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Osteoclast-driven bone resorption
2%
4/188
Increased production of parathyroid hormone
13%
25/188
Ectopic parathyroid hormone release
45%
84/188
Increased intestinal absorption of calcium
28%
52/188
Increased renal calcium reabsorption
11%
21/188
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This patient with sarcoidosis presents with symptoms of hypercalcemia, including abdominal pain, polyuria, and kidney stones. Sarcoidosis can cause hypercalcemia through increased vitamin D production leading to increased intestinal absorption of calcium. Sarcoidosis and other granulomatous diseases are characterized by the presence of macrophage-containing granulomas. These macrophages produce 1a-hydroxylase, which converts 25(OH) vitamin D (calcidiol) into 1,25(OH)2 vitamin D (calcitriol), the active form of vitamin D. This excess of active circulating vitamin D can lead to increased intestinal calcium absorption and hypercalcemia. Carroll and Schade describe the evaluation and management of hypercalcemia. Measuring the level of intact parathyroid hormone is an important first step. Intact parathyroid hormone levels are elevated with primary hyperparathyroidism and decreased with hypercalcemia secondary to malignancy or excess vitamin D, as with over-the-counter vitamin D overdose or granulomatous disease. Treatment with intravenous hydration, loop diuretics, as well as bisphosphonates and calcitonin is indicated when patients are symptomatic or if calcium levels are greater than 14 mg/dL. Parathyroidectomy is necessary in some cases. Baughman et al. studied vitamin D levels and the prevalence of hypercalcemia in two cohorts of patients with sarcoidosis. Sarcoidosis associated hypercalcemia (SAHC) was present in 6% of patients. Elevated 1,25(OH)2 vitamin D levels were seen in patients with hypercalcemia. Treating for sarcoidosis and discontinuing vitamin D supplementation led to a decrease in calcium levels. Of note, renal insufficiency was found in 42% of patients with SAHC and responded to treatment of hypercalcemia. Illustration A depicts the various etiologies of hypercalcemia. The pathophysiology of hypercalcemia secondary to sarcoidosis and other granulomatous diseases is shown on the upper left. Incorrect Answers: Answer 1: Osteoclast-driven bone resorption occurs secondary to IL-1 production in multiple myeloma. Answer 2: Increased production of parathyroid hormone, referred to as primary hyperparathyroidism, occurs with parathyroid adenomas. Answer 3: Ectopic release of parathyroid hormone related peptide (PTHrP) is seen with certain malignancies, including squamous cell lung cancer. Answer 5: Certain drugs, including thiazide diuretics, cause increased calcium reabsorption from renal tubules.
4.1
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