Hypercalacemia

ü  低鈣àPTH釋放àbone resorption, calcium reabsorption in the kidney, and increased production of activated vitamin D in the kidneyà升鈣

ü  PTH-mediated bone resorption is mediated by the RANKRANK ligand-OPG system.

ü  Hypercalcemia is an elevation of free, ionized calcium in the serum.

ü  Levels <12 mg/dL are asymptomatic; levels >15 mg/dL may cause severe symptoms. Rapidly progressing hypercalcemia is more likely to be symptomatic.

ü  The two most common causes of hypercalcemia: primary hyperparathyroidism and malignancy.

ü  原因:

²  increased bone resorption

Ø  PTH高: 80%是adenoma，還有hyperplasia, carcinoma, MEN

Ø  CKD: 因為鈣低、Vit-D缺乏à2^nd hyperparathyroidismàtertiary

Ø  Malignancy:

u  PTHrP: primarily in squamous cell carcinomas, can also be seen in cancers of the kidney, ovary, and bladder. It is a frequent complication in lymphomas associated with HTLV-1.

u  Cancers with extensive skeletal metastases (multiple myeloma, breast cancer): release of cytokines (TGF-b, IL-1, IL-6, and macrophage inflammatory protein-1α) leads to osteoclast differentiation and inhibition of osteoblasts.

u  Ectopic: carcinomas of the lung, thymus, ovary, and undifferentiated neuroendocrine tumors

u  lymphoma and some ovarian dysgerminomas: increasing 1-hydroxylation of vitamin Dà higher 1,25-OH-vitamin D àincreased calcium absorption

Ø  Thyrotoxicosis: increased bone turnover

Ø  Excessive intake of vitamin A (>50,000 to 100,000 IU daily): IL-6增加

Ø  Prolonged immobilization

²  Vitamin D-dependent mechanisms

Ø  Chronic ingestion of more than 50,000 to 100,000 IU/day of ergocalciferol (vitamin D2) or cholecalciferol (vitamin D3)

Ø  Excessive or accidental ingestion of 1,25(OH)2D (calcitriol)àshould resolve within days.

Ø  Granulomatous: conversion of 25(OH)D to 1,25(OH)2D by macrophages

²  Milk–alkali syndrome: ingestion of milk or calcium carbonate, in the treatment of dyspepsia or osteoporosis. à associated with metabolic alkalosis and renal insufficiency

²  Other hormonal mechanisms

²  Drugs:

Ø  Thiazide: mild and transient (1 to 2 weeks)

Ø  Lithium: shifts the set point for calcium

Ø  Additional medications: estrogens, growth hormones, ganciclovir, omeprazole, 8-Cl-cAMP chemotherapy, manganese toxicity, foscarnet, hepatitis B vaccination, theophylline

²  Familial hypocalcuric hypercalcemia: 無症狀，heterozygous loss-of-function mutation in the calcium sensing receptoràincreased set point for calcium homeostasisàmildly elevated PTH, hypocalcuria, and hypermagnesemia

²  Miscellaneous other causes: adrenal insufficiency, pheochromocytoma, pancreas islet cell tumors, rhabdomyolysis恢復期, aluminum intoxication(diminished osteoblastic activity and reduced calcium incorporation into the skeleton)

ü  S/S: Neuropsychiatric symptoms, arrhythmia, constipation, polyuria and polydipsia, nephrolithiasis, Skeletal manifestations (osteoporosis or osteitis fibrosa cystica)

ü  先抽iPTH

²  高à驗尿鈣: 如果FeCa<1%猜FHH，>1%猜primary hyperpara

²  低à猜惡性、驗Vit-D: 如果1,25OH高猜lymphoma、granulomatous，如果25OH高猜Vit-D中毒。如果Vit-D正常猜雜七雜八的東西。