Spectrum of Pituitary Alteration with Mild and Severe Thyroid Impairment* †

Fifty women with known thyroid disease and elevated basal serum TSH concentrations were classified according to reductions in serum T4 concentrations and compared with a control group of healthy women without thyroid or pituitary disease. Control subjects had normal T4 (mean = 7.1 μg/dl) and normal TSH (mean = 1.3 μU/ml). Groups I and II had normal T4 (mean = 7.0 and 4.9 μg/dl, respectively) and elevated basal TSH (mean = 5.3 and 13.3 μU/ml). Groups III and IV had subnormal T4 (mean = 2.8 and 0.9 μg/dl, respectively) and more elevated TSH (mean = 63 and 149 μU/ml). Basal serum T3 was not significantly different from control subjects (115 ng/dl) in Group I (119 ng/dl), Group II (103 ng/dl), or Group III (101 ng/dl), but was low (43 ng/dl) in Group IV. After TRH stimulation, all study groups had peak TSH responses (Group I = 39, Group II = 92, Group III = 196, Group IV = 343 μU/ml) which were significantly greater than control values (mean = 11 μU/ml) and proportional to their basal levels. The basal and peak TSH concentrations correlated better with serum T4 than T3 concentrations. The mean TRH stimulated absolute change in TSH, TSH–β, and common α subunit was significantly greater than control in all study groups. Furthermore, TRH mediated absolute changes in TSH, TSH–β, and α were more sensitive indicators of impaired thyroid function than the thyroidal response either to exogenous bovine TSH or to endogenous TRH stimulated TSH. The change in T3 after either exogenous bovine TSH or endogenous TSH could not reliably distinguish Group I from control subjects. Other pituitary functions including prolactin secretion and the GH or cortisol responses to hypoglycemia became significantly abnormal only in the more severe forms of hypothyroidism (Groups III or IV) and correlated better with reduced serum T3 than T4. Sella volume enlargement was found in a significant number of patients with impaired thyroid function. There was a statistically significant inverse correlation between either T4 or T3 and sella volume. These data provide evidence for the concept that thyrotroph cell function is augmented even in mild thyroid impairment, and further distortions of pituitary function and structure became apparent in severe primary hypothyroidism.