PRESENTATION
BROCHURE Edward C. Feldman Federico Fracassi Mark E. Peterson
FELINE ENDOCRINOLOGY FELINE ENDOCRINOLOGY
Edward C. Feldman Federico Fracassi Mark E. Peterson
Edward C. Feldman Federico Fracassi Mark E. Peterson
Feline Endocrinology
FELINE ENDOCRINOLOGY
This book is unique, developed by the main worldwide experts in this issue. It is an extremely valuable tool for any veterinary practitioner willing to deepen into physiopathology, clinical signs, diagnosis, treatment and prognosis of feline endocrine diseases, with an approach and contents never published so far.
FELINE ENDOCRINOLOGY Edward C. Feldman Federico Fracassi Mark E. Peterson
TARGET AUDIENCE:
✱ General companion animal veterinary practitioners. ✱ Veterinary specialists in endocrinology, feline medicine, internal medicine. ✱ Veterinary students. FORMAT: 18,9 x 24,6 cm NUMBER OF PAGES: 680 NUMBER OF FIGURES: 480 BINDING: hardcover ISBN: 978-88-214-4837-9
RETAIL PRICE
€149
Editors EDWARD C. FELDMAN, DVM, DACVIM (SAIM) Emeritus Professor of Small Animal Internal Medicine University of California, Davis (USA) FEDERICO FRACASSI, DVM, DECVIM-CA (INTERNAL MEDICINE) Associate Professor of Small Animal Internal Medicine Department of Veterinary Medical Sciences University of Bologna (Italy)
MARK E. PETERSON, DVM, DACVIM (SAIM) Animal Endocrine Clinic, New York City Adjunct Professor of Medicine Departament of Clinical Sciences Cornell University, College of Veterinary Medicine (USA)
KEY FACTS:
➜ Developed by the best worldwide specialists in feline internal medicine and endocrinology, who have the broadest experiencie and prestige in this fields, and have authored numerous peer-reviewed publications and books. ➜ Reference book unique in its field, entirely dedicated to feline endocrinology. It includes the most updated information and the best specific diagnostic and therapeutic techniques. ➜ Outstanding graphic design and access to videos through QR codes. ➜ Essential in the library of any veterinary practitioner interested in feline medicine. It brings in information never published before about this issue in a single book.
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Feline Endocrinology
Presentation of the book The main purpose of the book is to provide the veterinary practitioners and students with the most exhaustive and thorough facts about physiopathology, clinical signs, diagnosis and differential diagnosis, and treatment of feline endocrine disorders. Feline medicine has drastically evolved in the last years, and as there is a huge amount of data about endocrine diseases, this is the ideal time to create a book entirely dedicated to them. The best experts in every field of all contents included in every section the book is divided in, have participated from hypothalamus and pituitary, thyroid, parathyroid, and adrenal glands, and endocrine pancreas. An additional section dedicated to issues related to endocrine diseases like obesity, lipid metabolism disorders, ematiation and sarcopenia, and hypertension is also included. The contributors and editors have included the most updated information and the latest techniques to perform diagnoses and treatments, specifically dedicated to the cat as a unique patient, not extrapolating data from canine patients, making this book unique in its field, and a piece of work that is surely essential in any feline veterinary practitioner’s library, whether he or she is a specialist in endocrinology or internal medicine, or a generalist practitioner.
Editors Edward C. Feldman, DVM, DACVIM (SAIM) Emeritus Professor of Small Animal Internal Medicine University of California, Davis USA
Federico Fracassi, DVM, DECVIM-CA (Small Animal Internal Medicine) Associate Professor of Small Animal Internal Medicine Department of Veterinary Medical Sciences University of Bologna Italy
Mark E. Peterson, DVM, DACVIM (SAIM) Animal Endocrine Clinic New York, NY Adjunct Professor of Medicine Department of Clinical Sciences Cornell University, College of Veterinary Medicine USA
Feline Endocrinology
Contributors Charlotte R Bjørnvad, PHd, DECVCN. University of Copenhagen, Denmark. Michael R. Broome, DVM, MS, DABVP. Advanced Veterinary Medical Imaging. USA. Sylvie Daminet, DACVIM (SAIM), DECVIM-CA, Msc, PhD. Ghent University, Belgium. Lucy J. Davison, MA, VetMB, PhD, DSAM, DECVIM-CA, MRVCS. The Royal Veterinary College. Wellcome Trust Centre for Human Genetics. United Kingdom. Duncan C. Ferguson, VMD, PhD, DACVIM (SAIM), DACVCP. University of Illinois. USA. James A. Flanders, DVM, DACVS. Cornell University. USA. Linda M. Fleeman, BVSc, PhD, MANZCVS. Animal Diabetes Australia. Australia. Lisa M. Freeman, DVM, PhD, DACVN. Tufts University. USA. Sara Galac, DVM, PhD. Utrecht University. The Netherlands. Chen Gilor, DVM, PhD, DACVIM (SAIM). University of California, Davis. USA. Ruth Gostelow, BVetMed(Hons), MVetMed, DACVIM (SAIM), DECVIM-CA, PhD. The Royal Veterinary College. United Kingdom.
Thomas K. Graves, DVM, PhD, DACVIM (SAIM). Midwestern University of Arizona. USA. Guy C.M. Grinwis, DVM, PhD. Utrecht University. The Netherlands. Hans S. Kooistra, DVM, PhD, DECVIM-CA. Utrecht University. The Netherlands. John P. Loftus, PhD, DVM, DACVIM (SAIM). Cornell University. USA. Thomas A. Lutz, Prof. Dr. med. vet. University of Zurich. Switzerland. Philipp D. Mayhew, BVM&S, MRCVS, DACVS. University of California, Davis. USA.
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Susan Gottlieb, BVSc, MANZCVS. The Cat Clinic. Australia.
Björn Meij, DVM, PhD, ECVS. Utrecht University. The Netherlands. Carlos Melián, DVM, PhD. University of Las Palmas de Gran Canaria. Spain. Meredith L. Miller, DVM, DACVIM (SAIM). Cornell University. USA. Jeffrey Mitchell, DVM. University of California, Davis. USA. Carmel T. Mooney, MVB, MPhil, PhD, DECVIM-CA. University College Dublin. Ireland. Stijn J.M. Niessen, DVM, PhD, DECVIM, PGCertVetEd, FHEA, MRCVS. The Royal Veterinary College, London. The VetCT Telemedicine Hospital, Cambridge. UK. Dolores Pérez Alenza, DVM, PhD. Complutense University of Madrid. Spain. Laura Pérez-López, DVM. University of Las Palmas de Gran Canaria. Spain. Pascaline Pey, DVM, PhD, DipECVDI, MRCVS. University of Bologna. Italy. Juan José Ramos-Plá, University Cardenal Herrera-CEU. Spain. Ian Ramsey, BVSc, PhD, DSAM, DECVIM-CA, FHEA, FRCVS. University of Glasgow. United Kingdom. Jacquie Rand, DVM, PhD, DACVIM (SAIM). University of Queensland. Australia. John F. Randolph, DVM, DACVIM (SAIM). Cornell University. USA. Dan Rosenberg, DVM, PhD. MICEN VET Referal Center. France. Claudia E. Reusch, Prof., Dr. med. vet.,PhD, DECVIM-CA. University of Zurich. Switzerland. Elena Salesov, Dr. med. vet. University of Zurich. Switzerland. Johan P. Schoeman, BVSc, MMedVet (Pretoria), PhD (Cantab), DSAM (RCVS-UK), DECVIM-CA, MRCVS. University of Pretoria. South Africa. Nadja S. Sieber-Ruckstuhl, Prof., Dr. med. vet., DACVIM (SAIM), DECVIM-CA. University of Zurich. Switzerland. Barbara J. Skelly, MA, VetMB, PhD, CertSAM, DACVIM (SAIM), DECVIM-CA, MRCVS. University of Cambridge. United Kingdom.
