Hypothyroidism Wendy Blount. DVM.

Hypothyroidism Wendy Blount. DVM

Thyroid Terms thyros – shield
cretinism – congenital lack of thyroid hormones In dogs and cats there are 2 thyroid glands left and right lobes T4 – thyroxine – in blood T3 – 3,5,3-triiodothyronine – active form in tissues Increases metabolism and enzyme activity Stored as thyroglobulin (TG) in the thyroid follicle

Function of Thyroid Glands
maintain metabolic rate and tissue repair Inotropic, chronotropic effects on the heart Enhance catecholamine response Critical to fetal development Especially neurologic and skeletal

Hypothyroidism Classification
Primary hypothyroidism (95%) Destruction of the thyroid gland 75-80% of the gland must be destroyed Secondary hypothyroidism (5%) Decreased TSH Often part of pituitary insufficiency Tertiary hypothyroidism Decreased TRH Very rare

Primary Hypothyroidism
Hashimoto’s Thyroiditis Two common types – possible continuum Lymphocytic-plasmacytic destruction (50%) Idiopathic atrophy (50%) Rare types Iodine deficiency Goitrogen ingestion Congenital Neoplasia Drug toxicity Surgery or radioactive I131

Secondary Hypothyroidism
Failure of pituitary thyrotrophs Thyroid gland hypoplasia or atrophy Causes Congenital – rare Destruction by neoplasia – rare Head trauma Drug thyrotoxicity – most common of the uncommon Glucocorticoids hyperadrenocorticism

Kirk Reese Whitehouse TX

Cretinism Congenital hypothyroidism – rare
Hallmarks are decreased growth and delayed mental development Puppies relatively normal at birth except low birth weight Causes early puppy death (2-12 weeks) Stenotic ear canals and delayed eye opening A goiter can develop Disproportionate dwarfism, delayed dental eruption, retained puppy coat Can be caused by iodine deficiency - rare

Hallmarks are decreased growth and delayed mental development Puppies relatively normal at birth except low birth weight Causes early puppy death (2-12 weeks) Stenotic ear canals and delayed eye opening A goiter can develop Disproportionate dwarfism, delayed dental eruption, retained puppy coat Can be caused by iodine deficiency - rare Mixed breed pup Before treatment

Hallmarks are decreased growth and delayed mental development Puppies relatively normal at birth except low birth weight Causes early puppy death (2-12 weeks) Stenotic ear canals and delayed eye opening A goiter can develop Disproportionate dwarfism, delayed dental eruption, retained puppy coat Can be caused by iodine deficiency - rare after 20 days treatment

Hallmarks are decreased growth and delayed mental development Puppies relatively normal at birth except low birth weight Causes early puppy death (2-12 weeks) Stenotic ear canals and delayed eye opening A goiter can develop Disproportionate dwarfism, delayed dental eruption, retained puppy coat Can be caused by iodine deficiency - rare 7 month GSD pup before treatment

Hallmarks are decreased growth and delayed mental development Puppies relatively normal at birth except low birth weight Causes early puppy death (2-12 weeks) Stenotic ear canals and delayed eye opening A goiter can develop Disproportionate dwarfism, delayed dental eruption, retained puppy coat Can be caused by iodine deficiency - rare after 1 year therapy

Clinical Presentation
Onset over 1-3 years, but can vary Onset young to middle age adult Four Stages Stage I - subclinical thyroiditis Positive thyroid autoantibodies (TAb) Stage 2 – subclinical hypothyroidism increased TSH, positive TAb Normal T3, T4 Stage 3 – clinical hypothyroidism Low T3, T4 Positive TAb, + increased TSH (pituitary exhaustion) Stage 4 – atrophic hypothyroidism TAb go negative Thyroid autoantibodies may be a screening test in predisposed breeds

Breed Predisposition English & Irish Setter Chesapeake Bay & Golden Retriever Rhodesian Ridgeback Shetland Sheepdog (onset older) Boxer Siberian Husky Cocker Spaniel Thyroid autoantibodies may be a screening test in predisposed breeds

