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Canine H po h oidi m, An O e ie

Veterinar Clinical Patholog Clerkship Program

Canine H poth roidism, An Overview E i Be , DVM; Ke Ca f Ge e h S. La i e , DVM, PhD; B f Pa h g ce E. LeR , DVM, PhD; H ,M e) C M ege e, DVM f Ve e i a Medici e, U i e i

f 2005 (Be ) a d De a e gia, A he , GA 30602-7388

(La i e , LeR

Introduction H h idi i d e i ai ed d ci a d ec e i f he h id h e , hich e ab ic a e.1 I i he c e d c i ah f he d g. The c i ica ig a e i a ga e a be i ed. Ve e i a ia ha e a i f diag ic e f e e i i a f a c i ica i a i . The ef e, c i icia a be ca ef i i e . H e e , he e a e i e be e ecific a d e i i e e f h id f c i f i g a c i e e a ge e a e ie f ca i e h h idi , ih ecia e e ha a e c e a ai ab e a e a hei ad a age a d di ad a age . Etiolog A h gh d f c i a he e i he h ha a ic- i i a -ad e a a i a e i h id h e deficie 95% f he c i ica ca e fh h idi i d g a ea e f de ci f he h id g a d ( i a h h idi ).1 The a h id g a d c ai e f ic e i ed b c b ida c a e i he i di g a e fc id (Fig. 1). P i a h h idi e f h c ic h idi i , idi a hic h a h , , e a e , e a ia.1 5 A i a e 50% f he ca e f i a h h idi a e d e 7 Ca i e h h c ic h idi i . idi i i be ie ed be i e- edia ed a d i cha ac e i ed hi gica diff e i fi a i f he g a d b h c e , a a ce , a d ac hage (Fig. 2). I fi a i b e e e i g e i e de ci f f ic e a d ec da fib i .1 , 1 1 A i h g b i a ib die a e e e 42% 59% f d g ih h idi i .7 c ,> e i a dec ea ed e a iab e a d a h id f c i , h e e e e ai f he e c i ica e.8 The ha i he diag ic

id b i a

Figure 1: a ade f ic e , h a ) a d a af

h id g a d c ed f c idid f ic a e i he ia ce (b ac ic a C -ce ( hi e a ).

Figure 2: h id g a d i h h c ic h idi i . A f ic e (b ac a )i ded b a de e ce a i fi a e f h c e a d a a ce ( hi e a ). a e

Idi a hic h id a h i cha ac e i ed hi gica b f h id a e ch a a d e ace e f he c id-fi ed f ic e (Fig. 3) i h adi e i e.1 M d g ih h id e a ia a e e h id beca e h h idi d e cc i a ea 75% f he h id a e ch a ha bee de ed.7 H e e , d g ha e bee e ed be h e h id d e he e e ce f f c i a h id ca ci a .8

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Fig re 3: an atrophic thyroid gland composed of degenerate thyroid epithelial cells. A single follicle containing colloid and degenerate cells is present (white arrow). Secondary hypothyroidism, resulting from inadequate secretion of thyrotropin (thyroid stimulating hormone or TSH) from the pituitary gland, is less commonly recognized, probably because a validated assay for canine TSH has been unavailable until recently. C auses of acquired secondary hypothyroidism include pituitary neoplasia and pituitary malformations such as a cystic craniobuccal (Rathke s) pouch.1 5 Because of the nonselective nature of the resulting compressive atrophy and replacement of pituitary tissue by such large tumors, deficiencies of other (one or more) pituitary hormones also usually occur.1 Tertiary hypothyroidism results from a deficiency of hypothalamic thyrotropin-releasing hormone (TRH). This entity has yet to be documented in the dog.7 C ongenital hypothyroidism (cretinism) is rarely diagnosed in dogs. C ongenital primary hypothyroidism may result from iodine deficiency, thyroid dysgenesis, or dyshormonogenesis (inability to organify iodide). C ongenital secondary hypothyroidism (associated with disproportionate dwarfism, lethargy, gait abnormalities, and constipation) due to TSH or TRH deficiency has been documented in a family of Giant Schnauzers and in a young Boxer.7 Iatrogenic causes of hypothyroidism include radioactive 1 2 5 I treatment, administration of antithyroid drugs, and surgical thyroidectomy. Because of the presence of accessory thyroid tissue, permanent hypothyroidism is rare after thyroidectomy.7 Clinical Signs Although the age of onset is variable, hypothyroidism most commonly occurs in dogs from 4 to 10 years of age. It usually affects mid- to large-size breeds and is rare in toy and miniature breeds.1 The clinical signs of hypothyroidism may be vague and insidious in onset, therefore hypothyroidism may be considered in the differential diagnosis of a wide range of medical problems. Lethargy, mental dullness, weight gain, unwillingness to exercise, and cold intolerance are classical signs of hypothyroidism and are the result of a decreased metabolic rate. Dermatological manifestations occur in 60% of hypothyroid dogs.7 These may include a dry hair coat, seborrhea, alopecia, hyperpigmentation, and pyoderma (Fig. 4). While hair loss occurs in a bilaterally symmetrical pattern, it initially occurs in areas of friction such as the tail, around the neck, lateral trunk, and ventral thorax. Accumulation of excessive amounts of glycosaminoglycans (mostly hyaluronic acid) in the dermis results in the myxoedematous appearance (tragic facial expression) found in some dogs.1 3 Glycosaminoglycan accumulation may also occur in the gastrointestinal tract, heart, and skeletal muscles. Neurological, cardiovascular (bradycardia), and reproductive manifestations have also been recognized. Myxedema coma, a rare syndrome, is the extreme expression of severe hypothyroidism.1