Feline Endocrinology
Christopher J. Scudder, BVSc, PhD, DACVIM (SAIM), MRCVS. The Royal Veterinary College, London. Southfields Veterinary Specialists, Southfields. UK. Robert E. Shiel, MVB, PhD, DECVIM-CA. University College Dublin. Ireland. Andy H. Sparkes, BVetMed, PhD, DECVIM-CA, MANZCVS, MRCVS. Veterinary Director. International Cat Care and International Society of Feline Medicine (ISFM). UK.
Tim Williams, MA, VetMB, PhD, FRCPath, Dip. ECVCP, MRCVS. University of Cambridge. United Kingdom. Panagiotis G. Xenoulis, DVM, Dr. med. vet., PhD. University of Thessaly. Greece. Mª Pilar Xifra, BVSc. Nuclear Medicine Small Animal Service, Leganés Norte Veterinary Clinic. Iodocat. Spain. Eric Zini, Prof., Dr., DECVIM-CA. University of Zurich. Switzerland. University of Padova. Istituto Veterinario di Novara. Italy.
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Alain P. Théon, MS, PhD, Dip ACVR-RO. University of California, Davis. USA.
Table of contents Section 1. Hypothalamus and pituitary 1. Pituitary anatomy and physiology Pituitary anatomy Pituitary physiology Hormones of the adenohypophysis (AL) Hormones of the neurohypophysis
2. GH excess: acromegaly (hypersomatotropism) Background and history Incidence and pathogenesis Pituitary pathology Consequences of pituitary pathology Clinical features and diagnosis Treatment Prognosis
3. Other pituitary tumors
5. Pituitary irradiation Introduction Clinical presentation Advanced imaging Role of radiation therapy Modalities of radiation therapy Nonfunctioning tumors Growth hormone-secreting pituitary tumors and acromegaly Adrenocorticotropic hormone-secreting pituitary tumors and feline Cushing’s disease Radiation-related adverse effects
6. Pituitary GH deficiency and pituitary dwarfism Introduction Etiopathogenesis Clinical features Differential diagnosis for failure to grow Diagnosis Treatment
7. Polyuria, polydipsia and diabetes insipidus
Pituitary masses: hyperplasia, adenoma or carcinoma?
Introduction
Incidence and cell origins of pituitary tumors
Urine concentrating ability in healthy cats
Effect of pituitary tumors on target organs and the direct effects of large tumors Functional consequences of autonomous hormone production
4. Pituitary surgery Introduction and general observations Surgical anatomy Imaging of the feline pituitary gland Pituitary adenomas Transsphenoidal hypophysectomy Postoperative care Complications after pituitary surgery Prognosis
Water requirements in healthy cats Mechanisms of water retention Causes of polyuria and polydipsia in cats The diagnostic approach to polyuria and polydipsia Treatment of central diabetes insipidus Prognosis
Section 2. Thyroid gland 8. Thyroid anatomy and physiology Anatomy of the feline thyroid gland General thyroid physiology Serum protein binding of thyroid hormones Hypothalamic-pituitary-thyroid axis Extrathyroidal metabolism of thyroid hormone Thyroid hormone kinetics in the cat Action of thyroid hormone
9. Hyperthyroidism: background, etiopathogenesis and changing prevalence of feline thyroid disease History of thyroid disease in cats Studies into the etiopathology of feline hyperthyroidism Epidemiology of hyperthyroidism: a common worldwide disorder of senior to geriatric cats Why has feline nodular goiter reached such epidemic proportions? Conclusions
10. Hyperthyroidism: clinical signs and physical examination findings Signalment Clinical signs Physical examination
11. Hyperthyroidism: laboratory diagnosis
12. Thyroid and kidney disease in cats Hyperthyroidism and chronic kidney disease (CKD) Effect of hyperthyroidism on serum test results of renal function Effect of hyperthyroidism on urinary markers of renal function Effect of hyperthyroidism on systolic blood pressure Effect of treatment of hyperthyroidism on renal function Effect of azotemia on how hyperthyroid cats are managed Suggested management strategies for hyperthyroid cats with CKD
13. Thyroid imaging Introduction Thyroid embryology, radiographic anatomy, and ectopic thyroid tissue Normal thyroid Hyperthyroidism Ectopic thyroid Thyroid carcinoma Thyroid cysts Hypothyroidism
14. Treatment of hyperthyroidism: antithyroid drugs Considerations prior to initiating therapy with antithyroid drugs Mechanism of action of antithyroid drugs
Clinicopathologic abnormalities associated with hyperthyroidism
Formulations of antithyroid drugs
Thyroid hormone abnormalities associated with hyperthyroidism
Adverse reactions with antithyroid drugs
Other diagnostic tests Conclusion
Dosages of antithyroid drugs Monitoring cats treated with antithyroid drugs Other drugs of interest in managing hyperthyroid cats Success rate and survival in hyperthyroid cats managed with an antithyroid drug Renal function and hyperthyroidism Conclusion
15. Treatment of hyperthyroidism: surgical thyroidectomy Introduction and overview Anatomy of the thyroid gland and surrounding structures Preoperative evaluation General anesthesia Feline thyroidectomy techniques Perioperative complications Postoperative recurrence of hyperthyroidism Surgical excision of thyroid adenocarcinoma Summary and conclusions
16. Treatment of hyperthyroidism: radioiodine Introduction Advantages and disadvantages of radioiodine treatment of hyperthyroidism
18. Treatment of hyperthyroidism: severe, unresponsive, or recurrent hyperthyroidism Introduction Etiology and pathogenesis of severe, unresponsive or recurrent hyperthyroidism Correlation between the severity and duration of hyperthyroidism and the severity of clinical signs Causes for treatment failure Therapy for severe, unresponsive hyperthyroidism Summary
19. Hypothyroidism Introduction Causes of hypothyroidism Clinical subtypes of hypothyroidism Refractory hypothyroidism
Principles of radioiodine treatment Specific indications for radioiodine treatment Patient selection and preparation before radioiodine treatment Thyroid scintigraphy for evaluation of hyperthyroid cats before 131I treatment
Section 3. Calcium and parathyroid glands
Estimation of the radioiodine dose to administer to cats with hyperthyroidism
20. Hypercalcemia
Adverse effects or complications associated with radioiodine treatment
Calcium physiology
Overview
Follow-up thyroid function testing after radioiodine treatment
Laboratory testing
Prognosis after radioiodine treatment
Differential diagnosis of hypercalcemia
17. Treatment of hyperthyroidism: diet General nutritional assessment for the hyperthyroid cat Weight loss and muscle wasting Nutrients needed for the hyperthyroid cat Nutritional management of feline hyperthyroidism: feeding a low-iodine diet
Initial investigation in hypercalcemic cats
21. Feline primary hypoparathyroidism and hypocalcemia Introduction Distribution of calcium in the body Control of calcium (Ca) homeostasis Hypocalcemia in people and dogs Hypoparathyroidism in cats Differential diagnosis of hypocalcemia Diagnostic testing Treatment
Section 4. Adrenal glands 22. Adrenal anatomy and physiology Adrenal anatomy Adrenal physiology
