Hyperparathyroidism

Hyperparathyroidism is the pathological state resulting from the continued increase in the production of parathyroid hormone (PTH).

How is it produced?

The parathyroid glands are glands, usually 4 in number, located in the front of the neck and behind the thyroid gland. On occasion, one of the 4 glands may be located somewhat far from the neck. And they are not always 4 glands; they can be between 2 and 6 glands.

These glands produce PTH, which is the hormone that regulates the level of calcium in the body. This hormone increases calcium in the blood. When the level of calcium in the blood decreases (for example, in diets with little or no calcium), the cells of these glands make and release PTH into the blood. PTH binds to kidney and bone cells to produce an increase in calcium in the blood: the kidney does not remove as much calcium into the urine and the bone releases calcium from its structure. In addition, PTH stimulates the synthesis of vitamin D by the kidney; Vitamin D increases the absorption of calcium in the intestine, which helps to increase the level of calcium in the blood. In turn, PTH secretion causes the kidney to lose phosphorus, causing a decrease in the level of phosphorus in the blood. When the level of calcium in the blood normalizes, the parathyroid glands stop making PTH.

Calcium is an essential element to make our bones and teeth. But in larger quantities than necessary and in a sustained manner (hyperparathyroidism), this excess calcium is deposited in other tissues, such as the kidney, blood vessels and joints, and calcifies or hardens them. Calcification of these other tissues causes their malfunction. Similarly, if there is little calcium in the blood and in a sustained manner (hypoparathyroidism), the bone or teeth cannot form (replace) and there is a high risk of fractures.

Therefore, it is important to keep the calcium level within "normal" limits, which are defined by a blood calcium concentration between 8.5 and 10.5 mg / dL (= 2.1-2.6 mmol / L ). However, there are disorders that cause a continuous increase in PTH and that, consequently, will maintain calcium levels above normal values ​​constantly (hypercalcemia) and low phosphorus (hypophosphatemia).

The causes of hyperparathyroidism can be divided into three large groups from a conceptual and functional point of view:

Primary hyperparathyroidism: This name includes all the disorders that originate in the parathyroid glands themselves and that are characterized by producing a continuous release of PTH into the blood and the consequent constantly high levels of calcium (hypercalcemia) and constantly low levels of phosphorus (hypophosphatemia). This includes abnormal growths of the cells that make up these glands and make PTH: benign tumor (adenoma) of the parathyroid glands, malignant tumor (cancer) of the parathyroid glands, and diffuse growth (hyperplasia) of the parathyroid glands. cells of these glands. Adenomas are solitary lesions but double adenomas are also described. Hyperplasia can be symmetric (all glands are enlarged) or asymmetric (only one or two of the glands are enlarged). Adenoma is the most frequent lesion, representing slightly more than 80% of the causes of primary hyperparathyroidism; primary hyperplasia represents 15% and carcinoma 2-3%. Tumors and primary hyperplasia of the parathyroid glands can be part of a group of tumors of other endocrine glands known as Multiple Endocrine Neoplasia. Hyperplasia and adenomas can be seen in patients receiving lithium treatment. There is a familial form of hypercalcemia without other endocrine alterations called Familial Hypocalciuric Hypercalcemia (which occurs only with calcium high in the blood and low in the urine).

It should be mentioned that some malignant tumors that do not originate in the parathyroid glands but in other tissues are capable of manufacturing a substance similar to PTH, causing hyperparathyroidism. But it cannot be considered "true" hyperparathyroidism.

Secondary hyperparathyroidism: There is also an excessive production of PTH, but this hyperproduction of PTH is due to a malfunction of some of the organs that participate in the metabolism of calcium and phosphorus, such as the kidney or intestine. This is seen in chronic renal failure (the most common cause of secondary hyperparathyroidism) and in vitamin D deficiency due to low intake or lack of sun, in the processes of intestinal malabsorption of vitamin D and calcium, in treatment with anticonvulsants and in rickets.

