VICSD July 2011 I-131 Therapy CE Seminar for Veterinarians

Feline Hyperthyroidism and I-131: 

Feline Hyperthyroidism and I-131 Seth Wallack DVM, DACVR Veterinary Imaging Center of San Diego, Inc. www.vicsd.com www.aavr.org www.vetology.net www.askta.com VICSD 2011

Outline: 

Outline The Disease Diagnostics T4, free T4, Thyroid scan, T3 level, TSH Associations Methimazole , 131 I and other treatments Work-up for 131 I therapy Treatment T:B ratio and VICSD’s 131 I Guarantee Post-treatment

Hyperthyroidism: 

Hyperthyroidism Most common endocrine disorder in cats since 1970- 1 in 300 cats No breed of sex predisposition Two breeds are less likely Overfunctioning follicular cells Spontaneous hyperthyroidism Not due to Thyroid Stimulating Immunoglobulins

Predisposing factors: 

Predisposing factors Litter usage- 3x risk Eating canned cat food- 2x risk Fish based Use of pesticides/ topical ectoparasite tx Flame retardants Soy products

The Disease: 

The Disease Weight loss, hyperactivity, increased appetite/ thirst, vomiting, diarrhea, tachycardia (>240 bpm ) / arrhythmia, +/- reversible systemic hypertension Apathetic hyperthyroidism Depression and Inappetance Thyroid carcinoma

El Corazon: 

El Corazon Hyperthyroidism is associated with wall thickening 10-15% of hyperthyroid cats develop heart failure ECG abnormalities associated with hyperthyroidism Arrhythmia, tachycardia, increased R-wave amplitude (lead II), prolonged QRS, shortened Q-T interval

Kidneys: 

Kidneys GFR increased Increased GFR can accelerate renal damage Decreased GFR associated with 131 I treatment can unmask renal disease Reason # 1 for the Tapazole trial Reason #2- concurrent disease/ lymphoma

Bloodwork: 

Bloodwork Liver values ALT, Alk Phos ., bilirubin Bone isoenzyme Higher ammonia Lower cholesterol (2007) Hyperthyroid cats with elevated liver values do not have underlying liver disease

Diet: 

Diet Short term vs. Long term T4 with excess or deficient iodine intake

Total T4 and freeT4 by ED: 

Total T4 and freeT4 by ED Thyroid activity is related to unbound T4 and T3 Euthyroid and hyperthyroid cats can have similar amounts of free (unbound) T4 Total T4 is best measure False negatives Older cat T4 should be in lower 2/3rds Natural fluctuations Concurrent disease- hyperthyroid sick Higher GFR can lower TT4

Free T4 by ED: 

Free T4 by ED High sensitivity 98% Poor specificity 20% sick euthyroid cats have elevated free T4 results Use with T4- sick euthyroid typically in lower half

Thyroid Scan: 

Thyroid Scan Thyroid (Technetium) scan Off Methimazole T:S ratio of 1.2:1 On Methimazole T:S ratio of 1.5:1 I123 scan

Thyroid: Salivary Ratio: 

Thyroid: Salivary Ratio Not perfect but very good 2006- Tendency for lack of inter-examiner agreement with higher count/pixel densities Page R., et. al. Vet. Rad & Ultr . 47 (2) 206-211 2006 Measurement of salivary region can be variable and open to interpretation -Page R., et. al. Accuracy of Increased Thyroid Activity During Pertechnetate Scintigraphy by Subcutaneous Injection for Diagnosing Hyperthyroidism in Cats. Vet. Rad & Ultr. 47 (2) 206-211 2006

T3 level: 

T3 level Total T3 level not recommended 25-30% of hyperthyroid cats have normal value

T3 Suppression: 

T3 Suppression Hyperthyroidism T4- less than 35% suppression or >20 nmol /L Euthyroid T4- greater than 50% suppression or <20 nmol /L Requires Pre and post T3 levels 1 dose every 8 hours orally x 7 doses

TSH level: 

TSH level No feline TSH assay in US Canine only Detects approximately 35% of feline TSH Hyperthyroid should have low TSH Negative feedback Normal value probably rules out hyperthyroidism European fTSH study (2002) was very accurate

Optimal Hyperthyroid Evaluation: 

Optimal Hyperthyroid Evaluation We are seeing more “falsely-high T4 levels ” If unsure, repeat total T4 Treat concurrent disease first Free T4 by ED Thyroid scan Clinical signs

Associations: 

Associations Hyperparathyroidism- 77% Lower ionized calcium Folate / Cobalamine (low) and hyperthyroidism Malabsorption vs. hypermetabolism Prednisone (10 mg/ cat) causes TT4 to lower in euthyroid cats but not hyperthyroid cats

Associations continued: 

Associations continued Delayed glucose clearance (non-reversible ) Diabetic/ hyperthyroid-Lower fructosamine level Proteinuria and hyperthyroidism No association with renal failure development post Tx Typically resolves with euthyroid state

Associations continued: 

Associations continued Chronic renal disease and lower TT4 Increased GFR vs. euthyroid sick

Methimazole: 

Methimazole Side effects- 20% of cats Facial excoriations, WBC, thrombocyto penia , liver toxicity, vomiting Transdermal Mean 2 year survival on methimazole Twice daily dosing optimal

131I: 

131 I Perfect treatment- iodine selective for overactive thyroid gland

Methimazole vs. 131I Tx: 

Methimazole vs. 131 I Tx Renal dz and methimazole – avg. 2 yr survival 131 I therapy- avg. 4 yr survival

Alternative Treatments: 

