Small Animal Endocrine Diseases, Dr. Danielle Davignon, 10/10/15
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Small Animal Endocrine Diseases, Dr. Danielle Davignon, 10/10/15
- 1. Latest Advances in the Diagnosis,Latest Advances in the Diagnosis, Treatment and Monitoring of SmallTreatment and Monitoring of Small Animal Endocrine DiseasesAnimal Endocrine Diseases Danielle Davignon, MS, DVM Small Animal Internal Medicine Upstate Veterinary Specialties
- 2. Feline HyperthyroidismFeline Hyperthyroidism • T4 – 91% sensitive, 100% specific – When can it be (falsely) within the normal range? • Early hyperthyroidism • Mild hyperthyroidism – normal daily fluctuation • Concurrent non-thyroidal illness (NTI) • Drugs? DIAGNOSISDIAGNOSIS
- 3. Feline HyperthyroidismFeline Hyperthyroidism • What to do in these questionable cases? – MILD clinical signs repeat T4 (days-weeks) – If NTI repeat T4 once illness resolved, if possible – SEVERE signs (need diagnosis) FREE T4 • Equilibrium dialysis methods preferred (vs chemiluminescent assay) • Always use in conjunction with T4 – NEVER alone! – High FT4 & T4 in high end of normal range = likely hyperthyroid – High FT4 and low normal or low T4 confirm with another test, or re-test DIAGNOSISDIAGNOSIS
- 4. Feline HyperthyroidismFeline Hyperthyroidism • What about TSH? – Canine assay – low sensitivity in cats, but can be useful – At normal geriatric screening appointments: cats with undetectable TSH were significantly more likely to be diagnosed with hyperthyroidism (Wakeling et al., JVIM, 2011) – 98.2% of hyperthyroid cats had TSH concentrations at or below the level of quantification (<0.03 ng/mL) • 98.2% sensitive, 49.3% specific (Peterson et al., ACVIM Forum 2015) DIAGNOSISDIAGNOSIS Conclusion: Not useful in the diagnosis of HYPERthyroidism in the clinical setting…
- 5. Feline HyperthyroidismFeline Hyperthyroidism • Notes about transdermal methimazole: – Significantly fewer GI side effects – Slower onset of control of hyperthyroidism – Lower efficacy – cats may be harder to regulate/higher doses are required TREATMENTTREATMENT
- 6. Feline HyperthyroidismFeline Hyperthyroidism TREATMENTTREATMENT • most topical formulations use pluronic lecithin organogel (PLO) as the vehicle which may not be suitable for a lipophilic drug like methimazole • In this 12 week study, ONCE DAILY transdermal administration of a novel lipophilic topical product was as safe and effective as twice daily carbimazole • Later pharmacokinetic studies (Hill et al. N Z Vet J. 2014) show it can be absorbed from the skin of healthy cats; half the bioavailability of oral medication This may be coming soon…keep an eye out!
- 7. Feline HyperthyroidismFeline Hyperthyroidism • Radioactive Iodine Therapy (RAIT) – Administration of 131 I by SQ injection – 95% success rate with one treatment – Can be used to treat thyroid carcinomas TREATMENTTREATMENT animalendocrine.com
- 8. Feline HyperthyroidismFeline Hyperthyroidism • Radioactive Iodine Therapy (RAIT) – pre tx: – Confirm no significant azotemia once euthyroid on methimazole prior to pursuing therapy – Withdrawal methimazole 1-2 weeks prior – Iodine limited diets should be discontinued 2 weeks prior • Pre-treatment workup: – complete blood count, chemistry panel, urinalysis, T4 – Additional considerations: thoracic radiographs, abdominal ultrasound, urine culture, echocardiogram TREATMENTTREATMENT
- 9. Feline HyperthyroidismFeline Hyperthyroidism • Radioactive Iodine Therapy (RAIT) – post tx: – Radiation safety guidelines for 2 weeks – Rechecks at 1, 3, 6, 12 mo • 15% still hyperthyroid at discharge, but become euthyroid by 6 mo • Some exhibit transient/permanent hypothyroidism – T4 + TSH may help to diagnose true hypothyroidism – Supplement (0.05 – 0.1 mg levothyroxine SID-BID) if: » Persistently hypothyroid at 6 mo » Clinical signs of hypothyroidism » azotemia TREATMENTTREATMENT