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Figure 4: generalized alopecia in a hypothyroid dog. Diagnosis Hypothyroidism in dogs is probably one of the most over diagnosed diseases in small animal practice. The clinical signs of many diseases and conditions can mimic those of hypothyroidism, and some of these clinical signs, even in dogs with normal thyroid function, can improve after administration of exogenous thyroid hormone.1 For this reason, clinicians need to have a clinical suspicion for hypothyroidism prior to ordering diagnostic tests. There is no single hematologic or biochemical test that is conclusive for hypothyroidism and even hormonal tests must be interpreted in light of historical and physical findings.8 The wide variety of clinical signs and findings associated with hypothyroidism necessitates specific testing of thyroid function to establish a definitive diagnosis. Tests currently available for diagnosing thyroid disease include total thyroxine (TT4), total 3,5,3 -tri-idothyronine (TT3), free T4 (fT4), endogenous canine thyroid stimulating hormone (cTSH), TSH response test, TRH response test, T4 and T3 autoantibodies, antithyroglobulin antibodies, nuclear scintigraphy, and thyroid gland biopsy.1 3 TT4, fT4 by dialysis, and cTSH are tests that are recommended routinely. Factors affecting th roid hormone concentrations: Age, breed, obesity, systemic illness, and drugs may all affect thyroid hormone concentrations. Thyroid hormone concentrations may be elevated from 2 to 5 times the adult level during the first three months of a puppy s life. Information is accumulating that certain breeds have considerably lower ranges of normal thyroid hormone concentrations. Greyhounds and Scottish Deerhounds have serum T4 concentrations considerably lower than the reference ranges commonly used by most diagnostic laboratories. Mild increases in T3 and T4 concentrations have been reported in obese, euthyroid dogs due to excessive caloric intake. The effects of nonthyroidal illnesses that depress thyroid hormone concentrations are collectively called the "euthyroid sick syndrome." A lowering of TT3 alone (low T3 syndrome) is less likely to be observed than is the lowering of TT4 and TT3 (low T4 state of medical illness). Drugs used in veterinary medicine which lower thyroid hormone concentrations include the glucocorticoids, anticonvulsants, quinidine, salicylates, phenylbutazone, sulfa antimicrobials, and radiocontrast agents.4 , 7 , 8 Nonspecific clinicopathologic abnormalities: The severity of these nonspecific abnormalities usually correlates with the severity and chronicity of the hypothyroid state. These abnormalities may be associated with many other diseases, but their presence adds supportive evidence for a diagnosis of hypothyroidism in a dog with appropriate clinical signs. The classic hematologic finding associated with hypothyroidism is a mild, normocytic, normochromic, nonregenerative anemia. The classic serum biochemical abnormality is hypercholesterolemia, which occurs in about 80% of dogs with hypothyroidism, making it an excellent screening test. Other clinicopathologic abnormalities may include high serum concentrations of triglycerides and increased activity of alkaline phosphatase and creatine kinase. The electrocardiogram may show low amplitude and inverted T waves with bradycardia.1 , 8 Total T4 Concentration: Measurement of serum TT4 concentrations remains a useful screening test for hypothyroidism. Accuracy of TT4 in evaluating thyroid function is 85 to 90%. However, it is important to remember that several factors can artificially affect serum TT4 values.2 TT4 infrequently is within the reference interval in hypothyroid dogs, although early hypothyroidsm does result in a low normal TT4. TT4 