Alternative Treatments Propylthiouracil (PTU) Decreases thyroid hormone production 10% of cats develop immune mediated drug reactions, liver failure, anorexia, coagulopathy and IMHA Ipodate 66% effective at treating mild hyperthyroidism

L-Carnitine: 

L- Carnitine 250-500 mg/day D- carnitine is potentially toxic Affect on T4 and T3 entrance into cells Doesn’t reduce T4 levels

Surgery: 

Surgery Debulking for large carcinomas

Prior to 131I Tx: 

Prior to 131 I Tx TAPAZOLE TRIAL Begin methimazole dose at 1.25mg OAD Increase dose as needed CBC, Chem , UA, T4 Done by RDVM VICSD available for questions Recheck blood work monthly T4 level WNL- refer for 131 I Tx Monitor renal values Monitor liver values WBC penias

Incomplete Tapazole Trial: 

Incomplete Tapazole Trial Facial excoriations WBC penia Thrombocytopenia , L iver toxicity GI Upset Trial waiver Tapazole reaction Unable to pill and use transdermal USG> 1.045 GFR study GFR stabilizes

Prior to 131I Tx: 

WHAT DOES VICSD REQUIRE? CBC CHEM UA Whole body radiographs Most recent lab work and radiographs must within 6 weeks of planned start of 131 I Tx . Prior to 131 I Tx

131I Treatment Package: 

131 I Treatment Package In-depth owner consultation Thorough physical exam Thyroid Scan Cardiac Ultrasound 131 I Treatment Boarding (5 days ) With completed Radiologist reports

Thyroid Scan- Is it needed for known hyperthyroid cases?: 

Thyroid Scan- Is it needed for known hyperthyroid cases? Confirm hyperthyroidism Identify thyroid carcinoma Use for treatment dose and predicting failure? While no treatment is 100% effective, owner displeasure with 131 I retreatment is 100% certain

131I Treatment Success : 

131 I Treatment Success Studied for >20 years 1990- 4mCi fixed dose - 92% resolved hyperthyroidism (3% hypothyroid) No thyroid scan Meric S., JAVMA 197(5) 621-623 1995- Dose determined by clinical signs, thyroid size and T4 level- 94% response Peterson M,. JAVMA 207(11) 1422-1428 1995

Why Do Treatments Fail in People: 

Why Do Treatments Fail in People Human research Portugal Dec 2006 Free T4 > 4 ng /dl, large thyroid, dose < 10mCi result in higher failure Germany Feb 2001 Absorbed energy dose < 200 Gy Ethiopia Jan 2001 Low dose regimen = 50% failure India Mar 1995 Standard 10mCi dose resulted in 10% failure Nodules > 3cms China Dec 1990 Large thyroid size, higher T4 and T3 = higher failure

Why Do Treatments Fail in People: 

Why Do Treatments Fail in People Larger thyroid- “Discriminant analysis of pretreatment variables suggested that those patients who were still hyperthyroid at the end of the first year had significantly larger goiter size, and higher serum T4 and T3 levels.” “Patients having nodules larger than 3 cms . relapsed after first dose of 10 mci of radioiodine” Higher T4 level- “On logistic regression analysis, free T4 > 4 ng /dl, large goiter, RAI dose < 10 mCi were related to lower cure rates” Inadequate 131 I dose- “The low dose regimen we used in this study, though economical in a situation of limited I-131 supply, resulted in a high failure rate of 50%.”

Why Do Treatments Fail in Cats: 

Why Do Treatments Fail in Cats 2002- 4 mCi treatment predictors Relationship between pre and post-treatment thyroxine values Relationship between thyroid to salivary ratio and thyroxine values pretreatment and 1 week post tx No relationship between thyroid to salivary ratio and thyroxine values > 1 week post tx Chun R., Vet. Rad and Ultrasound 43(6) 587-591, 2002

The Problem with the 4 mCi Plan: 

The Problem with the 4 mCi Plan 6-8 % of cats fail first time 131 I therapy with standard 4 mCi dosing

VICSD Original Research: 

VICSD Original Research T:B ratio is a predictor for treatment failure when using 4 mCi 131 I for feline hyperthyroidism Retrospective study-153 cats treated in 2006/2007

T:B Ratio: 

T:B Ratio Thyroid:Background protocol Select A:B ratio Select V/D chest zoom- 2.0 zoom Teal color Outline border of overactive thyroid gland Use standard size circle as background in left or right axillary region

Thyroid: Background Ratio: 

Thyroid: Background Ratio

Results: 

Results Successes 30 Range- 1.77-52.75 Mean- 7.92 27/30 T/B ratio < 11 Failures 8 Range- 5.76- 75.16 Mean- 29.87 6/8 T/B ratio > 11

Success vs. Failure: 

Success vs. Failure

The VICSD Way: 

The VICSD Way T:B ratio < 11 4 mCi T:B ratio >11 7 mCi 98-99 % success No increase in permanent hypothyroidism 5 day stay- cation 3 day hotness Money back guarantee VICSD guarantees 1 st treatment success $500 back or 2 nd treatment free

Post Tx: 

Post Tx Owner Two weeks of limited close contact 20 minute/day Separate quarters Follow-up blood work analysis Recommended post 131 I bloodwork at 1,3,6,12 months post-treatment. Cat GFR Decreases and stabilizes at 1 month Hypothyroid Bilateral disease 3 months (typical) 6 months (supplement)

Post Tx: 

Post Tx Small percentage recurrence > 2 years post Renal insufficiency Systemic hypertension Cardiac changes One offs Severe anemia Pleural effusion (ectopic tissue) Contrast CT prior to tx is a no no 24 hours before scan

Questions?: 

Questions?