Etiologies of Hypercalcemia

table of etiologies of hypercalcemia 󰒗

hyperparathyroidism (HPT)

• (NEJM 2018;379:1050; Lancet 2018;391:168)

詳見Primary Hyperparathyroidism.

• 1°: adenoma (85%), hyperplasia (15–20%; spont. vs. MEN1/2A), carcinoma (<1%), meds (Lithium → ↑ PTH)
• 3°: after long-standing 2° hyperparathyroidism (as in renal failure) → autonomous nodule develops, requires surgery
• Secondary hyperPTH

Familial hypocalciuric hypercalcemia (FHH)

Inact. mut. in Ca-sensing receptor (FHH1), Gα11 (FHH2), AP2S1 (FHH3) → ↑ Ca set point; ± mild ↑ PTH Acquired form due to autoAb vs. Ca-sensing receptor (rare) FECa [(24-h UCa/serum Ca) / (24-h UCr/serum Cr)] <0.01

Malignancy

(NEJM 2022;386:1443) PTH-related peptide (PTHrP) → humoral ↑ Ca of malignancy (eg, squamous cell cancers, renal, breast, bladder) Cytokines → ↑ osteoclast activity (eg, hematologic malig) ↑ 1,25-(OH)2D (eg, rare lymphomas) Local osteolysis (eg, breast cancer, myeloma)

Vitamin D excess

Granulomas (sarcoid, TB, histo, GPA) → ↑ 1-OHase → ↑ 1,25-(OH)2D. Vitamin D intoxication.

↑ Bone turnover

Hyperthyroidism, immobilization + Paget’s disease, vitamin A

Miscellaneous

Thiazides; Ca-based antacids or massive dairy consumption (milk-alkali syndrome); adrenal insufficiency

Among inPts w/ hypercalcemia: 45% have cancer, 25% 1° HPT, 10% CKD → 3° HPT