•Renalchanges.PTH-inducedhypercalcemiafavorstheformationofurinarytractstones(nephrolithiasis)aswellascalcificationoftherenalinterstitiumandtubules(nephrocalcinosis).
•Metastaticcalcificationsecondarytohypercalcemiaalsomaybeseeninothersites,includingthestomach,lungs,myocardium,andbloodvessels.
Primary hyperparathyroidism usually is a disease of adults and is much more common in women than in men (gender ratio of nearly 4:1). The most common manifestation of primary hyperparathyroidism is an increase in serum ionized calcium. In fact, primary hyperparathyroidism is the most common cause of clinically silent hypercalcemia. Other conditions also may produce hypercalcemia (
Table 20.4 ). The most common cause of clinically apparent hypercalcemia
Table20.4CausesofHypercalcemia
PTH, Parathyroidhormone;PTH-rP, PTH-relatedprotein.*Primaryhyperparathyroidismisthemostcommoncauseofhypercalcemiaoverall.
†Secondaryandtertiaryhyperparathyroidismaremostcommonlyassociatedwithprogressiverenalfailure.
http://ebooksmedicine.net in adults is cancer, which can cause hypercalcemia through a variety of mechanisms, including secretion of PTH-like polypeptides and osteolytic bone metastases (Chapter 6). The prognosis for patients with malignancy-associated hypercalcemia is poor, because it often occurs in those with advanced cancers. In individuals with hypercalcemia caused by parathyroid hyperfunction, serum PTH is inappropriately elevated, whereas serum PTH is low to undetectable in those with hypercalcemia caused by nonparathyroid diseases, including malignancy. Other laboratory alterations referable to PTH excess include hypophosphatemia and increased urinary excretion of both calcium and phosphate.
Primary hyperparathyroidism traditionally has been associated with a constellation of symptoms that include painful bones, renal stones, abdominal groans, and psychic moans. Pain, secondary to fractures of bones weakened by osteoporosis or osteitis fibrosa cystica and resulting from renal stones, with obstructive uropathy, was at one time a prominent manifestation of primary hyperparathyroidism. Because serum calcium is now routinely assessed in most patients who need blood tests for unrelated conditions, hyperparathyroidism is usually detected early in its course. Hence, many of the classic clinical manifestations, particularly those referable to bone and renal disease, are seen much less frequently. Additional signs and symptoms that may be encountered in some cases include the following:
Gastrointestinal disturbances, including constipation, nausea, peptic ulcers, pancreatitis, and gallstones
Central nervous system alterations, including depression, lethargy, and seizures
Neuromuscular abnormalities, including weakness and hypotonia
Although some of these alterations (e.g., polyuria and muscle weakness) are clearly related to hypercalcemia, the pathophysiology of many of the other manifestations of the disorder remains poorly understood.
Secondary hyperparathyroidism is caused by chronic depression of serum calcium levels, most often as a result of renal failure, leading to compensatory overactivity of the parathyroids. The mechanisms by which chronic renal failure induces secondary hyperparathyroidism are complex and not fully understood. Chronic renal insufficiency is associated with decreased phosphate excretion, which in turn results in hyperphosphatemia. The elevated serum phosphate levels directly depress serum calcium levels. In addition, loss of renal α1-hydroxylase activity, which is required for the synthesis of the active form of vitamin D, reduces the intestinal absorption of calcium (Chapter 8). These alterations cause chronic hypocalcemia, which stimulates the activity of the parathyroid glands.