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Serum thyroid hormone and TSH concentrations were measured before and after oral TRH (40 mg) administration in 46 women with preclinical hypothyroidism. Preclinical hypothyroidism was defined as serum T4 in the normal range, a normal or elevated basal serum TSH, and an exaggerated serum TSH response to TRH, in the absence of clinical manifestations of hypothyroidism. The results were compared to those in 22 normal women of the same age and body mass index. Overall, the patients had significantly lower mean values for basal T4 [total T4, free T4 index (FT4 index), and free T4] but not for T3; all indices of T4 were lower in those with an elevated basal TSH, but only the FT4 was lower in patients who had normal basal TSH levels and exaggerated TSH responses to TRH. Thyroid reserve, or the increase in serum thyroid hormones after TRH (delta T4, delta FT4, and delta T3) showed an inverse correlation with basal TSH (for delta T4, r = -0.518 and P less than 0.001; for delta FT4, r = -0.442 and P less than 0.05; for delta T3, r = -0.645 and P less than 0.001). Thyroid reserve was lower than normal in those with elevated basal TSH levels, but was normal in those with exaggerated TSH responses to TRH who had normal basal TSH levels. Thus, an elevated basal TSH level, even with basal serum T4 and T3 levels in the normal range, indicates deficient thyroid reserve.

In a prospective study of 60 patients with T3 and/or T4 values within +/- 10% of the upper limit of normal, the suppressibility of thyroid storage values before and after oral administration of 3 mg L-thyroxine was tested and compared with the results of an intravenous TRH test. In 46 patients the results of the two methods agreed (77%): in 31 patients (52%) radioiodine uptake could not be suppressed nor TSH stimulated in the TRH test. Physiological suppression of the storage values in normal TSH stimulation after TRH as a sign of completely euthyroid function was present in 15 (25%). In the remaining 14 patients, 13 had a suppressed TRH test. In all patients radioiodine uptake could be suppressed either normally (above 50%) or partially (20-30%). A normal T4 suppression test in the absence of TSH rise after TRH indicates that biologically active TSH is circulating, even though not demonstrated by radioimmuno-assay. A normal T4 suppression test is an important argument against treating a given case of hyperthyroidism. The T4 suppression test reveals smooth gradation between euthyroid and hyperthyroid states. If the TRH test is normal one can assume a physiological T4 suppression test and no further tests are needed. If the TRH test is negative and there is only slight elevation of the thyroid hormones, the T4 suppression test is indicated before definitive treatment of hyperthyroidism is initiated.

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