Factors Affecting Suppression of Endogenous Thyrotropin Secretion by Thyroxine Treatment: Retrospective Analysis in Athyreotic and Goitrous Patients*

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Abstract
Factors affecting TSH suppression by l-T4 administration were retrospectively evaluated in 452 patients: 180 who were athyreotic after total thyroidectomy and remnant radioiodine ablation for differentiated thyroid carcinoma and 272 with nontoxic diffuse or nodular goiter. All patients were considered clinically euthyroid. TSH secretion was assessed by vi TRH stimulation testing. The T4 dose associated with an undetectable basal serum TSH level and no increase in serum TSH after TRH administration (suppressive dose) averaged 2.7 ± 0.4 (sd) μg/kg body weight (BW)/day in athyreotic patients and 2.1 ± 0.3 μg/kg BW/day in goitrous patients (P < 0.001). The 25th–75th percentile intervals were 2.5–2.9 μg/kg BW/day for athyreotic patients and 1.9–2.3 μg/kg BW/day for goitrous patients. The suppressive dose of T4 was dependent in both groups on patient age, younger patients needing higher doses than older patients. The duration of treatment also proved to be an important parameter, since in both groups the percentage of patients with suppressed TSH secretion increased if TRH testing was carried out after at least 6 months after the initiation of therapy. Serum total T4, total T3, free T3 (FT3), free T4 (FT4) index, and FT3 index values did not differ in the two groups and were significantly higher (P < 0.001) than in normal subjects. Mean serum FT4 was significantly higher in athyreotic patients than in goitrous patients with suppressed TSH secretion. Among athyreotic patients with suppressed TSH secretion, 24% had elevated serum FT4 and FT3, and 47% had elevated serum FT4 alone. Of goitrous patients with suppressed TSH secretion, 20% had elevated serum FT4 and FT3, and 27% had elevated serum FT4 alone. On the other hand, 35% of athyreotic patients and 14% of goitrous patients whose TSH secretion was not suppressed had elevated serum FT4. Serum sex hormone-binding globulin concentrations were measured in 3 groups of goitrous women. Values above normal limits were found in 13/26 patients (50%) with high serum FT4 and FT3, in 4/30 patients (13%) with elevated serum FT4 alone, and in 1/25 patients (4%) with normal FT4 and FT3. In conclusion: 1) TSH suppression requires daily doses of T4 between 2.5 and 2.9 μg/kg BW in athyreotic patients and between 1.9 and 2.3 μg/kg BW in goitrous patients, with appropriate adjustments in relation to the age of the patient; 2) Assessment of the adequacy of treatment should not be carried out before 6 months after the institution of therapy.

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