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Is the Thyrotropin-Releasing Hormone Test Necessary in the Diagnosis of Central Hypothyroidism in Children

London Center of Pediatric Endocrinology and Metabolism and Institute of Child Health, London, United Kingdom WC1N 1EH

Address all correspondence and requests for reprints to: Dr. Mehul Dattani, Pediatric Endocrinology, Institute of Child Health and Great Ormond Street Children’s Hospital, 30 Guilford Street, London, United Kingdom WC1N 1EH. E-mail: mdattani{at}ich.ucl.ac.uk.

To determine the value of the TRH test, we analyzed the unstimulated serum T₄ and TSH concentrations in 54 children with central hypothyroidism. A TRH test was performed in 30 patients. Midline brain defects (septo-optic dysplasia, 28; holoprosencephaly, 2) and combined pituitary hormone deficiencies were present in 30 and 52 patients, respectively. The mean serum free T₄, total T₄, and basal TSH concentrations were 0.6 ng/dl, 4.0 µg/dl, and 2.8 µU/ml, respectively. Five patients demonstrated elevated basal serum TSH concentrations. A normal TRH test [increase () in TSH, 4.5–17.8], based on data from 30 controls, was documented in 23.3% of patients. Brisk (TSH, >17.8), absent/blunted (TSH, <4.5), and delayed responses were documented in 16.7%, 30%, and 30% of patients, respectively. The mean age at diagnosis was 2.8 yr, with 8 patients evolving into TSH deficiency. It was not possible to differentiate patients as having pituitary or hypothalamic disease based solely on the TRH test results. Patients with septo-optic dysplasia were diagnosed earlier and had elevated basal serum TSH and PRL concentrations, diabetes insipidus, and evolving disease. Although full pituitary function assessment is mandatory to identify combined pituitary hormone deficiencies, a TRH test is not essential, and the diagnosis should be made by serial T₄ measurements.

This work was supported by Medical Research Council Career Establishment Grants (to M.T.D. and A.M.) and a grant from Novo Nordisk, United Kingdom (to A.M.).

Abbreviations: CH, Central hypothyroidism; CPHD, combined pituitary hormone deficiencies; FT₄, free T₄; GN, gonadotropin; H-P, hypothalamo-pituitary; HPE, holoprosencephaly; M/F, male/female ratio; MRI, magnetic resonance imaging; TSH, increase in TSH; SOD, septo-optic dysplasia; TT₄, total T₄.

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