23. Cushing’s syndrome (hypercortisolism) Introduction Etiology Clinical features Clinicopathological findings Endocrine testing Diagnostic imaging Treatment Prognosis
24. Primary hyperaldosteronism (Conn’s syndrome) Introduction Primary hyperaldosteronism
25. Other adrenal cortical tumors and pheochromocytoma Introduction and differential diagnosis Working up a feline adrenal mass Excessive progesterone production Combined excesses in progesterone and aldosterone Excessive androgen or estradiol production Pheochromocytoma Non-functional adrenal tumors
26. Adrenal surgery via open and laparoscopic approaches Introduction Diagnostic evaluation Case selection Patient preparation Surgical techniques Post-operative care Complications
27. Feline hypoadrenocorticism Introduction Prevalence Causes Age, breed and gender Clinical signs Clinical pathology Diagnostic imaging Electrocardiography and echocardiography Endocrine tests Differential diagnoses Treatment Prognosis
28. Glucocorticoid therapy Physiology Pharmacology Therapeutic applications Adverse effects Glucocorticoid reduction protocol
Section 5. Endocrine pancreas 29. Anatomy, histology and physiology of the feline endocrine pancreas Anatomy of the feline pancreas Cell types Cross-differentiation General function of islet hormones Secretory control Relative importance of pancreatic hormones and their contribution to the pathophysiology of diabetes mellitus Pancreatic amyloid as the most typical histological finding in diabetes mellitus
30. Pathogenesis and clinical observations of uncomplicated diabetes mellitus Introduction Prevalence and epidemiology Risk factors Pathophysiologic mechanisms Diabetes mellitus and pancreatitis Clinical and laboratory findings Survival and prognostic factors
31. Diabetic ketosis, ketoacidosis, and the hyperosmolar syndrome Introduction Glucose homeostasis Clinical presentation of DKA and HHSr Principles of management of DKA and HHS Fluid and electrolyte therapy Insulin therapy Additional supportive therapy in DKA and HHS Prognosis of DKA and HHS in cats
32. Insulin treatment of diabetes mellitus Aims of the treatment and management plan Insulin therapy Choosing an insulin Frequency of insulin administration, initial insulin dose and change in the type of insulin Storage, mixing and dilution of insulin Owner education Insulin dosing pens
33. Gastrointestinal hormones and the use of non-insulin therapies for diabetes mellitus Introduction Incretin hormones physiology and pharmacology Metformin Glipizide Acarbose SGLT-2 antagonists Challenges in managing feline DM and potential uses of non-insulin therapies
34. Dietary management for diabetes mellitus Overview Learning outcomes Case 1: feeding cats that refuse or dislike their “diabetes diet” Case 2: an insulin overdosed diabetic cat that has just recovered from a severe “hypo” (neuroglycopenia) Case 3: non-prescription diet alternatives Case 4: achieving weight loss in a diabetic cat Case 5: managing diabetes in a cat with concurrent disease Case 6: the client has looked up a lot of information about diabetes in cats on the internet
35. Monitoring diabetes in cats
38. Hypoglycemia
Clinical signs
Introduction
Blood glucose monitoring
Pathophysiology of hypoglycemia
Continuous glucose monitoring systems (CGMS) and flash glucose monitoring systems
Blood glucose measurement
Urine glucose measurement Fructosamine concentration
Specific diseases or syndromes associated with hypoglycemia in cats
Glycated hemoglobin
Diagnostic approach
36. Diabetic remission
Differential diagnoses
Treatment of hypoglycemia
Definition of diabetic remission Physiology of diabetic remission Incidence of diabetic remission Predictors of diabetic remission Maximizing the likelihood of diabetic remission Identification and management of the diabetic cat in remission Prognosis and diabetic relapse Conclusions
37. The unstable diabetic Overview Initial goals of therapy and factors that influence remission Classification of diabetes mellitus and relevance to unstable diabetic cats Inappropriate choice of insulin Inappropriate dosing Choice of intensive versus conservative insulin management of newly-diagnosed diabetics
Section 6. Blood pressure, body condition and nutrition 39. Feline obesity Epidemiology Pathophysiology of obesity Obesity-related diseases Treatment
40. Disorders of lipid metabolism Introduction The basics of lipoprotein metabolism Definitions and measurement of feline serum lipid concentrations
Client factors
Effect of lipemia on the measurement of other analytes
Underlying diseases
Causes of feline hyperlipidemia
Rebound hypoglycemia (Somogyi)
Clinical consequences of hyperlipidemia in cats
The brittle diabetic
Diagnostic approach to cats with hyperlipidemia
Monitoring
Treatment of feline hyperlipidemia
Other management strategies Conclusion
41. Cachexia and sarcopenia Cachexia Sarcopenia Diagnosis of cachexia and sarcopenia Potential interventions for cachexia and sarcopenia Practical approach to treatment of cachexia and sarcopenia in cats Conclusion
42. Hypertension Introduction Measurement of blood pressure in cats Defining hypertension and deciding when to treat Consequences of hypertension Endocrine causes of hypertension Management of hypertension
43. Conversion tables Conversion to Systeme International (SI) Units
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Aids in diagnosis of thyroid carcinoma (SHIM-RAD tumor cats) Thyroid scintigraphy also provides valuable information in the diagnosis and evaluation of hyperthyroid cats with suspected thyroid carcinoma (Fig. 16.6). Our studies suggest that, although thyroid carcinoma is rare in cats with recently diagnosed hyperthyroidism, the prevalence of carcinoma progressively increases in cats treated long term with antithyroid medications.25,29 Of cats with more than 4 years of medical treatment, over 20% had scintigraphic evidence of thyroid carcinoma.29 Diagnosis of thyroid carcinoma can be challenging, even with histopathology (see chapter 18), but without pretreatment thyroid scintigraphy these cases would go undetected. In those cats in which a thyroid biopsy is not feasible or histopathological results are inconclusive, we have come up with the acronym “SHIM-RAD”
to characterize this subgroup of cats clinically based on their history, clinical features, and scintigraphic findings. These SHIM-RAD cats are defined on the basis of 5 characteristics: 1) Severe hyperthyroidism (serum T4 >24 μg/dl or >300 nmol/l); 2) Huge thyroid tumor size or volume; 3) Intrathoracic tumor nodule(s); 4) Multifocal disease pattern [≥3 nodules]; and Resistance to Antithyroid Drug treatment).29 All of the cats included in Fig. 16.6 met the criteria to be labeled as SHIM-RAD cases. Because of the large tumor volume associated with thyroid carcinoma (or SHIM-RAD), as well as the potential for local invasion and metastasis, most of these cats require very high doses of radioiodine (e.g., 30 mCi, 1100 MBq) in order to completely ablate all thyroid tissue, thereby curing the cat’s thyroid carcinoma or SHIMRAD tumor (Fig. 16.6).
