From the Guidelines
For a 42-year-old obese male with mildly elevated alkaline phosphatase (133) and calcium (11) who is asymptomatic, the most appropriate next step is to confirm hypercalcemia with a repeat calcium level and measure ionized calcium, followed by ordering intact parathyroid hormone (PTH) to differentiate between PTH-dependent and PTH-independent causes, as primary hyperparathyroidism is a likely differential diagnosis 1. The differential diagnoses for this patient include primary hyperparathyroidism, vitamin D toxicity, malignancy, granulomatous diseases, and medication effects.
- Primary hyperparathyroidism is a significant consideration, given the patient's mildly elevated calcium level, and is typically diagnosed by biochemical testing, specifically serum calcium and serum PTH 1.
- Vitamin D toxicity and malignancy are also potential causes of hypercalcemia, and can be evaluated with additional tests such as 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels, and PTHrP testing, respectively.
- Granulomatous diseases, such as sarcoidosis, can also cause hypercalcemia, and can be evaluated with tests such as chest X-ray and serum angiotensin-converting enzyme (ACE) levels. The next steps in workup should include:
- Confirming hypercalcemia with a repeat calcium level and measuring ionized calcium
- Ordering intact parathyroid hormone (PTH) to differentiate between PTH-dependent and PTH-independent causes
- Additional tests, such as:
- 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels
- Phosphorus, magnesium, renal function tests (BUN, creatinine)
- 24-hour urine calcium
- Complete metabolic panel
- Liver function tests to determine if the alkaline phosphatase elevation is hepatic or bone-related
- A bone-specific alkaline phosphatase can help differentiate between hepatic and bone-related causes of alkaline phosphatase elevation
- Imaging studies, such as neck ultrasound or chest X-ray, may be indicated based on initial lab results
- A detailed medication review is essential, as some medications can cause hypercalcemia The patient's obesity may contribute to vitamin D deficiency, which paradoxically can be associated with primary hyperparathyroidism, so this relationship should be considered during evaluation 1.
From the Research
Differential Diagnoses
- Primary hyperparathyroidism (PHPT) is a possible diagnosis, as it is the most common cause of hypercalcemia in the outpatient setting 2
- Other causes of hypercalcemia, such as malignancy, vitamin D intoxication, and familial hypocalciuric hypercalcemia, should also be considered
- The mildly elevated alkaline phosphatase level may indicate bone involvement, but it is not specific to any particular diagnosis
Next Steps in Workup
- Measure parathyroid hormone (PTH) level to confirm or rule out PHPT 2
- Check vitamin D level to assess for deficiency or intoxication 3
- Perform renal function tests to evaluate for impaired renal function 2
- Consider imaging studies, such as ultrasound or sestamibi scan, to evaluate the parathyroid glands 4
- Review the patient's medical history and perform a physical examination to look for signs of hypercalcemia or target organ damage 2