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The Parathyroid Hormone Circadian Rhythm Is Truly Endogenous—A General Clinical Research Center Study¹

Endocrine-Hypertension Division, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School (G.E.-H.F., E.B.K., E.M.B., C.A.C.); and the Statistics Research Laboratory, Department of Anesthesia, Massachusetts General Hospital, Harvard Medical School (E.N.B., Y.C.), Boston Massachusetts 02115

Address all correspondence and requests for reprints to: Ghada El-Hajj Fuleihan, M.D., Endocrine-Hypertension Division, Brigham and Women’s Hospital, Harvard Medical School, 221 Longwood Avenue, Boston, Massachusetts 02115.

While circulating levels of PTH follow a diurnal pattern, it has been unclear whether these changes are truly endogenous or are dictated by external factors that themselves follow a diurnal pattern, such as sleep-wake cycles, light-dark cycles, meals, or posture.

We evaluated the diurnal rhythm of PTH in 11 normal healthy male volunteers in our Intensive Physiologic Monitoring Unit. The first 36 h spent under baseline conditions were followed by 28–40 h of constant routine conditions (CR; enforced wakefulness in the strict semirecumbent position, with the consumption of hourly snacks). During baseline conditions, PTH levels followed a bimodal diurnal rhythm with an average amplitude of 4.2 pg/mL. A primary peak (t_1max) occurred at 0314 h, and the secondary peak (t_2max) occurred at 1726 h, whereas the primary and secondary nadirs (t_1min and t_2min) took place, on the average, at 1041 and 2103 h, respectively. This rhythm was preserved under CR conditions, albeit with different characteristics, thus confirming its endogenous nature. The serum ionized calcium (Ca_i) demonstrated a rhythm in 3 of the 5 subjects studied that varied widely between individuals and did not have any apparent relation to PTH. Urinary calcium/creatinine (UCa/Cr), phosphate/Cr (UPO₄/Cr), and sodium/Cr (UNa/Cr) ratios all followed a diurnal rhythm during the baseline day. These rhythms persisted during the CR, although with different characteristics for the first two parameters, whereas that of UNa/Cr was unchanged. In general, the temporal pattern for the UCa/Cr curve was a mirror image of the PTH curve, whereas the UPO₄/Cr pattern moved in parallel with the PTH curve.

In conclusion, PTH levels exhibit a diurnal rhythm that persists during a CR, thereby confirming that a large component of this rhythm is an endogenous circadian rhythm. The clinical relevance of this rhythm is reflected in the associated rhythms of biological markers of PTH effect at the kidney, namely UCa/Cr and UPO₄/Cr.

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