Table 2.

Diseases leading to hypercalcemia and indications for diagnosisa

CategoryConditionMechanismIndications for Diagnosis
aPTH, parathyroid hormone; PTHrP, PTH-related peptide; IL, interleukin; TNF, tumor necrosis factor; TSH, thyroid-stimulating hormone; ACE, angiotensin-converting enzyme.
PTH-induced, parathyroidpHPTIncreased intestinal Ca2+ absorption, renal Ca2+ absorption, osteolysisCa2+ ↑, PTH ↑
Tertiary hyperparathyroidismSameHistory: long-lasting secondary hyperparathyroidism, Ca2+ ↑, PTH ↑
Lithium-induced (long-term treatment)SameHistory: long-lasting lithium treatment, Ca2+ ↑, PTH ↑
Nonparathyroid paraneoplasticHumoral hypercalcemia of malignancySecretion of osteolytic factors like PTHrP, IL-1, IL-6, TNF, prostaglandins, and calcitriolStaging for malignancy, tumor markers ↑, PTHrP ↑, calcitriol ↑, PTH ↓
mechanicalImmobilization at preexisting bone diseases, e.g., multiple fractures (in young patients), osteoporosis, Paget's disease of bone, acute intermittent porphyriaCalcium release from the skeleton attributable to immobilizationHistory, x-rays, exclusion of pHPT (PTH ↓)
thyroidalThyrotoxicosisIncrease in bone turnoverT3 ↑, T4 ↑, TSH suppression, PTH ↓
corticoadrenalAcute disease in glucocorticoids, acute Addison's disease, postoperatively in Cushing's diseaseLack of a PTH antagonistGlucocorticoid diagnostic tests, history, PTH ↓
renalAcute renal insufficiencyDecrease in calciuriaHistory, renal function ↓
ExsiccosisDecrease in calciuriaHistory, renal function ↓
FHHDecrease in calciuria attributable to a calcium sensor defectCalciuria ↓, phosphaturia normal, PTH normal or ↑, Ca2+ clearance/creatinine clearance, <0.01
Hard-water syndromeDialysis using too great a calcium gradientControl of dialysate
calcitriol-inducedSarcoidosisOverproduction of calcitriolX-ray of lungs, ACE ↑, calcitriol ↑
Tuberculosis, histoplasmosis (lepra)Overproduction of calcitriolX-ray of lungs, tuberculosis diagnostic tests, serologic findings, calcitriol ↑
viralAIDSOsteolysis by virusesHistory, serologic findings
PTHrP-inducedInfantile idiopathic hypercalcemia(PTHrP ↑ ?)Age, exclusion of other causes, PTH ↓, PTHrP ↑
iatrogenic/induced by medicationsVitamin D intoxicationCalcium absorption ↑, osteolysis ↑History, calcidiol ↓, PTH ↑
Vitamin A intoxicationOsteolysisHistory
Thiazides (in conditions prone to hypercalcemia)Calciuria ↓History
Tamoxifen in metastatic breast cancer“Flare up” because of paradoxical receptor activationHistory
Salicylic acid intoxication?History