Effects of Supraphysiological Doses of Levothyroxine on Sleep in Healthy Subjects: A Prospective Polysomnography Study

Abstract

Disrupted sleep is prevalent in both mood and thyroid disorders. Given the emerging use of thyroid hormones in the treatment of mood disorders, we investigated the effects of supraphysiological doses of levothyroxine (L-T4) on sleep. In an open-label design, 13 healthy subjects received up to 500 μg/day for an eight-week period. A baseline night was polysomnographically recorded (PSG) followed by PSG under the maximum tolerated dose of L-T4. All subjects developed hyperthyroxinemia. The heart rate and respiration rate increased significantly with treatment; a significant increase in body temperature was observed in men but not in women. Surprisingly, treatment with supraphysiological doses of L-T4 did not cause significant effects on sleep architecture. However, the increase in body movements and REM density was close to reaching statistical significance. Here, we report on the sleep data, thyroid hormone levels, and physiological parameters during sleep. We conclude that experimentally induced hyperthyroidism does not profoundly change the sleep structure in healthy individuals underlining the good tolerability of treatment with supraphysiological doses of L-T4 in patients with mood disorders.

Association Between Thyroid Function and Objective and Subjective Sleep Quality in Older Men: The Osteoporotic Fractures in Men (MrOS) Study

“…Limited previous studies showed no difference in sleep quality between hyperthyroid and hypothyroid patients compared with euthyroid subjects (5,6). Our findings regarding subclinical thyroid diseases were consistent with these previous reports.…”

“…There are limited data regarding the associations between thyroid hormone abnormalities and sleep disturbance. Kraemer et al (5) studied the effects of hyperthyroxinemia induced by supraphysiologic dosing of levothyroxine (500 µg/day) in 13 healthy subjects for an 8-week period. Sleep architecture evaluated by polysomnography at baseline did not differ from that evaluated while the subjects were hyperthyroxinemic.…”

Histological and ultrastructural alterations of rat thyroid gland after short-term treatment with high doses of thyroid hormones

“…Data on possible side effects of such therapies in humans are still inconsistent and vary depending on tissue, organ or function examined. Despite the fact that hyperthyroidism is commonly associated with insomnia, high doses of T4 used for treatment of mood disorders did not cause sleep impairment in otherwise healthy patients (Kraemer et al, 2011). Also, it seems that supraphysiological doses of T4 are not necessarily associated with bone mineral density loss even after a very long period of treatment (Ricken et al, 2012; but see also Chen et al, 2004).…”

A comparative cross-sectional study on sleep quality in patients with a history of differentiated thyroid carcinoma and its correlation with quality of life

“…Kramer et al [38] observed that the short-term administration of supra-physiologic dosages of L-T4 in healthy subjects did not change sleep architecture. On the other hand, in a recent Chinese study [39] in which PSQI was administered to a large number of subjects, the proportion of poor sleepers was higher in the sub-clinical hypothyroid subjects than the euthyroid subjects.…”