is, however, frequently below the reference interval in dogs with normal thyroid function. This occurs because of physiological fluctuations in thyroid hormone concentrations as well as the effects that drugs and non-thyroidal illness have on TT4.1 3 The sole determination of TT4 concentration by radioimmunoaassay is truly diagnostic only if the value is within the reference interval or elevated, in which case, hypothyroidism can be excluded. Dogs with hypothyroidism can, in most cases, be distinguished from healthy dogs on the basis of a low resting TT4 concentration. However, nonthyroidal conditions on the list of differential diagnoses, certain drugs, and even the time of day may also lower baseline TT4 and TT3 concentrations. Therefore, reduced basal TT4 or TT3 concentrations are not specific enough to serve as reliable indicators of hypothyroidism. It is always wise to confirm the diagnosis of hypothyroidism with a more specific test, such as fT4, cTSH, or TSH response.8 Total T3 Concentration: As T3 is the most potent thyroid hormone at the cellular level, it would seem logical to measure its concentration for diagnostic purposes.8 However, measurement of TT3 concentrations is less accurate than TT4 measurement for distinguishing euthyroid from hypothyroid dogs. T3 concentrations undergo normal fluctuations out of the reference interval to a greater extent than T4 concentrations in euthyroid dogs.7 Although concentrations of T4 are low in the late stages of hypothyroidism, concentrations of T3 are often within the reference interval in many hypothyroid dogs. One likely reason for this involves the compensatory mechanisms occurring in the failing thyroid and its ability to shift secretion, releasing more T3 as failure progresses. Additionally, elevated or nondetectable results may occur owing to anti-T3 antibodies. For this reason it is not recommended to measure TT3 in the evaluation of hypothyroidism in dogs.7 , 1 0 Free T4 Concentration: Serum fT4 is a better test of thyroid function than TT4 concentrations because it is less affected by factors that alter protein binding. The accuracy of fT4 measurement is largely dependent on the assay method. The most accurate method of measurement available in clinical laboratories is a modified equilibrium dialysis technique.1 3 The diagnostic sensitivity of fT4 equilibrium dialysis is 98%, specificity is 93%, and accuracy is 95%.2 Because fT4 by dialysis is expensive and time consuming, single-stage solid-phase (analog) radioimmunoassays for human fT4 are commonly used for measurement of canine fT4. However, canine fT4 concentrations measured by analog methods are lower than those measured by equilibrium dialysis and have no diagnostic advantage over measurement of TT4.7 Endogenous Canine Th rotropin (cTSH) Concentration: The recently developed assay to measure cTSH was anticipated as a potentially accurate and sensitive method of assessing thyroid function. Serum TSH is the most accurate test of thyroid function in humans, where it allows diagnosis of hypothyroidism at a very early, even subclinical, stage. Unfortunately, assay performance of cTSH in the dog has been disappointing when it is used as a single test.1 2 Serum TSH concentrations would be expected to be high in dogs with primary hypothyroidism because of the loss of negative feedback of T4 and T3 on the pituitary gland. Unfortunately, from 18 to 38% of dogs with primary hypothyroidism have cTSH concentrations within reference intervals. Furthermore, 0 to 14% of euthyroid dogs have an elevated cTSH.1 3 This results in an assay sensitivity of only 63 to 82%. Possible reasons that dogs with hypothyroidism might have a cTSH concentration within the reference interval include secondary or tertiary . e . ga.ed /VPP/cle k/bell/inde .php

