Feline hyperthyroidism: Outline

Transcription

1 FELINE HYPERTHYROIDISM: AN UPDATE ON TREATMENT RECOMMENDATIONS J Catharine Scott-Moncrieff Purdue University, West Lafayette IN J. Catharine Scott-Moncrieff Purdue Universit Feline hyperthyroidism: Outline Diagnosis feline hyperthyroidism Diagnosis in presence concurrent illness When to treat feline hyperthyroidism Reversible treatment Anti-thyroid drugs Iodine restriction Definitive treatment Radioactive iodine Thyroidectomy Ancillary treatment Feline Hyperthyroidism: Diagnosis History/Physical examination Minimum data base CBC, biochemistry, urinalysis Blood pressure Thoracic radiographs Total T 4 concentration* Free T 4 (dialysis) T 3 suppression/trh stimulation TSH concentration? Radioisotope scan 1

2 Free T4 concentration In study of 917 hyperthyroid cats TT4 increased 91.3 % FT4 increased 98.5 % n Peterson 2001 But 6% sick euthyroid cats had ft4 Free T4 only measure in conjunction TT4 Total T4 and free T4 Peterson 2001 Free T4 assays in cats Assay Sensitivity Specificity Accuracy (%) (%) (%) Feline Feline Feline Immulite Analog Free T MED Free T4 IVD MED Free T4 ANTECH Gammacoat Free T Diasorin 2

3 Measurement TSH in cats Low sensitivity and specificity for diagnosis of feline hyperthyroidism Most useful for monitoring after treatment Increased TSH/low T4 3-6 months after treatment consistent iatrogenic hypothyroidism Hypothyroidism in cats with azotemia or clinical signs should be treated with l-thyroxine Scintigraphy: Technetium 99m Helpful for diagnosis in cats with severe concurrent illness Qualitative Quantitative Also used prior to surgery or radioactive iodine unilateral versus bilateral identify ectopic sites detect evidence malignant neoplasia 3

4 Diagnosis feline hyperthyroidism in presence concurrent illness Challenging TRH stimulation test/t3 suppression test do not perform well in cats with concurrent illness and a normal or low TT4/fT4 Thyroid scintigraphy very helpful in this situation Chancy 8 yr old FS DSH History Weight loss restlessness inappetance Diarrhea and occasional vomiting Diagnosed hyperthyroidism Adverse reaction to methimazole Physical examination T 102 F, P 200, R 40 Weight 3.5 kgs Palpable bilateral thyroid lobes 2/6 systolic murmur 4

5 Chancy: Minimum data base CBC/chemistry panel/ua NSF TT µg/dl Ref range µg/dl Chancy: Further thyroid testing Date Total T4 µg/dl ( ) Free T4 pmol/l (10-50) TSH ng/ml (0-0.32) 08/10/ >100 <0.03 Chancy: Additional diagnostics Diagnostic imaging Abdominal radiographs/ultrasound normal Endoscopy Moderate diffuse lymphoplasmacytic enteritis 5

6 Chancy: Diagnosis and Treatment Inflammatory bowel disease Treated dexamethasone Weight loss, vomiting and diarrhea resolved Persistent problems Owner still perceives restlessness Physical examination n Systolic murmur n Tachycardia Chancy: Follow up Thyroid testing Date Total T4 µg/dl ( ) Free T4 pmol/l (10-50) TSH ng/ml (0-0.32) 08/10/ >100 < /01/ /04/ Chancy: technetium scan 6

7 Chancy: Follow up Treated with 131 iodine based on Clinical signs PE findings Technetium scan Excellent response to treatment Clinical signs resolved Chancy: Follow up 2011 Spinal toxoplasma granuloma 2011 Stage II CKD 2011 Hypothyroidism 2012 Pyelonephritis 2013 Acute pancreatitis 2013 Stage III CKD 2014 Chronic pancreatitis 2015 Euthanasia Chancy: Take-home points Hyperthyroidism may be difficult to diagnose in cats with concurrent illness Free T4 concentration difficult to interpret in cats with concurrent illness or T4 in lower half reference range Radioisotope scanning most helpful diagnostic test in cats with other illness TSH suppressed in 98% hyperthyroid cats but some euthyroid cats also have suppressed TSH 7

