Congenital hypothyroidism is a critical cause of elevated thyroid-stimulating hormone (TSH) in newborns; evaluate all neonates with an elevated TSH for congenital hypothyroidism (strength of recommendation [SOR]: A). Other causes of an elevated TSH include transient hypothyroidism due to neonatal illness, prematurity, iodine excess or deficiency, and maternal medication or maternal thyroid disease

Crotteau, Charles A.

Kovach, Fran E.

Rowland, Kathleen

University of Missouri: MOspace

CliniCal InquIrIes From the Family Physicians Inquiries Network	 vol	57,	no	3	/	March	2008	 185www.jfponline.com  What are the causes  of elevated TSH in a newborn?congenital	hypothyroidism	is	a	critical	cause	of	elevated	thyroid-stimulating	hormone	(Tsh)	in	newborns;	evaluate	all	neonates	with	an	elevated	Tsh	for	congenital	hypothyroidism	(strength	of	recommendation	[sor]:	A).		 other	causes	of	an	elevated	Tsh	include	transient	hypothyroidism		due	to	neonatal	illness,	prematurity,		iodine	excess	or	deficiency,	and		maternal	medication	or	maternal		thyroid	disease.Another cause of elevated TSH?Drawing the TSH too earlyI	practice	in	a	state	that	screens	newborns	using	Tsh	levels	instead	of	T4	levels.	In	my	experience,	the	most	common	reason	for	an	elevated	Tsh	is	that	the	metabolic	screen	was	drawn	too	early,	before	the	initial	physiologic	peak	after	birth	has	returned	to	the	screening	cutoff	level.	In	these	cases,	a	repeat	Tsh	is	almost		always	normal.		 however,	there	have	been	several	children	with	transient	hypothyroidism	that	I	have	seen	over	the	years	with	mild	Tsh	elevations	on	repeat	testing.	The	developmental	implications	for	the	infant	are	serious	enough	in	these	children	to	warrant	endocrinology	follow-up.Grant Hoekzema, MDMercy	Family	Medicine	residency,	st.	louis,	Moz Evidence summaryFeeding difficulties, inadequate weight gain, and unusual physical exam find-ings may lead providers to assess thy-roid function in newborns. Addition-ally, while measurement of free T4 is more common, some states use TSH as the required newborn screening assay to evaluate for congenital hypothyroid-ism. Whether ordered as a screening test or in response to symptoms, an elevated TSH in a newborn requires further in-vestigation. Congenital hypothyroidism is the most serious cause of an elevated TSH in a newborn. If left untreated, congeni-tal hypothyroidism leads to developmen-tal delay and mental retardation; how-ever, with early treatment, intellectual outcomes are greatly improved. New-borns with an elevated TSH should be evaluated with repeat TSH and free T4 measurements in order to assess for con-genital hypothyroidism. TSH >50 mU/L increases chances of congenital hypothyroidismNot surprisingly, higher levels of TSH increase the likelihood of con-genital hypothyroidism. A study from the Netherlands examined diagno-ses of infants with an increased TSH Kathleen Rowland, MD and Charles Crotteau, MDUniversity of Illinois at Chicago/ Illinois Masonic Family Medicine ResidencyFran Kovach, MliS, aHiPSouthern Illinois University School of Medicine, SpringfieldClinical commentaryEvidence-based answerfast trackAll neonates with high TSH should be evaluated  for congenital  hypothyroidismfast trackCliniCal InquIrIes186 vol	57,	no	3	/	March	2008		THE JournAl of fAmily PrACTiCEon newborn screening heelstick. Of 112 newborns with a TSH >50 mU/L, 110 (98%) had congenital hypothyroid-ism on further examination. However, only 34 of 594 (5.7%) newborns with a TSH between 9 and 20 mU/L were diag-nosed with congenital hypothyroidism. Nineteen of 46 newborns (41%) with levels between 20 and 50 mU/L had con-genital hypothyroidism.1Other common causes  of hypothyroidismWhile TSH is generally an accurate mea-surement of thyroid function, other fac-tors can also lead to an elevated level. The same Dutch study mentioned above explored the presumed causes of elevated TSH among children who were diagnosed with transient hypothyroidism (initially elevated TSH level found to be normal on follow-up testing). The most common causes were thyroid-binding globulin de-ficiency (200/548 or 36% of newborns with transient hypothyroidism), severe illness (36%), prematurity (8%), and errors in screening procedures (4%). Another study confirmed that TSH levels were higher in infants born pre-term; babies with the earliest gestational ages had the highest TSH levels. The same study also found that TSH levels in-creased with increasing degrees of illness. Very preterm babies, those with cerebral pathology, low Apgar scores, respiratory distress syndrome, persistent ductus arte-riosus requiring treatment, and necrotiz-ing enterocolitis were at highest risk for having abnormally elevated TSH levels in this study.2 If a sample is drawn from a newborn exhibiting symptoms (such as poor feeding or hypotonia), the TSH level may