In primary hyperparathyroidism, an abnormality of the parathyroid glands causes inappropriate, excess PTH secretion. The cause of primary hyperparathyroidism ordinarily is a tumor of one of the parathyroid glands; such tumors occur much more frequently in women than in men or children, mainly because pregnancy and lactation stimulate the parathyroid glands and therefore predispose to the development of such a tumor.
Hyperparathyroidism causes extreme osteoclastic activity in the bones. This elevates the calcium ion con-centration in the extracellular fluid while usually depressing the concentration of phosphate ions because of increased renal excretion of phosphate.
Bone Disease in Hyperparathyroidism. Although in mildhyperparathyroidism new bone can be deposited rapidly enough to compensate for the increased osteo-clastic reabsorption of bone, in severe hyperparathy-roidism the osteoclastic absorption soon far outstrips osteoblastic deposition, and the bone may be eaten away almost entirely. Indeed, the reason a hyper-parathyroid person seeks medical attention is often a broken bone. Radiographs of the bone show extensive decalcification and, occasionally, large punched-out cystic areas of the bone that are filled with osteoclasts in the form of so-called giant cell osteoclast “tumors.” Multiple fractures of the weakened bones can result from only slight trauma, especially where cysts develop. The cystic bone disease of hyperparathyroidism is called osteitis fibrosa cystica.
Osteoblastic activity in the bones also increases greatly in a vain attempt to form enough new bone to make up for the old bone absorbed by the osteoclastic activity. When the osteoblasts become active, they secrete large quantities of alkaline phosphatase. There-fore, one of the important diagnostic findings in hyper-parathyroidism is a high level of plasma alkaline phosphatase.
Effects of Hypercalcemia in Hyperparathyroidism. Hyper-parathyroidism can at times cause the plasma calcium level to rise to 12 to 15 mg/dl and, rarely, even higher. The effects of such elevated calcium levels, as detailed earlier, are depression of the central and peripheral nervous systems, muscle weakness, constipa-tion, abdominal pain, peptic ulcer, lack of appetite, and depressed relaxation of the heart during diastole.
Parathyroid Poisoning and Metastatic Calcification When, onrare occasions, extreme quantities of PTH are secreted, the level of calcium in the body fluids rises rapidly to high values. Even the extracellular fluid phosphate con-centration often rises markedly instead of falling, as is usually the case, probably because the kidneys cannot excrete rapidly enough all the phosphate being absorbed from the bone. Therefore, the calcium and phosphate in the body fluids become greatly supersatu-rated, so that calcium phosphate (CaHPO4) crystals begin to deposit in the alveoli of the lungs, the tubules of the kidneys, the thyroid gland, the acid-producing area of the stomach mucosa, and the walls of the arter-ies throughout the body. This extensive metastatic dep-osition of calcium phosphate can develop within a few days.
Ordinarily, the level of calcium in the blood must rise above 17 mg/dl before there is danger of parathyroid poisoning, but once such elevation develops along with concurrent elevation of phosphate, death can occur in only a few days.
Formation of Kidney Stones in Hyperparathyroidism Mostpatients with mild hyperparathyroidism show few signs of bone disease and few general abnormalities as a result of elevated calcium, but they do have an extreme tendency to form kidney stones. The reason is that the excess calcium and phosphate absorbed from the intes-tines or mobilized from the bones in hyperparathy-roidism must eventually be excreted by the kidneys, causing a proportionate increase in the concentrations of these substances in the urine. As a result, crystals of calcium phosphate tend to precipitate in the kidney, forming calcium phosphate stones.Also, calcium oxalate stones develop because even normal levels of oxalate cause calcium precipitation at high calcium levels.
Because the solubility of most renal stones is slight in alkaline media, the tendency for formation of renal calculi is considerably greater in alkaline urine than in acid urine. For this reason, acidotic diets and acidic drugs are frequently used for treating renal calculi.