A 52-year-old woman comes to the physician for routine follow-up. She has no complaints and thinks of herself as "pretty healthy." She takes lisinopril and hydrochlorothiazide for hypertension and lansoprazole for gastroesophageal reflux disease. She was treated with isoniazid for latent tuberculosis 7 years ago. Her mother died of uterine cancer at age 62. The patient does not smoke. She jogs 3 miles a day and eats a balanced diet. She takes 2000 units of vitamin D3 a day orally as a dietary supplement.
Her blood pressure is 139/82 mm Hg and pulse is 74/min. Her BMI is 28 kg/m². There are no neck masses or lymph node enlargement. Breast examination is unremarkable. Lungs are clear to auscultation. The spleen is not palpable. There are no skin rashes.
Laboratory results are as follows:

Repeat calcium level is 12.1 mg/dL. Hydrochlorothiazide is discontinued.
Which of the following is the most likely diagnosis?

Question

A 52-year-old woman comes to the physician for routine follow-up. She has no complaints and thinks of herself as "pretty healthy." She takes lisinopril and hydrochlorothiazide for hypertension and lansoprazole for gastroesophageal reflux disease. She was treated with isoniazid for latent tuberculosis 7 years ago. Her mother died of uterine cancer at age 62. The patient does not smoke. She jogs 3 miles a day and eats a balanced diet. She takes 2000 units of vitamin D3 a day orally as a dietary supplement.
Her blood pressure is 139/82 mm Hg and pulse is 74/min. Her BMI is 28 kg/m². There are no neck masses or lymph node enlargement. Breast examination is unremarkable. Lungs are clear to auscultation. The spleen is not palpable. There are no skin rashes.
Laboratory results are as follows:

Repeat calcium level is 12.1 mg/dL. Hydrochlorothiazide is discontinued.
Which of the following is the most likely diagnosis?

Quizplus · Accepted Answer

Primary hyperparathyroidism is the most common cause of hypercalcemia. Patients with primary hyperparathyroidism are usually asymptomatic and present with incidental hypercalcemia on routine laboratory testing. However, the serum calcium in primary hyperparathyroidism is only mildly elevated. Hydrochlorothiazide can also slightly increase serum calcium to a borderline high range by increasing renal tubular calcium absorption. Patients who have overtly high serum calcium on hydrochlorothiazide generally have underlying primary hyperparathyroidism. This patient is asymptomatic and was incidentally found to have mild hypercalcemia. The most likely etiology of her hypercalcemia is primary hyperparathyroidism, which is most often caused by a parathyroid adenoma. (Choice A) Granulomatous diseases (eg, sarcoid, fungal infections, tuberculosis) cause hypercalcemia by extrarenal production of 1-alpha-hydroxylase, which in turn increases the formation of 1, 25 (OH)2 vitamin D. However, these patients generally have symptoms of the primary disease. (Choice B) Malignancy is the second most common cause of hypercalcemia. Most patients with hypercalcemia of malignancy have rapid onset with moderate to high serum calcium levels (>13 to 14 mg/dL) associated with symptoms of hypercalcemia or the primary malignancy. (Choice C) Hypercalcemia is not a feature of primary osteoporosis. (Choice E) Ingestion of very high doses of vitamin D is required for the development of toxicity. This patient is taking 2000 units of vitamin D3 daily as a supplement, which is unlikely to cause toxicity. Most guidelines state that the "tolerable upper limit" of daily vitamin D3 intake is 4000 units. Educational objective: Primary hyperparathyroidism is the most common cause of hypercalcemia. Serum calcium in hydrochlorothiazide-induced hypercalcemia is typically high normal or modestly elevated. The majority of hydrochlorothiazide-treated patients with overt hypercalcemia have underlying primary hyperparathyroidism. __________ References: Differential diagnosis of hypercalcemia. (http://www.ncbi.nlm.nih.gov/pubmed/1763670)

A 52-Year-Old Woman Comes to the Physician for Routine Follow-Up