Pharm Final - Thyroidal Diseases

Front 1

(1) what kind of hormonal effect does Thyroid horrmone have (one word-general)? (2) what are the physiologic effects?

Back 1

multisystemic

Hint 1

increases metabolic rate of most tissues, calorigenesis, catabolic effects on protein, enhance catecholamine response, normal grwoth and development of brain and skeleton

Front 2

(1) describe the basic physiological pathway of thyroid hormones? (2) how is the system regulated?

Back 2

hypothalamus > TRH > anterior pituitary > TSH > thyroid > T4, T3, rT3 > target tissues

Hint 2

free hormone provides negative feedback

Front 3

(1) which form of thyroid hormone is biologically active? (2) which is the predominant circulating form?

Back 3

T3

Hint 3

T4 (prohormone)

Front 4

(1) what is the basic process of thyroid hormone synthesis? (2) what stimulates it?

Back 4

stimulation > iodide trapping > oxidation > organification> coupling > cleavage > deiodination

Hint 4

TSH binds TSH-R on thyroid follicular cell

Front 5

(1) what occurs during iodide trapping? (2) what occurs during oxidation?

Back 5

I- enters cell

Hint 5

I- > (H2O2 thyroidal peroxidase = TPO) > I in cell

Front 6

(1) what occurs during organification? (2) what occurs during coupling?

Back 6

I + Tg-tyrosine > (iodinase) > iodotyrosine (in follicular colloid)

Hint 6

iodotyrosine > T4, T3, rT3 - Tg (in follicular colloid)

Front 7

(1) what occurs during cleavage (2) what occurs during deiodination?

Back 7

T4, T3, rT3 - Tg > lysomal proteases > T4, T3, rT3 (in cell)

Hint 7

T4 > T3 (in gland and peripheral tissues

Front 8

(1) thyroglobulin-bound TH stored in colloid represents what? (2) where is most of the TH in circulation?

Back 8

a large reserve of hormone

Hint 8

bound to proteins: albumin, thyroxine-binding globulin (varies with species)

Front 9

(1) how does the majority of T3 formation occur? (2) where do we see hyperthyroidism in vet med?

Back 9

in target tissues through deiodination

Hint 9

cats > dogs > horses (thyroid carcinoma)

Front 10

(1) what is the etiology of hyperthyroidism in cats? (2) what is the signalment?

Back 10

functional thyroid adenoma (adenomatous hyperplasia; multinodular, single or diffuse) involving one (30%) or both (70%) of lobes. Independent of feedback loop. Adenocarcinomas are rare (1-3%)

Hint 10

middle-age to older cats (range of >4 to 20+ yrs w/95% > 10yrs, fewer than 5% < 8yrs) with median age of 13 yrs. No breed or sex predilection.

Front 11

(1) what are the PE findings of hyperthyroidism in cats?

Back 11

enlarged thyroid gland, low BCS, tachypnea, murmur/tachycardia/gallop, hyperthermia, unkempt haircoat, ventral neck flexion, CHF, GI signs (weight loss w/increased appetite, diarrhea, vomiting, abdominal pain), increased activity, PU/PD, (rarely aggressive behavior, tremors, seizures, decreased activity, weakness), hypertension, retinal detachment (suddne blindness),

Front 12

(1) what are the hematologic abnormalities in hyperthyroid cats? (2) what are the chemistry abnormalities?

Back 12

CBC abnormalities (mild erythrocytosis, macrocytosis, Heinz bodies), stress leukogram (neutrophilia, lymphopenia, eosinopenia)

Hint 12

elevated liver enzymes, mild hyperglycemia, hypokalemia (mild-severe), elevated creatine kinase

Front 13

(1) wat is the best screening test for thyroid? (2) how accurate is it?

Back 13

TT4: measures free and bound levels

Hint 13

91% of true hyperthyroid cats have T4 above ref range but diagnosis should not be excluded based on 1 normal/borderline value because T4 fluctuates (hours/days) and sick hyperthyroidism-concurrent illness falsly lowers values

Front 14

(1) when does suppresion of thyroid hormone occur in cats? (2) what can aid in the diagnosis of occult hyperthyroidism?

Back 14

with nonthyroidal disease; occurs in both euthyroid (T4 value commonly suppressed to low values with moderate to severe illness) and hyperthyroid cats (values suppressed from high to within ref range, but usually at high end)

Hint 14

free T4 via dialysis; free T4 is less influenced by nonthyroidal illness than total T4 concentrations, so it is a useful marker when T4 is normal to high-normal (25-50 nmol/L or 2.5-4 mg/dl), but free T4 is unexplainable high in some sick euthyroid cats

Front 15

(1) what are the advantages of measuring free T4 concentration for hyperthyroidism? (2) disadvantages?