Pseudohyperparathyroidism: The sites where the hormone acts (kidney and bone) are resistant to the action of the hormone; Consequently, the effects of hypercalcemia and hypophosphatemia due to PTH do not appear. Thus, calcium levels in the blood do not increase or continue to fall, which maintains a strong stimulus on the parathyroid glands to continue manufacturing more PTH. Over time, the cells of the parathyroid glands that make PTH increase in size and number to cope with this sustained stimulus of "low blood calcium levels." Ultimately, the parathyroid glands work properly, and what fails is the end organ (target organ). There is talk of hyperparathyroidism, although strictly it behaves like the opposite, that is, with hypocalcemia, although this is sometimes not very marked.

Symptoms

The clinical manifestations are due to alterations in the levels of calcium (increase) and phosphorus (decrease) in the blood. If the calcium figure is only slightly high, there is usually weakness or fatigue. Somewhat higher calcium levels in the blood cause loss of appetite, nausea, vomiting, constipation, repeated episodes of kidney stones, kidney problems, increased urination, pancreatitis, cardiac arrhythmias and mental disorders (which can vary from depression, anxiety and psychosis to mental dullness and coma). The relationship between the severity of hypercalcemia and symptoms varies from patient to patient and also varies with the rapidity of onset of hypercalcemia.

Because the bone loses calcium, fractures may develop over time. Since the detection of hypercalcemia is easy, today it is difficult to see the so-called cystic fibrous osteitis, which was the typical bone manifestation of hypercalcemia due to long-standing hyperparathyroidism (years). The long-term action of PTH on the bones causes a large outflow of calcium and progressive destruction of the bone, so that the bone adopts a typical radiological image: loss of the smooth surface in the finger bones and replacement by an irregular ridge .

Hypercalcemia had been associated with the development of arterial hypertension and peptic ulcer in the patient with hyperparathyroidism, but this cause-effect relationship is not clear.

In the case of secondary hyperparathyroidism, the symptoms will also be those derived from the underlying disease that causes the increase in PTH.

However, since blood tests are performed frequently, it is possible to discover an increase in calcium levels due to hyperparathyroidism without the patient having symptoms or a very mild clinical picture and where the blood test was done for any other reason. This occurs in more than half of patients with hyperparathyroidism. And in almost the other half, hyperparathyroidism is a chronic, slow-onset disorder whose manifestations may only appear over months or years.

Very rarely, hyperparathyroidism develops or worsens suddenly and is accompanied by serious complications from the sudden increase in calcium in the blood, such as severe dehydration and coma, which is what has been called a hypercalcemic hyperparathyroid crisis.

Diagnosis

The suspicion of hyperparathyroidism often begins with the accidental detection of an increase in calcium in the blood test, or because in the face of nonspecific symptoms (fatigue, etc.) a blood test is requested. The detection of high calcium in the blood forces to request another blood test with PTH, phosphorus, albumin and, in some cases (when a vitamin D deficiency is suspected), a determination of vitamin D will be requested. It may be helpful to do a urinalysis to determine the elimination of calcium and phosphorus by the kidney.

The main biochemical characteristics of primary hyperparathyroidism are high blood PTH levels, high blood and low urine calcium, low blood and high urine phosphorus. In secondary hyperparathyroidism, phosphorus in the blood is generally high, and other alterations such as increased urea and creatinine also appear in kidney failure. In pseudohypoparathyroidism, calcium levels are not high, although PTH is high.

The history and medical examination will help to find the origin of the hyperparathyroidism and to request other studies. For example, we must know if there is kidney failure or if the individual is being treated with lithium. Likewise, a family history of endocrine gland disorders should be asked.

In hypercalcemia associated with a malignancy (cancer), the underlying disease is usually evident; the usual is that the symptoms of cancer lead the patient to the consultation and hypercalcemia is discovered when performing the tests.

