Hypercalcemia in two patients with sarcoidosis and Mycobacterium avium intracellulare not mediated by elevated vitamin D metabolites.

INTRODUCTION: To describe 2 unusual cases of hypercalcemia due to granulomatous diseases with normal vitamin D metabolites and no other ready explanation for the hypercalcemia. METHODS: We present the clinical, laboratory and pathologic findings of 2 patients with hypercalcemia and review previous reports of hypercalcemia in granulomatous diseases without elevated vitamin D metabolites. RESULTS: Hypercalcemia was described in various granulomatous diseases including sarcoidosis, tuberculosis, berylliosis, leprosy and, rarely, in fungal infections. Elevated serum level of vitamin D or its metabolites was linked to the pathogenesis of hypercalcemia in these disorders. The authors present the clinical, laboratory and pathologic findings in 2 patients who presented with hypercalcemia and normal vitamin D metabolites with no other ready explanation for the hypercalcemia. The first patient was diagnosed with Mycobacterium avium, whereas the second patient was found to have sarcoidosis. CONCLUSION: Although hypercalcemia in granulomatous diseases has been attributed to be mediated by elevated vitamin D metabolites, there have been several case reports that documented normal values of active vitamin D metabolites. This report illustrates the regulatory feedback mechanisms of vitamin D synthesis and introduces the term "inappropriately normal" vitamin D metabolites levels in light of low levels of parathyroid hormone.

Hypercalcemia secondary to leprosy.

Despite the high prevalence of leprosy in undeveloped countries, hypercalcemia secondary to leprosy is rare. One of most important mechanisms responsible for this disorder seems to be high serum concentrations of 1,25-dihydroxyvitamin D produced extrarenally by the granulomatous tissue. Serum levels of parathyroid hormone-related protein (PTHrP) have never been analyzed in this disorder. We report here a case of hypercalcemia in a patient with leprosy. Serum levels of 1,25-dihydroxyvitamin D were normal in spite of low levels of 25-dihydroxyvitamin D and acute renal failure. Suppressed serum levels of parathyroid hormone and PTHrP were also remarkable. In this case, PTHrP seems not to play an important role in the pathogenesis of hypercalcemia. Our data indicate that this disorder may be due, at least in part, to abnormal calcitriol overproduction by granulomatous tissue. Further investigations of the prevalence and pathogenesis of this type of hypercalcemia are needed.