Thyrotropin receptor antibodies (TRAb) may be mildly elevated in a variety of thyroid disorders, but a TRAb level >10 U/L increases the probability of Graves' disease by a moderate to large degree (strength of recommendation [SOR]: B, cross-sectional study). A positive or negative thyroid peroxidase antibody (TPOAb) test increases or decreases the probability of autoimmune thyroid disease by only a small to moderate degree (SOR: B, 3 cross-sectional studies)

Downs, Heather

Flake, Donna

Meyer, Albert A.

University of Missouri: MOspace

CliniCal InquIrIes Evidence Based Answers from the Family Physicians Inquiries Network	 vol	57,	no	9	/	september	2008	 615www.jfponline.comfast trackThyroid  autoantibodies can help diagnose Graves’ disease and autoimmune thyroid disease; they can also  help predict  hypothyroidism Heather Downs, DO,  and albert a. Meyer, MDNew Hanover Regional Medical Center, Wilmington, NCDonna Flake, MSlS, MSaSCoastal Area Health Education Center, Wilmington, NC  How useful are autoantibodies  in diagnosing thyroid disorders? Evidence-based answerthey’re	useful	in	diagnosing	Graves’	disease	and,	to	a	lesser	extent,	autoimmune	thyroid	disease;	they	can	also	help	predict	hypothyroidism.	thyrotropin	receptor	antibodies	(trAb)	may	be	mildly	elevated	in	a	variety	of	thyroid	disorders,	but	a	trAb	level	>10	u/l	increases	the	probability	of	Graves’	disease	by	a	moderate	to	large	degree	(strength	of	recommendation	[sor]:	B,	cross-sectional	study).	A	positive	or	negative	thyroid	peroxidase	antibody	(tpoAb)	test	increases	or	decreases	the	probability	of	autoimmune	thyroid	disease	by	only	a	small	to	moderate	degree	(sor:	B,	3	cross-sectional	studies).		 thyroid-stimulating	hormone	(tsH)	levels	>2	mu/l,	although	still	in	the	normal	range,	can	be	followed	up	with	tpoAb	testing	to	determine	whether	the	patient	has	an	increased	probability	of	developing	hypothyroidism	(sor:	B,	cohort	study	with	a	vague	hypothyroidism	reference	standard).	Clinical commentaryIn equivocal situations and pregnancy, antibodies may helpunder	most	circumstances,	hypo-	and	hyperthyroid	disorders	can	be	diagnosed	by	testing	tsH	and	free	t4,	without	thyroid	antibody	testing.	radionuclide	uptake	and	scan	provide	diagnostic	information	for	hyperthyroid	states.		 thyroid	antibody	tests	may	help	in	equivocal	situations,	such	as	a	normal	radioiodine	study	in	hyperthyroidism	or	evaluating	the	cause	of	hypothyroidism	when	infiltrative	disorders,	reidel’s	thyroiditis,	or	subacute	granulomatous	thyroiditis	are	suspected.	tpoAb	may	help	predict	the	development	of	clinical	hypothyroidism	in	patients	with	tsH	in	the	range	of	5-10	mu/l.		 pregnancy-related	hyperthyroidism	requires	antibody	testing	because	radioiodine	scans	are	contraindicated.	Antibody	titers	also	may	estimate	the	risk	of	pregnancy-related	adverse	outcomes. Ron Solbrig, MDIdaho	state	university,	pocatelloz  Evidence summaryAlthough TSH followed by free T4 re-main the initial screening tests for thyroid disorders, adding thyroid autoantibodies may refine the diagnosis. Three princi-pal thyroid antibodies—TPOAb, thyro-globulin, and TRAb—can be positive in a variety of autoimmune thyroid disor-ders. TPOAb represents a specific antigen of antimicrosomal antibody (AMA). It has largely replaced AMA testing in most laboratories and clinical settings. Antibodies point to Graves’,  autoimmune disorders A cross-sectional study of 267 Singa-Copyright® Dowden Health Media  For personal use onlyFor mass reproduction, content licensing and permissions contact Dowden Health Media.fast trackCliniCal InquIrIes616 vol	57,	no	9	/	september	2008		ThE Journal of famIly PraCTICEporean patients with previously diag-nosed thyroid disorders measured TRAb, AMA, and thyroglobulin (TABLE). TRAb levels >10 U/L were found to have a posi-tive likelihood ratio (LR+) of 13 and a negative likelihood ratio (LR−) of 0.2 for Graves’ disease.1 Two cross-sectional studies com-pared AMA to TPOAb in healthy patients and those with autoimmune thyroid and nonthyroid disorders. One study of 235 people in a university endocrinology department found that a TPOAb level >190 U/mL yielded an LR+ of 10.75 and an LR− of 0.15 for chronic autoimmune (Hashimoto’s) thyroiditis [CAHT]; the AMA-positive sera yielded an LR+ of 13.67 and an LR− of 0.19. Both TPOAb and AMA test characteristics were highly associated with CAHT (P<.001). TPOAb is more sensitive  than AMA and thyroglobulinIn the second study comparing AMA to TPOAb, the thyroid antibody test results of 32 healthy patients were compared with those of 262 clinic patients. In those with known thyroid dysfunction, TPOAb was found to be a more sensitive assay than AMA for autoimmune thyroid dis-orders. The sensitivity of TPOAb levels >3.1 U/mL was 