Screening for congenital hypothyroidism: the significance of threshold limit in false-negative results.
BACKGROUND
In our neonatal program, a number of infants with congenital hypothyroidism (CH) had escaped diagnosis, when a spot RIA-TSH value of 20 mU/liter whole blood was used as a cutoff point.


OBJECTIVE
The objective of the study was to find out prospectively the additional number of newborns with CH if the TSH cutoff point is lowered to 10 mU/liter.


METHODS
The study included 311,390 screened newborns. The children with CH were followed up for a period of 3 yr.


RESULTS
Twenty-eight percent of infants diagnosed with CH had neonatal TSH values between 10 and 20 mU/liter (56 of 200). Forty of 47 infants, who were reevaluated later on (85.1%), suffered permanent CH. A thyroid scintiscan and/or echogram revealed that eight of 40 children (20.0%) had a structural defect, and the remaining (32 of 40) had a functional defect of the thyroid gland without anatomical abnormality; 14 of 32 cases were familial. Eighteen of the 47 reevaluated infants were prematurely born (38.3%) and 15 of these 18 had permanent CH (83.3%). The lowering of TSH cutoff point from 20 to 10 mU/liter resulted in a 10-fold increase of recall rate.


CONCLUSIONS
A significant number of cases with permanent CH are missed when a TSH threshold of 20 mU/liter is applied. Almost 40% of the missed CH cases were premature. A mild increase of TSH at screening is not a predictor of transient CH. The increase in recall rate constitutes a serious drawback and should be balanced against the possible consequences of thyroid dysfunction at this important developmental stage.
Mengreli
Chryssanthi
C
Department of Biochemical Laboratories, Institute of Child Health, Aghia Sophia Children's Hospital, 11527-Goudi, Athens, Greece. chmengreli@ich.gr
Kanaka-Gantenbein
Christina
C
Girginoudis
Panagiotis
P
Magiakou
Maria-Alexandra
MA
Christakopoulou
Ioulia
I
Giannoulia-Karantana
Aglaia
A
Chrousos
George P
GP
Dacou-Voutetakis
Catherine
C
D002648:Child; D002675:Child, Preschool; D003409:Congenital Hypothyroidism / Q000175:diagnosis*; D003940:Diagnostic Techniques, Endocrine / Q000592:standards*; D005188:False Negative Reactions; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007234:Infant, Premature / Q000097:blood; D057230:Limit of Detection; D015997:Neonatal Screening / Q000379:methods; D012016:Reference Values; D013972:Thyrotropin / Q000032:analysis / Q000097:blood / Q000592:standards
D013972:Thyrotropin