Role of corticotropin-releasing hormone testing in assessment of hypothalamic-pituitary-adrenal axis function in infants with congenital central hypothyroidism.
BACKGROUND
The Dutch neonatal congenital hypothyroidism (CH) screening program detects infants with CH of central origin (CH-C). These infants have a high likelihood of multiple pituitary hormone deficiencies. ACTH deficiency especially poses an additional risk for brain damage and may be fatal.


OBJECTIVE
Our objective was to evaluate different tools for assessment of the integrity of the hypothalamus-pituitary-adrenocortex (HPA) axis in young infants, aiming for a strategy for reliable and timely diagnosis.


METHODS
This is a Dutch nationwide prospective study (enrollment 1994-1996). Patients were included if neonatal CH screening results were indicative of CH-C and HPA axis function could be tested within 6 months of birth.


METHODS
Nine male and three female infants with CH-C and four infants with false-positive screening results or transient hypothyroidism were included in the study.


METHODS
CRH test results, multiple cortisol plasma concentrations, and cortisol excretion in 24-h urine were measured.


RESULTS
Six (50%) of the CH-C patients had abnormal CRH test results. Three of them had discordant test results: impaired increase of plasma cortisol in response to CRH, despite substantial increase of plasma ACTH. The other three infants, with concordant impaired responses of both ACTH and cortisol to CRH, had a very low urinary cortisol excretion in comparison with the subjects with normal CRH test results.


CONCLUSIONS
The CRH test proves to be a fast and reliable tool in the assessment of HPA axis (dys)function. It enables timely diagnosis in (asymptomatic) neonates at risk for serious morbidity and mortality. The discordant response type, which has not been described before, may be an early phase of HPA axis dysfunction. Alternatively, patients with this response type may constitute a separate pathogenetic subset of HPA axis-deficient patients.
van Tijn
David A
DA
Department of Pediatric Endocrinology, Academic Medical Center, University of Amsterdam, 1100 DE Amsterdam, The Netherlands. tijn1@planet.nl
de Vijlder
Jan J M
JJ
Vulsma
Thomas
T
D000324:Adrenocorticotropic Hormone / Q000032:analysis / Q000097:blood; D000465:Algorithms; D001921:Brain / Q000000981:diagnostic imaging; D003409:Congenital Hypothyroidism / Q000097:blood / Q000000981:diagnostic imaging / Q000503:physiopathology*; D003346:Corticotropin-Releasing Hormone / Q000032:analysis* / Q000097:blood; D003663:Decision Trees; D003940:Diagnostic Techniques, Endocrine; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000032:analysis / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology*; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D015997:Neonatal Screening / Q000379:methods; D010913:Pituitary-Adrenal System / Q000503:physiopathology*; D011859:Radiography; D012680:Sensitivity and Specificity; D013997:Time Factors
D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D006854:Hydrocortisone