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Hyperparathyroidism

March 1, 2010 by Staff  
Filed under Health Conditions / Ailments

Hyperparathyroidism is overactivity of the parathyroid glands resulting in excess production of parathyroid hormone (PTH). The parathyroid hormone regulates calcium and phosphate levels and helps to maintain these levels. Excessive PTH secretion may be due to problems in the glands themselves, in which case it is referred to as primary hyperparathryroidism and which leads to hypercalcemia (raised calcium levels). It may also occur in response to low calcium levels, as encountered in various situations such as vitamin D deficiency or chronic kidney disease; this is referred to as secondary hyperparathyroidism. In all cases, the raised PTH levels are harmful to bone, and treatment is often needed. Recent evidence suggests that Vitamin D deficiency/insufficiency plays a role in the development of hyperparathyroidism.

Classification

Primary hyperparathyroidism

Primary hyperparathyroidism results from a hyperfunction of the parathyroid glands themselves. There is oversecretion of PTH due to adenoma, hyperplasia or, rarely, carcinoma of the parathyroid glands.

Secondary hyperparathyroidism

Secondary hyperparathyroidism is the reaction of the parathyroid glands to a hypocalcemia caused by something other than a parathyroid pathology, e.g. chronic renal failure.

Tertiary hyperparathyroidism

Tertiary hyperparathyroidism result from hyperplasia of the parathyroid glands and a loss of response to serum calcium levels. This disorder is most often seen in patients with chronic renal failure.

Symptoms and signs

Asymptomatic hyperparathyroidism

Many patients presenting with hyperparathyroidism will have no signs or symptoms, with diagnosis being made on further investigation after a coincidental finding of hypercalcemia. It is, however, reported that many patients will report that they feel better after treatment for hyperparathyroidism.

Symptomatic hyperparathyroidism

Of those patients who do present with symptoms, they are commonly associated with the effects of an increased level of calcium. Since calcium is involved in trans-synaptic communication in the nervous system, high blood calcium levels have a direct effect on the nervous system. Thus, most of the symptoms of parathyroid disease are "neurological" in origin. Common manifestations of hyperparathyroidism include weakness and fatigue, depression, aches and pains, decreased appetite, feelings of nausea and vomiting, constipation, polyuria, polydipsia, cognitive impairment, kidney stones and osteoporosis. Surgical removal of a parathyroid tumor will eliminate the symptoms in most patients.

Osteoporosis

Osteoporosis associated with hyperparathyroidism is caused by the high parathyroid hormone secreted by overactive parathyroid gland(s). Excess parathyroid hormone (PTH) acts indirectly on osteoclasts as they lack a PTH receptor. Instead, PTH stimulates osteoblasts, which in turn increases their expression of RANKL. RANKL is then able to bind osteoclasts which stimulates their activation which ultimately leads to the removal of calcium from the bones. Thus, the high calcium in the blood comes from the bones. Removing the offending parathyroid gland will restore normal bone density over several years.

Laboratory tests

Serum calcium

In cases of primary hyperparathyroidism or tertiary hyperparathyroidism heightened PTH leads to increased serum calcium (hypercalcemia) due to:

  1. increased bone resorption, allowing flow of calcium from bone to blood
  2. reduced renal clearance of calcium
  3. increased intestinal calcium absorption

By contrast, in secondary hyperparathyroidism effectiveness of PTH is reduced.

Serum phosphate

In primary hyperparathyroidism, serum phosphate levels are abnormally low as a result of decreased renal tubular phosphate reabsorption. However, this is only present in about 50% of cases. This contrasts with secondary hyperparathyroidism, in which serum phosphate levels are generally elevated because of renal disease.

Alkaline phosphatase

Alkaline phosphatase levels are not elevated in all types of hyperparathyroidism. Kumar and Clark 6th edition states that alkaline phosphatase levels do not increase in primary hyperparathyroidism but may increase in secondary hyperparathyroidism.

Diagnosis

The gold standard of diagnosis is the Parathyroid immunoassay. Once an elevated Parathyroid hormone has been confirmed, goal of diagnosis is to determine whether the hyperparathyroidism is primary or secondary in origin by obtaining a serum calcium level.

Tertiary hyperparathyroidism has a high PTH and a high serum calcium. It is differentiated from primary hyperparathyroidism by a history of chronic kidney failure and secondary hyperparathyroidism.

Treatment and monitoring

Endocrinologists diagnose diseases affecting glands and should be consulted for hyperparathyroidism. Treatment for the three different types of hyperparathyroidism vary. Generally treatment is first and foremost directed at hypercalcemia; if symptomatic, patients are sent for surgery to remove the parathyroid tumor (parathyroid adenoma) or parathyroid gland (see hypercalcemia). Most experts now believe that almost all patients with hyperparathyroidism should be evaluated for surgery. If hyperparathyroidism is caused by a tumor, it will almost always progress as the tumor grows.

Testing for hyperparathryroidism:

  • Calcium level
  • Bone density
  • Vitamin D
  • Phosphorus

Calcimimetics

A calcimimetic (cinacalcet) is a new type of drug to be considered as a potential therapy for some people with primary and secondary hyperparathyroidism on dialysis. It is recognised by the body as if it is calcium, in other words, it mimics the effect of calcium in your tissues. This tricks your body into thinking there is more calcium in the blood which reduces PTH release from parathyroid glands, leading to lower calcium and phosphorus levels in your blood. Calcimimetics control PTH release from parathyroid glands without increasing calcium and phosphorus levels. The most common side effects of calcimimetics are mild or moderate nausea and vomiting.
 

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