Hypothyroidism in Cats—How is it Diagnosed and Treated?

Earlier this year, Dr. Mark Peterson participated in an Endocrinology course organized by the American College of Veterinary Internal Medicine (ACVIM). An overview of his lecture on feline hypothyroidism was summarized by Dr. Jennifer Garcia and published in the July 2015 issue of Veterinary Medicine. To access this article online, click here.

Hypothyroidism in cats—how is it diagnosed and treated? 
More cats may be affected by this disease than you think, and even cats with subclinical or mild forms may benefit from thyroid replacement therapy. In his presentation at the American College of Veterinary Internal Medicine (ACVIM) Small Animal Internal Medicine Endocrinology Course “Feline hypothyroidism: Current aspects on prevalence, diagnosis, and treatment,” Mark E. Peterson, DVM, DACVIM, noted that the number of cats with this disorder may be higher than we think and that many of these cats may benefit from therapy. Peterson explained that most cases of hypothyroidism in cats are iatrogenic in nature—after iodine-131 therapy, antithyroid drug therapy or thyroidectomy. Congenital and adult-onset forms of the disease occur but are considered rare.

As clinicians, we need to be more aware of this disease since even cats with subclinical or mild forms may benefit from thyroid replacement therapy. Peterson pointed out that up to 20% to 50% of cats with hypothyroidism may have azotemia, which will improve with treatment of the hypothyroidism. Diagnosing hypothyroidism in cats could be challenging, as even cats that are ultimately diagnosed with this disorder may initially have a thyroxine (T4) concentration in the low end of the reference range. The same can be true of a free T4 concentration, even if performed by using equilibrium dialysis.

Patient evaluation and monitoring
For patients in which hypothyroidism is suspected, either based on clinical signs or history (e.g. post iodine-131 therapy), Peterson recommends evaluating the T4 concentration in conjunction with a thyroid-stimulating hormone (TSH) concentration. While the only commercially available TSH assay is canine-specific, the assay cross-reacts with feline TSH as well. As in dogs, finding a low or low-normal T4 concentration in conjunction with an elevated TSH concentration is supportive of a diagnosis of hypothyroidism in cats.

Three months after iodine-131 therapy or antithyroid drug therapy is initiated or a thyroidectomy is performed, Peterson recommends monitoring T4 concentrations for up to six months. This should be considered sooner in cats that develop evidence of renal disease. He suggests that a post-treatment T4 concentration should be in the mid-normal range. Cats with values lower than this should have a measurement of their TSH concentration, but Peterson says some cats will experience an increase in their TSH concentration prior to a decrease in their T4 concentration.

Treatment recommendations 
So which cats should be treated with thyroid hormone therapy? Peterson suggests that cats that have supportive clinical signs—lethargy and weight gain—and low T4 or high TSH concentrations should be treated. Cats that have no clinical signs but have supportive laboratory test results and azotemia should also be treated.

For cats that require thyroid hormone supplementation, Peterson recommends a starting dose of levothyroxine 0.075 mg orally twice a day. This is higher than what is commonly used in dogs because cats metabolize the hormone much more quickly and don’t absorb it as well as dogs. Administration on an empty stomach is recommended. To monitor cats that are receiving replacement therapy, Peterson recommends a four-hour post-pill T4 concentration with a therapeutic goal in the mid-normal range.

When To Start Thyroid Hormone Replacement in Cats Treated with Radioiodine (I-131)

I have a question about thyroid hormone supplementation for iatrogenic hypothyroidism, especially in cats treated with radioiodine (I-131). More specifically, how long after radioactive iodine therapy do you wait before recommending supplementing hypothyroid cats with thyroxine?

I work as a small animal internist at a referral hospital where we treat hyperthyroid cats with radioiodine. After treatment, we routinely run serum T4 and free T4 concentrations and full blood work 30 and 90 days after the cat is discharged. I have found that about 20% of these cats are biochemically hypothyroid (low total or free T4 values) at the 30-day recheck, but many of these cats will revert to normal by the 90-day recheck. The other internist at my practice supplements these cats with L-thyroxine at the first recheck if the serum T4 and free T4 values are low. She does this even if they are not azotemic, with the rationale being that the studies show that hypothyroid cats develop worsening azotemia, which can affect their survival (1).

I am not sure if this is the best approach since I have heard that the residual thyroid follicles may take a few months to regain full function after being suppressed by the over-active thyroid tissue for so long. However, I just want to do what's best (don't we all!)

Thank you so much. I enjoy reading your website and attending your lectures at conferences.

My Response:

First of all, I don't find that free T4 determinations are all that helpful in the diagnosis of feline hypothyroidism (2-4). Many cats treated with radioiodine with maintain low-normal values for both total and free T4 but develop high serum TSH concentrations, a situation commonly referred to as subclinical hypothyroidism in human patients. The problem with our cats, however, is that although most of these cats do remain nonclinical for hypothyroidism, many will develop azotemia that will progressively worsen without treatment with thyroid hormone replacement.

So what I do is as follows: at 30-days post-treatment, I monitor serum concentrations of T4, free T4, and TSH, along with a serum chemistry panel to follow kidney values. If T4 or free T4 values fall into the lower third of the reference range (below 1.5-2.0 µg/dl; reference interval ≈1-4 µg/dl) and TSH rises (above 0.5-0.6 ng/dl; reference range, 0.03-0.03 ng/ml), then the cat is mildly hypothyroid. Some of these cats will recover enough thyroid function to end up as euthyroid, but most remain mildly hypothyroid at both 3 and 6 months, at least based on the finding of high TSH concentrations.

In these cats with mild or subclinical hypothyroidism, I don't like to treat with levothyroxine (LT4) at this time unless evidence of chronic kidney disease (CKD) has developed, with serum creatinine values rising from normal to greater than 2.0 mg/dl. However, this definitely indicates the need for LT4 replacement in order to help maintain renal perfusion and stabilize the serum creatinine concentrations (3-5).

If we decide not to treat (which is generally the case unless new azotemia has developed), then we monitor again with the same thyroid and renal profiles at 3- and 6 months. Again, if T4 falls into the low-normal range (less than 1.5-2.0 µg/dl) and TSH is clearly high (above 0.5-0.6 ng/dl), I would definitely supplement if new or worsening azotemia is detected. If no azotemia is present, I generally continue to monitor and don't supplement with LT4 unless azotemia does develop.

Now, if the serum T4 is below normal and the TSH is clearly high at 3 or 6 months (or later), then the cat has overt hypothyroidism (no longer subclinical) and I would definitely supplement with L-T4 (2-4). Many of these cats are still not very symptomatic, but that may simply be a matter of time. If left untreated for 1 to 2 years, most of those cats will develop classical signs of hypothyroidism (eg, lethargy, hair loss, etc).

So in your case, I would add-in serum TSH to your monitoring protocol. If your owners find that too expensive, then I would replace the free T4 measurement with TSH determination, which is more more helpful in monitoring for cats treated with radioiodine.

References:

1. Williams TL, Peak KJ, Brodbelt D, et al. Survival and the development of azotemia after treatment of hyperthyroid cats. J Vet Intern Med 2010;24:863-869. 
2. Peterson ME. Feline focus: Diagnostic testing for feline thyroid disease: hypothyroidism. Compend Contin Educ Vet 2013;35:E4.  
3. Peterson ME. Diagnosis and management of iatrogenic hypothyroidism In: Little SE, ed. August's Consultations in Feline Internal Medicine: Elsevier, 2014;in press.
4. Peterson ME, Guterl JN.Subclinical iatrogenic hypothyroidism in the cat: Clinical, laboratory, and thyroid scintigraphic findings in 35 cases. J Vet Intern Med 2015;29:448-449.
5. Williams TL, Elliott J, Syme HM. Effect on renal function of restoration of euthyroidism in hyperthyroid cats with iatrogenic hypothyroidism. J Vet Intern Med 2014;28:1251-1255.