- 10. Feline HyperthyroidismFeline Hyperthyroidism • Iodine restricted diet: – 71% of cats euthyroid between 21-60 days – 96% euthyroid between 61-180 days – Must be fed exclusively – Long term effects unknown TREATMENTTREATMENT
- 11. Feline HyperthyroidismFeline Hyperthyroidism • Retrospective study of 80 cats • Proportion of cats with azotemia was significantly greater in the hypothyroid (16/28) than the euthyroid (14/47) group • 68% of cats with TT4 below ref range had increased TSH concentrations • Hypothyroid cats that developed azotemia within the follow-up period had significantly shorter survival times than those that remained non- azotemic (MST 456 days and 905 days, respectively)
- 12. Feline HyperthyroidismFeline Hyperthyroidism • Hyperthyroid cats and cats with HCM had plasma NT-proBNP and cTNI concentrations that were significantly higher than those of healthy cats, but there was no significant difference between hyperthyroid cats and cats with HCM • In hyperthyroid cats that were re-evaluated 3mo after RAIT treatment, plasma NT- proBNP and cTNI concentrations as well as ventricular wall thickness had decreased significantly Clinical Relevance: • Neither NT-proBNP nor cTNI could distinguish hypertrophy associated with hyperthyroidism from primary HCM • Therefore, the thyroid status of older cats should be ascertained before interpreting NT-proBNP and cTNI concentrations
- 13. Canine Adrenal DisordersCanine Adrenal Disorders • Urine Cortisol:Creatinine Ratio – Good screening test: if negative, not Cushing’s • Exception: Atypical Cushing’s? • ACTH stim = gold standard – Less affected by concurrent illness – Post-ACTH cortisol >21 ug/dL diagnostic IF supporting clinical signs, adrenomegaly, etc • LDDST DIAGNOSISDIAGNOSIS
- 14. Canine Adrenal DisordersCanine Adrenal Disorders • Mitotane vs Trilostane? – Mitotane: complete adrenocortical insufficiency in 6-10% of cases – Trilostane: adrenal necrosis can occur leading to prolonged or permanent cortisol deficiency – Both can lead to mineralocorticoid deficiency which has been shown to NOT be predicted by electrolyte values (Reid et al. JVIM 2014) – Median survival time in HAC is not significantly different if using mitotane vs trilostane TREATMENTTREATMENT
- 15. Canine Adrenal DisordersCanine Adrenal Disorders • Mitotane: – Give with fatty meal to maximize absorption – PDH: • Induction: 40-50 mg/kg divided BID • Maintenance: 50 mg/kg per week – 60% of dogs relapse within 1 year – ACTH stims 1, 3, 6 mo later, then q3mos • Ideal pre/post-ACTH cortisoL: 1-5 ug/dl (up to 9 if asymptomatic) • Re-test 1 month after any dose adjustments TREATMENTTREATMENT
- 16. Canine Adrenal DisordersCanine Adrenal Disorders • Mitotane – AT: most are more resistant to effects of mitotane • Treat using same protocol as PDH OR • Ablative protocol: (goal: pre/post-ACTH <0.3ug/dL) – Load: 50-75 mg/kg/day » Give physiologic pred concurrently – Maintenance: 50-75mg/kg/week + daily pred TREATMENTTREATMENT
- 17. Canine Adrenal DisordersCanine Adrenal Disorders • Trilostane – 1 mg/kg BID; TID may be needed in some dogs – Give with food to maximize absorption – ACTH stim: 4-6 hours post-pill – First ACTH stim 10-14 days, or sooner if any signs of illness • This stim is only to r/o overdose – no dose adjustments until 30 days when drug reaches max effect! TREATMENTTREATMENT
- 18. Canine Adrenal DisordersCanine Adrenal Disorders • Trilostane (continued): – Ideal pre/post-ACTH cortisol: 1-5 ug/dL • Up to 9 is ok if dog is asymptomatic – Consider TID dosing if stims are in the normal range but owners still report clinical signs • Also consider alternate diagnoses TREATMENTTREATMENT
- 19. Canine Adrenal DisordersCanine Adrenal Disorders • Advanced Treatment Options (Cyberknife) VCA Animal Specialty Center, Yonkers NY • robotic system delivers targeted radiation with high accuracy • allows higher dose of radiation directly to the tumor while minimizing damage to surrounding tissues • 1-3 treatments vs 15-20 using traditional RT • Total cost (pituitary tumor) ~$10K TREATMENTTREATMENT
