DOSIER DE
Edward C. Feldman Federico Fracassi Mark E. Peterson
PRESENTACIÓN
ENDOCRINOLOGIA FELINA
ENDOCRINOLOGIA FELINA Edward C. Feldman Federico Fracassi Mark E. Peterson
Edward C. Feldman Federico Fracassi Mark E. Peterson
Endocrinología felina
Este es un libro único, desarrollado por los mayores expertos mundiales en el tema. Es una herramienta extremadamente valiosa para cualquier veterinario que quiera aproximarse en profundidad a la fisiopatología, signos clínicos, diagnóstico, tratamiento y pronóstico de las patologías endocrinológicas de la especie felina, con un enfoque y contenidos nunca publicados hasta ahora.
ENDOCRINOLOGIA FELINA
ENDOCRINOLOGIA FELINA Edward C. Feldman Federico Fracassi Mark E. Peterson
PÚBLICO OBJETIVO:
✱ Veterinarios generalistas de animales de compañía. ✱ Veterinarios especializados en endocrinología, medicina felina, medicina interna. ✱ Estudiantes de veterinaria. FORMATO: 18,9 x 24,6 cm NÚMERO DE PÁGINAS: 680 NÚMERO DE IMÁGENES: 480 ENCUADERNACIÓN: tapa dura
PVP
ESTIMADO
149 €
Editores EDWARD C. FELDMAN, DVM Profesor Emérito de Medicina Interna de Pequeños Animales Universidad de California, Davis (Estados Unidos) FEDERICO FRACASSI, DVM Profesor Asociado de Medicina Interna de Pequeños Animales Departamento de Ciencias Médicas Veterinarias Universidad de Bolonia (Italia)
MARK E. PETERSON, DVM Animal Endocrine Clinic, Nueva York Profesor Adjunto de Medicina Veterinaria Departamento de Ciencias Clínicas Universidad de Cornell (Estados Unidos)
PUNTOS CLAVE:
➜ Desarrollado por los mejores especialistas mundiales en medicina interna y endocrinología felinas, con la más amplia experiencia y mayor prestigio en su campo, que son autores de múltiples publicaciones de alto impacto. ➜ Libro de referencia único en su género, enteramente dedicado a la endocrinología felina. Incluye la información más novedosa y las mejores técnicas diagnósticas y terapéuticas específicas. ➜ Diseño gráfico excepcional y acceso a vídeos a través de códigos QR. ➜ Imprescindible en la biblioteca de todos los veterinarios interesados en medicina felina, aporta información nunca antes publicada sobre esta temática en una única obra.
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Endocrinología felina
Presentación de la obra El objetivo principal de la obra es aportar a los veterinarios clínicos y a los estudiantes la información más completa sobre la fisiopatología, signos clínicos, diagnóstico y diagnóstico diferencial y tratamiento de las patologías endocrinológicas de los gatos. La medicina felina ha evolucionado de forma espectacular en los últimos años, y dado que existe una cantidad inmensa de información sobre las enfermedades endocrinas, es el momento idóneo para crear un libro exclusivamente dedicado a ellas. En este libro han participado los mejores expertos en cada campo de todos los contenidos que se han incluido en cada una de las secciones en las que se divide, desde el hipotálamo y la hipófisis, la tiroides, paratiroides, adrenales, y páncreas endocrino. Se incluye una sección adicional dedicada a temas relacionados con las enfermedades endocrinas, como la obesidad, trastornos del metabolismo lipídico, emaciación y sarcopenia, e hipertensión. Los colaboradores y editores han incluido la información más novedosa y las técnicas más avanzadas para poder realizar el diagnóstico y el tratamiento, refiriéndose de forma específica al gato como paciente único sin extrapolar datos del paciente canino, haciendo que este libro sea único en su género, y una obra que sin duda es imprescindible en la biblioteca de cualquier veterinario que se dedique a la clínica de felinos, ya sea como especialista en endocrinología, pero también para cualquiera que ejerza la medicina interna como generalista.
