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The Effect of Lithium on Calcium-Induced Changes in Adrenocorticotrophin Levels¹

Endocrine-Hypertension Division (S.T.H., E.M.B., J.S., G.E.-H.F.) and Psychiatry Division (A.L.S.), Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115

Address all correspondence and requests for reprints to: Ghada El-Hajj Fuleihan, MD., M.P.H., Endocrine Division, American University of Beirut Medical Center, P.O. Box 113-6044, Bliss Street, Beirut, Lebanon. E-mail: gf01{at}aub.edu.lb

The calcium receptor (CaR) plays a central role in calcium (Ca) sensing by the parathyroid gland and other organs, including the brain. Chronic lithium (Li) therapy causes a significant alteration in Ca-sensing by the CaR-expressing parathyroid chief cells through an unknown mechanism, shifting the PTH set-point (the level of Ca that half-maximally suppresses PTH secretion) to the right. Ca is known to stimulate ACTH levels in normal subjects, and baseline ACTH levels are increased in patients with bipolar disorder. Because the stimulation of ACTH secretion by Ca likely involves the CaR, the aim of this study was to investigate the effects of Li on Ca-induced changes in ACTH levels, using Ca and citrate infusions in seven Li-treated patients and seven controls. During the Ca infusion, increments in serum-ionized Ca concentration (Ca_i) were accompanied by increments in ACTH levels that were significantly greater in the Li-treated group, P = 0.014, by ANOVA. Also, cortisol levels increased significantly in the Li-treated, but not the control group, during the Ca infusion, P < 0.0001. There was a statistically significant shift in the midpoint of the Ca_i/ACTH curve, to the right, in the Li-treated group, compared with the controls (P = 0.042), that was largely caused by an effect of Li on Ca_i. However, for comparable levels of Ca_i, there were no significant differences in the levels of ACTH between the two groups. Therefore, within the physiological range of Ca, there was no effect of Li on Ca_i-induced change in ACTH levels.

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