- 20. Canine Adrenal DisordersCanine Adrenal Disorders • Can Single Cortisol Measurements Be Used To Assess Control? – Cook et al. JAVMA 2010: 103 dogs on trilostane: • Baseline cortisol (4-6 hrs after trilostane) compared to STIM results • Baseline cortisol concentrations ≥ 1.3ug/dl accurately excluded excessive suppression (defined by post-ACTH cortisol <1.5 ug/dl) in 98% of dogs • Baseline cortisol concentrations ≤ 2.9 ug/dl correctly excluded inadequate control (defined as post-ACTH cortisol ≥ 9.1ug/dl) in 95% of dogs • During trilostane treatment, baseline cortisol concentrations between 1.3 ug/dl and either 2.9 ug/dl or ≤ 50% of pretreatment baseline cortisol concentration correctly predicted acceptable control of adrenal gland function in 88% of dogs MONITORINGMONITORING
- 21. Canine Adrenal DisordersCanine Adrenal Disorders • When is the best time to perform a stim? – We don’t know! • cortisol concentrations decreased significantly 2-4 hours after trilostane administration • suggests this may be the optimal time to perform ACTH stimulation tests MONITORINGMONITORING
- 22. Canine Adrenal DisordersCanine Adrenal Disorders • What is Atypical/Occult Hyperadrenocorticism? – Dog has history/CS consistent with Cushing’s but LDDST or ACTH stim does not support dx – Diversion of normal cortisol synthesis pathway overproduction of sex hormones – DX: perform ACTH stim and measure sex hormones pre & post (Tennessee) – TX – only if symptomatic – mitotane may be preferred – Monitor using ACTH stim (cortisol)
- 23. Canine Adrenal DisordersCanine Adrenal Disorders
- 24. Cushing’s in CatsCushing’s in Cats • most common reason for referral: unregulated diabetes • dermatologic issues = most common PE finding • LDDST a much better dx test in cats • 0.1mg/kg dexamethasone (higher dose than in dogs) • improved quality of life noted in cats treated with trilostane • MST 617 days (Mellett et al. JVIM 2014)
- 26. Diabetes MellitusDiabetes Mellitus TREATMENTTREATMENT Lantus® SoloStar® Pen (www.lantus.com) We Insulin Pens! Vetsulin® VetPen® (www.vetsulin.com)
- 27. • Recommendations for DOGS: – Dry > canned – Consider high fiber (>15% DM insoluble fiber or mixed soluble + insoluble) – Low glycemic index carbohydrates – Protein content to meet daily requirements but not excessive (18-25% DM) – Low fat content (<30% ME) Note: Can feed a well-balanced commercial diet initially and consider RX diet if difficulty regulating blood glucose. Diabetes MellitusDiabetes Mellitus NUTRITIONNUTRITION
- 28. Dietary Therapy - CanineDietary Therapy - Canine Diet Protei n (%DM) Carb Type Carb (%DM) Fat (%DM) Fiber Type and amount (%DM) Kcal/c up or can Hills w/d dry 19.2 Whole grain corn 50.8 8.7 Cellulose (16.4) 243 Hills w/d canned 17.9 Whole grain corn, cracked barley 52.6 12.7 Cellulose (12.4) 370 Hills Science Diet adult light dry 24.3 Whole grain corn, soybean 49.6 8.8 Cellulose (12.4) 295 Hills Science Diet adult light canned 19.5 Whole grain corn, soybean 56.8 8.6 Mixed (9.7) 322 Purina DCO 25.3 Corn, pearled barley 47.8 12.41 Mixed (7.6) 320 Purina OM dry 31 Whole corn, soybean germ 44.2 7.2 Mixed (10.2) 266 Purina OM canned 48 Corn, gluten meal 16.7 14.6 Mixed (12.7) 286 Purina Pro Plan weight management dry 30.5 Brewers rice, corn 40.7 10.2 Mixed (2.5) 337 Royal Canin diabetic HF 18 dry 18.0 Rice, ground corn 49.8 7.0 Cellulose (12.6) 273 Royal Canin Calorie Control CC High Fiber dry 22.5 Corn 36.3 8.0 Mixed (18.3) 237 Kirk’s Current Veterinary Therapy XV © 2014
- 29. • Recommendations for CATS = “CATKINS DIET” – Promote weight loss: • High Protein (>40-45% DM) • Low Carbohydrate (<5g/100kcal or <10% DM) • Low Fat (<4g/100kcal) – Canned > dry – Meal feed Diabetes MellitusDiabetes Mellitus NUTRITIONNUTRITION