Editores Edward C. Feldman, DVM Profesor Emérito de Medicina Interna de Pequeños Animales Universidad de California, Davis Estados Unidos
Federico Fracassi, DVM Profesor Asociado de Medicina Interna de Pequeños Animales Departamento de Ciencias Médicas Veterinarias Universidad de Bolonia Italia
Mark E. Peterson, DVM Animal Endocrine Clinic Nueva York Profesor Adjunto de Medicina Veterinaria Departamento de Ciencias Clínicas Universidad de Cornell Estados Unidos
Endocrinología felina
Colaboradores Charlotte R Bjørnvad, PHd, DECVCN. Universidad de Copenhague, Dinamarca. Michael R. Broome, DVM, MS, DABVP. Advanced Veterinary Medical Imaging. Estados Unidos. Sylvie Daminet, DACVIM (SAIM), DECVIM-CA, Msc, PhD. Universidad de Gante, Bélgica. Lucy J. Davison, MA, VetMB, PhD, DSAM, DECVIM-CA, MRVCS. The Royal Veterinary College. Wellcome Trust Centre for Human Genetics. Reino Unido. Duncan C. Ferguson, VMD, PhD, DACVIM (SAIM), DACVCP. Universidad de Illinois. Estados Unidos. James A. Flanders, DVM, DACVS. Universidad de Cornell. Estados Unidos. Linda M. Fleeman, BVSc, PhD, MANZCVS. Animal Diabetes Australia. Australia. Lisa M. Freeman, DVM, PhD, DACVN. Tufts University. Estados Unidos. Sara Galac, DVM, PhD. Universidad de Utrecht. Holanda. Chen Gilor, DVM, PhD, DACVIM (SAIM). Universidad de California, Davis. Estados Unidos.
Susan Gottlieb, BVSc, MANZCVS. The Cat Clinic. Australia. Thomas K. Graves, DVM, PhD, DACVIM (SAIM). Midwestern University of Arizona. Estados Unidos. Guy C.M. Grinwis, DVM, PhD. Universidad de Utrecht. Holanda. John P. Loftus, PhD, DVM, DACVIM (SAIM). Universidad de Cornell. Estados Unidos. Thomas A. Lutz, Prof. Dr. med. vet. Universidad de Zurich. Suiza.
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Ruth Gostelow, BVetMed(Hons), MVetMed, DACVIM (SAIM), DECVIM-CA, PhD. The Royal Veterinary College. Reino Unido.
Philipp D. Mayhew, BVM&S, MRCVS, DACVS. Universidad de California, Davis. Estados Unidos. Björn Meij, DVM, PhD, ECVS. Universidad de Utrecht. Holanda. Carlos Melián, DVM, PhD. Universidad de Las Palmas de Gran Canaria. España. Meredith L. Miller, DVM, DACVIM (SAIM). Universidad de Cornell. Estados Unidos. Jeffrey Mitchell, DVM. Universidad de California, Davis. Estados Unidos. Carmel T. Mooney, MVB, MPhil, PhD, DECVIM-CA. Universidad de Dublín. Irlanda. Stijn J.M. Niessen, DVM, PhD, DECVIM, PGCertVetEd, FHEA, MRCVS. The Royal Veterinary College, Londres. The VetCT Telemedicine Hospital, Cambridge. Reino Unido. Dolores Pérez Alenza, DVM, PhD. Universidad Complutense de Madrid. España. Laura Pérez-López, DVM. Universidad de Las Palmas de Gran Canaria. España. Pascaline Pey, DVM, PhD, DipECVDI, MRCVS. Universidad de Bolonia. Italia. Juan José Ramos-Plá, Universidad Cardenal Herrera-CEU. España. Ian Ramsey, BVSc, PhD, DSAM, DECVIM-CA, FHEA, FRCVS. Universidad de Glasgow. Reino Unido. Jacquie Rand, DVM, PhD, DACVIM (SAIM). Universidad de Queensland. Australia. John F. Randolph, DVM, DACVIM (SAIM). Universidad de Cornell. Estados Unidos. Dan Rosenberg, DVM, PhD. Centro de Referencia MICEN VET. Francia. Claudia E. Reusch, Prof., Dr. med. vet.,PhD, DECVIM-CA. Universidad de Zurich. Suiza. Elena Salesov, Dr. med. vet. Universidad de Zurich. Suiza. Johan P. Schoeman, BVSc, MMedVet (Pretoria), PhD (Cantab), DSAM (RCVS-UK), DECVIM-CA, MRCVS. Universidad de Pretoria. Sudáfrica. Nadja S. Sieber-Ruckstuhl, Prof., Dr. med. vet., DACVIM (SAIM), DECVIM-CA. Universidad de Zurich. Suiza. Barbara J. Skelly, MA, VetMB, PhD, CertSAM, DACVIM (SAIM), DECVIM-CA, MRCVS. Universidad de Cambridge. Reino Unido.
