A 48-year-old woman is admitted to the hospital from the emergency department due to fatigue and confusion. She had been well until 2 months prior to admission when she began to feel tired and lost her appetite. Over the next several weeks, the patient experienced nausea, constipation, and weight loss. Recently, she has also had difficulty concentrating at work, and on the day of admission her daughter visited her at home and found her confused. The patient has had no fever, chills, or depression. Medical history is notable for rheumatoid arthritis, which was previously treated with methotrexate but has been quiescent in the absence of therapy for several years. She is an ex-smoker with a 30-pack-year smoking history. Her mother died of lung cancer at age 50.
Blood pressure is 138/78 mm Hg and pulse is 89/min. Mucous membranes appear dry. There is no lymph node enlargement. Breast examination is unremarkable. The lungs are clear to auscultation. The spleen is not palpable. There are no skin rashes.
Laboratory results are as follows:
Serum calcium was normal 6 months ago. Which of the following is the most likely cause of this patient's hypercalcemia?

Question

A 48-year-old woman is admitted to the hospital from the emergency department due to fatigue and confusion.  She had been well until 2 months prior to admission when she began to feel tired and lost her appetite.  Over the next several weeks, the patient experienced nausea, constipation, and weight loss.  Recently, she has also had difficulty concentrating at work, and on the day of admission her daughter visited her at home and found her confused.  The patient has had no fever, chills, or depression.  Medical history is notable for rheumatoid arthritis, which was previously treated with methotrexate but has been quiescent in the absence of therapy for several years.  She is an ex-smoker with a 30-pack-year smoking history.  Her mother died of lung cancer at age 50.
Blood pressure is 138/78 mm Hg and pulse is 89/min.  Mucous membranes appear dry.  There is no lymph node enlargement.  Breast examination is unremarkable.  The lungs are clear to auscultation.  The spleen is not palpable.  There are no skin rashes.
Laboratory results are as follows:
 Serum calcium was normal 6 months ago.  Which of the following is the most likely cause of this patient's hypercalcemia?

Quizplus · Accepted Answer

11ec193a_96c4_f313_853d_77f86f26561b_MD0002_00 The most common causes of hypercalcemia are primary hyperparathyroidism and hypercalcemia of malignancy. Parathyroid hormone (PTH) levels should be obtained as part of the initial evaluation of hypercalcemia; however, patient symptoms and acuity of onset can help distinguish between these 2 causes. Primary hyperparathyroidism is characterized by an elevated PTH level and typically presents insidiously. Hypercalcemia is often chronic and calcium levels are usually mildly elevated (eg, <11 mg/dL). Symptoms are often absent or mild (eg, constipation, fatigue, kidney stones) (Choice B).Hypercalcemia of malignancy is typically characterized by a low PTH level and presents acutely. Hypercalcemia is often severe (>13 mg/dL) and patients develop significant symptoms (eg, marked muscle weakness, confusion, polyuria). Primary hyperparathyroidism is characterized by an elevated PTH level and typically presents insidiously. Hypercalcemia is often chronic and calcium levels are usually mildly elevated (eg, <11 mg/dL). Symptoms are often absent or mild (eg, constipation, fatigue, kidney stones) (Choice B). Primary hyperparathyroidism is characterized by an elevated PTH level and typically presents insidiously. Hypercalcemia is often chronic and calcium levels are usually mildly elevated (eg, <11 mg/dL). Symptoms are often absent or mild (eg, constipation, fatigue, kidney stones) (Choice B). Hypercalcemia of malignancy is typically characterized by a low PTH level and presents acutely. Hypercalcemia is often severe (>13 mg/dL) and patients develop significant symptoms (eg, marked muscle weakness, confusion, polyuria). Hypercalcemia of malignancy is typically characterized by a low PTH level and presents acutely. Hypercalcemia is often severe (>13 mg/dL) and patients develop significant symptoms (eg, marked muscle weakness, confusion, polyuria). Most cases (~80%) of hypercalcemia of malignancy are due to parathyroid hormone-related peptide (PTHrP) secretion by the tumor (humoral hypercalcemia of malignancy). The amino-terminal region of PTHrP is very similar to PTH, which allows PTHrP to bind and stimulate PTH receptors, leading to excessive bone resorption and hypercalcemia. PTHrP formation is most common in squamous cell cancer of the lung, renal cell carcinoma, bladder cancer, breast cancer, and ovarian cancer. This patient's history of heavy smoking, weight loss, and family history of lung cancer raises concern for a pulmonary malignancy. The acute onset (<6 months) of severe, symptomatic hypercalcemia suggests PTHrP formation, likely from squamous cell carcinoma of the lung. (Choice A) Osteolytic bone metastases are responsible for about 20% of malignancy-associated hypercalcemia and are most common in breast cancer and multiple myeloma; bone pain is expected. This patient is not in pain, her breast examination is normal, and she does not exhibit anemia or marked renal failure suggestive of myeloma. (Choice D) Rhabdomyolysis (heme pigment-induced kidney injury) can cause renal tubular dysfunction and hypercalcemia; however, marked electrolyte abnormalities (hyperphosphatemia, hyperkalemia) and acute kidney injury would be expected. (Choice E) Lymphomas (particularly Hodgkin) can produce 1-alpha hydroxylase, which in turn increases the formation of 1,25-dihydroxyvitamin D and leads to excessive gastrointestinal absorption of calcium. This is a relatively rare form of hypercalcemia of malignancy; in addition, lymphoma is less likely in this patient without lymphadenopathy or splenomegaly. Educational objective: Hypercalcemia of malignancy typically presents acutely with severe hypercalcemia (>13 mg/dL) and significant symptoms, whereas primary hyperparathyroidism typically presents insidiously with mild hypercalcemia (<11 mg/dL) and minimal symptoms. Most cases of malignancy-associated hypercalcemia are due to parathyroid hormone-related peptide secretion by the tumor. __________ References: Hypercalcemia of malignancy: an update on pathogenesis and management. (http://www.ncbi.nlm.nih.gov/pubmed/26713296)

A 48-Year-Old Woman Is Admitted to the Hospital from the Emergency