Hypercalcemia

1) Primary Hyperparathyroidism - #1 cause in patients < 60, usually present with mild hypercalcemia (<13).  Most often due to a parathyroid adenoma.

2) Malignancy - #1 cause in patients > 60, often present with significant elevation in Ca (>13).  Three mechanisms:

i) Osteolytic lesions – from multiple myeloma, or metastatic solid tumors to the bone (most common = breast). 

ii) Elevated PTHrP – most commonly from squamous cell ca (lung, ENT), other solid tumors, and lymphoma, and

iii) Increased production of 1,25 dihydroxyvitamin D by tumors – Hodgkins and some non-Hodgkins lymphoma.

Primary hyperparathyroidism and Malignancy account for > 90% of cases.

Other less common etiologies:
3) Granulomatous diseases – e.g. Sarcoidosis, TB – due to activation of calcitriol (1,25 di-OH vit D) by macrophages
4) Milk-Alkali Syndrome – excess calcium carbonate (tums), usually for dyspepsia
5) Immobilization – due to rapid bone turnover
6) Hyperthyroidism – causes increase in bone resorption

Clinical Manifestations of Hypercalcemia:
Neuro changes: confusion, ams, coma
Psychosis
GI ulcers (calcium increases gastric secretion)
abdominal pain, nausea and vomiting
constipation
kidney stones, renal failure
pancreatitis
polyuria, polydypsia (Calcium induced Diabetes insipidus)
bradycardia
AV block
short qt

Management:
1. IVF and Diuretics act quickly: IV NS increases GFR and filtering of Ca, while diuretics increase Ca secretion
2.Calcitonin acts within hours but only works for 2-3 days
3.Steroids only work if 1,25 OH vit D is increased. They act at the level of the macrophages and decrease production of 1,25 OH D, which in turn decreases GI absorption of Calcium. Steroids take weeks to decrease the calcium level
4. Bisphosphonates act at the level of the bone. They take days to work, but the effect may last for weeks to months. They are only effective when calcium is coming from the bone ie) lytic lesions, pth or pthrp-mediated hypercalcemia. 1,25 OH D mediated hypercalcemia may not respond to bisphosphonates

(Ellen Eaton MD, 7/29/10)

(Chanu Rhee MD, 12/14/10)