Parathyroid Hyperparathyroidism

Definition

Parathyroid glands (most often 4, however one may have 3 or 5 glands) are located in the neck usually next to the thyroid gland. The main role of these glands is to produce a substance called parathyroid hormone (PTH) which functions to keep serum calcium levels normal through mechanisms of action on the bones, kidneys and gastrointestinal tract. When one or more of these glands becomes overactive, increased amounts of PTH are generated in relation to the serum level of calcium resulting in a condition know as hyperparathyroidism. Oversecretion of PTH does not cease even in the face of elevated serum calcium levels. Hyperparathyroidism may come in a few different forms which influences diagnostic evaluation and the extent of surgery recommended to patients.

• Sporadic primary hyperparathyroidism: 100,000 new cases of this disorder will be diagnosed in the United States each year affecting 0.2% to 0.5% of the population. Women are more commonly affected than men and the incidence increases with age. In women over age 60, new cases occur in approximately two out of every 1,000 people each year. Most cases (85%) of hyperparathyroidism are the result of a single parathyroid gland malfunction and the development of a benign tumor, known as an adenoma. In nearly all other cases (15%), two or more glands grow into adenomas resulting in a condition called parathyroid hyperplasia.
• Parathyroid hyperplasia may present with persistent hypercalcemia following an operation for what was thought to be a single adenoma. Also, it is one of the most common causes of recurrent hypercalcemia in patients who have already had an operation for a high calcium level. Hyperplasia may occur sporadically by can also be inherited as an autosomal dominant trait in MEN-1 and MEN-2 (Multiple Endocrine Neoplasia). In MEN-1 associated abnormalities of other endocrine glands, the pituitary gland and pancreas occur. Hyperparathyroidism is the most common endocrine abnormality in MEN-1 (97% of cases) and generally presents before the other endocrine manifestations of the syndrome. Hyperplasia occurs in approximately 20% to 40% of patients with MEN-2 who have risk for development of tumors of the thyroid and adrenal glands. There are also familial forms of hyperparathyroidism that occur without other endocrine gland abnormalities.
• Parathyroid cancer is a rare cause of primary hyperparathyroidism. (see Parathyroid Cancer)
• Secondary Hyperparathyroidism: In this disorder, parathyroid levels are also abnormally high, however, this occurs in response to low serum calcium levels in the setting of renal failure or malabsorption syndromes. This is another example of parathyroid hyperplasia.
• Tertiary Hyperparathyroidism: In this disorder, patients with known renal failure or malabsorption syndrome develop high calcium levels when hyperplastic parathyroid glands begin to function autonomously.

Symptoms

The symptoms of hyperparathyroidism may range from none at all (asymptomatic) to severe life-threatening symptoms associated with very high calcium levels. Complications from elevated calcium levels may produce associated conditions for which therapy is indicated.

Patients may experience one or more of the following symptoms:

Patients with hyperparathyroidism may develop one or more of the following associated conditions or complications of elevated calcium levels and oversecretion of PTH:

Diagnosis

Because many patients are completely asymptomatic from this condition, diagnosis frequently occurs after detection of mildly elevated calcium levels discovered incidentally on routine blood work. Elevated PTH levels may also be noted as part of an evaluation of skeletal health. All patients with hyperparathyroidism, whether or not symptoms are present, should have diagnostic tests performed in order to determine if complications of hyperparathyroidism are present and to known if they could benefit from surgical correction of the disorder.

Diagnosis of primary hyperparathyroidism

• Blood tests
  • Elevated serum calcium
  • Elevated or inappropriately normal serum PTH level

Diagnostic tests used to determine possible complications of primary hyperparathyroidism

• Bone densitometry (dual x-ray absorptiometry): This test is essential to the complete evaluation and monitoring of patients with this disorder; it can help establish when surgery should be recommended and can be used to monitor the course of patients who are followed medically.
• 24-hour urinary excretion of calcium and creatinine: This may help to distinguish other etiologies of high calcium levels and serves as a measure of kidney function and risk for damage if calcium excretion is elevated.
• Renal US and X-ray: These tests may be helpful in patients with symptoms of stones in the urinary tract or high calcium levels in the urine.

Treatment Options

• Surgery to remove the affected gland(s) cures this disorder. In the few cases where all the parathyroid glands are involved, a portion of one of the glands is left in place, or a portion is transplanted into the forearm and the rest of the glands are removed. When performed by an experienced surgeon, the operation is successful in over 95% of cases and serious surgical complications are quite uncommon. Surgery is clearly recommended for patients who have overt symptoms or complications attributable to elevated calcium levels for definitive cure of the problem. Patients without symptoms are also recommended surgical treatment if any one of the criteria listed below are present according to the most recent National Institutes of Health consensus guidelines (Bilezikian et al, 2002).
  • Young age (50 years or less)
  • Significant decrease in bone mineral density (T score below -2.5 at any site)
  • 30% decrease in kidney function
  • The presence of significant calcium levels in the urine
  • A calcium level 1.0 mg/dl above the upper limit of normal
• Medical therapy may be appropriate for patients with mild hypercalcemia (excess calcium in the blood) with no associated symptoms or complications. Possibilities would include selective estrogen-receptor modulators in postmenopausal women and bisphosphates to prevent bone loss. If surgery is not performed, it is essential that patients be monitored regularly to avoid later complications. Most patients who do not meet criteria for surgery do well with no evidence for progression of the disorder or development of complications. However, up to 25% of patients may have worsening of blood calcium levels, increased excretion of calcium in the urine, and decreased bone density over time. The need for surgical intervention requires careful follow-up evaluation and individual assessment by an expert in the field. Appropriate recommended monitoring of patients with asymptomatic hyperparathyroidism who do not undergo surgery includes the following (Bilezikian, 2002):
  • Serum calcium levels every 6 months
  • Annual serum levels of kidney function (creatinine concentration)
  • Bone densitometry annually