skin lesion and thyroid gland, genetic mutation, and family pedigree. Skin histology and histochemistry were consistent with CLA. Serum calcitonin levels were moderately elevated. Thyroid histology demonstrated a 4mm focus of MTC. Measurements of serum parathormone, calcium, and plasma metanephrines were normal. DNA analysis demonstrated a mutation in codon 804 of the RET proto-oncogene resulting in a Valine to Methionine (V804M) substitution. Genetic testing in two siblings revealed the same mutation. Conclusions: This is the first description of a patient with CLA not associated with a mutation in codon 634. The patient is one of the few with a V804M mutation in whom the clinical expression did not fully conform to the definition of familial MTC.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78146/1/thy.2009.0021.pd

Pheochromocytoma, polycythemia and venous thrombosis

Polycythemia is rarely associated with pheochromocytoma. A patient with a 22-year history of malignant pheochromocytoma is presented in whom major complications developed as a result of long-standing polycythemia, apparently due to secretion of erythropoletin by the tumors. Despite attempts to reduce tumor burden by surgery, chemotherapy, and large doses of 1-131-metalodobenzyl guanidine, polycythemia persisted. Extensive venous thrombosis developed requiring hospitalization and anticoagulation. Thus, polycythemia itself may be a cause of major morbidity in patients with pheochromocytoma, and prophylactic measures may be warranted. Review of the 130 patients with benign and malignant pheochromocytoma studied since the introduction of I-131-metaiodobenzylguanidine in 1980 revealed another six patients with hematocrits over 50 but only one had a hematocrit greater than 55 and required regular phlebotomy. In contrast, anemia (hematocrit less than 35) due to variety of causes was present in 18 cases.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26991/1/0000558.pd

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.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140258/1/thy.2012.0380.pd

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 ≥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.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63166/1/10849780252824118.pd

Thyroid Carcinoma Metastasis to Skull with Infringement of Brain: Treatment with Radioiodine

Background: Infringement by differentiated thyroid carcinoma on the brain is rare but, when suspected, the patient deserves special attention. A patient with an enlarging metastasis of thyroid carcinoma to the skull that was impinging on the brain illustrates diagnostic and therapeutic strategies applicable to the treatment of metastatic carcinoma. Methods: A case study was performed. Computed tomography (CT) and magnetic resonance imaging (MRI) were done, serum thyroglobulin was measured, and tumor responses to thyroxine and 131I treatments were monitored. Tumor dosimetry, enabled by scintigraphy with 131I employing single photon emission tomography fused with CT (SPECT-CT), was performed. Results: The metastasis was from a follicular variant of papillary thyroid carcinoma. During thyrotropin stimulation the tumor enlarged. The tumor decreased in volume after each of two 131I therapies. Dosimetry indicated delivery of 1970 and 2870cGy to the tumor and 35 and 42cGy to the brain, respectively, in the two treatments. The patient has survived for more than 11 years since diagnosis. Conclusions: A metastasis from a follicular variant of papillary carcinoma increased in volume during hypothyroidism producing more infringement on the brain. Beyond the effects of thyroxine therapy, 131I treatments induced recession of tumor volume. In patients with metastases that concentrate 131I, dosimetry with SPECT-CT can predict absorbed doses of radiation to the tumor and to the adjacent organs and thus lay a basis for data-based decisions on 131I therapies. Therapy may induce prolonged survival in patients with metastases infringing on the brain.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78102/1/thy.2008.0426.pd

Radiation Safety in the Treatment of Patients with Thyroid Diseases by Radioiodine 131I: Practice Recommendations of the American Thyroid Association

Background: Radiation safety is an essential component in the treatment of patients with thyroid diseases by 131I. The American Thyroid Association created a task force to develop recommendations that would inform medical professionals about attainment of radiation safety for patients, family members, and the public. The task force was constituted so as to obtain advice, experience, and methods from relevant medical specialties and disciplines. Methods: Reviews of Nuclear Regulatory Commission regulations and International Commission on Radiological Protection recommendations formed the basic structure of recommendations. Members of the task force contributed both ideas and methods that are used at their respective institutions to aid groups responsible for treatments and that instruct patients and caregivers in the attainment of radiation safety. There are insufficient data on long-term outcomes to create evidence-based guidelines. Results: The information was used to compile delineations of radiation safety. Factors and situations that govern implementation of safety practices are cited and discussed. Examples of the development of tables to ascertain the number of hours or days (24-hour cycles) of radiation precaution appropriate for individual patients treated with 131I for hyperthyroidism and thyroid cancer have been provided. Reminders in the form of a checklist are presented to assist in assessing patients while taking into account individual circumstances that would bear on radiation safety. Information is presented to supplement the treating physician's advice to patients and caregivers on precautions to be adopted within and outside the home. Conclusion: Recommendations, complying with Nuclear Regulatory Commission regulations and consistent with guidelines promulgated by the National Council on Radiation Protection and Measurement (NCRP-155), can help physicians and patients maintain radiation safety after treatment with 131I of patients with thyroid diseases. Both treating physicians and patients must be informed if radiation safety, an integral part of therapy with 131I, is to be attained. Based on current regulations and understanding of radiation exposures, recommendations have been made to guide physicians and patients in safe practices after treatment with radioactive iodine.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90492/1/thy-2E2010-2E0403.pd