Latest Advances in the Latest Advances in the Diagnosis, Treatment and Diagnosis, Treatment and Monitoring of Small Monitoring of Small Animal Endocrine Animal Endocrine Diseases Diseases Danielle Davignon, MS, DVM Small Animal Internal Medicine Upstate Veterinary Specialties
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Small Animal Endocrine Diseases, Dr. Danielle Davignon, 10/10/15
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Latest Advances in the Diagnosis, Latest Advances in the Diagnosis, Treatment and Monitoring of Small Treatment and Monitoring of Small
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
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
• 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
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…
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
• 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!
Feline HyperthyroidismFeline Hyperthyroidism
• 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
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
• 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
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
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)
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
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
• 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
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
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
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
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
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
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
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
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)
Canine Adrenal DisordersCanine Adrenal Disorders
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
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
• 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
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
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!
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)