The effect of lithium on calcium-induced changes in adrenocorticotrophin levels

The calcium receptor (CaR) plays a central role in calcium (Ca) sensing by the parathyroid gland and other organs, including the brain. Chronic Lithiu m (Li) therapy causes a significant alteration in Ca-sensing by the CaR-exp ressing 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, an d baseline ACTH levels are increased in patients with bipolar disorder. Bec ause the stimulation of ACTH secretion by Ca Likely involves the CaR, the a im 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 patient s and seven controls. During the Ca infusion, increments in serum-ionized C a concentration (Ca-i) were accompanied by increments in ACTH levels that w ere significantly greater in the Li-treated group, P = 0.014, by ANOVA. Als o, cortisol levels increased significantly in the Li-treated, but not the c ontrol 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 lar gely caused by an effect of Li an Ca-i. However, for comparable levels of C a-i, there were no significant differences in the levels of ACTH between th e two groups. Therefore, within the physiological range of Ca, there was no effect of Li on Ca-i-induced change in ACTH levels.