A 35-year-old woman comes to the emergency department due to fatigue, exertional dyspnea, and cough. She has had subjective fevers but no upper respiratory symptoms, and no family members have had a similar illness. Medical history is unremarkable, and the patient does not use tobacco. Temperature is 37.5 C (99.5 F), blood pressure is 118/75 mm Hg, pulse is 90/min, and respirations are 22/min. Pulmonary examination shows normal air exchange with scattered crackles and no wheezes. The patient also has nontender cervical lymphadenopathy. Serum chemistry shows a calcium level of 12.0 mg/dL. Chest x-ray demonstrates scattered nodules and parenchymal infiltrates, as shown in the image below. Lymph node biopsy reveals noncaseating granulomas. Which of the following is the most likely cause of the elevated calcium level in this patient?

Question

A 35-year-old woman comes to the emergency department due to fatigue, exertional dyspnea, and cough.  She has had subjective fevers but no upper respiratory symptoms, and no family members have had a similar illness.  Medical history is unremarkable, and the patient does not use tobacco.  Temperature is 37.5 C (99.5 F), blood pressure is 118/75 mm Hg, pulse is 90/min, and respirations are 22/min.  Pulmonary examination shows normal air exchange with scattered crackles and no wheezes.  The patient also has nontender cervical lymphadenopathy.  Serum chemistry shows a calcium level of 12.0 mg/dL.  Chest x-ray demonstrates scattered nodules and parenchymal infiltrates, as shown in the image below.  Lymph node biopsy reveals noncaseating granulomas.  Which of the following is the most likely cause of the elevated calcium level in this patient?

Quizplus · Accepted Answer

11ec160b_3a1e_05b4_9249_0b9151e63f6b_MD0001_00 This patient, with systemic and respiratory symptoms, pulmonary infiltrates, lymphadenopathy, and noncaseating granulomas, has typical features of sarcoidosis. Hypercalcemia is a common feature of sarcoidosis, and even patients with normal serum calcium levels may have increased urinary excretion of calcium, suggesting abnormal calcium metabolism. In normal individuals, 25-hydroxyvitamin D is converted to 1,25-dihydroxyvitamin D by 1-alpha-hydroxylase in the kidneys. This step is regulated primarily by parathyroid hormone (PTH) in response to blood calcium levels. However, in sarcoidosis and other granulomatous disorders, 1-alpha-hydroxylase expression in activated macrophages in the lung and lymph nodes causes PTH-independent production of 1,25-dihydroxyvitamin D. This leads to increased intestinal absorption of calcium and subsequent hypercalcemia. (Choice A) Increased bone turnover may be seen in patients with sarcoidosis who have very high 1,25-dihydroxyvitamin D levels, but this is a less significant source than intestinal absorption of calcium. Regardless, the underlying cause of both of these mechanisms is excess 1-alpha-hydroxylase expression by activated macrophages. (Choice C) Osteolytic metastases can cause hypercalcemia due to increased bone resorption in areas surrounding malignant cells. However, this patient, a nonsmoker with noncaseating granulomas on biopsy, has no specific signs of malignancy. (Choice D) PTH levels in sarcoidosis are typically suppressed due to elevated levels of calcium and 1,25-dihydroxyvitamin D. (Choice E) Chronic renal failure causes phosphorus retention. The excess serum phosphorus can cause hypocalcemia by combining with intravascular calcium. Educational objective: Hypercalcemia in sarcoidosis is caused by parathyroid hormone-independent formation of 1,25-dihydroxyvitamin D by activated macrophages. This leads to increased intestinal absorption of calcium.

A 35-Year-Old Woman Comes to the Emergency Department Due to Fatigue