- 30. Dietary Therapy - FelineDietary Therapy - Feline Diet Protein (% DM) Carb (%DM) Fat (%DM) Kcal/cup or can Hills m/d dry 51.1 15.1 21.8 495 Hills m/d can 52.8 15.7 19.4 156 Purina DM dry 57.9 14.9 17.9 592 Purina DM can 53.4 4.5 32.9 191 Royal Canin diabetic DS 44 dry 44.0 23.1 11.0 239 Kirk’s Current Veterinary Therapy XV © 2014 Can also use commercial diets that meet specified guidelines for % carbs and protein. Options include: - some canned kitten diets - Fancy feast salmon (3 ounce) - Friskees turkey in gravy - Wellness beef and salmon can - Wellness CORE chicken, turkey can - EVO 95% beef can - EVO salmon/herring dry
- 31. • Concurrent Disease “trumps” the diabetes! – Chronic renal failure – Heart failure – Recurrent pancreatitis/hypertriglyceridemia Diabetes MellitusDiabetes Mellitus NUTRITIONNUTRITION
- 32. Diabetes MellitusDiabetes Mellitus • The ideal blood glucose curve: – Nadir: 80-150 mg/dl (100-150 in hospital) – BG < 250-300 mg/dl throughout the day MONITORINGMONITORING
- 33. • Other points to assess on the curve: – BG value at nadir: If BG <60 mg/dl, counter- regulatory hormone responses may kick in to increase BG concentration Diabetes MellitusDiabetes Mellitus MONITORINGMONITORING
- 34. Diabetes MellitusDiabetes Mellitus MONITORINGMONITORING • Other points to assess on the curve: – Duration of insulin action: • Time after insulin injection when BG rises above 250 (after an appropriate nadir!) – If <8-10 hours, animals will usually be clinical (PU/PD) – If >14 hours, risk of hypoglycemia due to insulin overlap 12h duration
- 35. • Teach owners how to perform BG curves at home – AlphaTRAK glucometer • www.alphatrakmeter.com Diabetes MellitusDiabetes Mellitus MONITORINGMONITORING
- 36. Diabetes MellitusDiabetes Mellitus MONITORINGMONITORING Continuous Glucose Monitoring Systems (CGMS) • small electrode inserted/fixed under the skin • measures BG in interstitial fluid • transmits readings wirelessly every 5 minutes • can stay in place up to 72h
- 37. Diabetes MellitusDiabetes Mellitus • When to consider switching insulin in dogs? – If insufficient duration of action and clinical signs, consider switching to longer-acting insulin • Detemir (Levemir) human insulin – VERY potent!! Use much lower dose (0.1 U/kg BID) – can be difficult in small dogs • Pro-Zinc – FDA approved for CATS only so this is off label! – JVIM 2012: effective in dogs; long duration may cause hypoglycemia with BID dosing, however – DOGS: 0.5 U/kg BID TROUBLESHOOTINGTROUBLESHOOTING
- 38. Diabetes MellitusDiabetes Mellitus • When to worry about insulin resistance? TROUBLESHOOTINGTROUBLESHOOTING • Poor control of hyperglycemia despite an insulin dosage >1-1.5U/kg • Control of hyperglycemia is erratic and insulin requirements are constantly changing • Serum fructosamine levels typically > 500 umol/L Always rule out technical problems with insulin administration first!
- 39. Causes of Insulin ResistanceCauses of Insulin Resistance Severe Insulin Resistance Mild or Fluctuating Insulin Resistance • Hyperadrenocorticism • Acromegaly (cat) • Progesterone excess (diestrus in female dogs) • Diabetogenic drugs (glucocorticoids, progestins) • Obesity • Infections (UTI!!!) • Chronic pancreatitis • Chronic inflammation • Diseases of oral cavity • Renal insufficiency • Hepatic insufficiency • Cardiac insufficiency • Hypothyroidism (dog) • Hyperthyroidism (cat) • Exocrine pancreatic insufficiency • Hyperlipidemia • Neoplasia • Glucagonoma • Pheochromocytopma • Insulin autoantibodiesKirk’s Current Veterinary Therapy XV © 2014 Think about these in an animal requiring high (>1-1.5U/kg) doses of insulin OR in a previously well- controlled diabetic that suddenly becomes uncontrolled. Think about these in an animal requiring high (>1-1.5U/kg) doses of insulin OR in a previously well- controlled diabetic that suddenly becomes uncontrolled.