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FIGURE 16.6. Thyroid scintigraphic imaging in four hyperthyroid cats with functional thyroid carcinoma (SHIM-RAD tumors), before and after treatment with high doses of radioiodine. (a, c, e, g) Before therapy, all of these cats had severe, long-standing hyperthyroidism, which could no longer be controlled on an increased dosage of antithyroid drugs. Notice the huge thyroid volumes, intrathoracic tumor location, and multifocal disease (≥3 nodules). (b, d, f, h) After treatment with high-dose 131I (30 mCi; 1,100 mBq). Note the complete ablation of all functional thyroid tissue 6-12 weeks after treatment with radioiodine.
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Chapter 16. Treatment of hyperthyroidism: radioiodine
Confirms adequate destruction of thyroid tumor nodules with preservation of adequate amounts of normal residual thyroid tissue The primary goal of treating hyperthyroid cats with radioiodine is to restore euthyroidism by delivering an adequate radiation dose to the autonomous tumor nodule(s), leading to necrosis and apoptosis of the tumor.71,72 A secondary goal is to avoid destroying normal (nonadenomatous thyroid tissue), thus preventing iatrogenic hypothyroidism. After 131I treatment, serum thyroid concentrations (T4 and TSH) should be monitored at 1 month and then periodically over the first year in all cats. Use of post-treatment thyroid scintigraphy can also be very useful in evaluating cats after 131I treatment (Fig. 16.7) to ensure adequate destruction of the tumor nodule.73-78 Follow-up thyroid imaging is of critical importance in cats with persistent hyperthyroidism to help determine the cause of treatment failure, and it can be helpful in confirming a diagnosis of iatrogenic 131I-induced hypothyroidism (Fig. 16.7). In addition, all cats with thyroid carcinoma (as well as SHIM-RAD cats) should have thyroid scintigraphy repeated 1 to 3 months after high-dose 131I therapy to confirm that the massive volume of malignant thyroid tissue has been completely ablated (Fig. 16.6).
Radioiodine facilities that do not use thyroid scintigraphy prior to 131I treatment
Despite the valuable information obtained by performing thyroid scintigraphy, it is not required prior to radioiodine therapy, and most 131I centers treat cats without the benefit of thyroid imaging. Nevertheless, we consider thyroid scintigraphy to be good medicine because of four major reasons: the imaging findings confirm the diagnosis of hyperthyroidism, identify thyroid tumors that may not be palpable (e.g., ectopic nodules), provide staging and prognostic information (e.g., cats with thyroid carcinoma or huge intrathoracic tumors), and aid in individualizing the 131I dose to administer. To us, treating a hyperthyroid cat with 131I without pretreatment imaging would be similar to treating a cat with cardiac disease without obtaining a chest radiograph or echocardiogram or administering pituitary irradiation to a cat with acromegaly without pretreatment pituitary CT or MRI imaging. Most experts would find lack of imaging
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for situations like these to be unthinkable, and we believe the same logic applies to treating hyperthyroid cats with radioiodine.
Estimation of the radioiodine dose to administer to cats with hyperthyroidism Ideally, treatment of a hyperthyroid cat with a single dose of radioiodine restores euthyroidism without inducing hypothyroidism. In other words, the goal of treatment should be to irradiate and destroy all abnormal thyroid tissue (adenomatous or carcinomatous) but to leave the normal (nonadenomatous) thyroid tissue intact. Radioiodine can be administered to cats orally,7,79 but the subcutaneous or intravenous route is easier and much less stressful for the cat. The major disadvantage of oral therapy is the high risk of spilling of the 131I dose, increasing the exposure of personnel and potential contamination of the premises, as cats may not always be cooperative. Today, most treatment facilities use the subcutaneous route of administration, which has proven to be as effective as the other routes of administration and safer for personnel.80-82 The optimal method for determining the amount of radioiodine required to both cure hyperthyroidism and prevent iatrogenic hypothyroidism in cats has yet to be determined, but it is now clear that most 131I-dosing protocols used in the past will result in a higher-than-desired rate of iatrogenic hypothyroidism.83 We now know that the key to diagnosing feline hypothyroidism is to measure serum concentrations of T4 (or free T4) together with serum TSH (see chapter 19).55 Use of serum TSH concentration is a very sensitive and specific diagnostic test for iatrogenic (131I-induced) hypothyroidism in cats. Without serum TSH determinations, cats with earlier hypothyroidism (cats that maintain low-normal serum T4 concentrations) will be missed. Compared to either serum T4 and free T4 concentrations, serum TSH concentration is better at both diagnosing hypothyroidism and in differentiating hypothyroid cats from euthyroid cats with CKD.55 We recommend that serum T4 and TSH concentrations both be monitored routinely in cats treated with radioiodine (see below).
