Primary Hyperparathyroidism

Excerpt

Primary hyperparathyroidism is a relatively common endocrine disorder characterized by increased secretion of parathyroid hormone and hypercalcemia that can result in significant renal and skeletal complications. However, most patients diagnosed in recent decades have relatively mild degrees of hypercalcemia. Although once known for the aphorism as a disease of "stones, bones, groans, and moans," as suggested by Fuller Albright, primary hyperparathyroidism is usually asymptomatic when initially diagnosed. Stones refers to nephrolithiasis caused by hypercalciuria. Groaning refers to abdominal pain from constipation often produced by hypercalcemia or bone pain, which can directly or indirectly result from abnormal remodeling, fractures, or osteoporosis. Neuropsychiatric complaints can also be symptoms of primary hyperparathyroidism. Some degree of depression, anxiety, fatigue, cognitive dysfunction, memory loss, and similar psychological symptoms are found in 23% of patients severely affected with hyperparathyroidism. Historically, primary hyperparathyroidism was diagnosed when patients presented with recurrent nephrolithiasis or bone disease. Radiological findings of primary hyperparathyroidism include osteitis fibrosa cystica, brown tumors of bones, evidence of subperiosteal bone resorption, "salt and pepper" erosions of the skull bones, and tapering of the distal portions of the finger bones and clavicles. While radiological evidence of primary hyperparathyroidism is now rare, bone densitometry can detect skeletal abnormalities well before these more obvious skeletal abnormalities become clinically apparent.

Primary hyperparathyroidism involves excess parathyroid hormone (PTH) production by 1 of the 4 very small parathyroid glands normally located peripherally along the margins on the posterior aspect of the thyroid gland. The average parathyroid gland is approximately 6mm by 4 mm, weighing only 20 to 40 mg. Surgery remains the definitive, curative treatment, but observation alone or medical therapy is appropriate for selected patients. PTH secretion is a tightly regulated process involving a complex interplay among serum calcium, serum phosphorus, vitamin D, activated vitamin D, and fibroblast growth factor-23 (FGF23). The primary regulator of PTH release is serum calcium, acting on the calcium-sensing receptors on the parathyroid surface. Calcitriol (ie, activated 1,25-vitamin D) and possibly phosphorus reduce PTH release. A basic understanding of normal calcium homeostasis and the natural history of primary hyperparathyroidism is essential to diagnose and properly manage patients with this disorder.