Feline Hyperthroidism Prof. Dr. Reto Neiger PhD, DACVIM, DECVIM CA Justus Liebig Universität Giessen Most common endocrinopathy of older cats (mean age: 12 13y; only 5% < 10y) Increased prevalence over last years No sex or breed predisposition Almost always adenomatous hyperplasia or adenoma unilateral: 30% bilateral: 70% Aetiology Autoantibodies uncommon not similar to Graves disease Resembles toxic nodular goitre of humans Increased risk factors: Use of cat litter Diet entirely of canned cat food Use of parasiticide Male sex? Decreased risk factor Siamese and Himalayan breed % Prevalence of feline hyperthyrodism (Kraft und Büchler 1999 Munich) History and clinical signs Symptoms in % Peterson et al., Broussard et al., Mooney et al., Dijl et al., 2008 114 Giessen 2011 1983 1995 2004 n=131 n=202?? n=83 n=196 Weight loss 98 87 92 83 71 Vomiting 44 55 38 5 42 Polyuria/Polydipsia 36 60 47 16 34 Change in behaviour 31 76 40 27 29 Inappetence 7 25 14 8 23 Diarrhoea 15 33 39 4 21 Dermatological 3 7 36 23 11
Physical examination Palpable goitre 89% Thin/weigh loss 76% Hyperactive 74% Tachycardia 40% Unkempt hair/alopecia 36% Small kidneys 34% Heart murmur 28% Easily stressed 18% Cachectic appearance 16% Premature beats 10% Gallop rhythm 8% Aggressive 6% Depressed/weak 4% Ventral flexion neck 1% Thyroid gland in thorax (not palpable) Palpable goitre 89% Thin/weigh loss 76% Hyperactive 74% Tachycardia 40% Unkempt hair/alopecia 36% Small kidneys 34% Heart murmur 28% Easily stressed 18% Cachectic appearance 16% Premature beats 10% Gallop rhythm 8% Aggressive 6% Depressed/weak 4% Ventral flexion neck 1% Thyroid size and T4 value Boretti et al JFMS 2009 General laboratory testing CBC Erythrocytosis 25% Increase in MCV 22% Leukocytosis 18% Lymphopaenia 16% Urinalysis SG > 1035 68% SG < 1015 6% Glucosuria 3% UTI 2% Biochemistry Increased ALT 88% Increased ALP 76% Azotaemia 34% Hyperphosphataemia 40% Electrolyte abnorm. 11% Hyperbilirubinaemia 3% Hyperglycaemia 3% Others Decreased fructosamine
Other tests Boretti et al JFMS 2009 Radiology Cardiomegaly, rarely evidence of congestive heart failure Ultrasound Hypertrophic cardiomyopthy Rarely dilated CMP ECG Sinus tachycardia Increased R wave amplitude Right bundle branch block Systolic blood pressure No significant difference Blood pressure (mmhg) Old cat... Eating well but loosing weight... Showing some vomiting and... Being aggressive... With increased ALT and ALP... And possibly a cardiopmyopathy Needs to undergo thyroid testing Euthyroid Hyperthyroid 171 ± 50 mmhg 174 ± 38 mmhg Thyroid testing in cats Basal T4 Basal T3 Free T4 (by equilibrium dialysis) T3 suppression test TRH stimulation test TSH stimulation test Scintigraphy Basal T4 and T3 T4 preferable to T3 Specificity: 98 100% Sensitivity 90% (all hyperthyroid cats) 60% (mild hyperthyroidism) T4 suppression by nonthyroidal illness Feldman & Nelson 2004
Basal T4 and T3 Free T4 (by equilibrium dialysis) T4 preferable to T3 Specificity: 98 100% Sensitivity 90% (all hyperthyroid cats) 60% (mild hyperthyroidism) T4 suppression by nonthyroidal illness T4 fluctuation Only useful if measured by equilibrium dialysis Sensitivity up to 95% Specificity 88% Use first TT4, if high normal but suspicion high then measure ft4 (ED) Feldman & Nelson 2004 mu/l TSH basal concentration TSH Sensitivity Specificity 0,02 mu/l 90,8% 92,5% 0,03 mu/l 93,4% 88,9% 0,04 mu/l 95,4% 82,3% non-hyperthyroid hyperthyroid n=226 n=179 Mathes, Giessen 2009 Sens and spec Sensitivity Specificity T4 91,3% 100% (?) ft4 98,5% 93,7% TSH 95,4% 92,5% Dynamic testing T3-Suppression test Drug Liothyronine Dose 15-25 mg q8h for 7 doses Route Oral Sampling times 0 and 2h post last dose Assay Total T4 (possibly T3) Euthyroididm Hyperthyroidism < 20 nmol/l with >50% suppression >20 nmol/l ± <35% suppression
Dynamic testing T3-Suppression test Dynamic testing TSH-stimulation test Drug Liothyronine Dose 15-25 μg q8h for 7 doses Route Oral Sampling times 0 and 2h post last dose Assay Total T4 (possibly T3) Euthyroididm Hyperthyroidism < 20 nmol/l with >50% suppression >20 nmol/l ± <35% suppression Drug Dose Route Sampling times Assay Euthyroididm Hyperthyroidism rh-tsh 25 µg/cat Intravenous 1 and 8 h Total T4 Median stimulation 127% (62-220%) Median stimulation 13% (0-120%) Müller & Neiger, ECVIM 2011 Dynamic testing TRH stimulation test Drug Dose Route Sampling times Assay Euthyroidism Hyperthyroidism TRH 0.1 mg/kg Intravenous 0 and 4h Total T4 < 60% increase > 50% increase Müller & Neiger, ECVIM 2011 Dynamic testing Thyroid Scintigraphy