Top Endocrine Publications of 2014: The Feline Thyroid Gland

In my fourth compilation of the canine and feline endocrine publications of 2014, I’m moving on to disorders of the feline thyroid gland. Listed below are 32 papers that deal with a variety of thyroid gland topics of issues of clinical importance in cats.

These range from from a survey of owners' perceptions and experiences after using radioiodine to treat their hyperthyroid cats (1) to the results of an online survey to determine owner experiences and opinions on the management of their cats using oral anti-thyroid medications (14); from case reports of methimazole or carbimazole-induced toxicity in cats with hyperthyroidism (3,5,19) to a number of publications involving various issues of medical treatment with methimazole (2,4,7,14,15,20); from a study of the concurrent diseases detected in hyperthyroid cats undergoing assessment for radioiodine treatment (25) to concurrent diseases and conditions in cats with renal infarcts (including hyperthyroidism (12); and finally, from studies investigating the efficacy of an iodine-restricted diet for management of cats with hyperthyroidism (9,30) to other forms of dietary management for this endocrine disease (19,24).

Finally, 2 investigations add further data concerning chronic renal disease in hyperthyroid cats (31,32), as well as the fact that iatrogenic hypothyroidism contributes to azotemia in these cats (31). A number of 2014 publications deal with the rising prevalence and/or etiopathogenesis of hyperthyroidism in cats (6,16,17,21,22,23,29). Unfortunately, further studies are needed to better define the cause(s) of this perplexing disease (download my review paper for more discussion) (23).

References:

1. Boland LA, Murray JK, Bovens CP, et al. A survey of owners' perceptions and experiences of radioiodine treatment of feline hyperthyroidism in the UK. J Feline Med Surg 2014;16:663-670. 
2. Boretti FS, Sieber-Ruckstuhl NS, Schafer S, et al. Transdermal application of methimazole in hyperthyroid cats: a long-term follow-up study. J Feline Med Surg 2014;16:453-459. 
3. Bowlt K, Cattin I, Stewart J. Carbimazole-associated hypersensitivity vasculitis in a cat. J Small Anim Pract 2014;55:643-647. 
4. Bruyette D. Methimazole management of feline hyperthyroidism. Today's Veterinary Practice 2014;July/August:38-41.
5. Castro Lopez J, Lloret A, Ravera I, et al. Pyogranulomatous mural folliculitis in a cat treated with methimazole. J Feline Med Surg 2014;16:527-531. 
6. Chow K, Beatty JA, Barrs VR, et al. PBDEs and feline hyperthyroidism. Vet Rec 2014;175:433-434. 
7. Daminet S, Kooistra HS, Fracassi F, et al. Best practice for the pharmacological management of hyperthyroid cats with antithyroid drugs. J Small Anim Pract 2014;55:4-13. 
8. Daniel GB, Neelis DA. Thyroid scintigraphy in veterinary medicine. Semin Nucl Med 2014;44:24-34. 
9. Fritsch DA, Allen TA, Dodd DE, et al. A restricted iodine food reduces circulating thyroxine concentrations in cats with hyperthyroidism. Intern J Appl Res Vet Med 2014;12:24-32. 
10. Fryers A, Elwood C. Hypokalaemia in a hyperthyroid domestic shorthair cat with adrenal hyperplasia. J Feline Med Surg 2014;16:853-857. 
11. Galgano M, Spalla I, Callegari C, et al. Primary hypothyroidism and thyroid goiter in an adult cat. J Vet Intern Med 2014;28:682-686. 
12. Hickey MC, Jandrey K, Farrell KS, et al. Concurrent diseases and conditions in cats with renal infarcts. J Vet Intern Med 2014;28:319-323. 
13. Higgs P, Costa M, Freke A, et al. Measurement of thyroxine and cortisol in canine and feline blood samples using two immunoassay analysers. J Small Anim Pract 2014;55:153–159. http://onlinelibrary.wiley.com/doi/10.1111/jsap.12181/abstract
14. Higgs P, Murray JK, Hibbert A. Medical management and monitoring of the hyperthyroid cat: a survey of UK general practitioners. J Feline Med Surg 2014;16:788-795. 
15. Hill K, Gieseg M, Bridges J, et al. The pharmacokinetics of methimazole in a novel lipophilic formulation administered transdermally to healthy cats. N Z Vet J 2014;62:208-213. 
16. Hill KE, Shaw IC. Does exposure to thyroxine-mimics cause feline thyroid hyperplasia? Vet Rec 2014;175:228-229. 
17. Kooistra HS. Feline hyperthyroidism: a common disorder with unknown pathogenesis. Vet Rec 2014;175:456-457. 
18. Kujawa A, Olias P, Bottcher A, et al. Thyroid transcription factor-1 is a specific marker of benign but not malignant feline lung tumours. J Comp Pathol 2014;151:19-24. 
19. Laflamme D, Gunn-Moore D. Nutrition of aging cats. Vet Clin North Am Small Anim Pract 2014;44:761-774, vi. 
20. Mardell EJ. Diagnosis and management of feline hyperthyroidism. In Practice 2014;35:162-170.
21. McLean JL, Lobetti RG, Schoeman JP. Worldwide prevalence and risk factors for feline hyperthyroidism: A review. J S Afr Vet Assoc 2014;85:1097. 
22. O'Neill DG, Church DB, McGreevy PD, et al. Prevalence of disorders recorded in cats attending primary-care veterinary practices in England. Vet J 2014;202:286-291. 
23. Peterson ME. Feline hyperthyroidism: an animal model for toxic nodular goiter. J Endocrinol 2014;223:T97-T114. 
24. Peterson ME, Eirmann L. Dietary management of feline endocrine disease. Vet Clin North Am Small Anim Pract2014;44:775-788. 
25. Puig J, Cattin I, Seth M. Concurrent diseases in hyperthyroid cats undergoing assessment prior to radioiodine treatment. J Feline Med Surg 2014. 
26. Rasmussen SH, Andersen HH, Kjelgaard-Hansen M. Combined assessment of serum free and total T4 in a general clinical setting seemingly has limited potential in improving diagnostic accuracy of thyroid dysfunction in dogs and cats (Letter). Vet Clin Pathol 2014;43:1-3. 
27. Sangster JK, Panciera DL, Abbott JA, et al. Cardiac biomarkers in hyperthyroid cats. J Vet Intern Med 2014;28:465-472. 
28. Schober KE, Kent AM, Aeffner F. Tachycardia-induced cardiomyopathy in a cat. Schweiz Arch Tierheilkd 2014;156:133-139. 
29. Stephens MJ, Neill DG, Church DB, et al. Feline hyperthyroidism reported in primary-care veterinary practices in England: prevalence, associated factors and spatial distribution. Vet Rec 2014;175:458. 
30. van der Kooij M, Becvarova I, Meyer HP, et al. Effects of an iodine-restricted food on client-owned cats with hyperthyroidism. J Feline Med Surg 2014;16:491-498. 
31. Williams TL, Elliott J, Syme HM. Effect on renal function of restoration of euthyroidism in hyperthyroid cats with iatrogenic hypothyroidism. J Vet Intern Med 2014;28:1251-1255. 
32. Williams TL, Elliott J, Syme HM. Association between urinary vascular endothelial growth factor excretion and chronic kidney disease in hyperthyroid cats. Res Vet Sci 2014;96:436-441. 