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Canine H po h oidi m, An O e ie hypothyroidism might have a cTSH concentration within the reference interval include secondary or tertiary hypothyroidism, effects of drugs or concurrent illness, and diurnal fluctuation of cTSH concentration.3 In secondary and tertiary hypothyroidism, TSH concentrations range from the low end of the reference interval to undetectable.1 5 Since the TSH concentration is within reference interval in 20 to 40% of hypothyroid dogs, it cannot be used alone for a diagnosis.2 , 1 4 Use of T4 in combination with TSH should increase the accuracy of diagnosis.1 5 While serum TT4 is a good screening test, fT4 and cTSH are the primary tests to confirm the diagnosis of hypothyroidism. When cTSH is measured with fT4, it can provide valuable evidence supporting hypothyroidism by increasing the diagnostic specificity to 98%. Test results within the reference interval indicate that the dog is not hypothyroid. Decreased fT4 and increased cTSH identify clinical hypothyroidism. The serum TT4 can be within the reference interval and TSH can be elevated in true hypothyroidism if there are circulating thyroid autoantibodies, as these often cross-react with TT4 assays.2 Measurement of cTSH concentration is a valuable adjunct to T4 assessment in the diagnosis of canine hypothyroidism but should not be used alone. Serum fT4 concentrations are more specific but may be less sensitive than TT4 estimations in the diagnosis of hypothyroidism. Given the expense of fT4 estimations, TT4 measurements are currently considered adequate in evaluating thyroid function.5
Th rotropin (TSH) Response Test: The TSH response test has long been recognized as an accurate measure of thyroid function and serves as the "gold standard" measurement in many studies evaluating thyroid function tests.1 3 This is because it provides important information about thyroid secretory reserve.8 Measurement of TT4 before and six hours after intravenous administration of 0.1 U/kg bovine TSH is the recommended protocol. Post-TSH TT4 concentrations above 30 mmol/L are normal in most laboratories, while TT4 less than 20 mmol/L is diagnostic for hypothyroidism.1 3 In pituitary forms of hypothyroidism, the thyroid gland should remain responsive to TSH. With the TSH response test, depression of baseline serum T4 concentrations due to drugs and illness may be distinguished from advanced primary hypothyroidism but not from other forms of hypothyroidism or from earlier stages of primary hypothyroidism. The rare cases of long-standing secondary (pituitary) or tertiary (hypothalamic) hypothyroidism with subsequent thyroid atrophy may require 2 or 3 consecutive daily doses of TSH to eventually demonstrate thyroid responsiveness.8 Unfortunately, although the TSH response test is accurate, bovine TSH is not licensed for use in the dog and is difficult and expensive to obtain.5 There have also been occasional reports of anaphylactic responses after bovine TSH administration. The TSH response test cannot be used to evaluate thyroid function in dogs receiving Lthyroxine because treatment causes thyroid atrophy. Supplementation must be discontinued 6 to 8 weeks before testing.7 Th rotropin Releasing Hormone (TRH) Response Test: The TRH response test is used in humans to differentiate primary from secondary hypothyroidism. In people with primary hypothyroidism, response of TSH to TRH administration is exaggerated, whereas in secondary hypothyroidism there is no response. In dogs, the test has been used in place of the TSH response test, and change in TT4 has usually been measured.7 The TRH response test is performed by measurement of TT4 before and four hours after intravenous administration of suggested doses of synthetic TRH that range from 0.2 mg/dog to 0.1 mg/kg. A normal response has been stated to be 1.5 times the baseline T4 concentration, but a very low baseline T4 could increase to that degree by normal fluctuations in hormone concentration over time.1 3 In theory, the administration of TRH should lead to an increase in T4 only if the pituitarythyroid axis is intact. Therefore, responsiveness to TRH should only be observed in healthy dogs and dogs with tertiary (hypothalamic) thyroid insufficiency, a condition not yet documented. Perhaps the main limitation of the TRH response test is that little information has been published on the effects of drugs or nonthyroidal illness.8 Results of the TRH response test are variable, with a significant percentage of dogs failing to respond with a substantial increase in T4.1 3 The TRH response test is incapable of accurately separating hypothyroid dogs from euthyroid dogs with nonthyroidal illness and can no longer be recommended.5 , 1 0 Antith roglobulin Antibod (ATA): ATA is found in 42 to 59% of hypothyroid dogs and is believed to be the result of leakage of thyroglobulin into circulation owing to lymphocytic thyroiditis. A commercially available ELISA for ATA is a sensitive and specific indicator of thyroiditis; false-positive results occur in < 5% of dogs with other endocrine disorders. It is important to recognize that a positive ATA titer is not an indicator of abnormal thyroid function. Whether all dogs with ATA ultimately develop hypothyroidism is unknown.7 , 9 Anti-T3 and -T4 Antibodies: Antibodies directed against T3 and T4 also occur in canine thyroiditis, although they are less prevalent than ATA. The incidence or recognition of anti-T3 antibodies appears to be greater than for anti-T4 antibodies. Because dogs with thyroiditis may still have adequate thyroid reserve, antithyroid antibodies are not indicators of hypothyroidism. Antibodies directed against T3 and T4 may interfere with hormone assays, leading to a spurious increase or decrease in the measured hormone concentration.7 The clinical significance of antithyroid hormone antibodies is primarily in their indication of the diagnosis of lymphocytic thyroiditis and the confusion they create for the interpretation of thyroid function tests.8 Scintigraph : Nuclear scintigraphy using radioiodine or technetium is rarely used as a method of diagnosing hypothyroidism because of the limited availability of the technique, exposure of the patient and personnel to radioactive isotopes, and accuracy of the procedure.1 3 Available only at referral institutions, thyroid uptake determinations are no longer used as a general screening test for canine hypothyroidism but are reserved as an aid in characterizing congenital defects of thyroid hormone synthesis.8 Th roid Biops : Thyroid gland biopsy is another rarely used tool for diagnosis of hypothyroidism. Thyroid gland biopsy may be a better method of diagnosing lymphocytic thyroiditis than primary hypothyroidism because early follicular atrophy may be difficult to detect in an incisional biopsy of one thyroid gland. It may be a useful method of differentiating primary from secondary hypothyroidism where enlarged follicles and flattened follicular epithelial cells are found because of deficient TSH secretion. Risks of thyroid gland biopsy include general anesthesia and damage to surrounding tissue such as the parathyroid glands and recurrent laryngeal nerves.1 3

