Radioiodine-Induced Bone Marrow Suppression in Dogs and Cats

In our feline practice, we have have a radioiodine facility and have been treating hyperthyroid cats for a few years. One of my colleagues recently told me that myelosuppression can occur following radiodine treatment. I have never appreciated this in the cats I've treated, nor have I seen it reported. However, it has apparently been reported in dogs treated with very large doses of radioiodine for thyroid carcinoma (1,2).

I'd appreciate your thoughts on this topic. Do you ever see radioiodine-bone marrow suppression in your cats?

My Response:

After administration of radioiodine to a patient (human, dog or cat) with hyperthyroidism, the thyroid gland receives the highest radiation dose because it actively takes up and concentrates the I-131 (3). Other tissues, such as the salivary glands, stomach wall, and bladder also receive a radiation dose higher than that of the total body since these organs will also concentrate iodine. However, the radioiodine uptake in these tissues is much less than that of the thyroid.  The other body organs (such as the bone marrow) will receive a "cross-fire" dose — i.e., radioactivity from photons emitted from the thyroid and, to a much lesser degree, from the salivary glands and stomach  (Fig. 1) (3,4).

Figure 1: Most of the administered dose of I-131 concentrates in the thyroid, but other nearby tissues will receive a much smaller "cross-fire" dose from the gamma radioactivity (photons) emitted from the thyroid tumor.

In general, radiation doses received by the organs that do not normally concentrate iodine, including the bone marrow, are very small; however, the radiation dose delivered to the marrow may be clinically significant if a large enough radioiodine dose was administered to the patient. For example, human patients with Graves' disease or toxic nodular goiter treated with routine doses of radioiodine (e.g., 15 mCi) will not develop myelosuppression (5).

However, patients with thyroid carcinoma are generally treated with very high doses (e.g., 150 mCi to 1000 mCi of 131-I). In this subgroup of patients, severe leukopenia and thrombocytopenia are well-recognized potential adverse effects of high-dose radioiodine administration (6-8).

Dogs with thyroid carcinoma
In dogs with thyroid carcinoma treated with high-doses of radioiodine, bone marrow suppression can develop (1,2,9). Transient hematologic abnormalities (e.g., leukopenia and thrombocytopenia) are most common, but severe and permanent radioiodine-associated myelosuppression has also been reported (1).

Almost all dogs that develop bone marrow suppression have been treated with doses greater than 4 mCi/kg body weight, so it has been recommended not to exceed that dose limit, if possible (1). A higher incidence of bone marrow suppression is also seen in dogs retreated with high-dose radioiodine therapy, so the cumulative 131-I dose may also be an important factor in bone marrow suppression.  In any case, careful and close monitoring is recommended for all dogs treated with high-dose radioiodine.

Cats with hyperthyroidism and thyroid carcinoma
In contrast to dogs, I have never seen a hyperthyroid cat treated with radioiodine develop bone marrow suppression. That's true even in cats with thyroid carcinoma that are treated with 131-I doses as high as 30 to 40 mCi (10-12), which represents a dose range of approximately 5 to 10 mCi/kg on a body weight basis.

For some reason, the feline bone marrow appears to be more resistant to the radiation effects than is the canine marrow. However, this may simply relate to the fact that hyperthyroid cats tend to be much more severely affected than are the dogs with thyroid carcinoma. Therefore, most feline thyroid tumors will take up and concentrate much more of the administered 131-I dose than do canine thyroid tumors (10-15); as more of the administered dose is delivered to the thyroid, this leaves less circulating activity that will be delivered to the rest of the body, including the bone marrow.

References:

1. Turrel JM, McEntee MC, Burke BP, et al. Sodium iodide I-131 treatment of dogs with nonresectable thyroid tumors: 39 cases (1990-2003). J Am Vet Med Assoc 2006;229:542-548. 
2. Adams WH, Walker MA, Danie lGB, et al. Treatment of differentiated thyroid carcinoma in 7 dogs utilizing 131-I. Vet Radiol Ultrasound 1995;36:417-424.
3. Wyszomirska A. Iodine-131 for therapy of thyroid diseases. Physical and biological basis. Nucl Med Rev Cent East Eur 2012;15:120-123. 
4. Lamart S, Bouville A, Simon SL, et al. Comparison of internal dosimetry factors for three classes of adult computational phantoms with emphasis on I-131 in the thyroid. Phys Med Biol 2011;56:7317-7335. 
5. Silberstein EB, Alavi A, Balon HR, et al. The SNMMI practice guideline for therapy of thyroid disease with 131-I 3.0. J Nucl Med 2012;53:1633-1651. 
6. Alexander C, Bader JB, Schaefer A, et al. Intermediate and long-term side effects of high-dose radioiodine therapy for thyroid carcinoma. J Nucl Med 1998;39:1551-1554. 
7. de Keizer B, Hoekstra A, Konijnenberg MW, et al. Bone marrow dosimetry and safety of high 131-I activities given after recombinant human thyroid-stimulating hormone to treat metastatic differentiated thyroid cancer. J Nucl Med 2004;45:1549-1554. 
8. Robbins RJ, Schlumberger MJ. The evolving role of 131-I for the treatment of differentiated thyroid carcinoma. J Nucl Med 2005;46 Suppl 1:28S-37S. 
9. Peterson ME, Kintzer PP, Hurley JR, et al. Radioactive iodine treatment of a functional thyroid carcinoma producing hyperthyroidism in a dog. J Vet Intern Med 1989;3:20-25. 
10. Turrel JM, Feldman EC, Nelson RW, et al. Thyroid carcinoma causing hyperthyroidism in cats: 14 cases (1981-1986). J Am Vet Med Assoc 1988;193:359-364. 
11. Peterson ME, Becker DV. Radioiodine treatment of 524 cats with hyperthyroidism. J Am Vet Med Assoc 1995;207:1422-1428. 
12. Hibbert A, Gruffydd-Jones T, Barrett EL, et al. Feline thyroid carcinoma: diagnosis and response to high-dose radioactive iodine treatment. J Feline Med Surg 2009;11:116-124. 
13. Rijnberk A. Hyperthyroidism in the dog and its treatment with radioactive iodide. Tijdschrift voor diergeneeskunde 1966;91:789-794.
14. Rijnberk A. Thyroid tumors and hyperthyroidism in dogs. In: Clinical Endocrinology of Dogs and Cats. Dordrecht/Boston:Kluwer Academic Publishers, 1996;55-59.
15. Mooney CT. Canine hyperthyroidism In: Mooney CT, Peterson ME, eds. BSAVA Manual of Canine and Feline Endocrinology. Quedgeley, Gloucester: British Small Animal Veterinary Association, 2012;86-91.