Top Endocrine Publications of 2013: The Feline Thyroid Gland

In my eighth compilation of the canine and feline endocrine publications of 2013, I’m moving on to disorders of the feline thyroid gland.

Listed below are 26 papers published in 2013 that deal with a variety of thyroid gland topics of issues of clinical importance in cats.

These range from from studies of the duration of serum T4 suppression in cats treated with methimazole (1) to the results of a long-term follow-up study of cats treated with transdermal methimazole (2); and from case reports of methimazole or carbimazole-induced toxicity in cats (3,6,19) to the results of an online survey to determine owner experiences and opinions on the management of their hyperthyroid cats using oral anti-thyroid medications (5).

Other studies report the variability in iodine concentrations found in commercial cats foods in the USA (7) to investigation of the radioactivity in the excreta of hyperthyroid cats treated with radioiodine (8); from a comparison of computed tomography and scintigraphy for thyroid imaging in hyperthyroid cats (9) to a review of the clinical usefulness of an assay for measurement of circulating B-type natriuretic peptide (BNP) concentration in hyperthyroid cats (11); and from an overview of the diagnostic tests useful for confirming feline hyperthyroidism (4,12,13,15,17) and hypothyroidism (14) to a study of the effects of an iodine-restricted diet for management of cats with hyperthyroidism (22); from investigations of the pathophysiological mechanism for altered calcium homeostasis in hyperthyroid cats (24) to studies of the renin-angiotensin-aldosterone system activity in hyperthyroid cats with and without hypertension (25).

References:

1. Boretti FS, Sieber-Ruckstuhl NS, Schafer S, et al. Duration of T4 suppression in hyperthyroid cats treated once and twice daily with transdermal methimazole. J Vet Intern Med 2013;27:377-381. 
2. Boretti FS, Sieber-Ruckstuhl NS, Schafer S, et al. Transdermal application of methimazole in hyperthyroid cats: a long-term follow-up study. J Feline Med Surg 2013;16:453-459. 
3. Bowlt K, Cattin I, Stewart J. Carbimazole-associated hypersensitivity vasculitis in a cat. J Small Anim Pract 2013; doi: 10.1111/jsap.12154. 
4. Bruyette D. Feline hyperthyroidism: Diagnosis and therapeutic modalities. Today's Veterinary Practice 2013;3:25-30.
5. Caney SM. An online survey to determine owner experiences and opinions on the management of their hyperthyroid cats using oral anti-thyroid medications. J Feline Med Surg 2013;15:494-502. 
6. Castro Lopez J, Lloret A, Ravera I, et al. Pyogranulomatous mural folliculitis in a cat treated with methimazole. J Feline Med Surg 2013;16:527-531. 
7. Edinboro CH, Pearce EN, Pino S, et al. Iodine concentration in commercial cat foods from three regions of the USA, 2008-2009. J Feline Med Surg 2013;15:717-724. 
8. Lamb V, Gray J, Parkin T, et al. Measurement of the radioactivity in the excreta of cats treated with iodine-131 for hyperthyroidism. Vet Rec 2013;172:45. 
9. Lautenschlaeger IE, Hartmann A, Sicken J, et al. Comparison between computed tomography and Tc-Pertechnetate scintigraphy characteristics of the thyroid gland in cats with hyperthyroidism. Vet Radiol Ultrasound 2013;54:666-673. 
10. North DL. Uptake of 131-I in households of thyroid cancer patients. Health Phys 2013;104:434-436. 
11. Oyama MA, Boswood A, Connolly DJ, et al. Clinical usefulness of an assay for measurement of circulating N-terminal pro-B-type natriuretic peptide concentration in dogs and cats with heart disease. J Am Vet Med Assoc 2013;243:71-82. 
12. Paepe D, Verjans G, Duchateau L, et al. Routine health screening: findings in apparently healthy middle-aged and old cats. J Feline Med Surg 2013;15:8-19. 
13. Peterson ME. More than just T4: Diagnostic testing for hyperthyroidism in cats. J Feline Med Surg 2013;15:765-777. 
14. Peterson ME. Feline focus: Diagnostic testing for feline thyroid disease: hypothyroidism. Compend Contin Educ Vet 2013;35:E4. 
15. Peterson ME. Feline focus: Diagnostic testing for feline thyroid disease: hyperthyroidism. Compend Contin Educ Vet 2013;35:E3. 
16. Ramoo S, Bradbury L, Anderson G, et al. Sedation of hyperthyroid cats with subcutaneous administration of a combination of alfaxalone and butorphanol. Aust Vet J 2013;91:131-136. 
17. Rasmussen SH, Andersen HH, Kjelgaard-Hansen M. Combined assessment of serum free and total T4 in a general clinical setting seemingly has limited potential in improving diagnostic accuracy of thyroid dysfunction in dogs and cats (Letter). Vet Clin Pathol 2014;43:1-3. 
18. Sabatino BR, Rohrbach BW, Armstrong PJ, et al. Amino acid, iodine, selenium, and coat color status among hyperthyroid, Siamese, and age-matched control cats. J Vet Intern Med 2013;27:1049-1055. 
19. Snead E, Kerr M, Macdonald V. Cutaneous lymphoid hyperplasia mimicking cutaneous lymphoma in a hyperthyroid cat. Can Vet J 2013;54:974-978. 
20. Sparkes A. Health screening of cats: some timely justification. J Feline Med Surg 2013;15:5. 
21. Taylor BE, Leibman NF, Luong R, et al. Detection of carcinoma micrometastases in bone marrow of dogs and cats using conventional and cell block cytology. Vet Clin Pathol 2013;42:85-91.
22. van der Kooij M, Becvarova I, Meyer HP, et al. Effects of an iodine-restricted food on client-owned cats with hyperthyroidism. J Feline Med Surg 2013;14:491-498. 
23. Whitehouse-Tedd KM, Cave NJ, Ugarte CE, et al. Isoflavone metabolism in domestic cats (Felis catus): Comparison of plasma metabolites detected after ingestion of two different dietary forms of genistein and daidzein. J Anim Sci 2013;91:1295-1306. 
24. Williams TL, Elliott J, Berry J, et al. Investigation of the pathophysiological mechanism for altered calcium homeostasis in hyperthyroid cats. J Small Anim Pract 2013;54:367-373. 
25. Williams TL, Elliott J, Syme HM. Renin-angiotensin-aldosterone system activity in hyperthyroid cats with and without concurrent hypertension. J Vet Intern Med 2013;27:522-529. 
26. Wongbandue G, Jewgenow K, Chatdarong K. Effects of thyroxin (T4) and activin A on in vitro growth of preantral follicles in domestic cats. Theriogenology 2013;79:824-832. 

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.

The Many Isotopes of Radioiodine and Their Uses in Medicine

My question is about using radioactive iodine (radioiodine) to treat hyperthyroidism. Is radioiodine-131 (131-I) the only radioisotope we can use to treat this condition? Have you (or anyone else) ever used other radioisotopes of iodine for treatment of hyperthyroidism, such as 123-I, 124-I, or 128-I?

If I-131 is the only form of radioiodine used to treat hyperthyroidism, do the other isotopes of radioiodine have any other medical uses for imaging or therapy?

My Response:

There are 37 known isotopes of iodine (I) from 108-I to 144-I, but only one, 127-I, is stable (i.e., nonradioactive). So as you stated, there are a number of forms of radioiodine other than 131-I (1,2).