Therapeutic Trial: When diagnostic tests do not provide a clear diagnosis of hypothyroidism, thyroid replacement therapy has been suggested as a valid diagnostic step. The cost of the diagnostic testing is often cited as hardship for the owner, but it should be emphasized that replacement therapy is generally required for the remainder of the animal s life. Therefore, an incorrect diagnosis can also be quite expensive, a delayed diagnosis of another disease could be detrimental, and diagnostic procedures following a therapeutic trial with equivocal results can be quite difficult to interpret because secretion of the healthy thyroid gland is inhibited by this procedure.8 A positive response to therapy should be interpreted with caution because clinical signs may also improve in euthyroid animals treated with . e . ga.ed /VPP/cle k/bell/inde .php

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Canine H po h oidi m, An O e ie therapy should be interpreted with caution because clinical signs may also improve in euthyroid animals treated with L-thyroxine. A diagnosis of hypothyroidism based on response to therapy should be confirmed by recurrence of clinical signs after withdrawal of supplementation.7
T ea men Note: Treatment of animals should onl be performed b a licensed veterinarian. Veterinarians should consult the current literature and current pharmacological formularies before initiating an treatment protocol. The initial treatment of choice is synthetic L-thyroxine, because it results in normalization of both T4 and T3 concentrations. Risk of iatrogenic hyperthyroidism is low because physiologic regulation of conversion of T4 to T3 is preserved. Bioavailability may vary greatly from one product to another, so it is advisable to use a brand-name product for initial treatment. It also is advisable to measure TT4 concentrations 4-8 weeks after changing the brand of supplement, particularly if a generic product is substituted for a name-brand product.7 With few exceptions, replacement therapy is necessary for the remainder of dog s life.1 Optimal dose and frequency of supplementation vary among dogs because of variability in L-thyroxine absorption and serum half-life. Treatment should be initiated at a dose of 0.02 mg/kg orally every 12 hours, and then the dose should be adjusted based on results of therapeutic monitoring. Using twice-daily treatment initially improves the likelihood of response to treatment in all dogs. After clinical signs resolve and TT4 concentrations stabilize within the therapeutic range, the majority of dogs can be maintained on 0.02 mg/kg once daily.6 , 7 The most important indicator of the success of therapy is clinical improvement. C linical resolution of metabolic signs such as lethargy and mental dullness can be expected within two weeks of starting therapy, while other abnormalities, including dermatologic signs, may take up to three months to resolve.6 Biochemical therapeutic monitoring is required because of variable individual response to treatment; dose adjustments are required in approximately half of all patients.6 Therapeutic monitoring of serum TT4 and cTSH levels should be started beginning four to eight weeks after starting supplementation. Serum TT4 concentrations should be measured at six- to eight-week intervals during the first six to eight months of treatment, because metabolism of T4 will change when the metabolic rate normalizes and dosage adjustments may be necessary. Once adequate serum TT4 concentrations are documented and the dog s dosage has stabilized, frequency of measurement of serum TT4 may be decreased to once or twice a year.7 With once-daily administration of T4, the peak serum concentration of T4 generally should be slightly high to highnormal four to eight hours after dosing and low-normal to normal 24 hours after dosing. Animals on a twice-daily administration probably can be checked at any time, but peak concentrations can be expected at the middle of the dosing interval (4 to 8 hours) and the nadir just before the next dose.1 Six hours after Soloxine administration on a once daily administration program, a median total T4 value of approximately 55 mmol/L is associated with good clinical control in most dogs, whereas values of less than 35 mmol/L usually indicate the need for an increase in dosage. Maintenance of an elevated circulating cTSH concentration is a reliable predictor of an increased therapeutic requirement but suppression of cTSH concentration into the reference interval does not guarantee the adequacy of therapy. A decrease in circulating cholesterol and triglyceride concentration and an increase in the RBC count can be used to indicate an overall effect of thyroid hormone replacement therapy but is not valuable in reliably confirming therapeutic efficacy.6 P ogno i Prognosis for return to normal function following treatment is excellent in most adult hypothyroid dogs. Prognosis in myxedema coma is dependent on early recognition. Resolution of clinical signs in puppies with congenital hypothyroidism is dependent on the age at which treatment is initiated.7 Refe ence 1. Aiello, SE (ed): Merck Veterinary Manual, 8th ed. Whitehouse Station, Merck & C o, 1998, pp 415-418. 2. Beaver, BV, Haug, LI: C anine behaviors associated with hypothyroidism. J Am Anim Hosp Assoc 39:431-437, 2003. 3. Bruner, JM, Scott-Moncrieff, JC , Williams, DA: Effect of time of sample collection on serum thyroid-stimulating hormone concentrations in euthyroid and hypothyroid dogs. J Am Vet Med Assoc 212:1572-1577, 1998. 4. Daminet, S, Ferguson, DC : Influence of drugs on thyroid function in dogs. J Vet Intern Med 17:463-466, 2003. 5. Dixon, RM, Mooney, C T: Evaluation of serum free thyroxine and thyrotropin concentrations in the diagnosis of canine hypothyroidism. J Small Anim Pract 40:72-74, 1999. 6. Dixon, RM, Reid, SW, Mooney, C T: Treatment and therapeutic monitoring of canine hypothyroidism. J Small Anim Pract 43:334-344, 2002. 7. Ettinger, SJ, Feldman, EC (eds): Textbook of Veterinary Internal Medicine, Diseases of the Dog and C at, 5th ed. Philadelphia, WB Saunders, 2000, pp 1420-1427. 8. Feldman EC , Nelson RW. C anine and Feline Endocrinology and Reproduction, 3rd ed. St. Louis, Saunders, 2004, pp. 244-245. 9. Ferguson, DC : Update on the diagnosis of canine hypothyroidism. Vet C lin North Am Small Anim Pract 24:515-519, 1994. 10. Iverson, L, Jenson, AL, Hoier, R, Skydsgaard, M, Kristensen, F: Development and validation of an improved enzyme-linked immunosorbent assay for the detection of thyroglobulin autoantibodies in canine serum samples. Domest Anim Endocrinol 15:525-532, 1998.