Back 15

more sensitive than total T4; less affected by nonthyroidal factors, free T4 is high in 98% of all hyperthryoid cats

Hint 15

less specific than total T4; can be altered in certain disease states (renal failure total T4 usually low to low-normal), risk of over diagnosis, should not be evaluated alone

Front 16

(1) what is occult hyperthyroidism? (2) how should it be handled?

Back 16

hyperthyroidism suspected based on history, clinical signs, palpable thyroid nodule but serum T4 is high-normal (2.5-4 ug/dl or 25-50 nmol/L)

Hint 16

rule out another nonthyroidal disease, repeate serum total T4 determination in 1-2 weeks (1-2 times, may need longer intervals), determine free T4 by equilibrium dialysis, consider thyroid function tests

Front 17

(1) when should dynamic thryoid function testing be performed? (2) what is it?

Back 17

rarely needed; only consider after multiple T4 and FT4 testing is incomclusive

Hint 17

T3 suppression tests, TRH stimulation, TSH stimulation

Front 18

(1) what is thyroid scintigraphy useful for? (2) how is it performed?

Back 18

most common as pre-Sx screening and can document ectopic tissue and metastases from carcinoma (requires special facilities, expense, sedation)

Hint 18

technetium 99 as pertechnetate given as IV injection; uptake should be 1:1 with salivary glands. Methimazole may be associated with increased uptake and is contraindicated

Front 19

(1) give an overview of hyperthryoid diagnosis? (2) how is hyperthryoid treated (general)?

Back 19

history/clinical signs, palpation of enlarged thyroid lobe/s, screening laboratory tests (CBC, serum biochemical profile), serum total T4 determination (dx >90% of cats), serum total and free T4 determinations, function testing if necessary

Hint 19

antithyroid drugs, surgical, thyroidectomy, radioactive iodine

Front 20

radioiodine (1) advantages (2) disadvantages

Back 20

>90% efficacy, single injection, few side effects, curative

Hint 20

high initial expense, somewhat limited availability, irreversible

Front 21

thyroidectomy (1) advantages (2) disadvantages

Back 21

~90% efficacy, curative

Hint 21

high initial expense, anesthetic risk, risk of hypoparathyroidism, risk of recurrent laryngeal nerve damage, irreversible

Front 22

methimazole (1) advantages (2) disadvantages

Back 22

low initial expense, ~90% efficacy, reversible

Hint 22

daily drug administration, drug side effects

Front 23

(1) what is the mechanism of action of methimazole? (2) what are the side effects?

Back 23

thyroid peroxidase inhibitor; does not block uptake of iodide or effect release of preformed hormones, is not cytotoxic so does not stop growth of hyperplastic tissue (thyroid nodule will not regress and may increase in size)

Hint 23

reversible with discontinuation. Affect ~18% of cats. Occur quickly (w/in first 3 months): GI upset (vomit/diarrhea/inappetance), facial/skin excoriation, anemai, thrombocytopenia, neutropenia, hepatotoxicity, coagulopathy (rare), ANA positive (common), acquired MG (rare)

Front 24

(1) how are blood dyscrasias from methimazole resolved? (2) how is methiamazole therapy monitored?

Back 24

generally resolve w/in a week of discontinuation, mechanism of neutropenia in cats is unknown but in humans neutropenia is assicated with inhibition of GM CFUs either by antibody or cytokine-mediated effects.

Hint 24

start with 2.5-5.0 mg/d (caution w/kidney dz), recheck T4, CBC, chem q2-3 wk for 1st 3 months (adjust dosage as indicated based on T4 and clinical signs), timing of testing post pill does not appear to be important in cats. Goal = resolution of hyperthryoid signs & T4 high-normal. if adequate control, recheck T4 q3-6m

Front 25

(1) how is transdermal methimazole used? (2) what are the disadvantages?

Back 25

formulated in pluronic lecithin organogel (PLO), absorption across stratum corneum of inner pinna (alternate ears), fewer GI effects than oral but other side effects are same and erythema may occur at dosing site

Hint 25

increased expense, lower efficacy compared to oral (over a 4 wk period 67% euthyroid compared to 82%) but lower efficacy may abate with chronic use (further study needed)

Front 26

(1) how is carbimazole used? (2) how is propylthiouracil (PTU) used?

Back 26

prodrug of methimazole used in Europe and Australia, anecdotally less side effects but shouldn't be used in cats with known side effects to methimazole

Hint 26

TPO inhibitor, less potent than methimazole (requires more frequent dosing), significant side effects (IMHA, hepatotoxicity, etc)

Front 27

(1) how is iopanoic acid/calcium ipodate used?