Therapy of feline hyperthyrodism Normal Adenoma Adenoma Options Medical management Oral (Transdermal) Radioactive iodine ( 131 I) (Surgery) (Ethanol ablation) Dietary Considerations Severity of clinical signs Presence of other illness Age of cat Accessibility of 131 I Compliance for drug administration Potential complications Cost Availability of skilled surgeon p. Tyroidectomy Carcinoma Carcinoma Medical therapy normally corrects disease well no anaesthesia or surgery initially inexpensive reversible (within 48 72h) no expensive equipment or hospitalisation ³ side effects of drugs ³ daily medication required (e.g. pilling cats) ³ rarely iatrogenic hypothyroidism Methimazole / Carbimazole Methimazole (Felimazole) licensed Carbimazole (Videlta) licensed Carbimazole immediately conversed to methimazole (5 mg carbimazole equals about 3 mg methimazole) Actively concentrated in thyroid gland Inhibits thyroid hormone synthesis Serum half live: 6 h (but intrathyroidal residence time ~ 20h) Dosing regiment Start on 2,5 mg q12 24h for 2 weeks Increase dose as needed (by 2,5mg) (most cats need 2,5 or 5 mg / day) Re assess initially q14 21 days and after every dose change Extremely rarely, may need to increase to 15 mg Measure T4 at every re assessment until WNL (also good if below reference range without clinical signs) When T4 WNL, re assess q4 6 months (may need increased dose as time passes) Percutaneous management Percutaneous management with methimazole possible Formulated in pluronic lecithin organogel (PLO) @ concentration approximating 5mg/0.1mL Starting dose as for p.o. Formulation, but takes longer until euthyroid (± 8 weeks) Fewer side effects (especially GI side effects) No licensed formulation available (stability?)
47 cats oral or transdermal (2,5mg q12h) 0, 2 and 4 weeks re evaluation oral more GI side effects No difference: Neutropenia Excoriation Side effects of medical therapy Side effects most common within first 3 months Common side effects: vomiting, anorexia (up to 15%) mostly transient Side effects that needs drug withdrawal: Excoriation of face Thrombocytopenia, agranulocytosis seen in < 5% Hepatotoxicity (incresaed liver enzymes) 131 I (radioactive iodine) only one treatment for most cats no pills no anaesthesia or surgery rapid reduction of thyroid hormone concentration ³ sophisticated facilities ³ medication risk to personnel ³ iatrogenic hypothyroidism ³ hospitalisation required ³ re treatment necessary in 2% ³ chronic renal failure non reversible Ireland: Dublin ESVONC Survey 2011 UK: Glasgow Edinburgh Ripon Treatment centers across Europe G E O G J U Newmarket Cardiff Bristol 23 centers reported by ESVONC members 3 recently stopped service 1 just started D R C N L N Norway: Sweden London Canterbury Oslo Göteborg Uppsala 16/19 responders C B L L M G G W B Denmark: Germany: Jönköping Copenhagen Norderstedt Giessen C Netherlands: Lienden B Belgium: France: Gent Maisons-Alfort Lille Switzerland: Bern Puille, 2011, ESVONC-congress Austria: Hungary: Wien Budapest
ESVONC Survey 2011 Hospitalization: 5 days 6 weeks? ft4 & TSH post radioactive iodine Mathes, Giessen 2009 ft4 post radioactive iodine % within Reference range Meric et al. Mathes et al Dijl et al. Meric et al. Mathes et al Mathes et al Days Peterson et al. Cost difference Medical management Felimazole (2,5 mg q12h) per annum: 200 Re evaluation (35 q3 m) per annum: 140 T4 (15 q3 m) per annum: 60 TOTAL per annum: 400 Radioactive iodine One therapy 1000 (in Giessen) Control in first year 1 2 times (35 70 ) T4 in first year 1 2 measurement (15 30 ) Meric et al., J Am Vet Med Assoc, 1986 Dijl et al., Tijdschr Diergeneeskd 2008 Peterson et al., J Am Vet Med Assoc, 1995 Mathes et al. Thesis Giessen 2011 Surgery corrects disease well thyroids easily accessible relatively inexpensive equipment readily available ³ anaesthetic risk ³ iatrogenic hypoparathyroidism ³ iatrogenic hypothyroidism ³ laryngeal nerve damage ³ failure to remove all tissue ³ chronic renal failure non reversible Thyreoidectomy
Ablation with ethanol only one treatment for most cats no pills thyroid easily accessible ³ ultrasound equipment and skill paramount ³ anaesthesia ³ iatrogenic hypothyroidism ³ only one side at one time ³ treatment success unclear ³ chronic renal failure non reversible Therapy dietary Iodine reduced diet Iodine concentration: 0,2 mg/kg Relative iodine deficiency euthyroidism No other food allowed! http://www.hillspet.com/products/ pd-feline-yd-can-canned.html http://www.hillspet.com/products/pd-feline-yd-dry.html T4 concentration during y/d in one cat TSH weiterhin < 0,03 µu/dl