. e . 11. Kemppainen, RJ, Behrend, EN: Diagnosis of canine hypothyroidism. Perspectives from a testing laboratory. Vet ga.ed /VPP/cle k/bell/inde .php

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11. Kemppainen, RJ, Behrend, EN: Diagnosis of canine hypothyroidism. Perspectives from a testing laboratory. Vet C lin North Am Small Anim Pract 31:951-956, 2001. 12. Lucke, VM, Gaskell, C J, Wotten, PR: Thyroid pathology in canine hypothyroidism. J C omp Pathol 93:415-420, 1983. 13. Marca, MC , Loste, A, Orden, I, Gonzalez, JM, Marsella, JA: Evaluation of canine serum thyrotropin (TSH) concentration: comparison of three analytical procedures. J Vet Diagn Invest 13:106-111, 2001. 14. Panciera, DL: Is it possible to diagnose canine hypothyroidism? J Small Anim Pract 40:152-155, 1999. 15. Ramsey, IK, Evans, H, Herrtage, ME: Thyroid-stimulating hormone and total thyroxine concentrations in euthyroid, sick euthyroid, and hypothyroid dogs. J Small Anim Pract 38:540-544, 1997. 16. Scott-Moncrieff, JC , Nelson, Rw, Bruner, JM, Williams, DA: C omparison of serum concentrations of thyroidstimulating hormone in healthy dogs, hypothyroid dogs, and euthyroid dogs with concurrent disease. J Am Vet Med Assoc 212:387-494, 1998. Ackno ledgement The watercolor "Dog on Beach" by C hriss Pagani is from her website Paintings: Oregon Impressions. The image is copyrighted and used with permission. ^ Top of page

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