Editor's Notes
- -In most hyperthyroid cats, despite normal daily fluctuation in T4, values are above the ref range, but in mild ranges, can fluctuate into normal range – so repeat test if case has CS of hyperT4 -illness lowers serum T4 concentration and severity of decrease is correlated with severity of dz – prognostic (mortality increases as T4 decreases) -T4 usually in the upper 50% of the reference range in these cases except SEVERE illness (can be below RR) -steroids, iodinated contrast agents
- -FT4: lower specificity than TT4 because some euthyroid cats w/nonthyroidal illness have FT4 above the reference range (6-12%) -other tests: scintigraphy? TSH?
- Wakeling 2011: note that not ALL cats became hyperthyroid in the study period (54 months) Peterson: TSH concentrations undetectable in 40% of normal cats and 14% of euthyroid cats suspected of having hyperT4 = POOR SPECIFICITY
- Montioring: CBC, CHEM, T4 q2-3 weeks until euthyroid Less cats euthyroid at 2wks vs oral, but NSD at 4 weeks
- Research out of New Zealand 10 mg TD SID vs 5mg PO BID
- Thyroid carcinomas are less than 2-3% cases
- -takes much longer than methimazole
- ACTH stim and freezing cortrosyn In-house cortisol tests
- Pre/post aldosterone levels are needed to establish dx in suspicious cases (measure 30 min post ACTH) AT: MST trilostane: 353 days; mitotane: 102 days
- -if post is 5-9, increase dose by 25% -if &gt;9, re-load then re-start maintenance at 50% higher dose
- -but we needed updated RRs for stims performed 2-4hr post -most important: SAME time for your patient
- 0.1 mg/kg dexamethasone typically rec in cats, though this study showed no diff in results when 0.1mg/kg or 0.01 mg/kg was used 3.3 mg/kg BID or 4.3 mg/kg SID were mean doses used in cats in Mellett study
- -dry foods empty slowest from stomach; have a greater effect on lowering post-prandial hyperglycemia when compared to canned -Highly soluble fibers (guar gum): have a great water-holding capacity and form a viscous gel-like solution in the lumen of the intestine -insoluble fibers (cellulose): increase bulk and reduce intestinal transit time, making nutrients (starch) less available for digestion -in normal dogs fed diets high in soluble fibers, more rapid glucose absorption occurs (unknown if same in diabetics) -studies of dogs comparing soluble, insoluble and mixed fibers: no diff on glucose tolerance, TGs; ONLY diff was that total serum cholesterol was lower in dogs fed mixed fiber -studies seem to suggest that diets high in insoluble fiber or mixed fiber may lead to improved glycemic control -there is not a uniform effect of fiber on all diabetics – recent study showed no difference in high vs moderate fiber -make decision on an individual basis & consider high fiber in: -dogs that need to lose weight -dogs with poor glycemic control with a normal maintenance diet -If dog refuses to eat high fiber diet, choose maintenance or WL diet containing low fat and high complex carbs -1 study: RICE based diets resulted in significantly higher post-prandial BG, whereas sorghum based diets (esp barley) resulted in lowest response -NOTE that many highly-digestible diets designed for GI disease often contain rice-based carbs may not be suited for DM dogs
- -most cats are overweight -high protein diets are essential to preserving muscle mass, preventing HL, and increasing metabolism to promote fat-burning -lean muscle tissue is an essential element of basal metabolism -many weight loss diets are low in calorie but not high enough in protein to preserve lean muscle tissue -studies in cats show high protein diets more effective for weight loss -this mixture is easily obtained with CANNED food -dry foods require a minimum amt of carbs for processing and may have increased carbs/fat -recent studies have shown cats fed diets high in carbs have longer postprandial hyperglycemia (8-10 hrs); even longer when obese (up to 18h) strain on beta cells -high fiber diets no longer emphasized in CATS (do not reduce PP hyperglycemia as well as high protein/low carb diets) and do not promote weight loss without loss of muscle mass -recent study: cats placed on insulin and high protein/low carb diet were 4x more likely to achieve clinical remission -if cat is eating a dry diet and getting some carbs, should be complex/low glycemic index carbs (e.g. whole grains such as barley) -arginine is high in meat based diets; potent stimulator of insulin release (important in cats that have become tolerant to hyperglycemia)
- -requires calibration every 12 hours (w/BG monitor)