Test your medicine knowledge with the MKSAP challenge, in partnership with the American College of Physicians.

A 67-year-old man is evaluated for a recent diagnosis of primary hyperparathyroidism after an elevated serum calcium level was incidentally detected on laboratory testing. Medical history is significant only for hypertension, and his only medication is ramipril.

On physical examination, temperature is 35.8 °C (96.4 °F), blood pressure is 120/68 mm Hg, pulse rate is 62/min, and respiration rate is 14/min. BMI is 32. The remainder of his examination is unremarkable.

Laboratory studies:

Creatinine	0.9 mg/dL (79.6 µmol/L)
Parathyroid hormone	98 pg/mL (98 ng/L)
25-Hydroxyvitamin D	19 ng/mL (47.4 nmol/L)
Estimated glomerular filtration rate	>60 mL/min/1.73 m2

A dual-energy X-ray absorptiometry (DEXA) scan shows T-scores of –1.3 in the right femoral neck, –1.0 in the lumbar spine, and –1.4 in the non-dominant forearm. Fracture Risk Assessment Tool (FRAX) score indicates a 13% risk of major osteoporotic fracture and a 1.9% risk of hip fracture over the next 10 years.

Which of the following is the most appropriate management of this patient?

A. Refer for parathyroidectomy
B. Start alendronate
C. Start calcitonin
D. Start cinacalcet
E. Start vitamin D₃ (cholecalciferol)

MKSAP Answer and Critique

The correct answer is E: Start vitamin D₃ (cholecalciferol).

The most appropriate treatment of this patient is to replete his vitamin D deficiency with a supplement such as vitamin D₃ (cholecalciferol). He has primary hyperparathyroidism as shown by his elevated serum calcium and parathyroid hormone levels. However, there is a high prevalence of concurrent vitamin D deficiency and insufficiency in patients with primary hyperparathyroidism, and low levels of 25-hydroxyvitamin D can stimulate parathyroid hormone secretion in non-adenomatous glands. Because of this, measurement of vitamin D levels should be ordered as part of the evaluation of primary hyperparathyroidism, and repletion should be provided if identified. In these patients, it is important to replace their vitamin D to a level of at least 30 ng/dL (75 nmol/L). After this level is reached, the patient should be placed on a vitamin D dosage to maintain that value. The choice to use cholecalciferol versus ergocalciferol is often based on the level of vitamin D deficiency. Since ergocalciferol is more readily available in the 50,000 U form and has a shorter half-life, it is recommended when a patient’s vitamin D level is less than 10 ng/mL (25 nmol/L). Cholecalciferol is often used when the level is between 20 and 30 ng/mL (50-75 nmol/L) or for maintenance. Since this patient already has hypercalcemia and low-dose repletion is desired, the lower doses (400 U daily) of vitamin D₃ (over-the-counter cholecalciferol) should be used. This patient’s serum calcium should be monitored at least monthly.

This patient does not meet the threshold for surgery. His serum total calcium level is less than 1 standard deviation from upper limit of normal, his bone density score is not in the osteoporotic or treatment range, he is older than 50 years of age, and his glomerular filtration rate is preserved.

Alendronate would be an excellent option for calcium reduction and simultaneous treatment of osteoporosis if his T-scores were lower or Fracture Risk Assessment Tool (FRAX) scores were higher. The FRAX calculator defines the 10-year fracture risk for patients with T-scores in the −1.0 to −2.5 range. The FRAX calculator incorporates multiple risk factors including sex, fracture history, femoral neck bone mineral density, steroid usage, smoking, BMI, age, and alcohol intake to determine projected fracture risk. If the risk of major osteoporotic fracture is greater than or equal to 20% or the risk of hip fracture is greater than or equal to 3%, the patient’s benefit from therapy exceeds the risk and treatment should be offered.

Calcitonin is an option for reducing his calcium levels, but he is currently asymptomatic and does not warrant calcium lowering.

Cinacalcet, a calcimimetic agent, is another option for lowering calcium for symptomatic patients with kidney involvement. This patient has preserved kidney function and no symptoms. Due to the cost and potential side effects of cinacalcet, it would not be indicated at this time.

Key Point

• In patients with primary hyperparathyroidism and concomitant vitamin D deficiency, 25-hydroxyvitamin D levels should be repleted to at least 30 ng/dL (75 nmol/L) to prevent further parathyroid hormone stimulation.

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