This study was designed to address the question of whether decreased hypothalamic TRH secretion was responsible for the transient decline in serum TSH levels characteristic of the early phase of fasting in man. Changes in serum TSH, total T₄ (TT₄), free T₄ (FT₄), and total T₃(TT₃)/TT₄ and total rT₃(TrT₃)/TT₄ ratiovalues together with plasma TRH levels were evaluated before, during, and after a constant 48-h infusion of either TRH (75 ng/min), or saline, initiated at 10 h into a 6 dayfast, in groups of six ambulating, mildly obese female subjects. On the first day of the fast, no change in serum TSH levels was seen with saline infusion relative to control, whereas mean TSH levels rose 2½-fold with TRH infusion. On the second day of the fast, serum TSH levels simultaneously declined in both the saline- (43%, P <0.005) and TRH- (52%, P <0.005)-infused groups relative to the previousday. On the third day of the fast, after stopping the infusions, mean serum TSH levels fell below control in both the saline- and TRH-treated groups, but subsequently returned to prefasting levels. A distinct circadian pattern of TSH release was present throughout the study. Plasma TRH values were unaffected by fasting in the saline-infused group, but rose 2½-fold in the TRH-infused group.

The sequence of changes in the serum thyroid hormone indices were similar for the two groups: a rapid rise in FT₄ was followed by a gradual fall in TT₃/TT₄ ratios during the first 24 h of fast, which was followed by a rise in TrT₃/TT₄ ratios after 48 h of fast. This study in fasting, mildly obese females suggests that: 1) The transient suppression of serum TSH during early fasting is not TRH mediated 2) Fasting does not alter plasma TRH levels. 3) A temporal sequence of changes in serum thyroid hormone indices occurs in fasting, this being an initial rise in FT₄ (10 h) followed by a fall in both serum TT₃/TT₄ (12–14 h) and TSH (30–36 h) and finally by a rise in TrT₃/TT₄ levels (48 h).

This sequence of events suggests that the initial inhibition of serum TSH levels in early fasting results from the acute elevation in FT₄ levels, and that the reestablishment of normal serum TSH levels with continued fasting is associated with declining serum TT₃ levels. (J Clin Endocrinol Metab56: 883, 1983)