A 65-year-old woman is brought to the emergency department by her family due to worsening generalized weakness and lethargy. She has had no fever, chills, vomiting, or diarrhea but has been urinating frequently over the past several days. Her family also notes that the patient has lost 5 kg (11 lb) over the past month. She takes no medications and has smoked 1-2 packs of cigarettes daily for the last 40 years. On physical examination, the patient appears ill with dry mucous membranes. There are no abnormal lung sounds or heart murmurs. The abdomen is soft and nontender. Laboratory testing shows serum calcium of 14.0 mg/dL and normal serum glucose and urinalysis. Imaging studies reveal an 8-cm right lung mass with enlarged mediastinal lymph nodes but no focal bony lesions. Serum levels of which of the following substances are most likely to be elevated in this patient?

Question

A 65-year-old woman is brought to the emergency department by her family due to worsening generalized weakness and lethargy.  She has had no fever, chills, vomiting, or diarrhea but has been urinating frequently over the past several days.  Her family also notes that the patient has lost 5 kg (11 lb) over the past month.  She takes no medications and has smoked 1-2 packs of cigarettes daily for the last 40 years.  On physical examination, the patient appears ill with dry mucous membranes.  There are no abnormal lung sounds or heart murmurs.  The abdomen is soft and nontender.  Laboratory testing shows serum calcium of 14.0 mg/dL and normal serum glucose and urinalysis.  Imaging studies reveal an 8-cm right lung mass with enlarged mediastinal lymph nodes but no focal bony lesions.  Serum levels of which of the following substances are most likely to be elevated in this patient?

Quizplus · Accepted Answer

11ec160b_3b54_fea6_9249_09fed6d57ceb_MD0001_00 This patient has symptomatic hypercalcemia, which typically occurs in patients with a serum calcium of >12 mg/dL and manifests with weakness, neuropsychiatric symptoms (eg, lethargy), gastrointestinal symptoms (eg, constipation, nausea), or kidney stones. Severe hypercalcemia results in impairment of the concentrating capacity of the distal tubule, leading to polyuria and volume depletion. Mild hypercalcemia is usually due to benign causes (eg, primary hyperparathyroidism), but serum calcium >13 mg/dL suggests an underlying malignancy. Humoral hypercalcemia of malignancy (HHM) is the most common cause of hypercalcemia in patients with malignancy and is due to secretion of parathyroid hormone-related peptide (PTHrP) by malignant cells. PTHrP closely resembles PTH at the bioactive amino-terminal region and causes increased bone resorption, decreased renal excretion of calcium, and increased renal excretion of phosphorus (leading to hypophosphatemia [Choice D]). However, unlike PTH, PTHrP does not significantly increase 1,25-dihydroxyvitamin D production due to structural differences after the first 13 amino acids. HHM occurs most commonly in squamous cell (ie, lung, head and neck), renal, bladder, breast, and ovarian carcinomas. This patient's heavy smoking history, weight loss, and lung mass suggest squamous cell carcinoma of the lung. Hypercalcemia can also occur due to osteolytic bony metastasis (eg, breast cancer, multiple myeloma), but this is less common than HHM and this patient has no lytic lesions visible on imaging. (Choice A) Hodgkin lymphoma and granulomatous diseases (eg, sarcoidosis) can express 1-alpha-hydroxylase, which increases the formation of 1,25-dihydroxyvitamin D, leading to hypercalcemia. However, this patient's large lung mass with regional lymph node enlargement is more suggestive of primary squamous cell carcinoma of the lung. (Choice B) Ectopic ACTH secretion causes paraneoplastic Cushing syndrome, characterized by hypertension, hyperpigmentation, and proximal muscle weakness. Laboratory studies typically show hyperglycemia rather than hypercalcemia. (Choice C) Ectopic production of PTH is a very rare cause of hypercalcemia in patients with malignancy. Patients with HHM have very low levels of PTH due to feedback suppression by hypercalcemia. (Choice F) Thyrotoxicosis can cause mild hypercalcemia due to increased bone turnover, but severe hypercalcemia is rare, and this patient's high calcium level and lung mass is more suggestive of an underlying malignancy. Educational objective: Serum calcium >13 mg/dL is suggestive of an underlying malignancy. Secretion of parathyroid hormone-related protein (PTHrP), which closely resembles parathyroid hormone at the bioactive amino-terminal region, is a frequent cause of malignancy-related hypercalcemia and is commonly seen with squamous cell carcinomas (eg, lung, neck). __________ References: Hypercalcemia of malignancy: an update on pathogenesis and management. (http://www.ncbi.nlm.nih.gov/pubmed/26713296)

A 65-Year-Old Woman Is Brought to the Emergency Department by Her