Symptoms - Common Dermatologic (70-80%) Endocrine alopecia, dry brittle faded coat, “rat tail,” hyperpigmentation, seborrhea, pyoderma, otitis, (Bx - orthokeratotic hyperkeratosis) myxedema (uncommon) General (50%) Lethargy (48%), mental dullness, weight gain despite poor appetite (49%), cold intolerance 15% reduction in energy expenditure

Symptoms Hematologic (30-40%) Anemia (36%), hyperlipidemia, high cholesterol Coagulopathy (?) Neuromuscular (2-12%) Weakness (12%) polyneuropathy, polymyopathy, vestibular signs, facial/trigeminal paralysis (2-4%) seizures, circling/disorientation, myxedema coma, altered behavior (hyperlipidemia) cervical spondomyelopathy (5%)

Symptoms Hematologic (30-40%) Anemia (36%), hyperlipidemia, high cholesterol Coagulopathy (?) Neuromuscular (2-12%) Weakness (12%) polyneuropathy, polymyopathy, vestibular signs, facial/trigeminal paralysis (2-4%) seizures, circling/disorientation, myxedema coma, altered behavior (hyperlipidemia) cervical spondomyelopathy (5%) laryngeal paralysis (? 4%), MG (?)

Symptoms Hematologic (30-40%) Anemia (36%), hyperlipidemia, high cholesterol Coagulopathy (?) Neuromuscular (2-12%) Weakness (12%) polyneuropathy, polymyopathy, vestibular signs, facial/trigeminal paralysis (2-4%) seizures, circling/disorientation, myxedema coma, altered behavior (hyperlipidemia) cervical spondomyelopathy (5%) laryngeal paralysis (? 4%), MG (?) aggression (?)

Symptoms Cardiovascular (10-60%) low voltage P & R waves (58%), bradycardia (10%), AV block dilated cardiomyopathy (?) Gastrointestinal (2-3%) diarrhea, constipation Megaesophagus (?) pancreatitis due to hyperlipidemia

Symptoms Reproduction (1%) Ocular (1%) Corneal lipid deposits KCS, conjunctivitis, corneal ulcers Horner’s Syndrome lipid in aqueous, uveitis, glaucoma

Dermatologic effects can vary Hypertrichosis can result in breeds that do not shed Loss of primary hairs can result in “puppy coat” Loss of undercoat can result in coarse coat with primary hairs only Some will show no changes unless clipped Will not regrow Tragic expression – myxedema of the face Demodicosis can result Check thyroid panel for adult onset Demodex

Dermatologic effects can vary Hypertrichosis can result in breeds that do not shed Loss of primary hairs can result in “puppy coat” Loss of undercoat can result in coarse coat with primary hairs only Some will show no changes unless clipped Will not regrow after clipping Tragic expression – myxedema of the face Demodicosis can result Check thyroid panel for adult onset Demodex

Neurologic signs – demyelination and mucin deposits If severe can result in paralysis LMN reflexes Cranial nerves especially predisposed Central and peripheral neuropathies Focal or multifocal Acute or chronic Static or progressive Check thyroid panel for mysterious neurologic disease & behavior problems

Reproductive failure Testicular atrophy and azoospermia Prolonged parturition Low puppy survival and unthriftiness Failure to cycle and prolonged estrus interval Silent heats, false pregnancy, prolonged estrual bleeding Fetal resorption Check thyroid panel for failure to reproduce

Joe Tomlinson Grapevine TX

Cardiovascular signs Association with atrial fibrillation Bradycardia and 1st & 2nd degree AV block are more common than Afib DCM Increased LVIDD and LVIDS Decreased LVWS and IVS Decreased FS Hypothyroidism alone rarely results in CHF or even DCM Check thyroid panel for myocardial failure

Check thyroid panel for KCS resistant to therapy Megasophagus (ME) and laryngeal paralysis (LP) seem to be likely to be concurrently present with hypothyroidism Cause and effect has not been established Little or no response the thyroid supplementation Hypothyroidism associated with decreased activity of coagulation factors VIII, IX and von Willebrand’s (?)