8 Feline Hyperthyroidism: Treatment Oral anti-thyroid drugs methimazole, carbimazole Iodine restricted diet Thyroidectomy Radioactive iodine Ancillary therapy Treatment of hypertension Management renal failure Thioureylene drugs Methimazole, carbimazole, propylthiouracil Inhibit thyroid peroxidase oxidation iodide iodination and coupling tyrosyl residues Methimazole Serum half life 4-6 hours Dose start 2.5 mg q 12 hrs range mg/day Twice daily treatment Response biochemical euthyroidism 1 week clinical signs improve 2-3 weeks 8

9 Methimazole Adverse effects Vomiting/Anorexia Lethargy Diarrhea n Skin lesions/ facial excoriations n Anemia/thrombocytopenia n ANA positive n Hepatopathy/jaundice Hypothyroidism n taper dose to minimum required Topical methimazole Option when owner cannot give oral or medications or there are GI side-effects Pleuronic lecithin organogel applied non-haired pinna permeation enhancer Disadvantages Lower absorption Client exposure Topical methimazole Sartor hyperthyroid cats 17 cats oral methimazole 27 cats topical methimazole 2.5 mg q 12 hrs 4 weeks percent euthyroid oral (9/11) 82% cats topical (14/21) 67% cats (diff NS) GI adverse effects n 24% with oral, 4% with topical (p=0.04) 9

10 Molly 20 year old FS Calico Diagnosed hyperthyroidism Feb 2009 (2.9 kg) Started on methimazole 2.5 mg PO q 12 hrs T4 1.4 µg/dl / 18 nmol/l (November 2009) T4 1.6 µg/dl / 20 nmol/l (August 2010) Weight loss and icterus (March 2012) (2 kg) n T4 < 0.4 µg/dl / <5 nmol/l n ALT 877 IU/l n ALP 374 IU/l n GGT 22 IU/l n Billirubin 2.2 mg/dl /38 µmol/l (conjugated/delta) n CBC mild NR anemia n Mild azotemia (BUN 14 mmol/l, Cr 221 µmol/l) Molly Differential diagnosis Methimazole induced hepatopathy Primary hepatopathy Diagnostic plan Discontinue methimazole Recheck liver enzymes Abdominal ultrasound Clinical signs hyperthyroidism recurred T4 increased to 13 µg/dl / 167 nmol/l Started iodine limited diet (y/d) Molly: Outcome Clinical signs of hyperthyroidism resolved T4 2.4, 2.8, 2.5 µg/dl during following 9 months T4 31, 36, 32 nmol/l Creatinine decreased Quality of life good Liver enzymes/bilirubin continued to increase Suspect primary hepatopathy Owner declined further evaluation Cat lost to follow up 10

11 Methimazole: Indications Long term therapy cats with renal failure, concurrent disease financial constraints Preparation thyroidectomy/ 131 Iodine clinical stabilization prior anesthesia assess effect of treatment on renal function n Methimazole trial Association between hyperthyroidism and renal disease Increased GFR masks underlying renal disease Some cats develop clinical renal failure after euthyroid state restored 17-49% cats develop azotemia after treatment No single test predicts development azotemia In study of 300 treated hyperthyroid cats n BUN/creatinine, globulins associated azotemia n Williams JVIM 2010 SDMA may be more predictive than creatinine 11

12 Protocol for methimazole trial Methimazole 2.5 mg q 12 hours Recheck 2 weeks T4 liver enzymes BUN, Creatinine CBC Stable renal function definitive treatment Deterioration renal function titrate dose to control clinical signs avoid hypothyroidism Methimazole: common questions What is ideal TT4 reference range in methimazole treated cats? How to balance hyperthyroidism and azotemia? Iodine restricted diets Diets limited to < 0.32 ppm reduces thyroid hormone into reference range hyperthyroid cats Alternative management strategy 80% cats euthyroid after 6 months 12

