Hyperparathyroidism

Parathyroid hormone increases ECF calcium levels. Regulated by calcium and vitamin D. Parathyroid hormone protects against hypocalcemia by causing calcium release from the bones and reabsorption from the kidneys. Calcium is a vital mineral that participates in various cellular processes, including muscle contraction, nerve conduction, bone and tooth formation, and blood clotting (for a full review of parathyroid hormone and calcium physiology, please see the tutorial on Parathyroid Hormone & Calcium Homeostasis). Physiology Review: Both calcium and phosphate are stored within the hydroxyapatite crystals of bone, and calcium can be retained or excreted in renal and digestive systems, depending on the body's needs. A typical reference blood calcium range is 2.2-2.6 mmol/L (8.6-10.3 mg/dL). Parathyroid gland location: posterior aspect of the thyroid gland. Other key organs that engage in calcium homeostasis: Kidneys, small intestine, particularly the duodenum and, bone. In response to reduced extracellular calcium concentration, the parathyroid glands secrete parathyroid hormone (PTH). Effects of parathyroid hormone on the bones and kidneys:

• Prolonged exposure to parathyroid hormone promotes resorption of old bone, and, therefore, the release of calcium and phosphate into extracellular fluid (episodic, transient binding of parathyroid hormone causes an increase in new bone synthesis).
• In the kidneys, parathyroid hormone works directly and indirectly to raise extracellular calcium levels:

Parathyroid hormone increases calcium reabsorption in the distal convoluted tubule of the nephrons. It also stimulates activation of Vitamin D (activated form = 1,25(OH)2-VD).

• Vitamin D acts on the nephron to increase reabsorption of calcium and phosphate.
• In the small intestine, Vitamin D increases calcium and phosphate reabsorption.
• In the bones, Vitamin D works with parathyroid hormone to facilitate skeletal remodeling, which requires both synthesis and resorption of bone.

Thus, the total effect of parathyroid hormone is to elevate extracellular calcium levels. If Vitamin D levels are high, parathyroid hormone secretion is inhibited. In most cases of hyperparathyroidism, partial or total gland removal is prescribed. Parathyroid gland removal can lead to "hungry bone syndrome" which manifests as severe and prolonged hypocalcemia after gland removal. Prior to gland removal, the bones were heavily shifted towards resorption and calcium release; it is thought that, after the glands are removed, bones shift towards growth and high calcium uptake. Patients tend to feel tired and weak, or can have more severe responses to the hypocalcemia, which we address in the next section. Too much parathyroid hormone production. Hyperplasia, adenoma, or carcinoma of the parathyroi glands. Elevated parathyroid hormones stimulate calcium release and retention, resulting in high calcium levels. Early and mild cases are often asymptomatic, or present with nonspecific symptoms like fatigue and depression. Because of increased screening for hormone and electrolyte imbalances, most people diagnosed with primary hyperparathyroidism fall into the asymptomatic or mild categories. Chronic and severe hyperparathyroidism experience a variety of signs and symptoms that can be remembered with the expression "stones, bones, abdominal groans, thrones, moans, neuropsychiatric overtones and blood flows." Renal effects include kidney stones (from excessive calcium retention), polyuria, and renal insufficiency – this accounts for the "stones and thrones" (thrones meaning the "porcelain throne" that patients spend more time on, thanks to the kidney stones and polyuria). Bone pain, fractures, and osteitis fibrosis cystica caused by hyperparathyroidism. In areas where detection of hyperparathyroidism is delayed, osteitis fibrosis cystica is still a classic marker of the disorder. We show three key features of osteitis fibrosis cystica:

• "Brown tumor" (shown in a distal phalange). Brown tumors are giant cell lesions caused by excessive bone resorption with fibrovascular tissue replacement and hemorrhaging (hence the reddish-brown color of the lesions and their name). These tumors are most often found in the extremities, clavicles, ribs, mandible, and pelvic girdle.
• Subperiosteal resorption of cortical bone (shown on middle phalange)
• "Salt and pepper skull" (aka, pepper pot skull) has numerous small but well-defined spots of trabecular bone resorption.

Be aware that osteitis fibrosis cystica is also associated with secondary hyperparathyroidism, which we'll address, soon. GI effects include nausea, vomiting, constipation, pancreatitis, and peptic ulcers. The volume depletion caused by renal and gastrointestinal effects of primary hyperparathyroidism (vomiting, polyuria) exacerbates hypercalcemia, so we need to pay attention to fluid loss in these patients. Muscle weakness is common, and accounts for the "moans." Lethargy and confusion; severe cases of hyperparathyroidism can lead to coma. Including hypertension, left ventricular hypertrophy, arrhythmias, calcium valvular deposit, a shortened QT interval, and heart failure. Patients present with primary hyperparathyroidism but have calcium levels within the normal range. In some studies, patients progressed to hypercalcemia over time, leading some authors to wonder if this is merely an early stage of Primary hyperparathyroidism. Chronic kidney disease Vitamin D or calcium deficiency. Chronic kidney disease is a significant cause of secondary hyperparathyroidism in the United States. As a result of diseased, ineffective renal functioning: Phosphate excretion and activation of Vitamin D are both reduced, and calcium reabsorption falls. As a result of low calcium and high phosphate levels, parathyroid hormone is elevated (recall that a key signal for parathyroid hormone release is low extracellular calcium levels). Renal osteodystrophy in patients with chronic kidney disease. Similar to patients with primary hyperparathyroidism, patients experience bone pain, increased fractures, and osteitis fibrosa cystica. Calciphylaxis can also occur; indicate that calcium-phosphate products deposit in the blood vessels, fat, and skin, leading to thrombosis and necrosis. Though rare, this is a serious complication of secondary hyperparathyroidism.