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.

Serum angiotensin converting enzyme in respiratory diseases.

More than 1700 estimations of serum angiotensin converting enzyme (SACE) were undertaken, mostly in respiratory disorders, to assess its value as a specific and/or a sensitive indicator of different diseases. Though highest levels were found in lepromatous leprosy consistently, it was also found almost always elevated in active stages of sarcoidosis. Since it is raised in a variety of respiratory disorders, it is not a specific diagnostic test. It is, however, a fairly sensitive index of disease activity in sarcoidosis whether on treatment or not. Sudden elevation, after a prolonged period of low or normal values may indicate relapse in sarcoidosis.

Monocyte functional and metabolic activity in malignant and inflammatory diseases.

Macrophages or monocytes produce CL upon exposure to ingestible particles such as opsonized zymosan or bacteria. In previous studies, we have demonstrated that activated macrophages from mice produce significantly more CL than do normal macrophages. In the present study, we have utilized the CL assay as well as 14C-1-glucose utilization to assess monocyte metabolic activity in a variety of malignant, infectious, and inflammatory diseases. Monocyte peak CL was significantly increased above control values (20.9 +/- 0.5 (S.E.) X 10(3) cpm) in 25 patients with lymphoma (26.7 +/- 1.5 x 10(3)). Markedly increased CL was also seen in inflammatory processes such as bacterial infections, tuberculosis, and sarcoidosis (32.2 +/- 2.7 x 10(3)). In contrast, monocytes from patients with solid tumors, including carcinomas of breast and gastrointestinal and genitourinary tracts, had peak CL values (22.4 +/- 1.6 x 10(3) which were not significantly different from controls. When studied by determining 14C-1-glucose utilization, hexose monophosphate shunt activity paralleled CL values. Monocyte metabolic activation appears therefore to accompany ongoing infectious or granulomatous processes and may also be present in certain malignancies associated with reticuloendothelial stimulation.

Serum angiotensin--converting enzyme (SACE) in sarcoidosis and other granulomatous disorders.

Serum angiotensin-converting enzyme (SACE) activity was significantly higher in 90 patients with sarcoidosis (55 +/- [S.D.] 23 nmol min-1 ml-1) than in 80 healthy controls (34 +/- 9 nmol min-1 ml-1). Steroid therapy modified SACE activity; 60 sarcoidosis patients who were not being treated with steroids had significantly higher enzyme activities (58 +/- 24 nmol min-1 ml-1) than 30 steroid-treated sarcoidosis patients (40 +/- 19 nmol min-1 ml-1). In 50% of the non-steroid treated sarcoidosis patients SACE activity was more than than 2 S.D. above the mean value for the controls. SACE activity was measured in 22 tuberculous patients (38 +/- 14 nmol min-1 ml-1), 20 leprosy patients (34 +/- 9 nmol min-1 ml-1), 31 with primary biliary cirrhosis (44 +/- 20 nmol min-1 ml-1), 26 with inflammatory bowel disease (31 +/- 9 nmol min-1 ml-1), eight with hepatic granulomatous disease, five with Hodgkin's disease, and two with schistosomiasis. The combined false-positive rate for these non-sarcoidosis patients was 10%. Serial SACE assays provide useful information on the course of sarcoidosis and response to steroid treatment.