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FIGURE 16.7. Thyroid scintigraphic imaging in four hyperthyroid cats with benign thyroid disease, before and after treatment with individualized doses of 131I, calculated as previously described.67 (a) A 12-year-old male DSH cat with 1-month history of mild hyperthyroidism (serum T4 = 4.8 µg/dl; T3 = 62 ng/dl, TSH <0.03 ng/ml). Scintigraphy reveals a “hot” unilateral, right thyroid nodule. The measured thyroid volume was 1.35 gm; the TcTU was 3.5%; and the 24-hour 131I uptake was 29%. The 131I dose was calculated as follows (see Tables 16.4 and 16.5): Volume = 1.35 mCi T4/T3 = 1.4 mCi TcTU = 1.8 mCi Average dose (1.35+1.4+1.8)/3 = 1.5 mCi Adjusted for 24-hour 131I uptake (1.5 mCi × 0.9) =1.37 mCi Final dose administered: 1.38 mCi
(b) Follow-up thyroid scintiscan on cat in (a), 6 months after 131I treatment. The serum T4 concentration (1.8 μg/dl) has fallen to within the reference interval (0.9-3.8 μg/dl), and the serum TSH concentration (0.08 ng/dl) has come up into the normal range and is no longer suppressed. The large right thyroid nodule has decreased in size and intensity to within normal limits. The previously suppressed left thyroid lobe is now visible with normal size and intensity of uptake, indicating that normal thyroid function has been restored. (c) A 16-year old female DSH cat with moderate hyperthyroidism (serum T4 = 11.0 µg/dl; T3 = 222 ng/dl, TSH <0.03 ng/ml). Scintigraphy reveals “hot” bilateral, asymmetric thyroid disease (left lobe > right lobe). The measured thyroid volume was 1.67 gm; the TcTU was 10.1%; and the 24-hour 131I uptake was 72%. The 131I dose was calculated as follows: Volume = 1.7 mCi T4/T3 = 2.1 mCi TcTU = 3.3 mCi Average dose (1.6+2.0+2.2)/3 = 2.4 mCi Adjusted (lowered) due to high 24-hour 131I uptake: (2.4 mCi × 0.75) =1.8 mCi Dose administered = 1.8 mCi (d) Follow-up thyroid scintiscan on cat in (c), 6 months after 131I treatment. The serum T4 concentration has fallen to within the reference interval (1.9 µg/dl), whereas the serum TSH concentration is slightly high (0.48 ng/ml). Both large thyroid nodules have decreased in size and intensity to within the lower end of normal limits. Both the high serum TSH concentration and the follow-up scintigraphic findings are consistent with subclinical (mild) hypothyroidism. Since the cat was not symptomatic and renal function remained normal, no levothyroxine supplementation was given and periodic monitoring was continued.
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Chapter 16. Treatment of hyperthyroidism: radioiodine
The reported methods to determine the 131I dose for cats with hyperthyroidism are quite variable. However, dosing regimens can be divided into four general categories, as described below.
Fixed radioiodine dosing
The fixed-dose approach, historically the most common method of treating hyperthyroid cats,84-90 assumes that most of these cats can be successfully treated by administering the same fixed, relatively high dose of radioiodine to all cats (i.e., 4-5 mCi [150-185 MBq]), regardless of the severity of hyperthyroidism or size of the thyroid tumor. Because no effort is taken to determine thyroid tumor size or to estimate severity of hyperthyroidism, this dosing method is the easiest, involving no calculations and requiring little in the way of nuclear medicine equipment. However, to attain a reasonable cure rate with this method, a large number of cats end up being overdosed with radioiodine, leading to hypothyroidism.83 For example, in our clinics, the median individualized dose given to our hyperthyroid cats is <2.0 mCi
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(<75 MBq), much less than the dosages administered with the fixed-dose approach. As a result, a large number of cats treated using the fixed-dose method will receive too high a 131I dose, exposing them to an unnecessary amount of radiation and increasing the prevalence of iatrogenic hypothyroidism. In support of that, one study reported a 3-fold higher rate of hypothyroidism in cats with mild to moderate hyperthyroidism treated with a standard 4-mCi (150 MBq) dose versus a lower 2-mCi (75 MBq) dose of radioiodine.83 In that study, the prevalence of iatrogenic hypothyroidism in cats treated with the standard, fixed 4-mCi dose was 64%, a rate that most veterinarians and owners would consider unacceptable. Although persistent hyperthyroidism is not common with standard 4-mCi (150-MBq) dosing, up to 10% of cats with very large, benign thyroid adenomas will require 131I doses that are much higher (i.e., 6 to 12 mCi [222 to 444 MBq]) than those typically administered with the fixed-dose approach.84,85,89 These cats will fail 131 I treatment and show persistent (or early recurrent) hyperthyroidism with the 4-mCi fixed-dose approach.
FIGURE 16.7. (cont.) (e) A 13-year old male DSH cat with moderate hyperthyroidism (serum T4 = 10.3 µg/dl; T3 = 203 ng/dl, TSH <0.03 ng/ml). Scintigraphy reveals a small right thyroid nodule, with a large left thyroid nodule that has fallen through the thoracic inlet into the thoracic cavity. The measured thyroid volume was 2.2 gm; the TcTU was 15.6%; and the 24-hour 131I uptake was 22%. The 131I dose was calculated as follows: Volume = 2.2 mCi T4/T3 = 2.0 mCi TcTU = 4.5 mCi Average dose (2.2+2.0+4.5)/3 = 2.9 mCi No adjustment needed for 24-hour 131I uptake Dose administered = 2.9 mCi (f) Follow-up thyroid scintiscan on cat in (e), 6 months after 131I treatment. The serum T4 concentration (1.5 µg/dl) has fallen to within the reference interval, whereas the serum TSH value (0.14 ng/dl) is normal but no longer suppressed. Both thyroid lobes have decreased in size and intensity to within normal limits. (g) An 11-year old female DSH cat with moderate hyperthyroidism (serum T4 = 8.9 µg/dl; T3 = 179 ng/dl, TSH <0.03 ng/ml). Scintigraphy reveals bilateral asymmetrical thyroid disease; the left thyroid lobe is much larger than the right, with more intense radionuclide uptake. The measured thyroid volume was 1.8 gm; the TcTU was 1.4%; and the 24-hour 131I uptake was 16.9%. The 131I dose was calculated as follows: Volume = 1.8 mCi T4/T3 = 1.8 mCi TcTU = 1.5 mCi Average dose (1.8+1.8+1.5)/3 = 1.7 mCi Adjusted (increased) due to low 24-hour 131I uptake: (1.7 mCi × 1.1) =1.87 mCi Dose administered = 1.9 mCi (h) Follow-up thyroid scintiscan on cat in (g), 6 months after 131I treatment. The serum T4 concentration (1.6 µg/dl) has fallen to within the reference interval, whereas the serum TSH concentration (0.18 ng/dl) is normal but no longer suppressed. The larger left-sided thyroid tumor has largely been destroyed, whereas the right thyroid lobe has decreased in size and intensity and is now within normal limits.
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Similarly, cats with thyroid carcinoma (or SHIM-RAD tumors) will also be greatly underdosed and will fail standard 131I treatment.24,76 So, although the fixed-dose method is the simplest to employ, the incidence of both long-term hypothyroidism and persistent hyperthyroidism are higher with this dosing method. We no longer recommend this relatively high, fixed-dosing method for 131I treatment in cats. Lowering the fixed dose of 131I to 3-mCi or even 2-mCi per cat will result in lower rates of iatrogenic hypothyroidism,91,92 but treatment failure becomes a bigger issue when treating cats with severe hyperthyroidism with these lower, fixed 131 I doses.
