Mass screening of newborns for congenital hypothyroidism of central origin by free thyroxine measurement of blood samples on filter paper.

OBJECTIVE To evaluate the effectiveness of mass screening of newborns for congenital hypothyroidism of central origin (CH-C) by measurement of free thyroxine (FT(4)) and thyroid-stimulating hormone (TSH). DESIGN Questionnaire-based survey of CH-C patients born between 1999 and 2008 in Kanagawa prefecture, Japan. METHODS TSH and FT(4) levels in dried blood spots on filter paper were measured using ELISA kits, and CH-C was diagnosed at FT(4) levels below a cutoff of 0.7 ng/dl (9.0  pmol/l). Survey results were collated with the database created by the screening organizer. RESULTS Twenty-four CH-C patients (18 males) were identified, 14 of whom had multiple pituitary hormone deficiencies (group M), eight had isolated CH-C (group I), and two had undetermined pituitary involvement (group U). In groups M, I, and U, the number of patients with FT(4) levels below the cutoff value at screening was five (36%), seven (88%), and one (50%) respectively; other patients had been diagnosed clinically. Thus, 13 patients were true positives, while nine were false negatives, yielding screening sensitivity of 59.1% and positive predictive value of 11.5%. The calculated sensitivity was 81.8% at a higher cutoff value of 0.9  ng/dl (11.6  pmol/l). The overall incidence of CH-C was estimated at 1 in 30, 833 live births, while that of CH of thyroidal origin (CH-T) is 1 in 3472 live births in Kanagawa prefecture (CH-T/CH-C, 8.9). CONCLUSIONS Newborn screening with combined FT(4) and TSH measurements can identify a significant number of CH-C patients before manifestation of clinical symptoms, but a more appropriate FT(4) cutoff value should be considered.