Hypercalcemia in sarcoidosis all are true except?
Correct Answer: Parathormone level is increased
Description: Ans. is 'a' i.e., Parathormone level is increased Calcium metabolism in sarcoidosis* Extrarenal synthesis ofcalcitriol is central to the pathogenesis of abnormal calcium metabolism in sarcoidosis.* Sarcoidosis causes an increase in 1, 25-dihydroxy vitamin D, the active metabolite of vitamin D, which is usually hydroxylated within the kidney, but in sarcoidosis patients hydroxylation of vitamin D can occur outside the kidneys, mainly inside the immune cells found in the granulomas and produces 1 alpha, 25(OH)2D3, which is the main cause for hypercalcemia in sarcoidosis.* Gamma-interferon produced by activated lymphocytes and macrophages, also plays a major role in the synthesis of 1 alpha, 25(OH)2D3.* Above 1-ahydroxylation is controlled by PTH and calcitriol. PTH is stimulated by circulating vitamin D metabolites and low levels of ionized calcium to form a bioregulatory loop 8c PTH release is inhibited by hypercalcaemia and high levels ofcalcitriol, which explains why the PTH level is suppressed in sarcoidosis.* PTHrP has similar properties to PTH, stimulating 1 -a hydroxylation of 25(OH)2D3 and affecting bone turnover but unlike PTH, PTHrP gene expression is not regulated by calcium and vitamin D metabolites, but rather by TNFa and IL-6, two cytokines that are up-regulated in sarcoidosis. They are produced by macrophages and have autocrine actions, up-regulating PTHrP expression and therefore increasing calcitriol synthesis* To date corticosteroids have been the first-line therapy in hypercalcaemic sarcoidosis because of their effectiveness in rapidly restoring normocalcaemia and the lack of a recognized alternative therapy.* It is generally accepted that a corrected serum calcium concentration of >3.0 mmol/1 or evidence of renal complications in the presence of a lesser degree of hypercalcaemia is an indication for therapy.
Category:
Pathology
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