Of all of these iodine radioisotopes, only 4 are used as tracers or therapeutic agents in medicine. These are 123-I, 124-I, 125-I, and 131-I. Essentially all industrial production of radioiodine isotopes involves these 4 useful radionuclides.

Of these, however, only I-131 is useful for treating hyperthyroidism. To understand why, let's review these 4 isotopes so you can understand what each of them can do for us in clinical medicine.

Iodine-131
Let's start with iodine-131 (I-131). This radioisotope of iodine has a half-life of 8 days and emits both beta-particles and gamma radiation (see Figure, above) (3-5). The beta-particles, which cause 90% of the tissue damage, are comparatively energetic, travel a maximum of 2 mm in tissue, and have an average path length of 400 μm. Therefore beta-particles are locally destructive to the thyroid tumor but spare adjacent atrophic thyroid tissue, parathyroid glands, and other cervical structures (3-5).

When very high doses are administered, it can also be useful to treat thyroid carcinoma in cats (5-7). In dogs, I-131 is less commonly used, but will work to destroy the thyroid tumor if it is functional and will take up enough I-131 to destroy the tumor (6,8).

I-131 also emits gamma radiation (about 10% of its energy), but this does little actual tissue damage. However, because of this emitted gamma radiation, I-131 can be "seen" by nuclear medicine imaging techniques (i.e., gamma cameras) (2,9). I-131 is almost never used for thyroid scintigraphy, however, since other less-damaging radioisotopes of iodine (I-123, see below) or technetium-99m are preferred in diagnostic situations when only nuclear imaging is required (9).

Figure 1— Decay of radioiodine-131 (I-131)  As I-131 decays (half-life of 8.0 days), it emits both beta-particles and gamma ray energy. The primary emissions of 131-I decay are electron (beta) particles, which are responsible for 90% of the thyroid tumor destruction. Most other radioisotopes of iodine are primarily gamma-emitters (no beta-particle emission).

Iodine-123
Radioiodine-123 is primarily a gamma-emitter with a relatively short half life (13 hours). The main use for I-123 is as a nuclear imaging tracer (i.e., thyroid scintigraphy) to evaluate the anatomic and physiologic function of the thyroid (2,9,10).

I-123 decays by electron capture (EC) to emit a high-speed internal conversion electron (not a beta ray), but this does little cellular damage due to the nuclide's short half-life and the relatively small fraction of such events. In addition, I-123 decays to emit a 159 keV gamma ray, which is well-suited for nuclear imaging (nuclear scintigraphy).

Most authorities consider I-123 to be the radionuclide of choice for imaging the thyroid gland (9,10). However, I-123 is worthless for treating hyperthyroidism because this gamma radiation doesn't help us in destroying thyroid tissue (we need the beta particles emitted by I-131 to do this).

Iodine-125
Iodine-125 (125-I) is a radioisotope of iodine which has uses in biological assays (e.g., radioimmunoassays) and in radiation therapy as brachytherapy (i.e., to treat prostate cancer and brain tumors). It also has a more limited role in nuclear medicine imaging.

Because of its relatively long half-life (59 days) and emission of low-energy photons which can be detected by gamma-counter crystal detectors, I-125 is a preferred isotope for tagging antibodies in radioimmunoassay and other gamma-counting procedures involving proteins outside the body (11). These same properties of the isotope make it useful for brachytherapy and for certain nuclear medicine scanning procedures, in which it is attached to proteins (albumin or fibrinogen), and where a longer half-life than provided by I-123 is required for tests lasting several days.

In addition to its use in biological assays, iodine-125 is also commonly used by radiation oncologists as brachytherapy to treat cancer at sites other than the thyroid, especially in human prostate cancer (12,13). When I-125 is used therapeutically, it is encapsulated in titanium seeds and implanted in the area of the tumor, where it remains. The low energy of the gamma spectrum in this case limits radiation damage to tissues far from the implanted capsule.

Again, I-125 is used therapeutically (to destroy tumor tissue) only in brachytherapy. Because this radioisotope does not emit any beta particles, I-125 is not effective for treatment of hyperthyroidism or ablation of thyroid carcinoma (3).

Iodine-125 has been used for thyroid imaging, but iodine-123 is preferred for this purpose, due to its better radiation penetration and shorter half-life (13 hours vs. 59 days) (10).

Iodine-124
Iodine-124 is a proton-rich isotope of iodine with a half-life of 4.18 days. Its modes of decay are about 75% electron capture and 25% positron emission. Like iodine-123 and I-125, this isotope emits no beta radiation and cannot be used for treatment of hyperthyroidism.

The main use of iodine-124 is to directly image the thyroid using positron emission tomography (PET scanning) (). Iodine-124 can also be used as a PET radiotracer with a usefully longer half-life compared with fluorine-18. In this use, the nuclide is chemically bonded to a pharmaceutical to form a positron-emitting radiopharmaceutical, and injected into the body, where again it is imaged by PET scan (14-16).

References:

1. Johnson PM, Sciarra JJ, Stickley EE. Radioactive iodine isotopes. Rev Argent Endocrinol Metab 1964;10:93-94. 
2. Croft BY, Tsui BMW. Nuclear medicine. In: Medical Imaging: Principles and Practices. Analoui M, Bronzino JD, Peterson DR (eds). Boca Roton, FL: CRC Press, Taylor & Francis Group. 2013:4-1.
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. Peterson ME. Radioiodine treatment of hyperthyroidism. Clin Tech Small Anim Pract 2006;21:34-39. 
5. Peterson ME, Broome MR. Radioiodine for feline hyperthyroidism In: Bonagura JD, Twedt DC, eds. Kirk's Current Veterinary Therapy, Volume XV. Philadelphia: Saunders Elsevier, 2013;in press.
6. Feeney DA, Anderson KL. Nuclear imaging and radiation therapy in canine and feline thyroid disease. Vet Clin North Am Small Anim Pract 2007;37:799-821, viii. 
7. 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. 
8. 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. 
9. Rault E, Vandenberghe S, Van Holen R, et al. Comparison of image quality of different iodine isotopes (I-123, I-124, and I-131). Cancer Biother Radiopharm 2007;22:423-430. 
10. Park HM. 123-I: almost a designer radioiodine for thyroid scanning. J Nucl Med 2002;43:77-78. 
11. Yalow RS. Radioimmunoassay. Annu Rev Biophys Bioeng 1980;9:327-345. 
12. Georgakopoulos J, Zygogianni A, Papadopoulos G, et al. Permanent implantation as brachytherapy technique for prostate carcinoma-review of clinical trials and guidelines. Rev Recent Clin Trials 2012;7:173-180. 
13. Schwarz SB, Thon N, Nikolajek K, et al. Iodine-125 brachytherapy for brain tumours--a review. Radiat Oncol 2012;7:30. 
14. Bailey DL, Townsend DW, Valk PE, et al. Positron Emission Tomography: Basic Sciences. Secaucus, NJ: Springer-Verlag, 2005.
15. Saha GB. Basics of PET Imaging: Physics, Chemistry, and Regulations. Second ed. New York, NY:Springer. 2010.
16. Budinger TF VanBrocklin HF. Positron-emission tomography. In: Medical Imaging: Principles and Practices. Analoui M, Bronzino JD, Peterson DR (eds). Boca Roton, FL:CRC Press, Taylor & Francis Group. 2013;7-1.

Relationship Between Stomatitis and Hyperthyroidism in Cats?

My patient is a 12-year-old, male hyperthyroid cat who had a full mouth extraction done 4 years ago because of severe oral disease. Since that time, this cat had required Depo-medrol injections every 1-2 months to help keep the stomatitis under control.

