Primary Hyperparathyroidism (PHPT):
PHPT is usually diagnosed by the clinician because of hypercalcemia found on routine laboratory evaluation with an inappropriately elevated or normal levels of PTH. Patients with PHPT typically have low phosphorus, because elevated PTH levels decrease the resorption of phosphorus in the kidneys. Most commonly, these patients are asymptomatic; however, a careful history and physical examination is necessary to rule out other causes of hypercalcemia. Other causes of hypercalcemia include conditions such as metastatic cancer, multiple myeloma, sarcoidosis and other granulomatous diseases, ingestion of calcium or vitamin D, milk-alkali syndrome, and other less common causes. Other rare disorders such as familial hypocalciuric hypercalcemia (FHH) will result in elevated levels of PTH and calcium. 24-hour urine calcium will show abnormally low levels of calcium in the urine in patients with FHH. Medications such as thiazides and lithium can result in elevation of PTH and calcium levels. Patients with tertiary hyperparathyroidism, who had a history of renal failure and subsequent renal transplantation, will also have elevated levels of PTH and calcium.
PHPT could be due to adenoma, four gland hyperplasia and rarely due to carcinoma. Most adults (80% to 85%) with PHPT have single benign parathyroid adenoma and the reminder could be due to more than one adenoma or four gland hyperplasia. Parathyroid carcinoma accounts for about 1% of the cases. In the MEN-1 and MEN-2 and the familial syndromes, hyperplasia is the primary etiology of the hyperparathyroidism. Differentiating adenoma from hyperplasia on frozen section is extremely difficult and it can primarily be used to distinguish parathyroid tissue from other tissue.
Secondary hyperparathyroidism is caused by chronic over stimulation of the normal parathyroid glands usually in the setting of chronic renal failure (Kidney disease). This is a result of a complex set of interactions. As a result of renal failure conversion of vitamin D to its active form is decreased resulting in decreased intestinal absorption of calcium and PTH levels increase resulting in mobilization of calcium from bone. Also elevated levels of phosphorus results in further stimulation of the parathyroid glands. Intact levels of PTH can reach over 1000 pg/ml. Secondary HPTH can also result from malabsorption in the setting of chronic pancreatitis and certain types of bariatric surgery. Secondary hyperparathyroidism is usually treated by treated the underlying cause of the disease such as renal transplant. Parathyroidectomy may be required in certain cases.
Long term stimulation of the parathyroid glands will result in alterations in the set point of the parathyroid cells to the feedback loop. Tertiary hyperparathyroidism occurs when the chronically stimulated parathyroid glands function independent of serum calcium levels. Parathyroid glands continue their over secretion of PTH despite correction of the underlying cause such as kidney transplantation. Treatment of choice for tertiary hyperparathyroidism is the surgical removal of three and half glands.
Overall incidence of parathyroid carcinoma is very low less than 2% of the cases. It is difficult to diagnose in part because of its rarity, lack of definitive diagnostic markers and overlapping clinical features of benign primary hyperparathyroidism. Small percentage of parathyroid carcinomas present with normal hormone levels. Parathyroid carcinoma usually has growth with a tendency for local invasion, and it occurs with equal frequency in men and women.