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Point-Of-Care in-house thyroid testing - IDEXX Laboratories

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cl<strong>in</strong>ical applications<br />

POINT-OF-CARE IN-HOUSE THYROID TESTING<br />

COMPARISON OF LABORATORY<br />

AND IN-HOUSE TESTS<br />

THE OFFICIAL PUBLICATION OF THE NORTH AMERICAN VETERINARY CONFERENCE<br />

SUPPLEMENT TO NAVC CLINICIAN’S BRIEF ® JANUARY 2007<br />

WWW.CLINICIANSBRIEF.COM<br />

POINT-OF-CARE IN-HOUSE T 4 TEST


POINT-OF-CARE IN-HOUSE T 4 TEST<br />

2<br />

cl<strong>in</strong>ical applications <br />

POINT-OF-CARE IN-HOUSE THYROID TESTING<br />

COMPARISON OF LABORATORY<br />

AND IN-HOUSE TESTS<br />

This study<br />

demonstrates a<br />

good correlation<br />

between 4<br />

different methods<br />

of thyrox<strong>in</strong>e<br />

(T4 ) test<strong>in</strong>g.<br />

Thyroid disease is relatively common <strong>in</strong> dogs and cats;<br />

however, dogs are most commonly hypo<strong>thyroid</strong> while cats<br />

are most commonly hyper<strong>thyroid</strong>. The measurement of total<br />

thyrox<strong>in</strong>e (T 4 ) is the ma<strong>in</strong>stay for diagnos<strong>in</strong>g <strong>thyroid</strong> disease <strong>in</strong> both<br />

species and for evaluat<strong>in</strong>g therapeutic success. Dogs suspected of<br />

be<strong>in</strong>g hypo<strong>thyroid</strong> (borderl<strong>in</strong>e or low concentrations of T 4 ) usually<br />

also have confirmation tests to determ<strong>in</strong>e free T 4 and/or <strong>thyroid</strong><br />

stimulat<strong>in</strong>g hormone (TSH or thyrotrop<strong>in</strong>) concentrations. In cats<br />

suspected of be<strong>in</strong>g hyper<strong>thyroid</strong> (<strong>in</strong>creased concentration of T 4 ), the total T 4 is usually sufficient<br />

to diagnose the disease, while levels <strong>in</strong> the mid to upper portion of the reference range are<br />

considered suspicious and warrant further test<strong>in</strong>g (such as measurement of free T 4 ).<br />

Historically, radioimmunoassay (RIA) <strong>in</strong> the laboratory has been considered the gold standard<br />

of T 4 test<strong>in</strong>g, but new methods and technology advancements have made other affordable,<br />

convenient, and time-sensitive methods available. Most RIA procedures have been designed for<br />

people but have been validated for use <strong>in</strong> domestic animals, and a total T 4 RIA test kit is<br />

marketed specifically for dogs. ELISA-based and chemilum<strong>in</strong>escent systems processed <strong>in</strong><br />

commercial laboratories<br />

KEY POINTS – Fel<strong>in</strong>e & Can<strong>in</strong>e Thyroid Disease<br />