About a year ago, the cat developed hyperthyroidism and was treated with radioiodine. Since that time, he has remained euthyroid. But unexpectedly, his stomatitis has also completely resolved, and no further steroid treatment has been needed.

Nothing else changed in the household — i.e., no diet changes, no other medications, and this has always been an indoor cat. I am happy for the cat (and the owner), but am curious if you have an explanation to explain the apparent connection between the stomatitis and hyperthyroidism?

My Response

I've seen a few hyperthyroid cats over the years whose concurrent oral disease improved after they were treated with radioiodine. I do not know for certain why their oral lesions sometime respond so well to correction of the hyperthyroid state.

Are some hyperthyroid cats iodine deficient?
One theory is that some of these hyperthyroid cats are iodine deficient (even on a "normal" iodine diet) because of their increased need for iodine to make thyroid hormone (1). Once we cure them with radioiodine, their need for iodine goes down because now they are no longer making excess amount of thyroid hormone.

Figure 1. Chemical structure of thyroxine.
Notice that each T4 molecule contains 4 atoms of iodine atoms 

Remember that each T4 molecule contains 4 iodine atoms (Figure 1), whereas each T3 molecule contains 3 iodine atoms.

Salivary glands normally concentrate iodine
Iodine appears to be very important for oral health (2,3). Normally, the salivary glands have the capacity to concentrate iodide as well as the thyroid tissue. The iodide is then secreted into saliva such that its salivary concentration has been reported to vary from 20 to 100 times that found in the serum (4,5).

Figure 2. Thyroid scintigraphy of a normal cat.
Notice the similar uptake of the tracer in the thyroid lobes and salivary glands. Also note that the stomach also concentrates the radionuclide to some extent (area of uptake on bottom of scan image).

In proof of this, remember that the salivary glands can be seen to concentrate ("take up") radioiodine with thyroid scintigraphy very well (see Figure 2) —equal to the thyroid glands in a normal cat (6-8).

Iodine deficiency and immunity
Based on a number of studies in man and other species, it's clear that iodine has many extra-thyroidal functions in the body. Iodine plays an important role in the immune response. It also has anti-inflammatory and anti-oxidative actions (2,3,9-12).

Bottom Line

Marked variation of iodine levels between cat foods have been reported in studies of commercial foods, in which the iodine content between foods varied by a factor of 30-fold (13-15). It also possible that some cats would be consistently fed a low-iodine diet for prolonged periods, leading to an iodine-deficient state.

So it is possible that this cat has been chronically iodine deficient, which may have become worse when hyperthyroidism developed. By treating the hyperthyroidism, the total body need for iodine would be expected to decrease. So that might explain why the stomatitis improved after correction of the hyperthyroidism with radioiodine.

Again, I'm not talking about the use of low-iodine diets (y/d) for hyperthyroidism here, but that diet could, at least theoretically, make the oral disease worse in these cats.

References:

1. Wakeling J, Elliott J, Petrie A, et al. Urinary iodide concentration in hyperthyroid cats. American Journal of Veterinary Research 2009;70:741-749. 
2. Venturi S, Venturi M. Iodine in evolution of salivary glands and in oral health. Nutrition and Health 2009;20:119-134. 
3. Brownstein, D. Iodine: Why you need it, Why you can't live without it. Medical Alternative Press; 3rd edition. 2004.
4. Myant NB. Iodine metabolism of salivary glands. Annals of the New York Academy of Sciences 1960;85:208-214.
5. Mason DK, Harden R McG, Alexander WD. The salivary and thyroid glands: A comparative study in man. British Dental Journal 1967;122:485-489. 
6. Beck KA, Hornof WJ, Feldman EC. The normal feline thyroid. Technetium pertechnetate imaging and determination of thyroid to salivary gland radioactivity ratios in 10 normal cats. Veterinary Radiology & Ultrasound 1985;26:35-38. 
7. Peterson ME, Becker DV. Radionuclide thyroid imaging in 135 cats with hyperthyroidism. Veterinary Radiology 1984;25:23-27.
8. Broome MR. Thyroid scintigraphy in hyperthyroidism. Clinical Techniques in Small Animal Practice 2006;21:10-16.
9. Marani L, Venturi S, Masala R. Role of iodine in delayed immune response. Israeli Journal of Medical Science 1985;21:864. 
10. Venturi S, Venturi M. Iodine, thymus, and immunity. Nutrition 2009;25:977-979.
11. Miller DW. Extrathyroidal benefits of iodine. Journal of American Physicians and Surgeons 2006;11:106-110. 
12. Ware CM, Wishner LA. The lipid antioxidant properties of iodine compounds. Lipids 1968;3:182-183.
13. Johnson LA, Ford HC, Tarttelin MF, et al. Iodine content of commercially-prepared cat foods. New Zealand Veterinary Journal 1992;40:18-20. 
14. Ranz D, Tetrick M, Opitz B, et al. Estimation of iodine status of cats. Journal of Nutrition 2002;132 (suppl 2):1751S-1753S. 
15. Edinboro CH, Scott-Moncrieff JC, Glickman LT. Feline hyperthyroidism: potential relationship with iodine supplement requirements of commercial cat foods. Journal of Feline Medicine Surgery 2010;12:672-679. 

When to Stop Methimazole Before Radioiodine Treatment

A client of ours has opted to have her cat's hyperthyroid disease treated by Radiocat. In their pre-treatment instructions they state that the cat must be off methimazole for 2 weeks prior to I-131 treatment. But then the client called another treatment facility, and they told her that the cat can stay on the methimazole right up until the treatment.

So my questions are the following:

1. Which is the right thing to do? Should we stop methimazole or not before the cat is admitted for radioiodine treatment?
2. Will methimazole interfere with the radioiodine treatment? 
3. What is the danger in stopping (or not discontinuing) the methimazole  What problems might develop? Can we protect the cat from those problems and if so, how?

Finally, I would like to get your opinion about the use of "fixed" versus "individualized" radioiodine doses for hyperthyroid cats.  I know that most facilities use a fixed dose (eg, 4 mCi), regardless of size of cat or how elevated the serum thyroid hormone values are in the cats.

My Response:

Should methimazole be stopped before radiodiodine treatment?
Methimazole treatment does NOT appear to interfere with the efficacy of I-131 treatment (1,2), so some facilities say that it's fine to continue the drug up to the day of treatment.

However, think about what we are doing in a hyperthyroid cat to the hypothalamic-pituitary-thyroid axis when we give methimazole (or y/d for that matter). Prior to treatment, all clinically hyperthyroid cats will have undetectable serum TSH levels (3-6)— the high circulating T4 and T3 feed back to the pituitary and shut off TSH secretion. Without any TSH, the "normal" thyroid tissue cannot continue to function and will atrophy. The thyroid tumor doesn't need TSH, and that's why the cat is hyperthyroid.

Untreated hyperthyroid cats generally have undetectable serum TSH concentrations.
Lowering the high serum T4 with methimazole may allow TSH secretion to return to normal. 

Now we give methimazole or y/d. By lowering the serum T4, we lose the negative feedback effect on the pituitary thyrotrophs and tell the pituitary to start secreting TSH once again (4,6,7). This will stimulate the normal, atrophied thyroid tissue to start to function again (8). Part of normal thyroid function is the ability to "take up" iodine from the circulation to make thyroid hormone.

