ANATOMY AND PHYSIOLOGY OF REPRODUCTIVE SYSTEM.pptx
Treatment and Monitoring of Small Animal Endocrine Diseases
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)
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)
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
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!
-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)