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.

Osteoporosis, bone turnover and hypogonadism in elderly men with treated leprosy.

In male hypogonadism associated with bone loss, it is important to determine whether bone loss continues with ageing and an increased risk of fracture. We studied bone metabolism in 86 male leprosy patients, who were classified according to the presence or absence of osteoporosis. Osteoporosis was present when men had lumbar compression fractures or a mean BMD-2SD that of normal Japanese men in each age decade. Four men had fractures. Serum concentrations of 1,25-dihydroxyvitamin D and high-sensitivity parathyroid hormone were almost normal in both groups, whereas free testosterone and oestradiol were significantly lower in the osteoporosis group than in the non-osteoporosis group (free testosterone: P < 0.01, oestradiol: P < 0.05). The urinary concentrations of pyridinoline and deoxypyridinoline, as a marker of bone absorption, were significantly higher in the osteoporosis group than in the non-osteoporosis group (pyridinoline: P < 0.01, deoxypyridinoline: P < 0.01). The serum concentration of osteocalcin, a marker of bone formation, was significantly higher in the osteoporosis group than in the non-osteoporosis group (P < 0.01). Elevated concentration means that bone repair is increased possibly because of compensation mechanisms for increased bone loss. In the osteoporosis group, hypogonadism occurred, and high bone turnover continued even in older men. We recommend clinical studies of treatment such as replacement therapy to prevent bone loss and increasing risk of fractures in older men with leprosy.

Calcium metabolism and its regulating hormones in patients with leprosy.

Calcium metabolism was studied in 47 patients with borderline or lepromatous leprosy. Total and ionized calcium, phosphorus, creatinine, total alkaline phosphatase, parathyroid hormone (PTH), 25-hydroxy vitamin D [25(OH)D], and 1,25-dihydroxy vitamin D [1,25(OH)2D] were measured in serum; calcium and total hydroxyproline were determined in urine. Total subperiosteal diameter and medullar cavity diameter were measured on an X-ray of the hand of all patients. Average values were within normal ranges for all of the biochemical determinations. Total serum calcium was moderately below the normal range in eight patients but ionized calcium levels were within the normal ranges in all of the patients. Four patients, all of them with lepromatous leprosy, had levels of 1,25(OH)2D higher than normal but none of them was hypercalcemic and PTH levels were within normal range. Although all values were within the normal ranges, lepromatous leprosy patients had lower total calcium, higher alkaline phosphatase, and higher urinary hydroxyproline than borderline leprosy patients (9.1 +/- 0.4 vs 9.4 +/- 0.3 mg%, p < 0.001; 10.3 +/- 2.9 vs 7.4 +/- 2.3 King-Armstrong units, p < 0.02 and 27.2 +/- 12 vs 19.4 +/- 5.6 mg/24 hr, p < 0.02, respectively). No differences were found between patients and controls in the average micrometric measurements of the second metacarpal bone but significant osteopenia was found in 19% of the patients. The main finding of the present study in a representative sample of leprosy patients is that the average total serum calcium was in the lowest limit of the normal range, but the ionized serum calcium was in the middle of the normal range.(ABSTRACT TRUNCATED AT 250 WORDS)

Hypercalcemia and abnormal 1,25-dihydroxyvitamin D concentrations in leprosy.

Two patients with lepromatous leprosy and hypercalcemia are presented. Serum immunoreactive parathyroid hormone and urinary cyclic adenosine monophosphate concentrations were suppressed. Serum 1,25-dihydroxyvitamin D [1,25-(OH)2D] concentrations were elevated in one patient and normal in the other. Urinary hydroxyproline excretion was slightly high in both patients. Hypercalcemia resolved excretion was slightly high in both patients. Hypercalcemia resolved with prednisone therapy. Abnormal 1,25-(OH)2D production and/or metabolism may play a role in the pathogenesis of hypercalcemia in some patients with leprosy.