So if we treat a hyperthyroid cat with I-131 that is currently well-controlled on methimazole or y/d, we take the risk that the thyroid iodine uptake in the "normal" tissue would be much greater than it would have been prior to the methimazole administration (2,8). In other words, treating with methimazole may allow more of the radioiodine to get taken up by any remaining normal thyroid tissue and would therefore increase the risk of iatrogenic hypothyroidism (2).

If we stop the methimazole for a few days, we can predict that the high T4 would again shut off TSH and decrease the percentage of I-131 uptake by any remaining "normal" thyroid tissue. That is the reason I like to stop the methimazole for 5-7 days prior to treatment.

In some cats with chronic, severe hyperthyroidism, however, the risk of "thyroid storm" outweighs the rise of iatrogenic hypothyroidism (9). In those cats, I generally continue the methimazole up to the day of treatment. In these select, unstable cases (most of which have been on methimazole for years), I don't want to risk having these cats develop a fatal arrhythmia or cardiac failure because we stopped the methimazole.

Which is better— Fixed I-131 doses or individual I-131 dose calculations?
Giving a fixed dose of 4 mCi of radioiodine to all hyperthyroid cats makes no sense to me, since over half of my cats respond completely to a dose less than 3 mCi, whereas other cats with very large benign goiters need doses of 10-12 mCi.  When I show a series of thyroid scintigraphic images (see Figure below) to cat owners and ask them if it is reasonable that the cats with smaller tumors would need much smaller I-131 doses then the cats with large to huge tumors, they universally agree!

Thyroid scintiscans from 4 hyperthyroid cats, with thyroid tumors ranging from small to very large in size. Obviously, cats with small to medium-sized thyroid adenomas require much lower I-131 doses to ablate their thyroid tumors than do the cats with the much large tumor volumes.

It certainly is much more difficult and requires more work to do individual I-131 dose calculations (thyroid uptakes and thyroid scintigraphy are needed) for hyperthyroid cats (2,10). Obviously, it is much easier for a radioiodine treatment facility to give a standard, fixed dose to all cats. I just don't believe it's better for the cats — those with severe hyperthyroidism can be undertreated, whereas cats with mild hyperthyroidism will be overtreated and are much more likely to develop hypothyroidism.  

References:

1. Nieckarz JA, Daniel GB. The effect of methimazole on thyroid uptake of pertechnetate and radioiodine in normal cats. Vet Radiol Ultrasound 2001;42:448-457. 
2. Peterson ME, Broome MR. Radioiodine for hyperthyroidism. In: Bonagura JD, Twedt DC (eds): Current Veterinary Therapy V. Philadelphia, Saunders Elsevier, 2012; in press
3. Wakeling J, Smith K, Scase T, et al. Subclinical hyperthyroidism in cats: a spontaneous model of subclinical toxic nodular goiter in humans? Thyroid 2007;17:1201-1209. 
4. Wakeling J. Use of thyroid stimulating hormone (TSH) in cats. Can Vet J 2010;51:33-34. 
5. Wakeling J, Elliott J, Syme H. Evaluation of predictors for the diagnosis of hyperthyroidism in cats. J Vet Intern Med 2011;25:1057-1065. 
6. Baral R, Peterson ME: Thyroid gland disorders, In: Little, S.E. (ed), The Cat: Clinical Medicine and Management. Philadelphia, Elsevier Saunders. pp. 571-592, 2012
7. Williams TL, Elliott J, Syme HM. Association of iatrogenic hypothyroidism with azotemia and reduced survival time in cats treated for hyperthyroidism. J Vet Intern Med 2010;24:1086-1092. 
8. Fischetti AJ, Drost WT, DiBartola SP, et al. Effects of methimazole on thyroid gland uptake of 99mTC-pertechnetate in 19 hyperthyroid cats. Vet Radiol Ultrasound 2005;46:267-272. 
9. Ward CR. Feline thyroid storm. Vet Clin North Am Small Anim Pract 2007;37:745-54.
10. Peterson ME, Broome MR. Thyroid scintigraphic findings in 917 cats with hyperthyroidism. J Vet Intern Med 2012; 26:754.

How Does Radioiodine Really Work to Treat Hyperthyroidism?

I had a general question regarding radioiodine (I-131) treatment for hyperthyroid cats. Although I have referred a number of feline patients for this treatment, I do not know that much about the details of the treatment.

Do all cats receive the same dose or do you vary the dose based upon the severity of the cat's hyperthyroidism? How does one actually administer the radioiodine dose? 

A little explanation would be appreciated. Thanks!

My Response:

Route of I-131 administration
We've been giving the radioiodine subcutaneously since 1986 (1). Prior to that, we initially tried the oral route, but that meant handling radioactive capsules (and hoping the cats wouldn't chew them) or stomach tubing the cats (and hoping the cats wouldn't vomit). In human patients, they generally put the radioiodine solution into a juice drink to cover up the "iodine taste" and the people just drink the solution. Obviously, that wouldn't work in cats.

Administering radioiodine
subcutaneously to a cat

From around 1980 to 1986 we gave all of the doses IV, which worked fine. However, that meant that two people always needed to be exposed when the dose is administered (now I generally do it by myself) and the cat needed to have a catheter placed for the injection. The IV administration worked well, but occasionally, I saw anaphylactoid reactions (rather terrifying!) upon treatment. Obviously, there is something in the solution that the cats don't like when the drug is given more than once intravenously. I have NEVER seen an anaphylactoid reaction when the radioiodine solution is given subcutaneously.

Calculation of the I-131 dose
As far as dosing goes, I dose the hyperthyroid cats differently than most treatment facilities, which use a fixed dose of 4 to 5 mCi administered to all cats, no matter how mild or severe the cat's hyperthyroidism.  I really do believe that facilities that use a fixed dose are overdosing most of the cats, and under-dosing others. Cats with thyroid carcinoma generally require much larger radioiodine doses, generally in amounts of around 30 mCi but sometimes even more (4,5).

Thyroid scintigraphy (scans) in 3 hyperthyroid cats. The cat on the far left has a very small unilateral nodule, the middle cat has small, assymetrical bilateral nodules,
and the cat on the right has larger bilateral disease. The calculated I-131 doses
that we administered to these cats ranged from 1.5 mCi to 3.5 mCi.

I currently give a range of doses from 1.5-10 mCi to cats with benign adenoma (adenomatous hyperplasia). This is based on severity of hyperthyroidism (both clinically and biochemically, ie, the T4 level), size of thyroid tumor(s) both on palpation and thyroid scintigraphy, age of the cat, and known concurrent diseases (2-5).

Goals of I-131 therapy: cure hyperthyroidism but avoid hypothyroidism
My goal of therapy is to 'cure' the hyperthyroid state without causing hypothyroidism. Everyone talks about the fact that they can cure 98% of hyperthyroid cats. Well, that's easy; anyone can order a big dose for all hyperthyroid cats and cure them, but many will become hypothyroid.

It becomes more difficult to titrate the doses because one has to think about the whole cat and it's thyroid uptake and iodine kinetics, but I do believe it's so very important. That's where this whole treatment issue becomes more tricky.

Hypothyroidism and the kidney
It's becoming increasing clear that both hyperthyroidism and hypothyroidism are bad for the kidneys (6), so the last thing we want to do is cure the hyperthyroidism but create iatrogenic hypothyroidism. And that is especially true if the owners cannot give oral medication or if the cat already has mild renal disease.

Well, this is probably much more than you ever wanted to know, but I hope it answers your questions.

Follow-up Question:

Thanks for the great explanation. Can I assume cats that receive a small dose of I-131 will be able to leave isolation earlier than cats that receive more substantial doses? Is there a required minimum stay for cats post treatment or is their stay based on their "radioactivity"?

