Alterations in circadian rhythm of serum thyrotropin in critically ill patients

To evaluate the 24-h pattern of serum thyrotropin (TSH) in critically ill patients, we measured serum concentrations of TSH in blood samples collected every 2 h for 24 h from nine patients (six with malignancy, two with liver cirrhosis, one with chronic renal failure), who had subnormal levels of both triiodothyronine (T3) and thyroxine (T4), in the absence of history, symptoms or signs of thyroid disease. Analysis of the data, performed using a second-order inferential statistical methodology for rhythmometry (cosinor method), demonstrated that critically ill patients still had daily oscillations of serum TSH which significantly adapted to the function approximating the circadian rhythms (R2 = 74.3%). However, the mean level (mesor) in the rhythm of the patients was found to be significantly lower than that of healthy subjects (0.96 vs 2.18 mU/l); the amplitude of rhythmical daily variations also was lower in patients than in healthy subjects (0.23 vs 0.56 mU/l), even though the amplitude/mesor ratio was similar (23% vs 26%). Lastly, the highest level in the TSH rhythm of the patients was found to be in the late afternoon, in contrast to healthy subjects, who had a TSH surge after midnight. Although these alterations are consistent with the existence of a dysregulation at suprahypophyseal level in critically ill patients, it remains to be established whether the state of low T3 and T4 may be ascribed to anomalous circadian rhythm of TSH.