Table 3. Causes of hypercalcemia.
PTH: parathyroid hormone; CKD: chronic kidney disease; PTHrP: parathyroid hormone-related protein; CaSR: Ca+2-sensing receptor
| Causes |
| PTH excess (primary hyperparathyroidism) due to parathyroid gland adenoma (80% of cases) or hyperplasia (10-15% of cases). Primary hyperparathyroidism is part of the multiple endocrine neoplasia (MEN) 1 and 2A. Parathyroid carcinoma is rare |
| Humoral hypercalcemia of malignancy |
| Osteolytic bone metastases as in multiple myeloma, and metastatic breast and lung cancers |
| Milk-alkali syndrome (increased intestinal absorption of Ca+2 due to excessive intake of Ca+2, antacids, and vitamin D) |
| 25(OH)D toxicity (usually due to excess intake of over-the-counter supplements) |
| 1,25(OH)2D excess as in excessive intake, lymphoma, and granulomatous disorders such as sarcoidosis, tuberculosis, leprosy, berylliosis, histoplasmosis, and Farmer’s lung |
| Immobilization |
| Paget’s disease |
| Thyrotoxicosis, acromegaly, pheochromocytoma, acute adrenal insufficiency |
| Thiazide diuretics (hypercalcemia is usually mild, and hyperparathyroidism should be excluded), lithium, theophylline, growth hormone, recombinant human PTH (teriparatide), and hyperalimentation solutions |
| Adynamic bone disease (decreased bone formation) as in patients with end-stage renal disease (ESRD) due to the inability of the bone to take up Ca+2 |
| Excess intake of dietary Ca+2 in patients with CKD and in children |
| Vitamin A toxicity (hypervitaminosis A) |
| Neonatal severe hyperparathyroidism (homozygous CaSR-inactivating mutations) |
| Familial hypocalciuric hypercalcemia (FHH), which is due to heterozygous CaSR-inactivating mutations |
| Hypercalcemia of pregnancy (uncommon) due to the production of PTHrP |