Back 27

transient inhibition of peripheral conversion of T3. Ipodate is no longer available. Poor longer terms control

Front 28

(1) what is adjunctive treatment used for? (2) what is used?

Back 28

controling hypertension or tachyarrythmias while normalizing T4

Hint 28

Beta-blockers: atenolol & propanolol (may block Tv > T3, don't use w/pulmonary disease) & Anti-hypertensive drugs (amlodipine, enalapril, benazepril)

Front 29

(1) what role does radioiodine treatment play in feline hyperthyroidism? (2) what does it do?

Back 29

considered treatment of choice for most cats, most specific treatment, useful in bilateral or ectopic thyroid disease or carcinoma

Hint 29

iodine is taken up only into thyroid tissue and is necessary for produciton of thyroid hormones, so radioactive 131I is concentrated preferentially into follicular cells of hyperplastic/neoplastic tissue. Normal tissue is atrophied and does not take up iodine.

Front 30

(1) what is the mechansism of action for radioiodine treatment? (2) what is the schedule for delivery and the elimination?

Back 30

131I emits B & y radiation; thyroid cells don't differentiate between natrural and radioactive iodine, B rays travel short distance (2mm) and are cytotoxic, spares parathyroid/surrounding tissue.

Hint 30

t1/2 is 8 days, 20-60% is taken into thyroid, excreted mainly through urine with small amount through feces

Front 31

(1) what are the advantages of radioiodine treatment? (2) disadvantages

Back 31

cures hyperthryoid state by irradiating and destroying adenomatous lesion (rapid effect in cats), no preparation with propranolol or antithyroid drug needed (unless severe clinical signs), no anesthesia required (may need sedation), T4 generally normalizing w/in 1 mo, no postop hypoparathyroidism, hypothyroidism is rare

Hint 31

expense, transient thyroiditis (can cause dysphagia, salivation, fever, lethargy), permenant hypothyroidism with clinical signs so treatment is necessary (rare), may unmask renal failure

Front 32

(1) what are the causes of canine hypothyroidism in vet med? (2) how common is it?

Back 32

congenital (rare), acquired primary hypothyroidism (50% lymphocytic thyroiditis, 50% idiopathic thyoird atrophy), neoplasia (rare), iatrogenic (rare)

Hint 32

most common endocrine disorder of dogs, commonly overdiagnosed

Front 33

(1) what are the possible causes of lymphocytic thyroiditis? (2) what does it look like cytologically?

Back 33

unknown; heritable, disorder of immunoregulation, likely multifactorial (breed, season, geography)

Hint 33

histologically similar to chronic autoimmune thyroiditis in humans, 50% of canine HT have circulating antithyroglobulin antibodies (TgAA)

Front 34

(1) how is lymphocytic thyroiditis diagnosed?

Back 34

a positive TgAA =/= hypothyroidism, animals with + results may progress to hypothroidism, rate of progression varies with breed, follow a + with sequential TSH but don't treat without other evidence

Front 35

(1) what is idiopathic thyroid atrophy? (2) what is the signalment of hypothyroidism?

Back 35

loss of normal thyroid parenchyma, replacement by fat and CT, likely represents end-stage thyroiditis

Hint 35

middle age (2-6yr), no apparent sex-related predilection, S/N affect unknown, breed predisposition (golden retriever, doberman pinscher, others)

Front 36

(1) what are the clinical signs of hypothyroidism? (2) clinical pathology?

Back 36

reflection of decreased metabolic rate; multisystemic disorder: lethargy, exercise intolerance, dermatologic changes (truncal alopecia, thinning hair coat with easily epilated hairs, hyperkeratosis/hyperpigmentation, superficial pyoderma), cardiovascular signs (sinus bradycardia, weak apex best, low QRS voltage, inverted T waves, reduced LV contractility, may exacerbate underlying cardiac dz), nervous system dysfunction (peripheral neuropathy, ataxia, weakness, decreased proprioception/spinal reflexes, cranial nerve dysfunction, association with myasthenia gravis, myxedema coma), may have ophthalmologic abnormalities

Hint 36

normocytic, mormochromic nonregenerative anemia, fasting hypertriglyceridemia, hypercholesterolemia

Front 37

how is hypothyroidism diagnosed?

Back 37

consistent history, clinical signs, labwork, serum total thyroxine (TT4), Free thyroxine by ED (FT4D), Serum Thyrotropin (TSH), Anti-Tg, T3, T4 (TgAA, T3AA, T4AA), TSH stimulation, thyroid ultrasonography,therapeutic trial, thyroidal scintigraphy/thyroid biopsy (gold standard)

Front 38

(1) what is total thyroxin concentration useful for? (2) what causes Thyroid hormone variation?