My Response:

The NRC rules have a minimum stay of 3 to 5 days, depending if there are children or pregnant women at home. Once that minimum stay is met, then the cat's radiation "reading," measured by a survey meter at a meter from the cat's neck must be less than 0.5 milliRoentgens per hour (mR/hr).

So, if a cat is treated with 2 to 3 mCi, we can almost guarantee that the radiation levels will fall to below 0.5 mR/hr by 3 days. If a cat gets, 4 mCi or more, it may take a few more days, depending on the effective half-life of the radioiodine and the residence time of I-131 in the individual cat's thyroid tumor. And if a cat with thyroid carcinoma is treated with 30 mCi, they may have to stay in the hospital for 2 to 3 weeks.

Some cats excrete the radioiodine from their thyroid gland —and therefore their kidneys—faster than other cats. Such faster clearance is not always good — we need to have the radioiodine within the tumor for enough time to deliver the radiation dose to the cat's thyroid tumor!

References:

1. Peterson ME, Becker DV. Radioiodine treatment of 524 cats with hyperthyroidism. Journal of the American Veterinary Medical Association 1995:207:1422-1428. 
2. Peterson ME: Radioiodine treatment for hyperthyroidism. Clinical Techniques in Small Animal Practice 2006;21:34-39.
3. Peterson ME: Radioiodine for hyperthyroidism. In: Bonagura JD, Twedt DC (eds): Current Veterinary Therapy XIV. Philadelphia, Saunders Elsevier, 2008, pp 180-184.
4. Mooney CT, Peterson ME. Feline hyperthyroidism. In: Mooney CT, Peterson ME, eds. BSAVA Manual of Canine and Feline Endocrinology. Quedgeley, Gloucester: British Small Animal Veterinary Association; 2012:92-110.
5. Peterson ME, Broome MR: Radioiodine for hyperthyroidism. In: Bonagura JD, Twedt DC (eds): Current Veterinary Therapy XV. Philadelphia, Saunders Elsevier, 2012; in press.
6. Williams T, Elliott J, Syme H. Association of iatrogenic hypothyroidism with azotemia and reduced survival time in cats treated for hyperthyroidism. Journal of Veterinary Internal Medicine 2010;24:1086-1092. 

Hypertension and Hyperthyroidism in Cats: What's the Correlation?

My patient is a 15-year old, FS, DSH cat who was successfully treated with radioiodine a year ago.

This cat is very fractious and extremely difficult to do a complete examination. At the time of her initial appointment (when the diagnosis of hyperthyroidism was established), her systolic blood pressure reading was high at 210 mmHg. But again, she was very upset and we were lucky to even get this blood pressure reading without being eaten!  So even though this blood pressure reading was high, we felt that it was likely due to "white coat hypertension" rather than true hypertension requiring treatment.

The following day, she was even more fractious but we did a fundic exam which was normal. Her repeat blood pressure reading was 185 mmHg, so I was not convinced that she was truly hypertensive based on these results. Her renal function tests and urinalysis were all normal. She was treated with the radioiodine and discharged without any therapy.

Four months later, the client had her examined because of decreased vision. Her systolic blood pressure now was very high (260 mmHg) and her fundic examination revealed bilateral detached retinas. Laboratory testing revealed a high serum urea nitrogen concentration (45 mg/dl) but a normal serum creatinine (1.3 mg/dl). Her urine specific gravity was only 1.016.

So my questions:

• What are your thoughts on the 4-month lapse of time between when I treated her and when she detached her retinas? 
• Should I have treated her for hypertension at time of the diagnosis of her hyperthyroidism?  In my experience with other cases that have been hypertensive due to hyperthyroidism, once their thyroid has normalized, they don't require continued treatment with amlodipine.
•  Or was her hypertension due to her subsequent chronic renal disease?

I'd love any comments you may have that would help me with this unfortunate situation.

My Response:

Hyperthyroidism does not lead to hypertension in human patients
In human patients, hyperthyroidism does not cause hypertension (1). Rather, hyperthyroidism tends to cause a small decrease in mean arterial blood pressure (mild hypotension). This decrease is attributable to a consequence of peripheral vasodilation and a 40–60% reduction in total peripheral resistance.  So the bottom line is this — hypertension is not characteristic of thyrotoxicosis in humans with the disorder.

So why do hyperthyroid cats develop hypertension?
Early feline studies suggested that systolic hypertension was a very common finding in hyperthyroidism (2,3). However, the case numbers in these studies were small and the criteria used for the diagnosis of hypertension were variable. In addition, it's likely that many of those cats probably had stress-induced or white coat hypertension (2-5).

Based on more recent studies, the prevalence of systemic hypertension in newly diagnosed hyperthyroid cats ranges from 9% to 23%, suggesting that systemic hypertension may be less prevalent in the hyperthyroid cat population than first reported (6,7).

Large case studies of hypertensive cats with retinopathy all find relatively few cats with hyperthyroidism as an underlying cause of the eye disease (8,9,10). Similarly, large retrospective studies of cats with hyperthyroidism have not found a high prevalence of either hypertensive retinopathy or choroidopathy (6,7,11).

Bottom line: In other words, hyperthyroidism is not a common cause of feline hypertension. And when hypertension does develop, these hyperthyroid cats tend not to develop any ocular changes.

So why do hyperthyroid cats develop hypertension?

Even though true hypertension appears to be relatively uncommon in untreated cats with hyperthyroidism, approximately 20% of these cats may develop systemic hypertension after treatment (5-7).

One study (7) reported that the median time from treatment to subsequent development of hypertension was 5.3 months. Of those cats that developed hypertension, 35% overtly azotemic (serum creatinine >2 mg/dl), whereas two-thirds had normal kidney function (7) This suggests that hypertension after treatment of hyperthyroidism does not always develop as a consequence of unmasking of underlying renal insufficiency. 

In cats without obvious renal disease, the mechanism of this post-treatment hypertension is unclear, this also highlights the importance of longitudinal assessment of blood pressure in cats diagnosed with and treated for hyperthyroidism.

Bottom line
I think you made the correct decision by not treating her for hypertension at the time of initial diagnosis of the cat's hyperthyroidism. Ideally, she would have had a follow-up blood pressure done 1-3 months after treatment because she may have had severe hypertension by that time.

Nevertheless, this is a very uncommon scenario, and it is extremely difficult to accurately diagnose hypertension in cats, especially when they are stressed, fractious, or difficult to handle.

References:

1. Saito I, Saruta T. Hypertension in thyroid disorders. Endocrinology and Metabolism Clinics of North America 1994;23:379-386.
2. Kobayashi DL, Peterson ME, Graves TK, et al. Hypertension in cats with chronic renal failure or hyperthyroidism. Journal of Veterinary Internal Medicine 1990;4:58–62.
3. Stiles J, Polzin DJ, Bistner SI. The prevalence of retinopathy in cats with systemic hypertension and chronic renal failure or hyperthyroidism. Journal of the American Veterinary Medical Association 1994;30:564–572.
4. Stepien RL. Feline systemic hypertension: Diagnosis and management. Journal of Feline Medicine and Surgery 2011;13:35-43. 
5. Jepson RE. Feline systemic hypertension: Classification and pathogenesis. Journal of Feline Medicine and Surgery 2011;13:25-34.
6. Syme HM, Elliott J. The prevalence of hypertension in hyperthyroid cats at diagnosis and following treatment [abstract]. Journal of Veterinary Internal Medicine 2003;17:754.
7. Morrow LD, Adams VJ, Elliott J, et al. Hypertension in hyperthyroid cats: prevalence, incidence and predictors of its development [abstract]. Journal of Veterinary Internal Medicine 2009;23:699.
8. Maggio F, Defrancesco TC, Atkins CE, et al. Ocular lesions associated with systemic hypertension in cats: 69 cases (1985–1998). Journal of the American Veterinary Medical Association 2000;217:695–702.
9. Littman MP. Spontaneous systemic hypertension in 24 cats. Journal of Veterinary Internal Medicine 1994;8:79–86.
10. Jepson RE, Brodbelt D, Elliott J, et al. Evaluation of the effects of control of systolic blood pressure on survival in cats with systemic hypertension. Journal of Veterinary Internal Medicine 2007;21:402–409.
11. van der Woerdt A, Peterson ME. Prevalence of ocular abnormalities in cats with hyperthyroidism. Journal of Veterinary Internal Medicine 2000;14:202-203.

