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

Cattedra di Endocrinologia e Medicina Costituzionak, University of Pisa Pisa, Italy
Cattedra di Endocrinologia, University of Cagliari Cagliari, Italy

Aldo Pinchera, Cattedra di Endocrinologia e Medicina Costituzionale, University of Pisa, Viale del Tirreno, 64, 56018 Tirrenia (Pisa), Italy.

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.

^* This study was supported in part by Grant 86.00532.44 from the National Research Council (C.N.R.), Rome, Italy (Progetto Finalizzato Oncologia, Sottoprogetto 10).

Received June 18, 1986.

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