Clues in the blood work Normocytic, normochromic anemia Leptocytes – target cells

Clues in the blood work Normocytic, normochromic anemia Leptocytes – target cells High cholesterol (75%) Hyperlipidemia Mild hypercalcemia Elevated liver enzymes (Hyponatremia if myxedema coma) Check thyroid panel for hyperlipidemia

Thyroid Testing TSH TT4 freeT4 (fT4) fT4 by ED (equilibrium dialysis)
rT3 TAb – T4Ab, T3Ab, TGAb

Thyroid Testing Thumb Rules
T3 is mostly intracellular, so T3 blood tests are rarely recommended TSH, TT4, fT4 – most common screening panel for dogs TT4, fT4 – most common screening panel for cats Add TAb + fT4 by ED when you suspect hypothyroidism, but TT4 not low, or when ruling out NTIS

Thyroid Testing OFA Thyroid Panel
free T4 by equilibrium dialysis (RIA) TSH (ChL) TgAA = TgAb (ELISA) Ask for OFA Thyroid panel at TVMDL $53 cost, plus accession and shipping Results delivered electronically to OFA OFA bills you $15 when they get the results Total clinic cost $74 plus shipping

Thyroid Testing Approved OFA Thyroid Laboratories Antech
Animal Health Laboratory – Guelph Cornell Diagnostic Endrocrinology Lab Endocrine Diagnostic Center – U Mich Idexx TVMDL UC Davis VTH Clin Path

Thyroid Testing TSH (Thyrotropin) High with hypothyroidism
Human assays can not be used for dogs All commercial assays have poor sensitivity for canine hypothyroidism Many false negatives Up to 40% of hypothyroid dogs have normal TSH Specificity is 92%+ 8% of normal dogs have high TSH TSH high = likely hypothyroid Either clinical now or will be in the future

Thyroid Testing Low TSH not clinically significant
Commercial tests cannot distinguish between low normal and low values Effective reference range goes down to zero

Thyroid Testing TT4 Lower in dogs (normal mcg/dl) than in people (normal 4-10 mcg/dl) Labs use RIA (radioimmunoassay) or CLIA (chemiluminescent immunoassay) In House – ELISA Helpful, but not as accurate If in doubt, send sample to outside lab for confirmation Best practice is to spin, freeze plasma/serum and send on ice in plastic tube, if assay will not occur within 5 days

Thyroid Testing TT4 Hyperlipidemia and hemolysis do not interfere with TT4 RIA Overlap in reference ranges between euthyroid and hypothyroid “borderline” reference range Most common reasons for falsely low TT4 are: Euthyroid sick (NTIS) Inaccurate in house ELISA

Thyroid Testing TT4 Different reference ranges for breeds
Sight hounds have lower TT4 and fT4 (T3 normal) Greyhound, Italian Greyhound, Whippet Saluki, Borzoi, Sloughi, Afghan, Basenji, Pharoah Hound, Rhodesian Ridgeback Deerhound, Wolfhound Canine athletes have lower baseline TT4 – studies in Alaskan sled dogs

Thyroid Testing fT4 fT4 by ED is the gold standard T4 assay
T3Ab and TGAb do not interfere The best single thyroid test, but it is by no means perfect fT4 by ED is 86-93% accurate TT4 is 75-85% accurate TT4 assays for humans *can* be used in dogs fT4 by ED assays for humans *cannot* be used in dogs Most common reasons for falsely low: Hyperadrenocorticism and drug therapy

Thyroid Testing Thyroid Antibodies (high stages 1-3)
15% of hypothyroid dogs have AntiT4 These don’t interfere with TT4 33% of hypothyroid dogs have antiT3 Also can have antiTG AntiT3 & antiTG can cause spuriously increased, normal or decreased TT4 Depends on the assay Falsely increased more common Positive TAb is more significant than negative Tab If in doubt run a fT4ED to remove all interfering Ab

Diagnosis If non-thyroid illness and low TT4
Treat illness and recheck TT4 If signs of hypothyroidism and no apparent non-thyroid illness CBC, panel, TSH, TT4, fT4 High TSH, low TT4 & fT4 – Eureka! High TSH & low fT4 likely hypoT4, regardless of TT4 Confirm with TAb + fT4ED Normal TSH, low TT4 & fT4 Likely hypoT4

Diagnosis If signs of hypothyroidism and no non-thyroid illness
Normal TSH & fT4, low TT4 consider euthyroid sick Investigate non-thyroid conditions that mimic hypothyroidism – other endocrinopathies, allergies, etc. Thyroxine trial if no non-thyroid illness found Normal TSH, TT4, fT4 Hypothyroidism ruled out If in doubt, do fT4ED + T3Ab, TGAb or recheck in 6 months If still confused, consider thyroxine trial