Endocrinología felina
Christopher J. Scudder, BVSc, PhD, DACVIM (SAIM), MRCVS. The Royal Veterinary College, Londres. Southfields Veterinary Specialists, Southfields. Reino Unido. Robert E. Shiel, MVB, PhD, DECVIM-CA. Universidad de Dublín. Irlanda. Andy H. Sparkes, BVetMed, PhD, DECVIM-CA, MANZCVS, MRCVS. Director Veterinario del International Cat Care y de la International Society of Feline Medicine (ISFM). Reino Unido.
Tim Williams, MA, VetMB, PhD, FRCPath, Dip. ECVCP, MRCVS. Universidad de Cambridge. Estados Unidos. Panagiotis G. Xenoulis, DVM, Dr. med. vet., PhD. Universidad de Thessalia. Grecia. Mª Pilar Xifra, BVSc. Servicio de Medicina Nuclear de Pequeños Animales, Clínica Veterinaria Leganés Norte. Iodocat. España. Eric Zini, Prof., Dr., DECVIM-CA. Universidad de Zurich. Suiza. Universidad de Padua. Italia.
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Alain P. Théon, MS, PhD, Dip ACVR-RO. Universidad de California, Davis. Estados Unidos.
Índice de contenidos Sección 1. Hipotálamo e hipófisis 1. Anatomía y fisiología de la hipófisis Anatomía de la hipófisis Fisiología de la hipófisis Hormonas de la adenohipófisis Hormonas de la neurohipófisis
2. Exceso de GH: acromegalia (hipersomatotropismo) Antecedentes e historia Incidencia y patogénesis Patología de la hipófisis Consecuencias de la patología de la hipófisis Signos clínicos y diagnóstico Tratamiento Pronóstico
3. Otros tumores hipofisarios Masas hipofisarias: ¿hiperplasia, adenoma o carcinoma? Incidencia y origen celular de los tumores hipofisarios Efecto de los tumores hipofisarios sobre los órganos diana y los efectos directos de los tumores grandes Consecuencias funcionales de la producción hormonal autónoma
4. Cirugía hipofisaria
5. Irradiación hipofisaria Introducción Presentación clínica Diagnóstico por imagen avanzado Papel de la terapia por radiación Modalidades de la terapia por radiación Tumores no funcionales Tumores hipofisarios secretores de hormona del crecimiento y acromegalia Tumores hipofisarios secretores de hormona adrenocorticotropa y enfermedad de Cushing felina Efectos adversos relacionados con la radiación
6. Deficiencia de GH hipofisario y enanismo hipofisario Introducción Etiopatogénesis Signos clínicos Diagnóstico diferencial de los fallos en el crecimiento Diagnóstico Tratamiento
7. Poliuria, polidipsia y diabetes insípida Introducción Necesidades de agua en gatos sanos Capacidad de concentración de la orina en gatos sanos Mecanismos de retención de agua Causas de poliuria y polidipsia en gatos
Introducción y observaciones generales
Aproximación diagnóstica a la poliuria y polidipsia
Anatomía quirúrgica
Tratamiento de la diabetes insípida central
Imágenes de la hipófisis felina
Pronóstico
Adenomas hipofisarios Hipofisectomía transesfenoidal Cuidados posquirúrgicos Complicaciones tras la cirugía hipofisaria Pronóstico
Sección 2. Glándula tiroides 8. Anatomía y fisiología de la tiroides Anatomía de la glándula tiroides felina Fisiología tiroidea general Unión a proteínas séricas de las hormonas tiroideas Eje hipotálamo-hipófisis-tiroides Metabolismo extratiroideo de la hormona tiroidea Cinética de la hormona tiroidea en el gato Acción de la hormona tiroidea
9. Hipertiroidismo: antecedentes, etiopatogénesis y cambio de la prevalencia de la enfermedad tiroidea felina Historia de la enfermedad tiroidea en gatos Estudios de la etiopatología del hipertiroidismo felino
12. Enfermedad tiroidea y renal en gatos Hipertiroidismo y enfermedad renal crónica (ERC) Efecto del hipertiroidismo sobre los resultados de los test séricos sobre la función renal Efecto del hipertiroidismo sobre los marcadores urinarios de función renal Efecto del hipertiroidismo sobre la presión sistólica sanguínea Efecto del tratamiento del hipertiroidismo sobre la función renal Efecto de la azotemia sobre cómo se manejan los gatos hipertiroideos Sugerencias de estrategias de manejo para gatos hipertiroideas con ERC
