A 61-year-old man comes to the office for follow-up of long-standing type 2 diabetes mellitus. Treatment currently consists of metformin, dietary modification, and regular exercise. On his current regimen, the patient's weight has been mostly stable over the last 2 years, but he has noticed some weight loss in the last 6 weeks. He also has mild constipation but no abdominal pain, nausea, or excessive urination. Medical history is significant for hyperlipidemia and hypertension, for which he takes atorvastatin, amlodipine, and valsartan. He also takes low-dose aspirin and a daily multivitamin. The patient does not drink alcohol but has a 45-pack-year smoking history. His father had type 2 diabetes mellitus and died of a stroke, and his mother had thyroid cancer that required surgery. Blood pressure is 134/80 mm Hg and pulse is 88/min. BMI is 30 kg/m². Neck examination is normal. Lungs are clear to auscultation. Abdominal examination reveals no masses or tenderness. Laboratory results are as follows:
Six months ago, his chemistry profile was normal.
The patient is scheduled for additional testing but is unable to return for evaluation. About 2 weeks after his visit, he is brought to the emergency department due to weakness, nausea, increased urination, and progressive constipation. Blood pressure is 90/70 mm Hg and pulse is 110/min. Mucous membranes are dry. Laboratory results show a serum parathyroid hormone level of 9 pg/mL, serum calcium of 14.1 mg/dL, and serum creatinine of 2.6 mg/dL. Which of the following is the most likely cause of this patient's hypercalcemia?

Question

A 61-year-old man comes to the office for follow-up of long-standing type 2 diabetes mellitus. Treatment currently consists of metformin, dietary modification, and regular exercise. On his current regimen, the patient's weight has been mostly stable over the last 2 years, but he has noticed some weight loss in the last 6 weeks. He also has mild constipation but no abdominal pain, nausea, or excessive urination. Medical history is significant for hyperlipidemia and hypertension, for which he takes atorvastatin, amlodipine, and valsartan. He also takes low-dose aspirin and a daily multivitamin. The patient does not drink alcohol but has a 45-pack-year smoking history. His father had type 2 diabetes mellitus and died of a stroke, and his mother had thyroid cancer that required surgery. Blood pressure is 134/80 mm Hg and pulse is 88/min. BMI is 30 kg/m². Neck examination is normal. Lungs are clear to auscultation. Abdominal examination reveals no masses or tenderness. Laboratory results are as follows:

Six months ago, his chemistry profile was normal.
The patient is scheduled for additional testing but is unable to return for evaluation. About 2 weeks after his visit, he is brought to the emergency department due to weakness, nausea, increased urination, and progressive constipation. Blood pressure is 90/70 mm Hg and pulse is 110/min. Mucous membranes are dry. Laboratory results show a serum parathyroid hormone level of 9 pg/mL, serum calcium of 14.1 mg/dL, and serum creatinine of 2.6 mg/dL. Which of the following is the most likely cause of this patient's hypercalcemia?

Quizplus · Accepted Answer

Explanation: 11ec2b69_c136_8a03_8f63_15384c0f644f_MD0005_00 The most common cause of non-parathyroid hormone (PTH)-dependent hypercalcemia is humoral hypercalcemia of malignancy (HHM), which is due to secretion of PTH-related protein (similar to PTH and binds PTH receptors). Hypercalcemia in primary hyperparathyroidism is usually mild (calcium <12 mg/dL) and often asymptomatic, whereas HHM is typically more acute and severe. Renal dysfunction may occur due to dehydration from polyuria and vomiting, and hypercalcemia-induced vasoconstriction of intrarenal blood vessels. Other causes of cancer-associated hypercalcemia include overproduction of 1,25-dihydroxyvitamin D (eg, certain lymphomas) and bony metastases (eg, multiple myeloma). This patient has severe hypercalcemia with suppressed PTH (<20 pg/mL), which, in light of his smoking history and associated weight loss, most likely represents HHM due to squamous cell carcinoma of the lung. Although HHM is most often seen in patients with known malignancy, hypercalcemia may occasionally be the presenting feature. HHM is typically seen in advanced malignancy and confers a poor prognosis. (Choices A and D) Secondary hyperparathyroidism is a compensatory rise in PTH due to hypocalcemia and is most commonly seen patients with chronic kidney disease (eg, diabetic nephropathy). Long-standing secondary hyperparathyroidism can lead to parathyroid hyperplasia and autonomous PTH secretion (tertiary hyperparathyroidism). However, this is typically seen in patients with end-stage renal disease and is characterized by hypercalcemia with very high PTH levels. (Choice C) This patient is not on any medication associated with hypercalcemia. Common causes of medication-induced hypercalcemia include thiazide diuretics, lithium, and excessive doses of calcium carbonate or vitamin D. (Choice E) Hypercalcemia due to thyrotoxicosis is usually mild and results from thyroid hormone-induced bone resorption. Educational objective: Hypercalcemia associated with malignancy is characterized by rapid onset of severely elevated calcium levels. Although most patients with malignancy-associated hypercalcemia have a known cancer, hypercalcemia can occasionally be the presenting feature. References: Hypercalcemia: an evidence-based approach to clinical cases. (http://www.ncbi.nlm.nih.gov/pubmed/19395781) Mechanisms and treatment of hypercalcemia of malignancy. (http://www.ncbi.nlm.nih.gov/pubmed/21897221)

A 61-Year-Old Man Comes to the Office for Follow-Up of Long-Standing