88.1%; AMA sensitivity was 70.2% (P<.001).2,3 A cross-sectional study (National Health and Nutrition Examination Sur-vey [NHANES III]) evaluated the pres-ence of thyroid antibodies in 17,353 people representing the geographic and ethnic distribution of the United States, 95% of whom were categorized as free of thyroid disease.4 The study found that TPOAb was more sensitive than thyro-globulin for diagnosing nonspecific thy-roid disease. The diagnosis of thyroid disease was based on abnormal TSH and free T4 levels. Abnormally high levels of TPOAb had an LR+ of 4.3 and LR− of 0.6 (P<.0001) for thyroid disease, com-pared with an LR+ of 3.4 and LR− of 0.7 (P<.01) for abnormally elevated thyro-globulin.TSH + TPOAb more accurate  than TSH in womenIn the early 1970s, a cohort study of 2779 adults from Great Britain attempted to es-tablish the incidence of thyroid disease in the general population by measuring TSH and TPOAb. Twenty years later, investiga-tors restudied 1708 people from the origi-nal sample to determine the incidence of hypothyroidism and the prognostic value of these 2 biochemical markers for its de-velopment. At follow-up, the definition of a new case of hypothyroidism was based on an “intention to treat by the general practitioner by meeting clear biochemical criteria and/or symptoms.” Autoimmune markers in thyroid disordersThyroId  dIsordErs % of sTudy PaTIEnTs % Trab >3.4 u/l% Trab >10 u/l% ama PosITIvE% ThyrogloBulIn PosITIvElr+ lr- lr+ lr- lr+ lr- lr+ lr-graves’ disease 68 4.6 0.1 13 0.2 1.3 0.6 1.1 0.9CahT 20 0.2 4.7 0.1 2.8 1.4 0.2 1.4 0.6subacute  thyroiditis4 0.2 3.0 0 2.4 0.1 3.6 0.5 1.5Thyroid nodules 6 0.2 3.4 0 2.4 0.1 4.1 0.1 2.0others 2 0.8 1.4 0 2.3 0 2.8 0 2.0AmA,	antimicrosomal	antibodies;	CAHt,	chronic	autoimmune	(Hashimoto’s)	thyroiditis;	lr+,	positive	likelihood	ratio;	lr-,	negative	likelihood	ratio;	trAb,	thyrotropin	receptor	antibodiessource:	Khoo	DHC,	et	al.1	 tablePregnancy-related hyperthyroidism requires antibody testing because radioiodine  scans are  contraindicatedCont InueD	 vol	57,	no	9	/	september	2008	 619The initial presence of abnormally high serum TPOAb levels and TSH >2.0 mU/L pre-dicted a 4.3% annual risk of developing hypo-thyroidism compared with a 2.6% annual risk with serum TSH >6.0 mU/L alone in women. This risk was not estimated for men because of the small number of cases.5 RecommendationsThe American Association of Clinical Endo-crinologists (AACE) makes no specific recom-mendations about laboratory testing of thyroid antibodies. Based on clinical judgment, the AACE states that antibodies may be considered in the workup of hyperthyroidism and hypo-thyroidism and to determine potential risk to the fetus in pregnant women diagnosed with Graves’ disease.6 The National Academy of Clinical Bio-chemistry (NACB) recommends TPOAb mea-surements in patients who have Down syn-drome, are pregnant, or have miscarried or failed in vitro fertilization. The NACB also advocates measuring TPOAb before treatment with amiodarone, lithium, interferon-α, or in-terleukin-2.7 nreferences	 1.	 	Khoo	 DHC,	 Fok	 ACK,	 tan	 Ce,	 et	 al.	 thyroid	 stimulating	hormone	receptor	antibody	levels	in	singaporean	patients	with	autoimmune	 thyroid	disease.	Ann Acad Med Singa-pore.	1997;26:435-438.		 2.	 	Feldt-rasmussen	u,	Hoier-madsen	m,	bech	K,	et	al.	Anti-thyroid	peroxidase	antibodies	in	thyroid	disorders	and	non-thyroid	autoimmune	diseases.	Autoimmunity. 1991;9:245-254.		 3.	 	Doullay	 F,	 ruf	 J,	 Codaccioni	 Jl,	 Carayon	 p.	 prevalence	of	 autoantibodies	 to	 thyroperoxidase	 in	 patients	 with	various	 thyroid	and	autoimmune	diseases.	Autoimmunity.	1991;9:237-244.		 4.	 	Hollowell	 JG,	 staehling	 nW,	 Flanders	 WD,	 et	 al.	 serum	tsH,	t4,	and	thyroid	antibodies	in	the	united	states	pop-ulation	 (1998	 to	 1994):	national	Health	 and	nutrition	ex-amination	survey	 (nHAnes	 III.)	J Clin Endocrinol Metab. 2002;87:489-499.		 5.	 	vanderpump	mpJ,	tunbridge	WmG,	French	Jm,	et	al.	the	incidence	of	thyroid	disorders	in	the	community:	a	twenty-year	 follow	 up	 of	 the	Whickham	 survey.	Clin Endocrinol (Oxf). 1995;43:55-68.	 6.	 	American	Association	of	Clinical	endocrinologists	thyroid	task	Force.	American	Association	of	Clinical	endocrinolo-gists	medical	guidelines	for	clinical	practice	for	the	evalua-tion	and	treatment	of	hyperthyroidism	and	hypothyroidism.	Available	at:	www.aace.com/pub/pdf/guidelines/hypo_hy-per.pdf.	Accessed	June	8,	2007.	 7.	 	Demers	 lm,	 spencer	 CA.	 Laboratory Medicine Practice Guidelines: Laboratory Support for the Diagnosis and Mon-itoring of Thyroid Disease.	Washington,	DC:	AACC	press;	2003.	thyroid disorders

How useful are autoantibodies in diagnosing thyroid disorders?

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