13 Figaro 16 year old MC DSH Diagnosed hyperthyroidism in 2006 Treated with 5 mci 131 Iodine Entry T µg/dl, exit T4 3.6 µg/dl Excellent clinical outcome Recurrence clinical signs in 2012 Weight loss, muscle atrophy Physical examination T 102 F, P 260 bpm, R 48/min BCS 3/9, BP 170 mmhg Small thyroid nodule Figaro: Minimum data base CBC/chemistry panel/ UA Increased ALT, ALP BUN/Creatinine WNL USG T microg/dl 13

14 Figaro: Treatment Definitive therapy not recommended Owner unable to give oral medication Started limited iodine diet (y/d) Two months later Clinical signs resolved Weight stable Thoracic mass unchanged T4 2.6 microg/dl Figaro: Outcome Date T4 (µg/dl) 07/06/ /18/ /15/2013 Euthanasia Necropsy Thyroid adenoma (R) Thyroid atrophy (L) Pulmonary adenocarcinoma with LN metastasis Lymphoma Focal myocarditis with bacteria present Membranous glomerulopathy Response to feeding y/d diet 14

15 Response to feeding y/d diet Response to feeding y/d Creatinine The Effect of Feeding an Iodine-Restricted Diet in 49 Cats with Spontaneous Hyperthyroidism Number of Euthyroid Cats Days Days /48 cats 39/47 cats 42% 95% CI 28-57% 83% 95% CI 69-92% 15

16 Days Fed Restricted Iodine Diet Median heart rate (bpm) does not significantly decrease over 180 days (p=0.218) 16

17 Days Fed Restricted Iodine Diet Median creatinine (mg/dl) did not significantly increase over 180 days (0.218) Weight (kg) Days Fed Restricted Iodine Diet Median body weight (kg) did not significantly increase over 180 days (p=0.652) Iodine limited diets: summary Iodine limited diet good option in cats with concurrent illness Although T4 usually well controlled cats tend to maintain their weight but not gain weight Factors influencing use iodine limited diets Access to other food/multi-cat households Medications that contain iodine Palatability Other concurrent illness that requires dietary modification Long-term outcome limited iodine diets unknown 17

18 Feline Hyperthyroidism: Treatment Oral anti-thyroid drugs methimazole, carbimazole Iodine restricted diet Radioactive iodine Thyroidectomy Ancillary therapy Treatment of hypertension Management renal failure 131 Iodine Treatment 131 Iodine half-life 8 days 131 Iodine concentrated in thyroid Incorporated into thyroglobulin γ and β emissions n β particles travel short distance n responsible for tissue damage 131 Iodine Treatment Technetium scan not necessary Discontinue methimazole 1-2 weeks 131 Iodine administered SC or IV Hospitalization 5-7 days 95-98% response rate 15% cats delayed response Some cats develop clinical hypothyroidism subclinical hypothyroidism more common 18

19 Iodine 131 dose estimation Fixed dose 4-6 mci Currently we use 5mCi Variable dose size of thyroid nodule T4 concentration severity clinical signs Cali 12 year old FS DSH 9 month history weight loss Diagnosed hyperthyroidism T4 15 µg/dl Methimazole 2.5 mg PO q 12 hours Stopped eating (methimazole discontinued) Lowest T4 8.2 mg/dl Referred radioactive iodine Physical examination 3.3 kg, TPR normal, BP 150 mm Hg III/VI systolic murmur Cali minimum data base Reference range CBC NSF BG 176 mg/dl BUN 40 mg/dl Creatinine 1.8 mg/dl ALT 1078 IU/l ALP 109 IU/l T µg/dl Urinalysis USG Protein 1+ Bacteria 2+ Urine culture NG 19

20 Cali Diagnostic plan Treated reduced dose 131 Iodine 3 mci Exit T4 2.6 mg/dl Recommend monitor monthly for first 3 months T4/TSH BP BUN/Cr Cali: Take-home points Important to avoid hypothyroidism in azotemic cats treated with radioactive iodine Risk factor for survival Monitor for iatrogenic hypothyroidism Consider methimazole or iodine limited diet in cats with severe azotemia Thyroidectomy Indications thyroidectomy Owner concerns about radioactive iodine Owner concerns about cost of treatment n Can be most affordable definitive treatment Suspected thyroid carcinoma Thyroid cysts Non-functional thyroid mass 20

