Isolated central hypothyroidism in short stature.

Mild hypothyroidism can be difficult to diagnose, particularly when it is caused by deficiency of TSH or TSH-releasing hormone (TRH). Such central hypothyroidism occurs most often in association with growth hormone deficiency (GHD). Isolated central hypothyroidism has been considered rare. The TSH surge test is the most sensitive test currently available for confirming the diagnosis. Results are abnormal in many cases where response to TRH is normal. Short children referred between 1986 and 1994 for evaluation (n = 235, 74 girls; height 2 or more SD below mean for age; no history of radiation therapy) were selected for study. TSH samples were obtained hourly for study of TSH surge (1400-1800 h and 2200-0400 h). Growth hormone (GH) samples were obtained every 20 min (2000-0800 h). GH stimulation tests included arginine, insulin, and L-dopa. Thirty-nine children were found to have GHD (peak GH < or = 7 micrograms/L) and 15 had mild primary hypothyroidism (TSH 5-15 mU/L). Of the remaining 181 children with apparent idiopathic short stature (ISS), 30 had a blunted TSH surge. All 30 had free thyroxine (FT4) in the lowest third of the normal range, consistent with values seen in documented central hypothyroidism. They were 13% of the total group, 16% of the ISS children, and 32% of the ISS children with FT4 in the lowest third of normal. (In comparison, diagnosis of GHD was made in 16% of the total group.) In conclusion, use of a direct FT4 assay to screen short children for possible subtle hypothyroidism (along with other appropriate testing) identifies a subgroup with a one in three possibility of an easily treated cause--isolated central hypothyroidism.