Thyroxine Trial Make sure you have a symptom to monitor
Not indicated if there are no symptoms Adding a T4 to a wellness panel can be problematic If there are no symptoms, many question the wisdom of pursuing a low T4 in a well animal Name brand (Soloxine®, Thyro-Tabs®, Leventa®) preferred to generic for trial

Euthyroid Sick Presence of non-thyroid illness
aka Non-Thyroid Illness Syndrome (NTIS) Illness decreases protein binding of T4 Low TT4, Normal TSH & fT4 fT4 can be high in cats with NTIS No response to thyroxine trial All thyroid tests can be affected by non-thyroid illness Euthyroid sick dogs can have TT4 <0.5 Hypothyroid dogs almost never have fT4 by ED > 1.5 mcg/dl

Factors Affecting Tests
Most common are Concurrent illness (NTIS) Drugs (especially glucocorticoids) Random fluctuations of thyroid hormones Others: Age, Breed, Athletic training Gender and OHE status Environmental and body temperature Body Condition & Nutritional Status

Concurrent Illness (NTIS, euthyroid sick) T3 more suppressed than T4, but tissue T3 levels are difficult to assay TT4 more affected by NTIS than fT4 TSH rarely elevated by NTIS (<8%) Any systemic illness, surgery or trauma Severity of illness is proportional to severity of suppression Inadequate calorie intake Dermatopathies and osteoarthritis are unlikely to cause NTIS It is nearly impossible to diagnose hypothyroidism in a significantly ill dog, unless illness is due *only* to hypothyroidism thyroid scan or therapeutic trial may be required

Drugs Glucocorticoids decrease TT4, fT4, T3, often into hypothyroid range No corresponding increase in TSH Topical can have same effect as internal Glucocorticoids withheld 4-8 weeks prior to thyroid testing Anticonvulsants Phenobarbital decreases TT4 and fT4 into hypothyroid range Also phenytoin, primidone, diazepam Bromide could potentially interfere with iodide uptake by the thyroid

Drugs Sulfonamide antibiotics Truly suppress the thyroid Interfere with T4 & T3 synthesis TT4 can decrease to hypothyroid range within 1-2 weeks TSH can increase within 2-3 weeks Clinical signs can result, chronic therapy can result in goiter Thyroid function returns to normal in 1-12 weeks (Sunny) I avoid sulfonamides in hypothyroid dogs

Drugs Sulfonamide antibiotics Truly suppress the thyroid Interfere with T4 & T3 synthesis TT4 can decrease to hypothyroid range within 1-2 weeks TSH can increase within 2-3 weeks Clinical signs can result, chronic therapy can result in goiter Thyroid function returns to normal in 1-12 weeks I avoid sulfonamides in hypothyroid dogs

Drugs NSAIDs Decrease TSH, T4 & T3 Only Etogesic caused clinical signs - KCS Tricyclic antidepressants Inhibit T4 and T3 synthesis Be sure these drugs are not used when assessing thyroid panel in dogs with behavior problems

Drugs Other drugs that decrease T3 & T4 Amiodarone (T3), propranolol, dopamine, nitroprusside, furosemide, heparin Androgens Imidazoles – methimazole Mitotane, propylthiouracil Penicillin phenothiazines Contrast agents – iodide, ipodate (T3)

Ileen Cooper San Angelo TX

Drugs Drugs that increase T3 & T4 Amiodarone (T4) Estrogens 5-fluoruacil Halothane Insulin Narcotic analgesics Contrast agents – ipodate (T4) Thiazide diuretics

Age, Breed, Athletic Training Progressive decline of TT4, fT4 & T3 with age Puppies at high end of normal range Geriatrics at low end of normal range Geriatrics have 30% less than puppies Older dogs have higher TSH and blunted TSH response Higher TAb in older dogs Smaller dogs may have higher TT4

OHE status for females Progesterone (diestrus) increases T4 and T3 Environmental and body temperature TT4 and fT4 increase in January and fall in outdoor dogs Body Condition & Nutritional Status Obese dogs have higher T3 and T4 Fasting >48 hours decreases T3 Starving dogs can have very low TT4