13. Diagnóstico por imagen tiroideo Introducción Embriología tiroidea, anatomía radiológica y tejido tiroideo ectópico Tiroides normal Hipertiroidismo Tiroides ectópico
Epidemiología del hipertiroidismo: un trastorno común mundial de gatos senior a geriátricos
Carcinoma tiroideo
¿Por qué ha alcanzado el bocio nodular felino tales proporciones epidémicas?
Hipotiroidismo
Conclusiones
10. Hipertiroidismo: signos clínicos y hallazgos de la exploración física Indicadores Signos clínicos Exploración física
11. Hipertiroidismo: diagnóstico laboratorial Anomalías clinicopatológicas asociadas con el hipertiroidismo Anomalías de la hormona tiroidea asociadas con el hipertiroidismo
Quistes tiroideos
14. Tratamiento del hipertiroidismo: fármacos antitiroideos Consideraciones previas a la iniciación del tratamiento con fármacos antitiroideos Mecanismo de acción de los fármacos antitiroideos Formulaciones de los fármacos antitiroideos Dosificaciones de los fármacos antitiroideos Reacciones adversas a los fármacos antitiroideos Monitorización de gatos tratados con fármacos antitiroideos
Otros test diagnósticos
Tasa de éxito y supervivencia en gatos hipertiroideos tratados con un fármaco antitiroideo
Conclusión
Función renal e hipertiroidismo Conclusión
15. Tratamiento del hipertiroidismo: tiroidectomía quirúrgica
18. Tratamiento del hipertiroidismo: grave, refractario o recurrente
Introducción y perspectiva
Introducción
Anatomía de la glándula tiroides y estructuras adyacentes
Etiología y patogénesis del hipertiroidismo grave, refractario o recurrente
Evaluación prequirúrgica
Correlación entre la gravedad y la duración del hipertiroidismo y la gravedad de los signos clínicos
Anestesia general Técnicas de tiroidectomía felina Complicaciones perioperatorias Recidiva perioperatoria del hipertiroidismo Escisión quirúrgica del adenocarcinoma tiroideo Resumen y conclusiones
16. Tratamiento del hipertiroidismo: yodo radiactivo Introducción Ventajas y desventajas del tratamiento del hipertiroidismo con yodo radiactivo Principios del tratamiento con yodo radiactivo Selección de pacientes y preparación antes del tratamiento con yodo radiactivo Escintigrafía de tiroides para la evaluación de gatos hipertiroideos antes del tratamiento con 131I Estimación de la dosis de yodo radiactivo a administrar a los gatos con hipertiroidismo
Causas del fracaso del tratamiento Tratamiento del hipertiroidismo grave refractario Resumen
19. Hipotiroidismo Introducción Causas del hipotiroidismo Subtipos clínicos del hipotiroidismo Hipotiroidismo refractario
Sección 3. Calcio y glándulas paratiroides 20. Hipercalcemia Perspectiva
Efectos adversos o complicaciones asociadas con el tratamiento con yodo radiactivo
Fisiología del calcio
Pruebas de seguimiento de la función tiroidea después del tratamiento con yodo radiactivo
Investigación inicial en gatos hipercalcémicos
Pronóstico después del tratamiento con yodo radiactivo
17. Tratamiento del hipertiroidismo: dieta
Pruebas de laboratorio Diagnóstico diferencial de la hipercalcemia
21. Hipoparatiroidismo e hipocalcemia felinas primarias Introducción
Evaluación nutricional general del gato hipertiroideo
Distribución del calcio en el organismo
Pérdida de peso y desgaste muscular
Hipocalcemia en humanos y perros
Nutrientes necesarios para el gato hipertiroideo
Hipoparatiroidismo en gatos
Manejo nutricional del hipertiroidismo felino: alimentación con dieta baja en yodo
Diagnóstico diferencial de la hipocalcemia
Control de la homeostasis del calcio (Ca)