FELINE HYPERTHYROIDISM<br />

Most often caused by<br />

hyperfunction<strong>in</strong>g <strong>thyroid</strong><br />

gland nodules (secretion of T 4<br />

and T 3 not controlled by TSH)<br />

Common cl<strong>in</strong>ical signs<br />

■ Weight loss<br />

■ Polyphagia<br />

■ Vomit<strong>in</strong>g<br />

■ Tachypnea<br />

■ Hyperactivity<br />

■ Dyspnea<br />

Differential Diagnosis<br />

■ Chronic kidney disease<br />

■ Chronic liver disease<br />

■ Neoplasia<br />

Diagnosis<br />

■ Total T 4 concentration<br />

above reference range<br />

■ High normal total T 4<br />

coupled with elevated<br />

free T 4<br />

CANINE HYPOTHYROIDISM<br />

Most common <strong>in</strong> middle-aged<br />

dogs; acquired primary disease<br />

(lymphocytic <strong>thyroid</strong>itis or<br />

idiopathic <strong>thyroid</strong> atrophy)<br />

Common cl<strong>in</strong>ical signs<br />

■ Lethargy<br />

■ Inactivity<br />

■ Mental dullness<br />

■ Weight ga<strong>in</strong><br />

■ Hair loss or excessive shedd<strong>in</strong>g<br />

■ Recurrent <strong>in</strong>fections<br />

Differential Diagnosis<br />

■ Exclude other endocr<strong>in</strong>e<br />

diseases such as<br />

hyperadrenocorticism<br />

Diagnosis<br />

■ Total T 4 below reference range<br />

screen<strong>in</strong>g test<br />

■ Decreased free T 4<br />

■ Increased cTSH levels may<br />

be seen<br />

also have been validated for<br />

total T 4 concentration<br />

test<strong>in</strong>g <strong>in</strong> dogs and cats. A<br />

po<strong>in</strong>t-of-care <strong>in</strong>-<strong>house</strong><br />

ELISA system (<strong>IDEXX</strong><br />

SNAP ® T 4 Test) for use by<br />

veter<strong>in</strong>arians <strong>in</strong> a practice<br />

sett<strong>in</strong>g is also commercially<br />

available. The study<br />

presented on the opposite<br />

page compared results<br />

from these 4 methods of<br />

analysis and demonstrated<br />

a good correlation among<br />

them. The data give the<br />

practitioner a good basis<br />

for select<strong>in</strong>g among<br />

currently available T 4 test<strong>in</strong>g<br />

methods, provid<strong>in</strong>g a<br />

greater range of solutions<br />

than has been available <strong>in</strong><br />

the past.<br />

c l i n i c i a n ’ s b r i e f ®


STUDY – Compar<strong>in</strong>g various methods of T 4 test<strong>in</strong>g 1<br />

■ Serum samples obta<strong>in</strong>ed from 98 dogs and 100 cats<br />

■ Samples were submitted to diagnostic lab to test the follow<strong>in</strong>g:<br />

Dogs<br />

Screen<strong>in</strong>g for hypo<strong>thyroid</strong>ism 41<br />

Assess<strong>in</strong>g adequacy of treatment 39<br />

Reason for request unknown 18<br />

Cats<br />

Screen<strong>in</strong>g for hyper<strong>thyroid</strong>ism 64<br />

Assess treatment with methimazole 17<br />

Reason for request unknown 19<br />

■ 12 pairs (24 animals) for comparison of the 4 assay methods for 2 species<br />

■ Precision estimates were determ<strong>in</strong>ed for each assay us<strong>in</strong>g serially diluted dog and cat serum<br />

■ Samples submitted to a veter<strong>in</strong>ary university endocr<strong>in</strong>ology lab<br />

■ T 4 concentration determ<strong>in</strong>ed by RIA T 4 assay with<strong>in</strong> 1 of 4 ranges<br />

0.5 to 1.5 µg/dl 3.1 to 4.9 µg/dl<br />

1.6 to 3.0 µg/dl 5.0 to 7.0 µg/dl<br />

T 4 Assay Methods* †<br />

Method Test Performed by Product maker<br />

A Can<strong>in</strong>e total T4 coated-tube RIA<br />

Diagnostic laboratory Coat-A-Count Can<strong>in</strong>e Total T4 Diagnostic Products Corp<br />

Los Angeles, CA<br />

B In-<strong>house</strong> enzyme- In-<strong>house</strong> (simulated)* SNAP ® l<strong>in</strong>ked immunosorbent<br />

T4 <strong>IDEXX</strong> <strong>Laboratories</strong><br />

assay (ELISA) kit Westbrook, ME<br />

C** RIA total T4 kit Mailed to company Coat-A-Count Total T4 Diagnostic Products Corp<br />

Los Angeles, CA<br />

D** CEIA kit Mailed to company Immulite Total T4 Diagnostic Products Corp<br />

Los Angeles, CA<br />

* Performed by a veter<strong>in</strong>ary student.<br />

† Sensitivity was 0.15, 0.5, 0.25, and 0.4 µg/dl for assays A, B, C, and D respectively.<br />

** Marketed for human, validated for use <strong>in</strong> dogs and cats.<br />

RESULTS<br />

■ Statistical comparisons of T 4 test method results revealed, <strong>in</strong> general, good correlation between T 4<br />

concentrations.<br />

■ Agreement was generally excellent for T 4 concentrations <strong>in</strong> low to middle portion of cl<strong>in</strong>ically normal<br />

ranges.<br />

■ Divergent results were seen for all methods at higher T 4 concentrations, but it is possible that factors<br />

such as lipemia, hemolysis, or method of serum collection contributed to these differences.<br />

■ In general, the T 4 concentrations obta<strong>in</strong>ed by assay method A were lower than those of the other<br />

methods. These differences were more profound at higher concentrations, and <strong>in</strong> cats.<br />

Discussion<br />

For hypo<strong>thyroid</strong>ism <strong>in</strong> dogs, most veter<strong>in</strong>arians use total T 4 concentrations as screen<strong>in</strong>g tests. Because<br />

factors other than hypo<strong>thyroid</strong>ism can cause low total T 4 concentrations, confirmation tests are needed<br />

to make a diagnosis. This study showed that a po<strong>in</strong>t-of-care system (method B) provided reliable and<br />

consistent results for screen<strong>in</strong>g and for assess<strong>in</strong>g adequacy of T 4 replacement treatment.<br />