Back 38

good initial screening, if normal consistent with ethyroidism except: ~10% hypothyroid dogs have T4AA where T4 can appear normal to high, if low rule out nonthyroidal illness, thyroid hormone alterations must be considered

Hint 38

Breed effects (sighthounds, basenji can have lower TT4 and fT4), Age effects (older animals generally have lower TT4), weight effects (heavier animals generally have higher TT4, fT4), drug effects (glucocorticoids, phenobarbital, sulfonamides, carprofen can decrease TT4)

Front 39

(1) what is euthyroid sick syndrome?

Back 39

systemic illness can have profound effects on thyroid hormone metabolism and secretion: decreased TH binding to carrier proteins, increased clearnace of thyroid hormones, decreased conversion of Tc and increased conversion to rT3, inhibition of TSH and/or T4 secretion

Front 40

(1) which drugs reduce TT4, fT4, TSH? (2) which drugs reduce TT4, fT4 but increase TSH, giving the appearance of hyperthyroidism?

Back 40

glucocorticoids, clomipramine, carprofen

Hint 40

phenobarbital, sulfonamides

Front 41

(1) what are the advantages of using free thyroxine by equilibrium dialysis? (2) disadvantages?

Back 41

unaffected by antibody interference, less affected by drugs and illness, highest accuracy, specificity of any single diagnostic

Hint 41

can be affected by severe illness, nondialysis methods consistently lower and less accurate

Front 42

(1) what are the advantages of testing TSH (serum thyrotropin? (2) disadvantages?

Back 42

helpful in dogs with low T4, has been used in cases of feline hypothyroidism

Hint 42

useless as a stand alone test, 30% of hypothyroids dogs have normal TSH

Front 43

(1) what are the advantages of testing T3 (total triiodothyronine?) (2) disadvantages?

Back 43

may be useful for testing sight hounds

Hint 43

poor screening test that varies widely, spurious results can occur from T3AA

Front 44

(1) when is TgAA (antithyroglobulin antibodies) present? (2) what are potential causes?

Back 44

~50% of hypothyroid dogs have a leakage of thyroglobulin into circulation from thyroiditis

Hint 44

in humans: early hypothyroid, recent vaccination, drug therapy, viral infection

Front 45

what role does T3AA and T4AA play in hypothyroidism?

Back 45

less prevalent than TgAA; T3AA in 30% of hypothyroid dogs, T4AA in 15% of hypothyroid dogs. Doesn't interfere with treatment

Front 46

(1) which test has the greatest sensitivity? (2) specificity?

Back 46

TT4

Hint 46

TSH/T4

Front 47

(1) what tests can we run for thyroidisms?(2) which test has the greates accuracy?

Back 47

TT4, fT4, TSH, TSH/T4, TSH/fT4

Hint 47

fT4

Front 48

(1) what process should be used to diagnos hypothyroidism? (2) how does T4 vary between dogs and humans?

Back 48

low T4 does not confirm hypothyroidism; if low T4 and rull out illness need to investigate for hypothyroism with TSH and fT4 (normal FT4/TSH = euthyroid, low TT4/High TSH = hypothyroid), positve TfAA does not confirm, low TT3 not useful with exception of breeds that have naturally low TT4

Hint 48

dogs have higher T4 metabolic rates and need higher doses, generally BID to maintain constant serum levels, dogs also bind less avidly than humans so more T4 is metabolised in dogs

Front 49

(1) what is the preferred treatment for hypothyroidism for dogs? (2) another treatment?

Back 49

L-thyroxine; main secretory product of thyroid gland, allows peripheral tissue autoregulation of T3 prodcution, available as a liquid

Hint 49

liothyronine is a synthetic T3 which removes autoregulation of tissues so at risk for iatrogenic thyrotoxicosis so not indicated for initial therapy (if T4 therapy fails, reconsider diagnosis, if confirmed, consider T3 therapy)

Front 50

(1) how do we monitor therapy for hypothyroidism? (2) what is the goal for therapy?

Back 50

evaluate clinical response, repeat T4 1-2m after therapy by obtaining sample 4-6hr after pill. If no clinical response with T4 low to low normal, increase dose and recheck in 8 wks. If no response in 2-3 mo (once T4 is within normal range) reconsider diagnosis

Hint 50

positive clinical response, T4 in normal to high normal range

Front 51

(1) how often do cats get hypothyroidism? (2) what is the most common cause of low serum T4?

Back 51

rarely, congenital (DSH, Abyssinian) or iatrogenic

Hint 51

nonthyroidal illness