Hypercalcemia and Osseous metastases

Today we discussed a case of a healthy middle-aged woman presenting with 2 months of left shoulder pain who was ultimately found to have poorly-differentiated rectal adenocarcinoma with diffuse metastases to bone (including a pathologic left humerus fracture) complicated by hypercalcemia and dense bone marrow infiltration leading to pancytopenia and coagulopathy. A couple of learning points:

1) Hypercalcemia diagnostic approach (adapted from this nice AAFP review):

  • Start with a careful H&P focusing on symptoms of hypercalcemia (recall your stones, groans, moans, bones, psychiatric overtones) and culprit meds (thiazides, lithium, Ca supplements, or high dose Vit A/ retinoids)
  • Labs: start with albumin (if low, consider ionized calcium), phosphate, parathyroid hormone (PTH) level, and vitamin D.
  • Consider the chloride-phosphate ratio in differentiating if the process is driven by hyperparathyroidism. If the ratio of Cl to phosis greater than 33; consider hyperparathyroidism or if it is less other causes. See the original Annals 1974 article here.
  • If the PTH is high or normal, check 24 hour urinary Ca level. If this is low, consider Familial hypocalciuric hypercalcemia; if high, consider hyperparathyroidism (keeping in mind that low vitamin D will cause elevated PTH and can be corrected with supplementation).
  • If the PTH is suppressed, malignancies, granulomatous diseases, and endocrinopathies are on the differential. Consider checking a PTHrp (PTH related peptide can be elevated in adenocaricinoma and squamous cell lung cancers), alkaline phosphatase (increased in bone lysis), SPEP/UPEP (for multiple myeloma), 1, 25 vitamin D (calcitriol which is elevated in granulomatous diseases)--and possibly TSH, cortisol, IGF-1.

2) Malignancies commonly metastasizing to bone include breast, thyroid, renal, and prostate. Colorectal cancer accounts for 1% of osseous metastases. Further, osseous metastases located distal to the pelvis and/or vertebrae are even rarer in rectal carcinoma and are associated with a poor prognosis.