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Endocrine Research: W. Russell, R. F. Harrison, N. Smith, K. Darzy, S. Shalet, A. P. Weetman, and R. J. Ross Free Triiodothyronine Has a Distinct Circadian Rhythm That Is Delayed but Parallels Thyrotropin Levels J Clin Endocrinol Metab 2008; 93: 2300-2306 [Abstract] [Full text] [PDF]

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Major effects of sleep and nutrition on free triiodothyronine nycthemeral rhythm

Bernard Goichot   (5 August 2008)

Major effects of sleep and nutrition on free triiodothyronine nycthemeral rhythm 5 August 2008
Bernard Goichot Endocrinology and Internal Medicine, Hopitaux Universitaires de Strasbourg, France Send letter to journal: Re: Major effects of sleep and nutrition on free triiodothyronine nycthemeral rhythm bernard.goichot{at}chru-strasbourg.fr Bernard Goichot	We would like to raise several points concerning the paper from Russell et al. (1) on free triiodothyronine (FT3) circadian rhythm. First, the observation of a temporal relationship between two nycthemeral rhythms is not sufficient to prove a physiological link between them. For instance, the rhythms may be independent from each other, but synchronized by the same environmental factors (as light, sleep, etc....) (2). Second, the TSH rhythm described by Russell et al. with an increase in the evening, a maximum near 0300AM, and a progressive decrease until morning is typical of sleep deprivation. They do not mention if sleep was controlled in their subjects. This is important because we demonstrated more than 15 years ago that sleep exerts an powerful inhibitory effect on the circadian endogenous TSH rhythm, an inhibitory effect directly linked to slow-wave sleep (3). In subjects falling asleep, TSH peaks at sleep onset and immediately decreases. The increase of FT3 during the second part of the night observed in Russell’s study has been described in sleep shift experiments in our laboratory and maybe due to the increase of TSH levels (that is, by the absence of normal decrease associated with sleep onset) or to other non specific effects associated with sleep deprivation in particularly sympathetic activation (4). We failed to demonstrate, using rapid blood sampling techniques in normal subjects under enteral continuous nutrition, any FT3 nycthemeral rhythm in normal night sleep conditions (5). Apart from sleep deprivation, the discrepancy with the study from Russell et al. may have two other origins. First, in our study, subjects remained in a supine position which was not the case in Russell’s study. A nycthemeral rhythm of total T3 had been described in old studies and had been retrospectively attributed to postural changes (6). To our knowledge, no study has directly addressed the influence of posture on free thyroid hormone levels but clearly, this parameter needs to be controlled in chronobiological studies. The second hypothesis is the effect of meals. As underlined by Russell et al., the main source of plasma FT3 is the peripheral conversion of T4 by type I deiodinase, a key enzyme of thyroid hormone metabolism which is strongly regulated by nutritional factors. The absence of FT3 nycthemeral rhythm under continuous enteral nutrition suggests a major role of dietary signals in the variations observed in Russell’s study. In our opinion, no definitive conclusions can be drawn from their study, which reminds us that all endogenous or exogenous factors that may influence nychtemeral rhythms have to be carefully controlled in chronobiological studies. References 1. Russell W, Harrison RF, Smith N, Darzy K, Shalet S, Weetman AP, Ross RJ. 2008. Free Triiodothyronine Has a Distinct Circadian Rhythm That Is Delayed but Parallels Thyrotropin Levels. J Clin Endocrinol Metab 93:2300-2306 2. Van Cauter E, Turek F 1995 Endocrine and other biological rhythms. In: DeGroot LJ ed. Endocrinology. Philadelphia: WB Saunders; 2487-2548 3. Goichot B, Brandenberger G, Saini J, Wittersheim G, Follenius M 1992 Nocturnal plasma thyrotropin variations are related to slow-wave sleep. J Sleep Res 1:186-90 4. Goichot B, Weibel L, Chapotot F, Gronfier C, Piquard F, Brandenberger G. 1998 Effect of the shift of the sleep-wake cycle on three robust endocrine markers of the circadian clock. Am J Physiol 275:E243-E248 5. Goichot B, Brandenberger F, Saini J, Wittersheim G, Follenius M 1994 Nycthemeral patterns of thyroid hormones and their relationships with thyrotropin variations and sleep structure. J Endocrinol Invest 17:181-187 6. Lucke G, Hehrmann R, von Meyersbach K, von zur Mühlen A 1977 Studies on circadian variations of plasma TSH, thyroxine and triiodothyronine in man. Acta Endocrinol (Copenh) 86:81-88