21 Applesauce 16 year old FS DSH One month history PU/PD Physical Examination T 99.9 ºF P 216, R 20 Body weight 4.3 Kg Generalized muscle wasting Minimum data base T4 5.9 µg/dl / 76 nmol/l Started on limited iodine diet Applesauce Good clinical response 8 weeks n T4 3.1 µg/dl / 40 nmol/l n BW 4 kg 7 months not eating y/d well n T4 4.8 µg/dl / 62 nmol/l n BW 3.5 kg n Bilateral thyroidectomy n Lowest Calcium 8.9 mg/dl ( mg/dl) n Excellent clinical response n Lived another two years after surgery (19 years) Applesauce: 123 Iodine scan 21

22 Applesauce Applesauce: Take-home points Iodine limited diets not ideal long-term option for many cats Palatability Inability to change diet or feed treats Surgery still appropriate option for some cats Radioisotope scans recommended prior to surgery Unilateral versus bilateral Ectopic tissue Hypocalcemia only requires treatment if associated clinical signs of hypocalcemia 22

23 Iatrogenic hypothyroidism 20% of cats treated with methimazole Aldridge % of cats treated with radioactive iodine Nykamp % of cats treated 4 mci radioactive iodine Peterson 2017 Diagnosis iatrogenic hypothyroidism Measure TT4 and TSH to assess thyroid status after treatment Increased TSH/low TT4 3-6 months after treatment consistent iatrogenic hypothyroidism Hypothyroid cats with azotemia or clinical signs should be treated with l-thyroxine n Williams JVIM

24 Ginger 15 year old MN DSH Presented for evaluation of weight loss History and physical examination consistent with hyperthyroidism Laboratory evaluation T μg/dl / 173 nmol/l BUN 23 mg/dl (15-35) Creatinine 0.6 mg/dl ( ) ALT 388 IU/l (20-108) USG BP 150 mmhg Ginger Owners unwilling to do methimazole trial Treated hyperthyroidism 5 mci 131 I Exit T μg/dl / 12 nmol/l 3 months post treatment Anorexia, lethargy, seborrhea sicca, alopecia BUN 69, Creatinine 2.8 USG T4 1.2 μg/dl / 15 nmol/l and TSH 1.5 ng/dl BP 180 mm Hg 24

25 Ginger Diagnosis Renal failure, hypertension, hypothyroidism Abdominal ultrasound bilateral renal infarcts Treatment Renal prescription diet Enalapril Thyroxine supplementation Outcome Marked clinical improvement Renal failure stable 18 months after treatment 25

26 Ginger: Take-home points Renal failure after definitive treatment for hyperthyroidism difficult to predict Iatrogenic hypothyroidism more common than previously recognized Increased TSH with low T4 supports diagnosis Hypothyroidism in azotemic cats decreases survival Hypertension may develop months after successful treatment Pathogenesis unclear Not always associated renal failure Prevalence hypertension in hyperthyroid cats Morrow /303 (13%) hyperthyroid cats diagnosed with hypertension >170 mmhg 2 occasions Compatible ocular signs 49/215 (23%) developed hypertension after treatment Median 5.3 months after treatment 35% had CKD at time of diagnosis hypertension Survival not different between hypertensive and normotensive cats Treatment of hypertension in hyperthyroid cats When to treat? BP > 180 mmhg Evidence TOD How to treat? Treat underlying thyroid dysfunction Add additional anti-hypertensive drugs Some cats may need long duration therapy 26

27 Feline Hyperthyroidism: Survival Retrospective study in 167 cats 55 treated 131-iodine alone 65 treated methimazole followed by 131-iodine 47 treated methimazole alone Median survival times in cats without RF 2 years methimazole alone 4 years 131-iodine alone Age, renal disease, also associated survival n Milner 2006 Summary: Feline hyperthyroidism Diagnosis hyperthyroidism may be confounded by presence concurrent illness Scintigraphy best test to identify affected cats Multiple treatment options for feline hyperthyroidism Ideal treatment depends Concurrent disease Age of cat Owner preference Financial constraints 27