A 72-year-old woman is evaluated due to a month of fatigue and shortness of breath on exertion. The patient has also had lower back pain but no fever or cough. She takes valsartan for hypertension. Temperature is 37.2 C (99 F) , blood pressure is 130/80 mm Hg, pulse is 84/min, and respirations are 14/min. On physical examination, the conjunctivae are pale. The remainder of the examination is normal. Laboratory results are as follows: X-rays of the lower back demonstrate multiple areas of radiolucency in the L4 and L5 vertebrae. Serum protein electrophoresis reveals a monoclonal gamma globulin spike. Further studies are most likely to show which of the following?

Question

A 72-year-old woman is evaluated due to a month of fatigue and shortness of breath on exertion. The patient has also had lower back pain but no fever or cough. She takes valsartan for hypertension. Temperature is 37.2 C (99 F) , blood pressure is 130/80 mm Hg, pulse is 84/min, and respirations are 14/min. On physical examination, the conjunctivae are pale. The remainder of the examination is normal. Laboratory results are as follows:

X-rays of the lower back demonstrate multiple areas of radiolucency in the L4 and L5 vertebrae. Serum protein electrophoresis reveals a monoclonal gamma globulin spike. Further studies are most likely to show which of the following?

Quizplus · Accepted Answer

11ec160b_3b55_9ae9_9249_cfde3b012a8b_MD0001_00 Multiple myeloma (MM) is a plasma cell malignancy that generates monoclonal immunoglobulin. It is classically characterized by anemia, bone pain/radiolucent lesions, and hypercalcemia due to tumor infiltration of the bone marrow; renal insufficiency can also occur due to hypercalcemia and clogging of the renal tubules with immunoglobulin light chains. MM tumor cells secrete potent osteolytic cytokines (eg, tumor necrosis factor-alpha) that liberate calcium from bone and result in hypercalcemia. Elevated serum calcium inhibits the release of parathyroid hormone (PTH) from parathyroid cells, which has several downstream effects including: Hypercalciuria - low PTH levels increase urinary calcium excretion due to reduced calcium reabsorption in the distal tubules and collecting ducts of the kidney (where PTH exerts its effects) Low 1,25 dihydroxyvitamin D levels - low PTH (and renal insufficiency) reduce the activity of renal 1-alpha-hydroxylase, the enzyme that converts 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D (the more active form) Therefore, patients with MM classically have low PTH and 1,25-dihydroxyvitamin D levels and elevated urinary calcium. (Choice A) Thiazide diuretics cause hypercalcemia by promoting calcium reabsorption in the distal convoluted tubule. This leads to reduced urinary calcium excretion and low serum PTH levels (elevated serum calcium reduces PTH release). Angiotensin receptor blockers (eg, valsartan) do not increase renal calcium reabsorption. (Choice B) Granulomatous diseases (eg, sarcoidosis, tuberculosis) can cause hypercalcemia due to production of 1,25-dihydroxyvitamin D by 1-alpha-hydroxylase in granulomatous tissue. This increases the intestinal absorption and urinary excretion of calcium (the latter effect being caused by concomitant suppression of PTH). (Choice C) Production of PTH-related protein (PTHrP) is the most common cause of hypercalcemia in malignancy (eg, squamous cell carcinoma). PTHrP increases osteoclast activity and renal calcium absorption with minimal effect on 1,25-dihydroxyvitamin D. The hypercalcemia seen in MM is not typically due to PTHrP; it is caused by osteolytic cytokines. (Choice E) Primary hyperparathyroidism is characterized by excessive PTH release, leading to increased bone resorption and 1,25-dihydroxyvitamin D formation. Urinary calcium excretion is elevated due to the increased filtered calcium load (despite the increased renal reabsorption induced by PTH). (Choice F) Familial hypocalciuric hypercalcemia is caused by inactivating mutations of the Ca²⁺-sensing receptor in the nephron and parathyroid glands. Renal calcium reabsorption is increased (urinary calcium excretion is low) and higher serum calcium levels are required to suppress PTH release (serum PTH is slightly elevated or inappropriately normal). Educational objective: Multiple myeloma is associated with increased bone resorption due to the production of tumor-related cytokines. This results in elevated serum calcium levels, which reduce parathyroid hormone (PTH) production. Low PTH decreases renal calcium reabsorption (hypercalciuria), and, in combination with renal insufficiency, reduces 1,25-dihydroxyvitamin D synthesis. __________ References: Multiple myeloma: from diagnosis to treatment. (http://www.ncbi.nlm.nih.gov/pubmed/24130968)

A 72-Year-Old Woman Is Evaluated Due to a Month of Fatigue