Deletion of a portion of the long arm of chromosome 18 is associated with poor growth, central nervous system hypomyelination and mental retardation(18q- syndrome). The mechanisms leading to these features are unknown; however, all could be related to inadequate/abnormal thyroid hormone(TH) production.

In order to further characterize the neuroendocrine axis in 18q- children, a TH test battery was performed on 6 children (age range 1-8 years, 4 female, 2 male). T4 and free T4 were normal and none were on TH replacement. Two had normal responses to clonidine and arginine (peak GH >10 ng/ml), and four had low responses (peak <7). Two GH deficient children were on GH treatment.

TRH (7 ug/kg) was administered i.v. push (catheter placed >30 mins prior to time). Blood samples were obtained at 0,15,30,45,60, 90 and 120 mins. Three criteria were used to evaluate the response: 1) magnitude (change between peak and basal), 2) peak time and 3) post-peakdecline (60 min TSH value, expressed as a percentage of the magnitude). Table

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Basal TSH (range 0.7-3.0 mU/L), peak (range 9.9-20.5) and magnitude were normal in all children. One child had a delayed peak time (normal range 15-45 mins.). All 6 children had 60 minutes post-peak declines which were abnormal(60 minute value should be <40% of the magnitude), consistent with hypothalamic dysfunction.

These results suggest that, in children with 18q- syndrome, alterations in TSH response to TRH are common. Nocturnal surge studies have not yet been undertaken. Abnormalities of GH and prolactin production, which appear to be hypothalamic in origin, have also been noted in many 18q- children. The mechanism leading to these abnormalities remains to be elucidated.