Clinical scoring systems for 131I dose determination
In a second method, the dose of 131I administered to hyperthyroid cats is determined by a clinical scoring system based on three factors that take into consideration the severity of clinical signs, the size of the cat’s thyroid tumor(s) (determined by palpation of the goiter on physical examination), and the pretreatment serum T4 concentration.82,93 Using this scoring system, a low, medium, or relatively high 131I dose is selected. For example, cats with mild clinical signs, small thyroid tumor(s), and only a slightly high serum T4 concentration would receive smaller doses of radioiodine (e.g., 2-3 mCi [80-110 MBq]); cats with severe clinical signs, very large thyroid tumor(s), and markedly high serum T4 concentrations would receive high doses of radioiodine (i.e., 5-6 mCi [185-220 MBq]); and cats that lie between these extremes would receive intermediate doses of radioiodine (e.g., 3-5 mCi [150 MBq]).82,93 In contrast to the traditional, fixed-dose method (4 mCi; 150 MBq), the total 131I dosage delivered to the cats with mild hyperthyroidism and smaller tumors, as determined with this individualized clinical scoring system, is lower. Thus, use of this protocol would be expected to lessen the chance of iatrogenic hypothyroidism. However, it is not clear if this is actually true. In one study that employed this scoring system, 79% of the 131I-treated cats had a low serum T4 concentration when rechecked 6-months after 131 I treatment; although serum TSH was not measured in those cats, most were likely overtly hypothyroid.94 In another study in which serum T4 and TSH were rechecked
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6 to 9 months after 131I treatment, 40% of the cats had overt hypothyroidism (low T4 and high TSH concentrations), and another 13% had subclinical hypothyroidism (low-normal T4 with high TSH concentrations).95,96 Thus, the overall prevalence of hypothyroidism may be higher than expected with this individualized 131I dosing protocol. As with the fixed-dosing scheme, some hyperthyroid cats, especially those with severe benign thyroid tumor disease, will not be cured with a single dose of radioiodine, as “estimated” by the clinical scoring dosing protocol.82,93 Similarly, cats with thyroid carcinoma (or SHIMRAD tumors) will also be greatly underdosed, so they will fail treatment and remain persistently hyperthyroidism. One major issue with this 131I dosing protocol is that two of the three variables used in the scoring system are quite subjective (i.e., clinical severity score, goiter size by palpation) and would be expected to vary from one clinician to another. Any ectopic thyroid tumor tissue or tumor within the thoracic cavity would not likely be palpated, so the tumor volume would be underestimated. Although the serum T4 concentration is an objective measure, the serum T4 value used for scoring can be measured by a variety techniques and laboratories, even within the same 131I treatment center. If the cat has been treated with antithyroid drugs, such medical treatment must be stopped for at least a week in order to measure a pretreatment serum T4 concentration that will provide a true estimate of the magnitude of the cat’s hyperthyroid state. If care is not taken to repeat the serum T4 concentration just prior to treatment (and after an adequate withdrawal time for antithyroid drugs), this sole objective measure may not be very meaningful. Overall, this individualized clinical scoring system for 131 I dosing is better in restoring euthyroidism (without inducing hypothyroidism) than a fixed-dosing regime in which all cats receive the same 131I dose, but it is far from perfect.
Quantitative dosing algorithm, with dose calculation based on thyroid scintigraphy, serum thyroid hormone concentrations, and thyroid uptake of radioiodine
In the last method that we now use in our clinics,69 the dose of radioiodine administered is based on a refinement of the scoring system outlined earlier. Again, this
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Chapter 16. Treatment of hyperthyroidism: radioiodine
algorithm takes into consideration the size of thyroid tumor and the pretreatment serum T4 and T3 concentrations. In addition, however, quantitative thyroid imaging is used to better estimate the volume of the thyroid tumor tissue, and overall functional metabolic activity of thyroid tumor is estimated by calculating the percent uptake of the 99mTcO4– (TcTU).48,52 An initial low dose of radioiodine to administer is then calculated from these measurements (Table 16.4). Twenty-four hours after administration of this initial radioiodine dose, the percent 131 I uptake is calculated and an additional 131I dose is administered, especially if the thyroid 131I uptake value is too low (Table 16.5).69,70 Tables 16.4 and 16.5, and Figs. 16.5, 16.8, and 16.9 provide a more detailed outline and description of our protocol that uses these four objective measures (i.e., calculated thyroid volume, serum T4 and T3 concentrations, TcTU, and 24-hour percent 131I uptake) to determine an individualized, calculated 131I dose for each cat.69 Note that the first three indices all represent different ways at looking at the severity of a cat’s hyperthyroid disease (i.e., higher T4 and T3 concentrations, higher percent TcTU, and larger thyroid tumor volume all indicate more severe hyperthyroid disease). The 24-hour percent 131I uptake, on the other hand, evaluates the ability of the thyroid tumor to take up and concentrate 131 I, which is required in order to deliver an adequate radiation dose to the tumor.61,97 If the 24-hour 131I uptake is too low, the delivered radiation dose may be inadequate to irradiate and ablate the thyroid nodule, resulting in treatment failure.70 On the other hand, if the 131I uptake is higher than expected, this would deliver an excessive dose to the thyroid nodule and may lead to iatrogenic hypothyroidism.70 Use of this 131I dosing protocol requires the following nuclear medicine equipment (Fig. 16.1): a gamma (scintillation) camera to perform thyroid scintigraphy (and determine thyroid volume and TcTU); a dose calibrator to accurately measure the 131I doses administered to the cats; and a survey meter/probe (Geiger counter) used to count the cat’s neck and thigh radioactive counts 24 hours after initial 131I treatment (Fig. 16.9), as well as a dose standard to calculate the percent 131I uptake (Fig. 16.8).98 In most instances, the survey meter used to measure the cats’ thyroid uptake values will be the same
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meter used for radiation safety monitoring purposes, as well as to determine when the radiation emitted from the cat has reached a level that poses no radiation safety threat to the general public (allowing the cat to be discharged).7-9 In our clinical experience of treating cats with this protocol,69 very low doses of radioiodine (e.g., 1.5-2 mCi [50-75 MBq]) result in the cure of almost all cats with mild to moderate hyperthyroidism with small but hyperfunctional thyroid tumors on thyroid imaging. These radioiodine doses are less than the lowest dose given with our original scoring system (2-3 mCi [75-110 MBq]) and much lower than doses administered with traditional fixed-dose methods (4-5 mCi [148-185 MBq]). In contrast, other cats with severe hyperthyroidism and large volumes of autonomously functional thyroid tissue (but without scintigraphic evidence of malignancy) may require up to 10-15 mCi (370-555 MBq) of 131I to restore euthyroidism. These calculated radioiodine doses are much higher than the highest dose given with the original scoring systems (5 mCi [185 MBq])82,93 or used with the fixed-dose methods (4 to 5 mCi [148 to 185 MBq]).84-90 With this quantitative dosing algorithm, about 20% still develop hypothyroidism after treatment, but it is relatively mild or subclinical (normal total T4 with high TSH concentrations) in most cats, with only about 5% developing overt hypothyroidism (low total T4 with high TSH concentrations).69 In addition, hypothyroidism is transient in about a third of these cats, with high TSH concentrations normalizing within a few months as thyroid function continues to recover.99 These prevalence rates are much lower than that expected with any of the other reported dosing techniques. Although physical palpation of the thyroid gland may yield equivalent information to that measured by thyroid imaging in a few cats, we find it very difficult to estimate an accurate thyroid volume by palpation alone. In addition, quantitative thyroid imaging avoids the subjective nature of thyroid palpation and expected variability in estimated tumor size between clinicians. Finally, compared to quantitative thyroid imaging, cervical palpation greatly underestimates the total thyroid volume in cats with thyroid nodules that cannot be palpated (e.g., intrathoracic, substernal, or ectopic thyroid masses).
