Review Question - QID 100918

The patient described above has sarcoidosis, which can be associated with increased serum calcium, secondary to increased conversion of 25-hydroxyvitamin D (calcidiol) to 1,25-dihydroxyvitamin D3 (calcitriol) by 1-alpha hydroxylase produced by the macrophages of granulomas.

Sarcoidosis is a multisystem disease that can affect nearly any organ system and often presents with non-specific complaints such as fatigue, weight loss, and fever. Hypercalcemia is rare (~11% of patients with sarcoidosis), but can be problematic since it may lead to kidney stones and other symptoms. Corticosteroids remain the mainstay of therapy for serious disease manifestations, including hypercalcemia, though a variety of steroid-sparing agents are also used. For example, anti-malarial agents, such as hydroxychloroquine, can be used alternatively to treat hypercalcemia.

Belfer et al. note the increased absorption of dietary calcium by patients with sarcoidosis because of elevated calcitriol levels. Though hypercalcemia is rare, high levels of serum calcium place the patient at risk for conditions such as calcium nephropathy, as well as renal failure. Hydroxychloroquine is a beneficial drug treatment.

Katakami discusses the process leading to hypercalcemia in patients with sarcoidosis. Gamma-interferon released by lymphocytes promotes the production of calcitriol by stimulating granuloma formation.

Figure A shows a CXR of a patient with bilateral lymphadenopathy.
Figure B shows the a biopsy of the interstitium of the lung of a patient with sarcoidosis. Notice the many discrete granluomas scattered throughout the interstitium.

Incorrect Answers:
Answer 2: Increased serum ACE is commonly reported in sarcoidosis, though it is not a reliable enough to be of diagnostic value.
Answer 3: Hypervitaminosis D not Hypovitaminosis D (from increased action of 1-alpha hydroxylase) is more consistent with sarcoidosis.
Answer 4: Increased ADH would be more consistent with small-cell carcinoma.
Answer 5: Increased PTHrP is more consistent with squamous-cell carcinoma.