Pulsatile TSH Secretion during 48-Hour Continuous TRH Infusions

Abstract

Thyroid-stimulating hormone (TSH), like other anterior pituitary hormones, is normally secreted in a series of pulses over 24 h. However, the factors that control TSH pulse generation are unknown. We investigated the potential role of thyrotropin-releasing hormone (TRH) in TSH pulse generation by measuring TSH pulses during constant TRH infusions. Two groups of subjects were studied: five healthy subjects and five subjects with treated primary hypothyroidism and normal TSH levels. Each subject underwent four separate studies: (1) TSH levels were measured every 15 min over 24 h (baseline study). (2) TSH levels were measured every 15 min over 48 h during TRH infusions at 0.1 microgram/min (low dose TRH study). (3) TSH levels were measured every 15 min over 48 h during TRH infusion at 0.5 microgram/min (medium dose TRH study). (4) TSH levels were measured every 15 min over 48 h during TRH infusions at 1.0 microgram/min (high dose TRH study). TSH pulses were located by cluster analysis. We found that constant TRH infusions at any of the doses utilized did not alter TSH pulse frequency in normal or treated hypothyroid subjects, although pulse amplitude increased. Normal subjects had lower TSH pulse amplitude than treated hypothyroid subjects at all TRH doses, perhaps due to slightly higher serum T3 levels. This suggests that, at least acutely, pulsatile input of TRH to the pituitary gland does not determine pulsatile TSH release. However, TRH may modulate TSH pulse amplitude.