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Therefore, objectively determining each cat’s thyroid tumor volume and measuring the percent thyroid uptake (of both 99mTcO4– and 131I) all play a role in calculating the optimal 131I dose needed to completely ablate all tumor tissue. This method of dose calculation also helps preserve any remaining normal thyroid tissue to help avoid iatrogenic hypothyroidism. For case examples that illustrate how we use this method to calculate individualized 131I doses, please see Fig. 16.7.
High-dose radioiodine treatment for thyroid carcinoma (SHIM-RAD tumors)
In cats with thyroid carcinoma (incidence <2.5% of all hyperthyroid cats),25 radioiodine offers the best chance for successful cure of the cancer because it concentrates in all hyperactive thyroid cells (i.e., carcinomatous tissue, as well as metastasis). Most cats that present with thyroid carcinoma (SHIM-RAD tumors) have been managed for many months to years with antithyroid drugs, which are no longer controlling the hyperthyroidism (in large part due to the huge thyroid size).29 Unlike cats with thyroid adenoma or adenomatous hyperplasia, the goal for 131I treatment in cats with thyroid carcinoma is to totally ablate all thyroid tissue, ensuring complete destruction of all malignant thyroid tissue (Fig. 16.6). Because the size and volume of thyroid carcinoma tissue are generally very large to massive, extremely high doses of 131I (generally 10- to 15-fold higher than needed for most cats with benign thyroid disease) are almost always needed to destroy all the malignant tissue. In most treatment centers that are licensed to treat with large doses of 131I, a high, fixed dose of 30 mCi (1110 MBq) is administered.22-24,76,77 Longer periods of hospitalization are required with such high-dose radioiodine administration because of the prolonged radioiodine excretion. Because the goal is to ablate all thyroid tissue, this high dose almost always leads to iatrogenic hypothyroidism, necessitating l-thyroxine (L-T4) replacement therapy (0.15 mg, once to twice daily) (see chapter 19 for more information).
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TABLE 16.4. Protocol for individual 131I dose calculation based on quantitative thyroid scintigraphy, serum thyroid hormone concentrations, and 24-hour thyroid uptake measurements. Day 1 (Admission day) 1. Collect serum for T4 and T3 concentration from hyperthyroid cat on day of admission for 131I, off all anti-thyroid drugs for a week. 2. Perform qualitative and quantitative thyroid scintigraphy.25,48 ■ Determine pattern of thyroid tumor disease (Figs. 16.4 and 16.6): ■ Unilateral vs. bilateral disease vs. multifocal disease. ■ Ectopic nodules. ■ Thyroid carcinoma (SHIM-RAD). ■ Measure thyroid volume46 (Fig. 16.5). ■ Calculate TcTU.48 ■ Thyroid counts minus background counts/total dose of
pertechnetate administered. ■ Corrected for decay and depth of tumor tissue.
3. Give an initial low 131I dose, ~1.5 mCi (55 MBq) per cat. 4. Make dose standard for 24-uptake studies (~400 µCi; 15 MBq). (Fig. 16.8). Day 2 5. 24 hours after administration of initial low 131I dose, place dose standard directly on probe of survey meter to measure activity (Fig. 16.9); use these counts (cpm or µSv/hour) to calculate the total number of radioactive counts that were administered to the cat. ■ For example, if at the time of admission day 131I dosing, the cat received 1.6 mCi (60 MBq) and the dose standard was measured as 400 µCi (15 MBq), the total radiation counts (cpm or µSv/hour) are multiplied by a factor of 4 to give the total radiation counts administered to the cat. 6. Place the probe of the survey meter directly on skin surface over the “hottest” thyroid nodule (refer to cat’s scintiscan) and measure the cat’s thyroid tumor counts, as well as a background count over the cat’s thigh (Fig. 16.9). 7. Calculate the 24-hour percent 131I uptake: ■ Thyroid counts – thigh counts/total counts of 131I administered. 8. Calculate the final 131I dose to administer based on the average 131I dose score for the following parameters: ■ Calculated thyroid tumor volume (131I dosed at 1 mCi/gram). ■ Serum T4 and T3 concentrations (Table 16.5). ■ TcTU (Table 16.5).
9. Adjust this 131I dose based on the 24-hour % 131I uptake value (Table 16.5). 10. See Fig. 16.7 for case examples of how to calculate and adjust final dose.
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Chapter 16. Treatment of hyperthyroidism: radioiodine
TABLE 16.5. Parameters for 131I dose calculation, based on measured thyroid tumor volume, serum T4 and T3 concentrations, TcTU, and 24-hour thyroid uptake measurements.
a
245
b
1. Calculate thyroid tumor volume ■ 1 mCi (37 MBq) per gram of tumor tissue. 2. Serum T4 and T3 concentration (see table below). ■ Average dose score of serum T4 and T3, if different. 3. TcTU (see table below)
Serum T4 and T3
TcTU (%)
mCi (MBq)
4-10 µg/dl (50-125 nmol/l) 50-200 ng/ml
<1% to 4%
1.3-1.9 (50-70)
>10-15 µg/dl (125-200 nmol/l) >200-300 ng/ml
>4-9%
2.0-2.9 (75-110)
>15-20 µg/dl (195-250 nmol/l) >300-400 ng/ml
>9-15%
3.0-4.4 (110-165)
>20-35 µg/dl (250-450 nmol/l) >400-600 ng/ml
>15-30%
4.5-6.9 (165-250)
>35 µg/dl (>450 nmol/l) >600 ng/ml
>35%
7.0-12.0 (260-450)
c
d
4. Calculate the mean 131I dose based on the thyroid tumor volume, serum T3 and T4, and TcTU (average 3 parameters and divide by 3; see Fig. 16.7 for case example calculations). 5. Measure 24-hour 131I uptake and adjust final dose, if needed, based on table below:
Percent 24-hour uptake
Multiply calculated dose by factor below
<6%
2.0
>6-10%
1.6
>10-14%
1.3
>14-18%
1.1
>18-22%
1.0
>22-28%
0.95
>28-34%
0.90
>34-40%
0.85
>40-46%
0.80
>46-52%
0.75
>52%
0.70
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FIGURE 16.8. Preparing a calibrated dose standard needed to calculate the 24-hour percent 131I thyroid uptake. (a) The 131I dose standard is prepared and counted at the time the cats are treated with an initial dose of ~1.5 mCi (55 MBq) of 131I (on Day 1, admission day). (b, c) Since the average 24-hour thyroid 131 I uptake reading in hyperthyroid cats is approximately 25%, dose standard is also calibrated to contain about a quarter of this initial 131I dose (~350-400 µCi; 15 MBq), as measured in a dose calibrator (Fig. 16.1). (d) 24 hours later, the 131I dose standard is counted by use of the survey meter (Geiger counter; Fig. 16.1) at the same time as the cat’s thyroid counts are being measured (Fig. 16.9). The measured counts of the dose standard are adjusted by a factor of about 4 to calculate the counts of 131I administered (Table 16.4).
