Improved diagnosis of mild hypothyroidism using time-of-day normal ranges for thyrotropin

To assess clinical utility of time-of-day-based thyrotropin (TSH) ranges.

Ranges for TSH at 8 am, 4 pm, and am/pm TSH ratio were developed from prior data in 94 typical children (age, 5 to 18 years). Data for these values in 227 short children (1.5 to 18 years) were compared with those in typical children.

Short children included idiopathic short stature (ISS, n=153), central hypothyroidism (Central, n=42), and mild primary hypothyroidism (Primary, n=32), referred for evaluation of growth. In typical children, ISS, and Primary, 8 am TSH was greater than 4 pm TSH (P<.05). In Primary, 8 am TSH was greater than normal. Only 4 with Primary had elevated 4 pm TSH (using usual laboratory range of 0.5 to 4 mU/L). In contrast, only 63% of 4 pm TSHs in Primary were elevated. compared with 95% confidence limits in typical children. In Central, 8 am TSH and 4 pm TSH were within normal time-of-day range, and FT4 was in lowest one-third of normal. am/pm TSH ratio was less than 95% confidence limits in 76% of those with Central.

Either 8 am TSH or 4 pm TSH (compared with time-of-day normal range) can identify TSH elevation. Low am/pm TSH ratio (FT4 in lowest one-third of normal) confirms central hypothyroidism. Thus, time-of-day TSH ranges should be used for accurate diagnosis and more appropriate cost-effective treatment of mild hypothyroidism.