Effects of long-term treatment with thyroxine on pituitary TSH secretion and heart action in patients with hypothyroidism

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Abstract
The effects of thyroxine (T4) treatment on pituitary thyrotroph cells and on the heart were studied in 68 female patients with hypothyroidism. During the initial 12 months of T4 treatment, relatively small doses of T4 (1.3 μg/kg) normalized serum T4, triiodothyronine (T3), TSH and lipid concentrations in mild hypothyroidism, while moderate doses of T4 (1.7–2.0 μg/kg) normalized serum T4, T3 and lipid concentrations but not serum TSH levels or the volume of sella turcica in moderate and severe hypothyroidism; however, serum TSH levels and the volume of sella turcica returned to normal with continuation of these doses of T4. Systolic time intervals (ET/PEP) can discriminate between euthyroid and hyperthyroid states and agree well with serum TSH levels. However, ET/PEP was unequivocally elevated in about 40% of treated hypothyroid patients with normal serum T3, T4 and TSH levels which had been maintained over 48–54 months. Since the reciprocal relationship between free T4 and TSH levels was maintained in all treated patients, elevated ET/PEP with normal TSH levels indicates that the heart is more sensitive to thyroid hormones than the pituitary thyrotroph in 40% of treated hypothyroid patients. During T4 treatment in patients with hypothyroidism, ET/PEP should be followed and T4 doses adjusted to maintain normal ET/PEP rather than normal serum TSH levels, especially in older patients in whom T4 may aggravate angina pectoris or provoke myocardial infarction.