The duration of hypercalcemia also helps, if we have any previous analysis. When the condition is short-lived or there is no data on the duration of hypercalcemia, consider a hidden cancer. If it takes months or years, consider a benign form of hyperparathyroidism.

The next step is the study with imaging and functional techniques of the parathyroid glands in search of a tumor or abnormal growth of the same. Ultrasound, tomography (CT), and magnetic resonance imaging of the neck are used to locate lesions such as an adenoma or cancer in the parathyroid glands. The labeled technetium (99Tc) scintigraphy gives us an idea of ​​whether these glands are functioning or not (hyperplasia, tumors) and where the uptake is located (to locate tumors in glands located outside their normal site or to locate tumors that make PTH but they are not in the parathyroids).

Other techniques such as studying bone density (lumbar spine, hip) may be indicated to see the repercussions of hyperparathyroidism on the bone.

Treatment

Surgery for parathyroid gland tumors is very effective in correcting primary hyperparathyroidism. In the first place, because it provides us with tissue that we can analyze and determine if it is a benign tumor or if it is malignant. Second, because it usually allows the cure of the disease. The surgical procedure for removal of the mass should be accompanied by examination of all the glands for tumors or growths on the other glands (eg, double adenomas). In parathyroid hyperplasia, almost all the glands are removed, leaving a small portion of the gland, which can be in the original site of the gland or can be relocated in the muscles of the forearm (because if the hyperfunction of the residual tissue, it will be easier to remove). In the case of adenomas and cancers, the gland that contains the tumor is removed.

In some individuals, for example, those aged over 50 years, low blood calcium, slow evolution of hypercalcemia, without kidney or bone damage, and who do not wish to operate, the treatment will only be medical surveillance.

When surgical intervention is successful, blood calcium falls below normal in the next 24 hours and lasts for about three to five days, until the remaining parathyroid tissue resumes hormone secretion and blood calcium finally normalizes. But in some individuals hypocalcemia may appear that does not normalize spontaneously (postsurgical hypoparathyroidism); This will happen if all the glands must be removed. During the days of mild hypocalcemia, patients can follow a diet rich in calcium or take calcium supplements by mouth. In cases of more severe hypocalcemia or symptoms, parenteral treatment with calcium is needed.

Treatment of secondary hyperparathyroidisms includes treatment of the underlying cause, for example, vitamin D intake in rickets or kidney transplantation in chronic kidney failure. If the cause cannot be corrected, medical treatment will be aimed at reducing the intake of phosphorus and calcium in the diet and blocking their absorption in the digestive tract.

In lithium-secondary hyperparathyroidism, lithium should be suppressed and calcium normalized. Since cases have been reported in which lithium treatment is associated with the development of adenomas, if hypercalcemia and elevated PTH levels persist after lithium administration has been discontinued, surgical treatment of adenoma resection will be indicated.

Occasionally, hypercalcemia is severe (calcium levels greater than 15 mg / dL / dL = 3.7 mmol / L) or of acute onset. In these cases, prompt treatment should be done in a hospital environment.

Precautionary measures

There are no specific measures to prevent the development of hyperparathyroidism, except in relatives of patients who have been diagnosed with a multiple endocrine glandular disorder or if there are isolated calcium alterations in relatives.

In the event of any suspicion, a blood test should be performed that includes calcium and phosphorus levels, which is usually sufficient for an early detection of this disease, and which will be confirmed with PTH values.

Conclusions.

Most of the disorders associated with the parathyroid glands are benign and, left to their own devices, very slow. For this reason, when they are detected, the symptoms are usually very mild or non-existent.

The diagnosis is made, in most cases, by an increase in calcium levels in a blood test requested for any other reason or by health check.

The diagnosis of hyperparathyroidism should involve the study of the parathyroid glands by imaging techniques to detect a tumor in them.

Surgical treatment is usually the best alternative in primary hyperparathyroidism, but not the only one. Observation and medical control may be indicated in some cases. Secondary hyperparathyroidism involves treating the cause of it.