Lithium, a very effective medication in the treatment of bipolar disorder, has a variety of well-documented renal side effects, including interstitial nephritis and nephrogenic diabetes insipidus. A less well-recognized complication is an increased prevalence of hyperparathyroidism in chronic lithium users.
Individuals with chronic Li use frequently have both elevated calcium levels as well as elevated PTH levels, and it can be very difficult to differentiate from primary hyperparathyroidism or familial idiopathic hypercalciuria. The mechanisms for why patients on Li therapy have these lab abnormalities is still up for debate, but this interesting article describes three potential mechanisms: first, Li has been shown to block Ca2+ influx into a variety of cells by competitive inhibition of Ca2+ transport across the cell membrane. The elevated ionized Ca2+ would then drive up PTH levels. In addition, there is some evidence that Li raises the threshold of the Ca-sensing receptor in parathyroid cells, and increased Ca2+ levels are necessary to keep PTH secretion under check. Finally, it is postulated that Li directly increases PTH transcription by virtue of its inhibitory effects on the enzyme glycogen synthase kinase 3b (GSK-3b), a known transcriptional repressor of PTH mRNA.
By the way, I learned today that Lithium is reabsorbed in the kidney via both the Na/H antiporter in the proximal tubule as well as ENac in the collecting duct. Therefore diuretics which block these transport mechanisms (e.g., amiloride) can have a dramatic lithium-lowering effect when acutely given to somebody on chronic Lithium.