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General Reference ⬇

Jama 2005;293:1772; Nejm 2004;350:1746

Pathophys and Cause ⬆ ⬇

Cause:

Pathophys:PTH is stimulated by low calcium; increases renal calcitrol (activated, 1.25 OH vit D) production (Ann IM 1994;121:633), which in turn increases gi calcium absorption, osteoclastic activity, and renal tubule calcium resorption and PO4 loss. Relative imbalance of latter can cause stones (Nejm 1980;302:421). Calcium set point is raised in primary hyperparathyroidism.

Epidemiology ⬆ ⬇

Most commonly sporadic nonfamilial; prevalence now dropping, unclear why (Ann IM 1997;126:433); 1/1000 prevalence in US, highest in postmenopausal women

Sometimes associated with multiple endocrine neoplasia (MEN) syndromes (Nejm 1990;322:723).

  • MEN type I: (95% have elevated PTH—Nejm 1986;314:1287): hyperparathyroidism; adenomas of pituitary (30%), often prolactin-producing; pancreatic adenomas, esp gastrinomas (causing ZE syndrome) or insulin-producing ones (37%). Autosomal dominant from loss of suppressor gene on chromosome 11 (Nejm 1989;321:218).
  • MEN type II: hyperparathyroidism, pheochromocytomas, and medullary carcinoma of thyroid

Signs and Symptoms ⬆ ⬇

Sx:of hypercalcemia (Hypercalcemia); asx cases found incidently by high calcium level on chem profiles often/usually are stable over many years and can simply be monitored

Si:of hypercalcemia, esp fatigue and muscular weakness (Ann IM 1975;82:474); palpable neck tumor occasionally

Course ⬆ ⬇

Carcinoma is invariably fatal w progressive hypercalcemia. Primary hyperparathyroidism does not progress in most patients.

Complications ⬆ ⬇

Renal stones in 20% of patients with elevated PTH; 5% of patients with stones have elevated PTH; and eventually, some renal failure

Osteoporosis, esp of distal cortical bone (Colles fx's), or even von Recklinghausen's syndrome with generalized decalcification and fractures, brown tumors and bone cysts, and renal stones

r/o hypocalciuric hypercalcemia (Hypercalcemia), which is not helped by parathyroidectomy

Lab and Xray ⬆ ⬇

Lab:

Chem:Serum Ca++ >10.5 mg %, 30% false neg. PTH level high, or PTH/Ca ratios high (PTH abnormally "normal"). Urinary Ca++ >250 mg (females), >300 mg/24 h (males); 10% false pos, 30% false neg

Xray:

Hands occasionally show punched-out lesions in phalanges, subperiosteal bone resorption distally with unique lacey appearance; dental films may show erosion of lamina dura, but many false pos and neg; clavicle may have distal end resorption

DEXA scan shows osteoporosis

Scan w technetium/sestamibi can localize for surgery and distinguish adenoma from hyperplasia (J Nuc Med 1992;33:1801; Arch Surg 1996;131:1074)

Treatment ⬆

Rx:

Surgical excision of adenomas, even if asx if young (under age 50 yr), if osteoporosis (T score <–2.5), high serum calcium levels >12 mg %), urinary Ca >400 mg/24 h, and/or renal stones; less urgent if asx and doesn't meet these criteria since no increase in vertebral fractures (Ann IM 1991;114:593); 5% of population have mediastinal and/or paraesophageal parathyroids

Cinacalcet (Sensispar) (Med Let 2004;46:80) 30+ mg po qd; a calcium mimetic, esp for secondary hyperparathyroidism, eg renal failure and functioning PTH-producing carcinomas; $10/d for 30 mg

Vit D 400 IU plus 1-1.5 gm of calcium po qd

Biphosphonates like alendronate

Raloxifene (Evista), a selective estrogen receptor modulator (Estrogen Replacement Therapy) perhaps (J Clin Endocrinol Metab 2003;88:1174); or high-dose estrogens like 1.25 mg po qd of conjugated estrogens, which increase calcium absorption in bones, but risks outweigh benefits

of hypercalcemia (Hypercalcemia)