be elevated in spite of normal thyroid function.Maternal thyroid disease can also cause a suppression of thyroid function in the newborn. One study1 found that of 34 children with transient hypothyroid-ism, 10 had mothers with undertreated or unrecognized Graves disease.Finally, either iodine excess or iodine deficiency can cause transient hypothy-roidism. Case reports have directly dem-onstrated the effects of topical iodine exposure on newborn TSH levels.3–5 De-ficiency of dietary iodine is a common cause of both congenital and transient hypothyroidism in newborns worldwide, although it is rare in the United States. The World Health Organization lists 54 countries with inadequate iodine intake; consider children from these countries at high risk for hypothyroid-ism due to iodine deficiency.6Draw TSH on the second  or third day of lifeIn term, healthy newborns, TSH levels normally increase to levels of 60 mU/L within 30 minutes of delivery. This is fol-lowed by a rapid decline in TSH levels over the first 5 days of life to <10 mU/L. An Australian study found more elevated TSH levels for samples drawn on day 2 of life compared with day 3 of life, likely Other common causes of elevated TSH include  prematurity, severe illness, and errors in the screening procedure©	2008	roberT	DeMaresTCommon causes  of elevated TSH  in newborns•	congenital	hypothyroidism•		Transient	hypothyroidism	due	to	neonatal	illness•	Prematurity•	Iodine	excess	or	deficiency•		Improper	screening		technique•		Incorrect	normal	result	intervals	for	age•		Maternal	medication	or	maternal	thyroid	disease	 vol	57,	no	3	/	March	2008	 187www.jfponline.comreflecting normal postnatal physiology.3 Age-specific reference ranges are neces-sary for interpretation of TSH levels dur-ing the first 5 days of life. The second or third day of life remains the optimal time for screening when appropriate reference ranges are used.Recommendations from othersThe United States Preventive Services Task Force (USPSTF),7 the American Academy of Family Physicians,8 the American Academy of Pediatrics,9 and the American Thyroid Association (ATA)10 all recommend routine screen-ing of asymptomatic newborns for con-genital hypothyroidism. The USPSTF recommends that clinicians evaluate ab-normal thyroid screening results with a supplemental lab test, using TSH as the primary test and T4 as the supplemental test.7 Additionally, the ATA endorses a second thyroid screening at 7 to 14 days of life to increase specificity of congenital hypothyroidism screening.10  nreferences	 1.	 	Kempers	MJ,	lanting	cI,	van	heijst	aF,	et	al.	neona-tal	screening	for	congenital	hypothyroidism	based	on	 thyroxine,	 thyrotropin,	 and	 thyroxine-bind-ing	globulin	measurement:	 potentials	 and	pitfalls. J Clin Endocrinol Metab	2006;	91:3370–3376.		 2.	 	simpson	J,	Williams	Fl,	Delahunty	c,	et	al;	scottish	Preterm	Thyroid	Group.	 serum	 thyroid	 hormones	in	 preterm	 infants	 and	 relationships	 to	 indices	 of	severity	 of	 intercurrent	 illness.	 J Clin Endocrinol Metab	2005;	90:1271–1279.		 3.	 	Mcelduff	a,	Mcelduff	P,	Wiley	v,	Wilcken	b.	neo-natal	 thyrotropin	 as	 measured	 in	 a	 congenital	hypothyroidism	 screening	 program:	 influence	 of	mode	 of	 delivery.	 J Clin Endocrinol Metab	 2005;	90:6361–6363.		 4.	 	Khashu	M,	chessex	P,	chanoine	JP.	 Iodine	over-load	 and	 severe	 hypothyroidism	 in	 a	 premature	neonate. J Pediatr Surg 2005;	40(2):e1–e4.		 5.	 	smith	vc,	svoren	bM,	Wolfsdorf	JI.	hypothyroid-ism	 in	 a	 breast-fed	 preterm	 infant	 resulting	 from	maternal	 topical	 iodine	exposure.	J Pediatr 2006;	149:566–567.		 6.	 	World	health	organization.	eliminating	 iodine	de-ficiency	 worldwide	 is	 within	 reach.	 available	 at:	www.who.int/mediacentre/news/releases/2004/pr93/en/.	accessed	February	4,	2008.	 7.	 	us	Preventive	services	Task	Force.	screening	for	congenital	hypothyroidism.	available	at:	www.ahrq.gov/clinic/uspstf/uspscghy.htm.	 accessed	 Febru-ary	5,	2008.	 8.	 	american	 academy	 of	 Family	 Physicians.	 rec-ommendations	 for	 clinical	 Preventative	 services	[Web	 page].	 leawood,	 Ks:	 american	 academy	of	 Family	 Physicians;	 2007.	 available	 at:	 www.aafp.org/online/en/home/clinical/exam/p-t.html.	accessed	February	5,	2008.		 9.	 	american	academy	of	Pediatrics	aaP	section	on	endocrinology	 and	 committee	 on	 Genetics,	 and	american	Thyroid	association	committee	on	Pub-lic	health.	newborn	screening	for	congenital	hypo-thyroidism:	 recommended	 guidelines.	 Pediatrics	1993;	91:1203–1209.		10.	 	Maniatis	aK,	Taylor	l,	letson	GW,	bloch	ca,	Kappy	Ms,	Zeitler	P.	congenital	 hypothyroidism	and	 the	second	newborn	metabolic	screening	in	colorado,	usa.	J Pediatr Endocrinol Metab	2006;	19:31–38.	Elevated TSH in newborns

What are the causes of elevated TSH in a newborn?

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