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With a highly sensitive time-resolved fluorometric immunoassay (TR-FIA), serum thyrotropin (TSH) levels were determined in various conditions in healthy subjects. In addition, we compared the thyroid function in 10 depressed female patients with that in 27 female controls. 1) We evaluated a highly sensitive time-resolved fluorometric immunoassay kit for serum TSH. The lower limit of detection of TSH in serum was 0.008 less than U/ml. The intraassay and interassay variances were 3.0 greater than 3.6% and 3.4 greater than 5.1%, respectively. There was a significant correlation between basal TSH levels and maximum TSH values after TRH administration (r = 0.797, p less than 0.01). 2) The mean TSH levels in 31 healthy controls of both sexes was 1.26 +/- 0.96 less than U/ml, but TSH levels in women were significantly higher than in men (p less than 0.01). A large intra-individual variation of serum TSH levels determined on different days was found equally in both men and women. The nyctohemeral elevation of TSH levels was not clearly seen prior to the onset of normal sleep, but the nocturnal rise of TSH levels was remarkably accentuated by sleep deprivation. 3) The serum TSH levels in depressed female patients were significantly lower than those in healthy female controls when the post-menopausal subjects were excluded. For the serum thyroid hormone concentrations, serum T4 levels were normal. Serum free T3 levels tended to be lower, although the reduction was not significant. The serum levels of these 3 thyroid hormones were not related to serum TSH values. The present study demonstrated a large variation of TSH levels in various conditions, even in the same individuals, indicating the necessity of strictly controlled conditions in the study of TSH secretion. A significant reduction in TSH levels was observed in the depressed female patients when the post-menopausal subjects were excluded. Our results suggest that the dysfunction of the regulating mechanism of the pituitary-thyroid axis in depression may occur at a pituitary or a suprapituitary level.

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Studies on the Factors Affecting Serum Thyrotropin Levels in Healthy Controls and on the Thyroid Function in Depressed Patients Using a Highly Sensitive Immunoassay