Calcium and vitamin D metabolism in sarcoidosis.

BACKGROUND

Sarcoidosis associated hypercalcemia (SAHC) may be secondary to excessive levels of 1,25-(OH)2 vitamin D3 produced by autonomous 1-alpha-hydroxylase activity within the granulomas.  The frequency, treatment, and consequences of hypercalcemia remain unclear.

STUDY DESIGN AND METHODS

Two patient cohorts were studied.  In Cohort 1, the prevalence of hypercalcemia in 1606 sarcoidosis patients seen during a six year period was analyzed along with treatment and outcome. Cohort 2 consisted of  261 sarcoidosis patients with measured 25-(OH) vitamin D3 and 1,25-(OH) vitamin D3 levels. In forty patients, serial levels of 25-(OH) vitamin D3 and 1,25-(OH) vitamin D3 were measured at least three months apart without change in therapy.

RESULTS

SAHC was identified in 97 of 1606 (6%) of patients studied and additional nine (0.6%) patients had primary hyperparathyroidism. Post treatment follow up was available in 86 SAHC patients. Hypercalcemia improved in >90% of patients, including eight patients treated solely with vitamin D supplement withdrawal. Renal insufficiency, documented in 41 (42%) of SAHC patients, improved with hypercalcemia treatment.  In 80% of Cohort 2 patients low 25-(OH) vitamin D3 levels were measured with only one patient having a low 1,25(OH)2 vitamin D3 level. Elevated 1,25(OH)2 vitamin D3 levels, which were measured in 11% of patients, were higher for those with a history of hypercalcemia.

CONCLUSION

Sarcoidosis associated hypercalcemia, which is often accompanied by renal insufficiency, responds to treatment of sarcoidosis and withdrawal of vitamin D supplementation. Measurement of serum vitamin 1,25(OH)2 vitamin D3 appears to best evaluate vitamin D status in sarcoidosis patients.