Pulsatile and nocturnal TSH secretion was investigated in 16 healthy controls (group A) and 21 patients with nonthyroidal illness (NTI; group B). Ten patients had normal plasma T3 and T4 values (group B1), and 11 patients had decreased plasma T3 with normal or low plasma T4 (group B2). Mean 24-h TSH secretion in NTI patients was higher than that in controls (3.1 +/- 0.7 vs. 1.7 +/- 0.7 mU/L; P < 0.01; mean +/- SD). This was associated with an increased TSH pulse amplitude in NTI patients relative to controls [Desade, 0.79 +/- 0.46 vs. 0.44 +/- 0.20 mU/L (P < 0.01); Cluster, 0.64 +/- 0.42 vs. 0.39 +/- 0.20 mU/L (P < 0.05)]. There was no difference in TSH pulse amplitude between subgroups B1 and B2. TSH pulse frequency was not different between NTI patients and controls (approximately 10 pulses/24 h). The mean 24-h TSH concentration was significantly related to the mean 24-h TSH pulse amplitude but not to the mean 24-h TSH pulse frequency. The absolute nocturnal TSH surge in NTI patients was lower than that in controls (0.6 +/- 0.6 vs. 1.0 +/- 0.6 mU/L; P < 0.05). The lower nocturnal TSH surge in patients with decreased plasma T3 (group B2) was associated with a loss of the usual nocturnal increase of TSH pulse amplitude; the usual nocturnal increase in TSH pulse frequency was preserved. This was also observed in the six patients (two in group B1 and four in group B2) in whom the nocturnal TSH surge was completely absent. The changes in nocturnal TSH secretion in NTI resemble those found in central hypothyroidism, suggesting that features of central hypothyroidism are involved in the euthyroid sick syndrome.