64-year-old man with constipation and calcium 13.8
A 64-year-old man with a 45-pack-year smoking history presents with 3 months of worsening fatigue, 6-kg unintentional weight loss, and new constipation. He also reports increased thirst and diffuse bone pain. Examination shows dry mucous membranes and mild proximal muscle weakness. Temperature is 36.8 C, blood pressure is 132/78 mm Hg, and pulse is 88/min. Laboratory studies show calcium 13.8 mg/dL, phosphorus 2.1 mg/dL, creatinine 1.6 mg/dL, albumin 4.0 g/dL, and intact parathyroid hormone suppressed below the reference range. Chest radiograph reveals a left hilar mass. Which of the following is the most likely mediator of this patient's metabolic abnormality?
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Post-Call Recovery Reads
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D
Explanation
Clinical Pearl:
In a patient with hypercalcemia, low phosphorus, suppressed intact parathyroid hormone, and a lung mass, humoral hypercalcemia of malignancy from parathyroid hormone-related peptide is the classic mechanism, especially with squamous cell carcinoma.
Explanation:
This patient has symptomatic hypercalcemia with suppressed intact parathyroid hormone, which points away from primary hyperparathyroidism and toward a malignancy-mediated process. The low phosphorus and hilar lung mass strongly suggest humoral hypercalcemia of malignancy caused by parathyroid hormone-related peptide, a well-known paraneoplastic syndrome in squamous cell lung cancer. Calcitriol-mediated hypercalcemia is more typical of lymphoma or granulomatous disease and usually does not fit this lung mass presentation. Osteoblastic metastases are classically associated with prostate cancer and tend to lower, not raise, serum calcium through new bone formation, whereas osteolytic metastases would be a different mechanism than the one listed. Ectopic adrenocorticotropic hormone causes Cushing syndrome rather than isolated severe hypercalcemia, and thyroid hormone excess is not a plausible explanation here. Current oncology and supportive care practice recognizes parathyroid hormone-related peptide-mediated humoral hypercalcemia as the most likely cause in this presentation.
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