Greta 10 yr old SF Chesapeake Bay Retriever CC: weight loss, lethargy
She stinks really bad History – repeated pyoderma Exam – T 98.3Fo, P 66, R 24 Papules, scaling – generalized Seborrhea and hair loss around the eyes and on the ventral neck She falls asleep on the exam table

Greta Skin Scraping – negative Skin Cytologies Thyroid Panel
Crusts – many cocci bacteria Seborrheic areas – many yeast Thyroid Panel TT4 - >7 mcg/dl (normal ) fT4 – 20 pmol/L (normal 12-33) TSH – 0.6 ng/ml (normal )

Greta fT4ED, TAb Diagnosis: Hypothyroidism fT4ED 3 pmol/L
(normal 12-33) T4Ab 29 (normal <20) T3Ab 9 (normal <10) TGAb 1912% (normal <200) Diagnosis: Hypothyroidism

Treatment Starting dose - 0.01 mg/lb PO BID
Maximum starting dose 0.8 mg Dose is 10x the human dose t1/2 of L-thyroxine is 9-14 hours BID administration results in less T4 fluctuation

Treatment 2. Recheck 6-8 weeks Draw blood 4-6 hours post pill
TT4 or fT4 should be upper half of normal to mildly increased (3-6 mcg/dl) TSH should be normal (<0.6 ng/ml) If TT4 or fT4 are lower half of normal If clinical signs controlled and TSH normal, there is no need to increase If symptoms not controlled, increase the dose Reduce dose of TT4 >6 mcg/dl Consider resolution of symptoms

Treatment 3. Adjust dose as needed
Might need to go as high as 0.02 mg/lb PO BID Higher than that – look for other problems, or try another brand Hyperadrenocorticism Drug therapy Concurrent illness Give on an empty stomach to improve absorption Make sure taking 4-6 hours post pill

Treatment Once controlled, may be able to reduce dose to SID
Long term monitoring Check TT4 2-4 weeks after dosage adjustment once yearly signs of thyrotoxicosis poor response the therapy Can also check TSH if initially elevated Can use fT4ED if autoantibodies are a problem in the patient Typically becomes less necessary with time

Treatment Special Exceptions Dilated cardiomyopathy
Thyroid supplementation increases myocardial oxygen demand, increases HR and may reduce filling time Starting dose at 25-50% of usual to prevent decompensation Increase dose incrementally as needed

Treatment Special Exceptions Diabetes mellitus
Hypothyroidism can result in insulin resistance Monitor for hypoglycemia for 1-2 weeks after introducing or increasing thyroxine dose Reduce insulin as needed

Treatment Special Exceptions Addison’s Disease
T4 increases cortisol clearance Monitor for Addisonian symptoms for 1-2 weeks after introducing or increasing thyroxine dose Increase or add glucocorticoids as needed If a patient crashes after starting L-thyroxine, run an ACTH Stim test

Treatment Special Exceptions
Anticonvulsant, Glucocorticoid therapy, Severe illness Target TT4 in lower half of normal range

Treatment Treatment Failure
If treating dermatopathy, consider other diagnoses that mimic hypothyroidism Atopy Other causes of endocrine alopecia If concurrent GI disease (poor absorption), try T3 supplementation (liothyronine) 4-5 mcg/kg PO TID monitor T3 rather than T4 Blood just before and 2-4 hours post pill May be able to reduce to BID when well controlled Risk of thyrotoxicosis is higher

Treatment T3/T4 Combination products (1:4) Liotrix®, Thyrolar®
Not recommended for hypothyroid dogs, because: T1/2 and frequency of administration differ for T3 and T4 Can result in T3 thyrotoxicosis More expensive

Treatment Thyroid Extracts Armour Thyroid®
Each mg tablet = 0.38mg T4, 0.09mg T3 (4:1) Challenges: Hypersensitivity Variability in shelf life and content Some concerns as similar drug combinations on previous slide

Treatment Thyrotoxicosis Toxicity of therapy is rare
Can happen with liver or renal failure If treatment results in thyrotoxicosis, reconsider diagnosis Symptoms: Panting, nervousness, anxiety, aggressive behavior Tachycardia, hypertension, blindness PU-PD, polyphagia with weight loss If concurrent cardiac disease - syncope Discontinue for 1-3 days, then resume lower dose