For hyper<strong>thyroid</strong>ism <strong>in</strong> cats, there was good agreement between methods for total T 4 concentrations<br />

above the reference range. Because some cats with hyper<strong>thyroid</strong>ism have total T 4 concentrations<br />

with<strong>in</strong> reference ranges, other test<strong>in</strong>g may be <strong>in</strong>dicated when <strong>thyroid</strong> disease is suspected but total T 4<br />

is with<strong>in</strong> the reference range.<br />

1. Measurement of total thyrox<strong>in</strong>e concentration <strong>in</strong> serum from dogs and cats by use of various<br />

methods. Kemppa<strong>in</strong>en RJ, Birchfield JR. Am J Vet Res 67:259-265, 2006.<br />

c l i n i c a l a p p l i c a t i o n s <br />

3<br />

POINT-OF-CARE IN-HOUSE T 4 TEST


4<br />

Commentary<br />

Can<strong>in</strong>e hypo<strong>thyroid</strong>ism and fel<strong>in</strong>e hyper<strong>thyroid</strong>ism are two of the most common endocr<strong>in</strong>e disorders<br />

seen <strong>in</strong> small animal practice. Because <strong>thyroid</strong> disorders typically respond well to therapy<br />

and have a good prognosis, it is important for the practitioner to be aware of both common and<br />

uncommon cl<strong>in</strong>ical signs and to rout<strong>in</strong>ely screen patients with suspected or potential disease.<br />

Serum total thyrox<strong>in</strong>e (T 4 ) concentrations commonly used for screen<strong>in</strong>g and therapeutic monitor<strong>in</strong>g<br />

are rout<strong>in</strong>ely offered by diagnostic laboratories us<strong>in</strong>g a radioimmunoassay or chemilum<strong>in</strong>escence test. The<br />

availability of an <strong>in</strong>-<strong>house</strong> T 4 test<strong>in</strong>g system can offer a convenient, cost-effective alternative. This study showed generally<br />

good correlation between the various methodologies and it appears that any of them, <strong>in</strong>clud<strong>in</strong>g the <strong>IDEXX</strong><br />

SNAP ® T 4 <strong>in</strong>-<strong>house</strong> test, is appropriate, dependable, and <strong>in</strong>dicated. It must be remembered that with any test, false<br />

negative and false positive results can occur for any number of reasons, and that results must be <strong>in</strong>terpreted <strong>in</strong><br />

light of the patient’s history, cl<strong>in</strong>ical signs, and other laboratory f<strong>in</strong>d<strong>in</strong>gs. — Peter P. K<strong>in</strong>tzer, DVM, DACVIM, Staff<br />

Internist, Boston Road Animal Hospital, Spr<strong>in</strong>gfield, Massachusetts<br />

SUGGESTED READING<br />

Can<strong>in</strong>e hypo<strong>thyroid</strong>ism. Dixon RM. BSAVA<br />

Manual of Can<strong>in</strong>e and Fel<strong>in</strong>e Endocr<strong>in</strong>ology,<br />

3rd ed. Mooney CT, Peterson ME. Gloucester,<br />

UK: BSAVA Publications, 2004, pp 76-94.<br />

Fel<strong>in</strong>e hyper<strong>thyroid</strong>ism. Mooney CT, Peterson<br />

ME. BSAVA Manual of Can<strong>in</strong>e and Fel<strong>in</strong>e<br />

Endocr<strong>in</strong>ology, 3rd ed. Mooney CT, Peterson<br />

ME. Gloucester, UK: BSAVA Publications, 2004,<br />

pp 95-111.<br />

Hypo<strong>thyroid</strong>ism. Feldman EC, Nelson RW.<br />

Can<strong>in</strong>e and Fel<strong>in</strong>e Endocr<strong>in</strong>ology and<br />

Reproduction (3rd ed). Feldman EC, Nelson<br />

RW. Philadelphia: WB Saunders Co, 2004, pp<br />

86-151.<br />

Measurement of serum concentrations of free<br />

thyrox<strong>in</strong>e, total thyrox<strong>in</strong>e, and total<br />

triiodothyron<strong>in</strong>e <strong>in</strong> cats with hyper<strong>thyroid</strong>ism<br />

and cats with non<strong>thyroid</strong>al disease. Peterson<br />

ME, Melian C, Nichols R. JAVMA 218:529-536,<br />

2001.<br />

© 2007 Educational Concepts<br />

<strong>IDEXX</strong> Product Profile<br />

<strong>IDEXX</strong> SNAP ® Reader<br />

■ Only <strong>in</strong>-<strong>house</strong> <strong>in</strong>strument that tests T 4, cortisol, &<br />

bile acids<br />

■ Easy to use<br />

■ Attaches to top of <strong>IDEXX</strong> VetTest ® Chemistry<br />

Analyzer, so no additional bench space needed<br />

■ Cost effective<br />

<strong>IDEXX</strong> SNAP ® T 4 test<br />

■ Diagnoses <strong>thyroid</strong><br />

disease<br />

■ Assesses geriatric<br />

preanesthetic cats<br />

■ Provides<br />

comprehensive, onevisit<br />

screen<strong>in</strong>g for cats, dogs, and horses<br />

■ Monitors response to treatment for immediate<br />

dosage adjustment<br />

This research summary is sponsored by an educational grant from <strong>IDEXX</strong> Corporation.<br />

09-65881-00<br />

c l i n i c a l a p p l i c a t i o n s

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