Context. A shortage of thyroid hormone during prenatal life and the first years after birth results in a spectrum of neuropsychological disorders, depending on the duration and severity of the deficiency. In the case of congenital hypothyroidism of central origin (CH-C), the majority of patients have multiple pituitary hormone deficiencies (MPHD). This condition poses an additional threat to postnatal CNS development, primarily on account of neuroglycopenia due to ACTH/cortisol deficiency with or without additional growth hormone deficiency. Therefore, in CH-C, rapid diagnosis is even more urgent than in congenital hypothyroidism of thyroidal origin.

Objective. In the assessment of hypothalamic-pituitary-thyroid function, we consider the pituitary response to intravenous administration of TRH (TRH test) pivotal. We evaluated the usefulness of the TRH test in a cohort of infants with neonatal CH screening results indicative of CH-C, by analyzing the results within the framework of investigations of the anatomical and functional integrity of the hypothalamo-hypophyseal system.

Design and Setting. Dutch nationwide prospective study (1994–1996). Patients were included if neonatal CH-screening results were indicative of CH-C, and patients could be tested within 3 months of birth.

Patients. Ten male and five female infants with CH-C, detected by neonatal screening and six infants with false-positive screening results, NTI or transient hypothyroidism.

Main Outcome Measures. Results of TRH tests, within the framework of extensive endocrinological examinations and cerebral MRI.

Results. All patients with type 3 TSH responses to TRH had MPHD, whereas the majority (67%) of patients with type 2 responses had isolated TSH deficiency.

Conclusions. The TRH test has a pivotal role in the diagnosis of TSH deficiency in young infants. Abnormal TRH test results, especially a type 3 response, urge immediate assessment of integral hypothalamic-pituitary function, as the majority of patients have MPHD.