Test diagnósticos Tratamiento
Sección 4. Glándulas adrenales 22. Anatomía y fisiología adrenal Anatomía adrenal Fisiología adrenal
23. Síndrome de Cushing (hiperadrenocorticismo) Introducción Etiología Signos clínicos Hallazgos clinicopatológicos Test endocrinos Diagnóstico por imagen Tratamiento Pronóstico
24. Hiperaldosteronismo primario (Síndrome de Conn) Introducción Hiperaldosteronismo primario
25. Otros tumores adrenales corticales y feocromocitoma Introducción y diagnóstico diferencial Evaluación de una masa adrenal felina Producción excesiva de progesterona Exceso combinado de progesterona y aldosterona Producción excesiva de andrógenos o estradiol Feocromocitoma Tumores adrenales no funcionales
26. Cirugía adrenal mediante abordaje abierto y laparoscópico Introducción Evaluación diagnóstica Selección de casos Preparación del paciente Técnicas quirúrgicas Cuidados postoperatorios Complicaciones
27. Hipoadrenocorticismo felino Introducción Prevalencia Causas Edad, raza y sexo Signos clínicos Patología clínica Diagnóstico por imagen Electrocardiografía y ecocardiografía Test endocrinos Diagnósticos diferenciales Tratamiento Pronóstico
28. Tratamiento con glucocorticoides Fisiología Farmacología Aplicaciones terapéuticas Efectos adversos Protocolo de reducción de glucocorticoides
Sección 5. Páncreas endocrino 29. Anatomía, histología y fisiología del páncreas endocrino felino Anatomía del páncreas felino
32. Tratamiento con insulina de la diabetes mellitus Objetivos del tratamiento y el plan de manejo Tratamiento con insulina Elegir una insulina Frecuencia de administración de insulina, dosis inicial de insulina y cambio en el tipo de insulina
Tipos celulares
Almacenamiento, mezcla y dilución de la insulina
Diferenciación cruzada
Educación del propietario
Función general de las células de los islotes
Plumas de dosificación de insulina
Control secretorio Importancia relativa de las hormonas pancreáticas y su contribución a la fisiopatología de la diabetes mellitus Amiloide pancreático como el hallazgo más típico en la diabetes mellitus
30. Patogénesis y observaciones clínicas de la diabetes mellitus no complicada Introducción Prevalencia y epidemiología Factores de riesgo Mecanismos fisiopatológicos Diabetes mellitus y pancreatitis Hallazgos clínicos y de laboratorio Factores de supervivencia y pronósticos
31. Cetosis diabética, cetoacidosis y síndrome hiperosmolar Introducción Homeostasis de la glucosa Presentación clínica de la cetoacidosis diabética y el síndrome hiperosmolar Principios del manejo de la cetoacidosis diabética y el síndrome hiperosmolar Tratamiento de fluidoterapia y electrolitos Tratamiento con insulina Tratamiento adicional de apoyo de la cetoacidosis diabética y el síndrome hiperosmolar Pronóstico de la cetoacidosis diabética y el síndrome hiperosmolar en gatos
33. Hormonas gastrointestinales y uso de tratamientos no insulínicos para la diabetes mellitus Introducción Fisiología y farmacología de la hormona incretina Metformina Glipizida Acarbosa Antagonistas de la SGLT-2 Retos en el manejo de la diabetes mellitus felina y usos potenciales de los tratamientos no insulínicos
34. Manejo dietético de la diabetes mellitus Perspectiva Resultados para aprenderse Caso 1: alimentación de gatos que rechazan o no les gusta su “dieta de diabetes” Caso 2: gato diabético sobredosificado con insulina que se acaba de recuperar de una hipoglucemia grave (neuroglicopenia) Caso 3: alternativas de dieta de no prescripción Caso 4: conseguir la pérdida de peso en un gato diabético Caso 5: manejar la diabetes en un gato con enfermedad concomitante Caso 6: el cliente ha buscado mucha información sobre la diabetes en gatos en internet
