I-131 Whole Body Scintigraphy in the Follow-up of Differentiated Thyroid Cancer

Joint Program in Nuclear Medicine

Najat A. Tureif, MD

J. Anthony Parker, MD PhD

November 2, 1993

Case Presentation:

A 45 year old male with history of childhood neck irradiation developed a neck mass 2 years before presentation. At surgery, he had a 5 cm right lower pole follicular carcinoma with one positive lymph node and evidence of vascular invasion. On the left side an incidental papillary carcinoma was found. One year prior to presentation, an I-131 whole body scintigraphy showed uptake in the thyroid bed. He was treated with 96 mCi of I-131 and resumed thyroxin suppressive therapy. The patient was entered into a protocol comparing whole body scintigraphy with recombinant TSH to scintigraphy after thyroxin withdrawn.

Findings:

Whole body scintigraphy with exogenous TSH (50k bytes) showed no abnormality. After thyroxin withdrawal (45k bytes) minimal uptake in the thyroid bed is identified arrow (54k bytes). (Anterior head, chest, abdomen, and pelvis are on the left; posterior chest, abdomen, and pelvis are on the right.) The patient was treated with 100 mCi of I-131. Scintigraphy 8 days after therapy ( anterior (41k bytes) head, chest, pelvis and posterior 18k bytes) chest) showed more extensive uptake in the thyroid bed and bilateral pulmonary uptake. (I-131 images are on the left; transmission images which show the position of the lungs are on the right)

Discussion:

There are more than 12,000 new cases of thyroid cancer diagnosed each year in the united states resulting in approximately 1000 deaths annually. Thyroid cancer is generally classified as either well differentiated or poorly differentiated. Well differentiated thyroid cancer represents approximately 80-90% of all thyroid cancers and consists of two major forms, papillary and follicular (60-70% and 20-25% of all thyroid cancers respectively). It is considered an indolent form of cancer with a low 5 year mortality rates (5-10% for papillary, 30-40 for follicular). The poorly differentiated forms represent the remaining 10-20% of thyroid cancer and also consists of two major forms, medullary and anaplastic (5-10% and 10-15% of all thyroid cancers, respectively). They are highly lethal cancers with most patients dying within 6-8 months.

After initial therapy of differentiated thyroid carcinomas, in most cases thyroidectomy and iodine-131 ablation of residual thyroid tissue, long term follow-up is currently based on periodic whole-body scintigraphy and serum thyroglobulin (Tg) determination. Both best performed after an adequate period without replacement therapy.

This protocol presumes that withdrawal of thyroxine therapy will result in an increase of endogenous thyroid stimulating hormone (TSH) and increased functional activity of any residual as well as metastatic thyroid tissue (thyroglobulin synthesis, I-131 uptake). However, withdrawing thyroxine induces hypothyroidism, which may not be well tolerated by the patient, and prolonged elevation of serum TSH levels may theoretically stimulate the growth of metastases.

As an alternative to hormonal withdrawal, exogenous TSH can be used to elevate serum TSH levels. Bovine thyrotropin was used for many years but has been associated with allergic reactions and the development of neutralizing antibodies to both bovine and human TSH, thereby hindering the accurate measurement in TSH assays and limiting the effectiveness of its repeated diagnostic use. Human pituitary derived TSH (h-TSH), obtained as a side product from the purification of human growth hormone, was also briefly used as a source of exogenous TSH. However, use of h-TSH has been discontinued due to potential transmission of Creutzfeldt-jacob disease.

Recently, a highly purified, recombinant form of the naturally occurring human protein TSH (Thyrogen) has been developed for use in elevating TSH levels in patients prior to both radioiodine scanning and thyroglobulin testing, while remaining on their hormone replacement therapy.

Thyrogen is produced by mammalian cell culture technology using a CHO ( Chinese hamster ovary) cell line co-transfected with recombinant plasmids containing DNA sequences encoding the alpha and beta subunits of TSH. Based on the fact that it has an amino acid sequence identical to that encoded by the human genome, it is unlikely that human subjects will mount an immune response to the drug as was observed with b-TSH. Animal studies have shown comparable biopotency and pharmacokinetics to those of natural pituitary TSH. Preliminary studies on safety of the drug suggest that it can be safely administered to patients with thyroid cancer with no incidence of serious or unanticipated side effects. A TSH serum concentration of greater than 100µ U/ml was achieved in thyroid cancer patients with a 10 IU two day dosing regimen, with TSH levels > 50 IU sustained for an average of 72 hr. Preliminary efficacy results suggest that it may be as effective as hormone withdrawal (endogenous TSH stimulation) in detection of remnants and metastases in patients with thyroid cancer undergoing I-131 whole body scanning. Both, however, were shown to be inferior to whole body scans obtained after a therapeutic dose of I-131. This is a not unexpected finding for it has been known from the results of several studies that one can find more and more remnants of thyroid tissues using higher and higher administered activity. Unfortunately, the larger the administered dose, the more likely is a sub lethal radiation effect on the metastasis which may lead to a decrease in its iodine concentrating ability and shorten the effective half life of iodine in the tumor, both will adversely affect the effectiveness of subsequent therapy.

Conclusions:

Based on these considerations, it is preferred to perform the diagnostic whole body scintigraphy with a 2-5 mCi dose. Alternatively a Thallium scan, which has been reported to have a high sensitivity in detection of thyroid cancer metastases, can be performed. Thallium imaging, however, is unlikely to provide information on the iodine concentrating capability of the tissues, important consideration in planning radioactive iodine therapy. If a therapeutic dose is given, a whole body study 7-10 days later may provide the best evaluation for metastatic disease.

References:

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3) Thotakura NR. et al: Biological Activity and Metabolic Clearance of a Recombinant Human Thyrotropin Produced in Chinese Hamster Ovary Cells. Endocrinology 1991;128 (1) 341-348.

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6)Giuseppe R et al: Can Iodine-131 Whole Body Scan be Replaced by Thyroglobulin Measurement in the Post- Surgical Follow-up of Differentiated Thyroid Carcinoma? J Nucl Med 1990;31: 1766-1773.

7) Wondisford FE et al: Cloning of the Human Thyrotropin B- Subunit Gene and Transient Expression of Biologically Active Human Thyrotropin after Gene Transfection. Mol Endocrinol 1988(2): 32-39.

8) Jeevanram RK et al: Influence of Initial Large Dose on Subsequent Uptake of Therapeutic Radioiodine in Thyroid Cancer Patients. Nucl Med Biol 1986;13(3): 277-279.

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J. Anthony Parker, MD PhD, Tony_Parker@bih.harvard.edu