NORMAL THYROXINE AND ELEVATED THYROTROPIN CONCENTRATIONS - EVOLVING HYPOTHYROIDISM OR PERSISTENT EUTHYROIDISM WITH RESET THYROSTAT

Background: The natural course in subjects manifesting normal serum th yroxine (T-4), and triiodothyronine (T-3), with an elevated thyrotropi n (TSH) level demonstrated two distinct outcomes, one progressing to w ell defined hypothyroidism as expressed by onset of subnormal T-4, T-3 and a further rise in TSH and the other remaining in the same state. However, thyroid hormone concentrations at the time of diagnosis fail to distinguish between the two groups. Therefore, we examined the infl uence of alteration in circulating TSH levels on thyroid gland functio n at the time of diagnosis in subjects with this syndrome to assess th e role of pituitary thyroid axis in these different outcomes. Methods: 24 hour I-131 thyroidal uptake was determined in 14 men and 3 women m anifesting normal T-4, T-3 and elevated TSH prior to and again after 1 ) subcutaneous administration of bovine TSH, 10 units daily for 3 days and 2) daily oral administration of L-triiodothyronine 75 mu g for 7 days in a randomized sequence at interval of 4 weeks. Subjects were th en followed for up to 16 years to assess the natural course. Results: Basal 24 hour I-131 uptake values were with in the normal range (10-35 %) in all subjects and increased on TSH administration and declined fo llowing LT, administration. However, in eight subjects, these response s were markedly fewer (< 20%) when compared with the minimum change (5 0%) noted in normal volunteers. These subjects progressed to manifest hypothyroidism requiring LT4 therapy within two years as reflected by a progressive decrease to subnormal T-4 levels with a further rise in serum TSH. The remaining nine subjects, demonstrated normal responses (> 50%) and only one of these became hypothyroid during the follow-up period of 16 years. Conclusion: All subjects with normal T-4 and T-4 w ith elevated TSH do not manifest ''subclinical or evolving hypothyroid ism''. Two distinct populations seem to exist, one with inhibited pitu itary thyroid axis progressing to hypothyroidism or true ''subclinical hypothyroidism'' at the time of diagnosis and the other with normal p ituitary thyroid axis, a state of euthyroidism with ''reset thyrostat' ' at a higher TSH concentration, a state probably persisting for their remaining life span. (C) 1997, Editrice Kurtis.