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b
c
d
e
f
FIGURE 16.9. Counting the hyperthyroid cat’s neck and thigh regions at 24-hours after initial 131I dose administration to determine the percent thyroid 131I uptake (i.e, the fraction of the administered 131I dose that accumulates in the thyroid after administration). (a-d) The GM probe of the survey meter (Geiger counter) is placed directly on the skin over the “hottest” region of uptake. If thyroid scintigraphy was performed, the probe is placed over the hottest thyroid tumor. (e and f) Probe of the survey meter (Geiger counter) is next placed directly on the skin of the mid-thigh region. Based on these readings, the thyroid uptake is calculated using the following relationship: Thyroid counts – Thigh counts Counts administered (calculated by multiplying the dose standard counts by a factor ~ 4) For example, a 131I dose of 1.5 mCi was administered to a hyperthyroid cat. At the same time, a 131I dose standard was prepared in the amount of 0.4 mCi (400 µCi). 24-hours later, neck, thigh, and dose standard counts were measured and inserted into our formula: Thyroid counts (345K cpm) – Thigh counts (25K cpm) Counts administered (1,125K cpm), calculated by multiplying the dose standard counts (300K cpm) by a factor 3.75 (1.5 mCi divided by 0.4 mCi) And
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320K = 28.4% 1,125K
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Chapter 16. Treatment of hyperthyroidism: radioiodine
Adverse effects or complications associated with radioiodine treatment Overall, side effects associated with radioiodine treatment of cats are uncommon. In extremely rare instances (<0.1%), cats receiving higher 131I doses can develop transient dysphagia (i.e., difficulty swallowing) and fever during the first few days after treatment (probably as a result of radiation thyroiditis), but this condition is self-limited and resolves spontaneously.82 Rarely, they can develop a voice change after treatment (due to irradiation of larynx and vocal cord paralysis),100,101 which may be permanent in some cases. A more serious issue is permanent hypothyroidism (see below and in chapter 19), which develops a few weeks to months after treatment in a variable percentage of cats, depending on the dose of 131I administered, as outlined above. In some cats with concurrent CKD, the hyperthyroid state masks preexisting renal disease by increasing the GFR and renal blood flow, and the CKD may become clinically apparent only after return of normal thyroid function.33,34,102 Most clinicians consider the development or worsening of CKD to be the most serious complication of radioiodine treatment. However, if renal disease does develop, it is not caused by the radioiodine itself but rather because, by correcting the hyperthyroid state, the GFR and renal blood flow fall as the cat’s cardiovascular status returns to normal. This development of azotemia occurs independently of treatment modality (i.e., it occurs with methimazole, surgical thyroidectomy, or radioiodine). Unmasking of CKD, with worsening in serum urea nitrogen or creatinine concentrations, occurs in about 20-30% of treated cats.33,34,102 This azotemia typically becomes manifest within 3-6 months of treatment of hyperthyroidism, rarely increases by more than one International Renal Interest Society (IRIS) stage,103 and is only slowly progressive. In other words, after this initial post-treatment period, the degree of azotemia tends to remain stable in most cats (see chapter 12 for more information).
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Other than the possible association between treatment of hyperthyroidism and the development of overt CKD in some cats, the long-term risk associated with administration of 131I in cats appears to be minimal. Therapeutic doses of radioiodine irradiate not only the thyroid gland but also the cat’s whole body to some degree; this raises concerns about possible long-term effects such as carcinogenesis, genetic damage, and fetal damage. However, a number of recent studies of large populations of humans treated with radioiodine failed to demonstrate a significant increased risk of death or total cancer mortality.104,105 Likewise, increased risk of genetic abnormality in offspring of humans administered 131I has not been identified. Obviously this is less of a concern in cats with hyperthyroidism because most are usually neutered before hyperthyroidism develops.
Follow-up thyroid function testing after radioiodine treatment The ideal goal of 131I therapy is to restore euthyroidism with a single dose of radioiodine without producing hypothyroidism. Indeed, most hyperthyroid cats treated with 131I are cured by a single dose. In general, the cats should be monitored at 1, 3, 6, and 12 months after discharge; at all of these recheck times, a complete physical examination as well as routine laboratory testing (e.g., CBC, serum chemistry panel, complete urinalysis) and a serum thyroid panel (total T4 and TSH determinations) are recommended.78 Iatrogenic hypothyroidism should always be excluded if new or worsening azotemia develops, since treatment of hypothyroidism improves or even reverses azotemia in many of these cats (see chapter 19).55 Serum thyroid hormone concentrations fall to within (or below) the respective reference intervals within 4 weeks of 131I treatment in approximately 80% of cats and in 95% of cats by 6 months. Although cats appear to feel better within days after treatment, the owner should notice gradual clinical improvement and resolution of the signs of hyperthyroidism during this period (Fig. 16.10, Video 16.1).
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c
b
d
FIGURE 16.10. Photographs of a 16-year old female DSH cat with moderate hyperthyroidism, before and after treatment with 131I (see this catâ&#x20AC;&#x2122;s thyroid scintiscan and follow-up results in Figs. 16.7c and d). (a) and (b) Before treatment, note evidence of weight loss and muscle wasting. (c) and (d) Six months after 131I treatment, note the marked gain in fat and muscle mass. The body weight increased from 2.0 kg to 3.9 kg.
VIDEO 16.1a.
VIDEO 16.1b. Before (a) and after (b) video of a cat with severe hyperthyroidism. Before treatment, notice the frantic appearance and respiratory distress, both of which completely resolve after 131I treatment. In addition, notice the marked gain in body weight that is seen after treatment.
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Iatrogenic hypothyroidism
Development of iatrogenic hypothyroidism following 131I therapy in cats results from damage to the nonadenomatous (i.e., normal or dormant) as well as all adenomatous thyroid tissue. Given the mechanism of localization and the limited range of the ablative β-particles, it appears that cats with bilateral adenomatous disease, in which tumor tissue generally infiltrates most of each thyroid lobe, are at increased risk of developing hypothyroidism after 131I treatment.106 With bilateral adenomatous disease, uptake of 131I by both thyroid lobes would lead to a higher radiation dose being delivered to any remaining nonadenomatous tissue (at least a few clusters of atrophied thyroid follicles can almost always be identified
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