35. Monitorización de la diabetes en gatos
38. Hipoglucemia Introducción
Signos clínicos
Fisiopatología de la hipoglucemia
Monitorización de la glucosa sanguínea
Medición de la glucosa sanguínea
Sistemas de monitorización continua de la glucosa (CGMS) y sistemas de monitorización de la glucosa instantánea
Diagnóstico diferencial
Medición de la glucosa urinaria Concentración de fructosamina Hemoglobina glucosilada
36. Remisión de la diabetes Definición de la remisión de la diabetes Fisiología de la remisión de la diabetes Incidencia de la remisión de la diabetes Predictores de la remisión de la diabetes Maximizar la probabilidad de la remisión de la diabetes Identificación y manejo del gato diabético en remisión Pronóstico y recidiva diabética Conclusiones
37. El diabético inestable Perspectiva Objetivos iniciales del tratamiento y factores que influyen en la remisión Clasificación de la diabetes mellitus y relevancia para los gatos diabéticos inestables Elección inadecuada de la insulina Dosificación inadecuada Elección de un manejo de la insulina intensivo frente al conservador de los diabéticos recién diagnosticados Factores relacionados con el cliente Enfermedades subyacentes Hipoglucemia de rebote (Somogyi) El diabético frágil Monitorización Otras estrategias de manejo Conclusión
Enfermedades o síndromes específicos asociados con la hipoglucemia en gatos Enfoque diagnóstico Tratamiento de la hipoglucemia
Sección 6. Presión sanguínea, condición corporal y nutrición 39. Obesidad felina Epidemiología Fisiopatología de la obesidad Enfermedades relacionadas con la obesidad Tratamiento
40. Trastornos del metabolismo lipídico Introducción Las bases del metabolismo lipoproteico Definiciones y medida de las concentraciones de los lípidos séricos felinos Efecto de la lipemia en la medida de otros analitos Casos de hiperlipidemia felina Consecuencias clínicas de la hiperlipidemia en gatos Enfoque diagnóstico a los gatos con hiperlipidemia Tratamiento de la hiperlipidemia felina
41. Caquexia y sarcopenia Caquexia Sarcopenia Diagnóstico de caquexia y sarcopenia Intervenciones potenciales de la caquexia y sarcopenia Enfoque práctico al tratamiento de la caquexia y sarcopenia en gatos Conclusión
42. Hipertensión Introducción Medición de la presión sanguínea en gatos Definición de la hipertensión y decisión de cuándo tratar Consecuencias de la hipertensión Causas endocrinas de la hipertensión Manejo de la hipertensión
43. Tablas de conversión Conversión a las unidades del Sistema Internacional
ENDOCRINOLOGIA FELINA Edward C. Feldman Federico Fracassi Mark E. Peterson
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THYROID GLAND
SECTION 2
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).
a
c
e
g
b
d
f
h
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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c
e
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b
d
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h
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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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
241
(<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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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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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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c
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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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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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