Impaired mineral metabolism in Cushing's syndrome: parathyroid function, vitamin D metabolites and osteopenia.

Abstract

To clarify the mechanism for the impaired mineral metabolism in Cushing's syndrome, the clinical features, biochemical parameters before and after oral calcium load, and vitamin D metabolism were compared between two groups of patients of endogenous Cushing's syndrome (17 cases) with and without osteopenia. The patients with osteopenia [OP (+): 7 cases, all female] were older (42.7 +/- 8.3 y. o.) and had a longer duration (117 +/- 75 M) of the syndrome than those without osteopenia [OP (-): 33.8 +/- 8.9 y. o., 36 +/- 25 M]. OP (-) showed a blunted hypercalciuria after oral calcium load (63.7 +/- 20.4 to 90.9 +/- 36.1 mg/g X Cr), while OP (+) had higher levels of urinary excretion of calcium (fasting: 120.4 +/- 37.5, and after oral calcium load: 235.6 +/- 72.6 mg/g X Cr), of cyclic AMP (7.6 +/- 1.1 nmol/dl X GF), and of plasma 1.25(OH)2D (76.6 +/- 34.0 pg/ml) than OP (-) (u-cAMP: 3.2 +/- 2.0 nmol/dl X GF, 1,25(OH)2D: 27.9 +/- 16.3 pg/ml). These results indicate that 1) elderly female patients with Cushing's syndrome of long duration are susceptible to OP, 2) during the early phases of the syndrome, reduced intestinal calcium absorption with sustained calciuria (probably through the inhibition of calcium reabsorptive effect of PTH by glucocorticoid) induces negative calcium balance, leading to 3) a development of secondary hyperparathyroidism which stimulates 1,25(OH)2D synthesis. Thus, the mechanism involving bone resorption stimulated by excess PTH along with the direct inhibition of bone formation by glucocorticoid seems to play an important role in a progressive development of OP in Cushing's syndrome.