treatment and monitoring of small animal endocrine diseases

Latest Advances in the Diagnosis, Latest Advances in the Diagnosis, Treatment and Monitoring of Small Treatment and Monitoring of Small

Animal Endocrine DiseasesAnimal Endocrine DiseasesDanielle Davignon, MS, DVM

Small Animal Internal MedicineUpstate Veterinary Specialties

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


• 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


• 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…


• 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

Feline HyperthyroidismFeline HyperthyroidismTREATMENTTREATMENT

• 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!


• Radioactive Iodine Therapy (RAIT)– Administration of 131I by SQ injection– 95% success rate with one treatment– Can be used to treat thyroid carcinomas

TREATMENTTREATMENT

animalendocrine.com


• 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


• 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


• 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


• 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)


• 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

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


• 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


• 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


• 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


• 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


• 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


• 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

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


• 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



• 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)

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)

Diabetes MellitusDiabetes MellitusTREATMENTTREATMENT

Diabetes MellitusDiabetes MellitusTREATMENTTREATMENT

Lantus® SoloStar® Pen (www.lantus.com)

We

Insulin Pens!

Vetsulin® VetPen®(www.vetsulin.com)

• 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 MellitusNUTRITIONNUTRITION

Dietary Therapy - CanineDietary Therapy - CanineDiet Protei

n (%DM)

Carb Type Carb(%DM)

Fat(%DM)

Fiber Type and amount (%DM)

Kcal/cup 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

• 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


Dietary Therapy - FelineDietary Therapy - FelineDiet 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


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

• Concurrent Disease “trumps” the diabetes!– Chronic renal failure– Heart failure– Recurrent pancreatitis/hypertriglyceridemia


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


• 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 MellitusMONITORINGMONITORING


• 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

• Teach owners how to perform BG curves at home– AlphaTRAK glucometer• www.alphatrakmeter.com



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


• 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


• 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!

Causes of Insulin ResistanceCauses of Insulin ResistanceSevere 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 autoantibodies


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.

treatment and monitoring of small animal endocrine diseases

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