Maddie 2 yr old F Doberman Wants thyroid screen for breeding
Exam – T 101.3Fo, P 96, R 24 No significant abnormal findings Michigan State Premium Thyroid Panel

Maddie 2 yr old F Doberman Wants thyroid screen for breeding
Exam – T 101.3Fo, P 96, R 24 No significant abnormal findings Michigan State Premium Thyroid Panel normal normal high high high

Maddie Diagnosis: Treatment: Follow-up:
Stage 2 – Subclinical Hypothyroidism Treatment: None at this time Follow-up: Recheck TSH, TT4, fT4 once to twice yearly, or sooner if symptoms of hypothyroidism develop

Maddie Breeding Recommendation:
Delay breeding until 3-4 years old, if no signs of hypothyroidism have developed Screen for other genetic predispositions DCM – echocardiogram for FS Neurologic exam for Cervical Vertebral Instability and Degenerative Myelopathy CERF eye certification OFA or Penn Hip certification VWDz Testing (Cornell) DNA for VWDz, DCM, DM + Narcolepsy (

Kristina Lem Houston TX

Prognosis Energy improves and mentation normalizes within 7-10 days of beginning therapy Lipemia and anemia resolve in 2-4 weeks Improve over 1-4 months: Dermatologic Neurologic Myocardium Reproductive (up to a year) Behavior can take 4-6 months

Prognosis Life expectancy if treated is normal for primary hypothyroidism Survival of myxedema coma depends on early recognition and aggressive treatment Secondary hypothyroidism – guarded to poor Long term survival for cretins is guarded Depends on severity of musculoskeletal changes and age of therapy Degenerative joint disease and angular limb deformities can be severe

Feline Hypothyroidism
Usually a result of therapy Radioactive iodine (I131) Bilateral thyroidectomy Anti-thyroid drugs Clinical signs very rare Often transient, resolving within 90 days Azotemia most likely Spontaneous hypothyroidism almost unheard of in the cat Due to head trauma equally rare Cretinism rare, but documented Inherited in Abyssinians

Eli 2 year old neutered male Great Pyrenees – Chow mix
CC – “Sometimes he looks at me like he doesn’t know me.” Also, he laid down in Lowe’s the other day and would not get up.

Eli Exam Cardiovascular exam Neurologic exam
overweight Cardiovascular exam NSAF – HR 80-90 Neurologic exam Cranial nerves, spinal nerves, postural reflexes normal CBC, panel (HW Test current) Cholesterol 385 (not fasted)

Eli In House TT4, send out Thyroid panel
TT4 < 0.5 mcg/dl (undetectable) TSH normal, TT4 0.3 mcg/dl, fT4 0.2 ng/dl Eventually settled on 1.0 mg PO BID Behavior returned to normal Died at 8 years of age of adrenal neoplasia The Story of Eli

Summary PowerPoint Client Handouts Drug Handouts - L-thyroxine
.pptx 1 slide .pdf , 6 slides per page .pdf Client Handouts Hyperlipidemia Hypothyroidism Drug Handouts - L-thyroxine Vet Handouts Idexx Canine TT4 Diagnostic Guide Treatment Algorithm – Hypothyroidism

Summary Laboratory Information Hidden Slides
MSU Endocrine Lab – Form, Fees, Ref Ranges , , , DNA Testing Cornell Comparative Coagulation Lab – von Willebrand’s Testing – form, guidelines, fees Hidden Slides Adenohypophyseal-pituitary pathophysiology TRH and TSH Stimulation tests Myxedema coma

Acknowledgements J Catharine Scott-Moncrieff. Canine & Feline Endocrinology, 4th Edition. Ch 3 – Hypothyroidism. Raymond P. Bouloy, DVM, Diplomate ABVP (canine / feline). Cypress Creek Pet Care, Cedar Park, TX. 2012 Western Veterinary Conference Roundtable Proceedings. Nutritional Management of Feline Hyperthyroidism, Hill’s Prescription Diets.

Acknowledgements Katherine Lund, ACVIM. North Carolina State University.

Hypothyroidism Wendy Blount. DVM.

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