Diagnosis: Sarcoidosis
The most likely diagnosis is sarcoidosis (Option E), based on the combination of hypercalcemia with elevated ACE levels, elevated 24-hour urinary calcium excretion, and PTH levels in the normal range despite hypercalcemia. 1
Diagnostic Reasoning
Key Laboratory Findings Point to Sarcoidosis
- Elevated ACE (88 IU/L, normal 10-70) is a characteristic finding in sarcoidosis, though not specific 1
- Hypercalcemia (2.89 mmol/L) with inappropriately normal PTH (7.0 pmol/L) indicates PTH-independent hypercalcemia 2
- Elevated 24-hour urinary calcium excretion confirms true hypercalcemia with increased intestinal calcium absorption, typical of granulomatous disease 1
- Normal renal function makes chronic kidney disease-related calcium disorders unlikely 1
Why Other Diagnoses Are Excluded
Primary hyperparathyroidism (Option D) is ruled out because PTH should be elevated or inappropriately normal-high (>9.3 pmol/L upper limit) in the setting of hypercalcemia, not mid-normal range 2. In PHPT, 24-hour urinary calcium is typically elevated, but the normal PTH in this context excludes this diagnosis 2.
Benign hypocalciuric hypercalcemia (Option A) is excluded because urinary calcium excretion is elevated, not low 2. BHH characteristically presents with low urinary calcium excretion due to increased renal calcium reabsorption.
ACE inhibitor-related hypercalcemia (Option B) is not a recognized cause of hypercalcemia 1. ACE inhibitors can cause hyperkalemia and renal dysfunction, but not hypercalcemia 3.
Hypercalcemia of malignancy (Option C) is less likely given the elevated ACE level and significant smoking history that ended 2 years ago 4. While malignancy causes approximately 45% of hypercalcemia cases requiring hospitalization, it typically presents with suppressed PTH (<1.6 pmol/L) and very rapid onset over days to weeks 2, 4. The constitutional symptoms and confusion could fit malignancy, but the elevated ACE strongly favors sarcoidosis 1.
Pathophysiology in Sarcoidosis
Granulomatous macrophages in sarcoidosis produce 1α-hydroxylase, which converts 25-(OH) vitamin D to active 1,25-(OH)₂ vitamin D (calcitriol), leading to increased intestinal calcium absorption and subsequent hypercalcemia and hypercalciuria 1. This mechanism explains why PTH is appropriately suppressed or normal-low in response to hypercalcemia 1.
Clinical Context Supporting Sarcoidosis
- Significant smoking history (30 pack-years) is relevant as environmental exposures can trigger sarcoidosis 1
- General malaise, confusion, and abdominal pain are constitutional symptoms consistent with hypercalcemia of any cause, occurring in approximately 20% of patients with mild hypercalcemia 2
- Elderly female presentation fits the demographic for sarcoidosis, which can present at any age 1
Critical Next Steps
Confirm sarcoidosis diagnosis with chest imaging (chest X-ray or CT) looking for hilar lymphadenopathy or pulmonary infiltrates, and consider tissue biopsy showing non-caseating granulomas if imaging is suggestive 1. Measure serum 1,25-(OH)₂ vitamin D levels, which should be elevated in sarcoidosis-related hypercalcemia 1.