Med/Psych Update

Lithium-associated hypercalcemia: Monitoring and management

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In contrast, LAHP is characterized by mild, intermittent, and/or persistent hypercalcemia and mildly increased PTH (Table 1).1,3,4 In some patients, it could improve without active intervention. Because lithium increases the absorption of urinary calcium, it is associated with hypocalciuria and a lower risk of renal stones. Additionally, lithium has osteoprotective effects and has not been associated with an increased risk of fracture. Some researchers have suggested that the presentation of LAHP is more like familial hypocalciuric hypercalcemia (FHC), which is also associated with hypocalciuria. FHC is a benign condition and does not require active intervention.3,4 Similar to those with FHC, many patients with LAHP may live with chronic asymptomatic hypercalcemia without any significant adverse outcome.

Difference between primary hyperparathyroidism and lithium-associated hyperparathyroidism

A suggested approach to monitoring

In most cases, LAH is an insidious adverse effect that is usually detected on blood tests after many years of lithium therapy.8 For patients starting lithium therapy, International Society of Bipolar Disorder guidelines recommend testing calcium levels at baseline, 6 months, and annually thereafter, or as clinically indicated, to detect and monitor hypercalcemia and hyperparathyroidism. However, these guidelines do not provide any recommendations regarding how to manage abnormal findings.9

Clinical laboratories report both total and adjusted calcium values. The adjusted calcium value takes into account albumin levels. This is a way to compensate for an abnormal concentration of albumin (establishing what a patient’s total calcium concentration would be if the albumin concentration was normal). Table 25 shows the categorization of adjusted calcium values. For patients receiving lithium, some researchers have suggested monitoring PTH as well as calcium.1

Categorization of adjusted calcium levels

The Figure outlines our proposed approach to monitoring for LAH in patients receiving lithium. An isolated high value of calcium could be due to prolonged venous stasis if a tourniquet is used for phlebotomy. In such instances, the calcium level should be tested again without a tourniquet.10 If the repeat blood test shows elevated calcium levels, then both PTH and serum calcium should be tested.

Monitoring for lithium-associated hypercalcemia

If the PTH level is higher than the midpoint of the reference range, LAH should be suspected, though sometimes hypercalcemia can present without raised PTH. LAH has also been reported to cause a transient increase in calcium levels. If hypercalcemia frequently recurs, PTH levels should be monitored. If PTH is suppressed, then the raised calcium levels are probably secondary to something other than lithium; common reasons for this include the use of vitamin D supplements or thiazide diuretics, or malignancies such as multiple myeloma.3,5,8

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