Q & A: If Nuclear Accidents Can Lead to Thyroid Cancer, Why Doesn't the I-131 Treatment?

Thanks for your great post on radioprotective therapies (see Radiation Protection after a Nuclear Accident).

But I'm confused. If radioidine-131 released into the atmosphere during an accident can result in a dramatic increase of thyroid cancer in children, why don't people or cats treated with I-131 for hyperthyroidism develop thyroid cancers?

My Response:

Good question. After a nuclear accident, people and animals will get exposed to varying amounts of radioiodine as I-131, as well as many other radioisotopes including cesium-137, strontium-90, and plutonium-241 (1). Some will receive a small dose to their thyroid, whereas others will get more, but it's generally not enough to destroy the thyroid — it "tickles" the thyroid and causes DNA damage, which can lead to thyroid tumors (2).  The exposure also tends to happen over a period of a few days to weeks, not all at once.

When we treat a patient (human, cat, dog) with radioiodine, we are delivering a huge, single dose of radiodine to the thyroid. This destroys the hyperfunctional adenoma/carcinoma. It tends not to be taken up by the normal, suppressed tissue. It is unclear why the remaining normal thyroid tissue doesn't develop cancer, but it appears related to the large, single dose of radioiodine administered, as opposed to chronic exposure of lower levels of radiation. It has been reported that spreading the total I-131 dose over time (from a few days to a few weeks or longer) may lower risk of thyroid cancer, probably due to the opportunity for cellular repair mechanisms to operate (3).

Infants and children have the peak risk as the result of the increased radiation sensitivity of their thyroid glands. As a result, most human patients that develop thyroid cancer after exposure to radioiodine are babies and young children (4-6), whereas adult individuals are at a lesser risk. This fact probably also contributes to why we don't see thyroid cancer developing in adult human or feline patients treated with radioiodine.

The latest study in Hiroshima and Nagasaki Atomic Bomb survivors in Japan has indicated that a biological effect from a single brief external exposure to ionizing radiation nearly 60 years in the past still occurs and can be detected (7). In childhood, once exposed even to low doses of ionizing radiation, either externally or internally, the cancer-prone cell damage within the thyroid gland can be preserved for a long time.

What Can We Do in an Nuclear Emergency?

Since children are at the highest risk to exposure to radioactive iodine, potassium iodide should be available to all children (8). Also, because of the risk to the developing fetus, pregnant women should also take potassium iodide in the event of a nuclear accident. Compared to children and the fetus, adults are at a lower risk but still would benefit from thyroid blockage with potassium iodide.

Iosat Tablets, one FDA approved KI preparation

Potassium iodide pills (sometimes abbreviated as KI: the K stands for potassium, the I for iodine) don’t prevent radioactive iodine from entering the body. But these pills do keep the radioiodine from accumulating in the thyroid gland. By flooding the body with non-radioactive iodine, the pills keep the gland from absorbing the radioactive iodine. Here is how the CDC fact sheet summed it up (9):

Because KI contains so much stable iodine, the thyroid gland becomes “full” and cannot absorb any more iodine—either stable or radioactive—for the next 24 hours.

ThyroShield and ThyroSafe, the 2 other FDA approved KI preparations

What Potassium Iodide Preparations Are Available?

The potassium iodide (KI) products approved by the Food and Drug Administration (FDA) include the following (10):

• Iosat Tablets (130 mg) 
• ThyroSafe Tablets (65 mg) 
• ThyroShield Solution (65 mg/ml) 

Properly packaged, potassium iodide’s shelf life is at least 5 years and possibly as long as 11 years. If you take a very old pill, it may not work but won't hurt you or do any harm.

What are the Recommended Potassium Iodide Doses?

For humans, the FDA recommends the following doses based on the patient's age:

• 0—1 months ........................................ 15 mg
• 1 months—3 years ............................30-35 mg
• 3—12 years ...........................................65 mg
• >12 years ............................................130 mg

As I discussed in my last post, the recommended dose of potassium iodide for a dog 1.4 mg/kg (11). In other words, a 20-kg dog would receive 25-30 mg, whereas a small dog or cat would receive about 5-10 mg.  The easiest way to prepare a 15-mg dose for a newborn is to dissolve a 130-mg pill in 8 oz of a clear liquid and feed the newborn 1 oz of the liquid. Similar measures could easily be used in dogs and cats.

A single dose of KI protects the thyroid gland for up to 24 hours. A one-time dose at the levels recommended by the FDA is usually all that is needed to protect the thyroid gland. In the rare instance that radioiodine is present in the environment for longer than 24 hours, continuing the dose of KI every 24 hours for a few days would be needed.

References:

1. Report of the Chernobyl Forum Expert Group. Environmental Consequences of the Chernobyl Accident and their Remediation: Twenty Years of Experience. International Atomic Energy Agency, Vienna, 2006. 
2. Awa A. Analysis of chromosome aberrations in atomic bomb survivors for dose assessment: studies at the Radiation Effects Research Foundation from 1968 to 1993. Stem Cells. 1997;15 Suppl 2:163-73.
3. Ron E, Lubin JH, Shore RE et al. Thyroid cancer after exposure to external radiation; a pooled analysis of seven studies. Radiation Research 1995;141:256-277. 
4. Jacob P, Kenigsberg Y, Zvonova I, et al. Childhood exposure due to the Chernobyl accident and thyroid cancer risk in contaminated areas of Belarus and Russia. British Journal of Cancer 1999;80:1461-1469. 
5. Ivanov VK, Gorski AI, Maksiutov MA, et al. Thyroid cancer incidence among adolescents and adults in Bryansk region of Russia following the Chernobyl accident. Health Physics 2003;84: 46-60. 
6. Cardis E, Kesminiene A, Ivanov V, et al. Risk of thyroid cancer after exposure to I-131 in childhood. Journal of the National Cancer Institute 2005;97:724-732. 
7. Imaizumi M, Usa T, Tominaga T, et al. Radiation dose-response for thyroid nodules and autoimmune thyroid diseases in Hiroshima and Nagasaki Atomic Bomb Survivors 55-58 years after radiation exposure. Journal of the American Medical Association 2006;295:1011-1022. 
8. National Research Council. Distribution and  administration of potassium iodide in the event of a nuclear incident, Washington, DC: National Academies Press, 2004.
9. Center for Disease Control and Prevention website. Potassium iodide factsheet. 
10. FDA website. Frequently asked questions on potassium iodide (KI). www.fda.gov
11. Ribela MT, Marone MM, Bartolini P. Use of radioiodine urinalysis for effective thyroid blocking in the first few hours post exposure. Health Physics 1999;76:11-16.