Hypoparathyroidism

How is it produced?

Hypoparathyroidism is the disease state resulting from the continued lack of parathyroid hormone (PTH) production.

 

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; it 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 smaller amounts than necessary and in a sustained manner (hypoparathyroidism), this lack of calcium will prevent the bone from forming (replacing itself) or teeth from forming and there is a high risk of fractures. Similarly, when calcium is in greater amounts than necessary and in a sustained manner (hyperparathyroidism), that 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.

 

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 decrease or absence of PTH and that, consequently, will maintain calcium levels below normal values ​​constantly (hypocalcemia) and high phosphorus (hyperphosphatemia).

 

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

 

Primary hypoparathyroidism: This name includes all disorders that originate in the parathyroid glands themselves and are characterized by the decrease or absence of PTH in the blood and the consequent constantly low calcium levels (hypocalcemia) and constantly high levels of phosphorus (hyperphosphatemia). The lack of PTH in the blood may be due to the absence of the parathyroid glands, or to the fact that the parathyroid glands have a defect in the manufacture of PTH. The absence of parathyroid glands can be congenital (already from birth), as in Di George syndrome, or acquired (after surgical removal of the parathyroid glands or after treatment with radiotherapy to the neck or radioactive iodine). In the case of defect in the manufacture of PTH, the parathyroid glands are normal but they do not manufacture the hormone. Failure to manufacture PTH is known as idiopathic hypoparathyroidism; It is very rare and can be due to an isolated defect in the function of the parathyroid glands (isolated hypoparathyroidism), or a familial defect (familial hypoparathyroidism) and in the context of alterations of other endocrine glands such as the adrenal glands, the thyroid gland and the pancreas (diabetes mellitus).

 

Secondary hyperparathyroidism: There is a lack of PTH and hypocalcemia due to a failure of the parathyroid glands caused by low levels of magnesium in the blood (hypomagnesemia).

 

Pseudohypoparathyroidism (or "not true" hypoparathyroidism): PTH is manufactured and released into the blood but this PTH is not effective because the organs where it has to act (bone and kidney) do not respond to the hormone, so there is a drop in calcium in the blood. This induces a secondary increase in PTH, but PTH remains ineffective. For practical purposes it is as if there was no manufacture of PTH although there is PTH in the blood; hence the name pseudohypoparathyroidism. In "true" hypoparathyroidism, there is little or no PTH. Pseudohypoparathyroidism is an inherited disorder characterized by signs and symptoms of hypoparathyroidism that are associated with peculiar defects in skeletal development.

 

Symptoms

The symptoms of hypoparathyroidism will be derived from the decrease in calcium levels in the blood. In cases of minor decreases in calcium and for a long time, the symptoms will be of very little intensity. If the decrease in calcium is considerable or if it occurs in a short time, the symptoms will be more pronounced.

 

Symptoms of hypocalcemia appear in both forms of primary hypoparathyroidism (hereditary and acquired), in pseudohypoparathyroidism and in hypoparathyroidism secondary to a decrease in magnesium in the blood, although hereditary hypoparathyroidism and pseudohypoparathyroidism usually begin more gradually and are associated to developmental defects that do not appear in the others.

 

Typical symptoms of hypocalcemia are as follows:

 

Neuromuscular disorders: There is an increase in the excitability of the muscles and the nerves that supply them, which produces muscle spasms, a tingling sensation and cramps through the mouth and spasms of the hands and feet (tetany), which can lead to seizures (especially in children ). Tetany may be revealed on physical examination (Chvostek and Trousseau signs).

 

Mental disorders: They can range from irritability to depression, neurosis, and psychosis.

Central nervous system disorders: memory loss, parkinsonism and involuntary movements of the limbs. Intracranial X-ray calcifications can be seen in nearly 20% of patients with sustained hypocalcemia, justifying parkinsonian-type syndromes.

 

Cardiac disorders: Abnormalities in the conduction of the electrical stimulus through the heart occur in the form of arrhythmias, prolongation of the QT interval, T wave alterations, and heart blocks. heart failure may also appear, that is, the inability of the heart to push blood.

 

Alterations in the skin and appendages: Dry, flaky skin appears, with brittle nails and rough hair. Hair can also fall out (alopecia). There is a higher frequency of fungal skin infection like Candida. These alterations are usually seen exclusively in hereditary hypoparathyroidism associated with failure of several endocrine glands.

 

Eye disorders: In long-lasting hypocalcemia, cataracts appear due to alterations of the lens.

 

In children, dental anomalies are frequent: defective enamel, lack of dental development and delayed tooth eruption.

 

Other alterations may also occur depending on the particular cause of hypoparathyroidism: rickets, osteomalacia, skeletal deformities, etc.

Diagnosis

The diagnosis of hypoparathyroidism is made based on the detection of low blood calcium. Phosphorus and PTH values ​​will differ depending on the cause of the hypoparathyroidism. The blood test may have been done on clinical suspicion by the patient's doctor, but on occasions, the symptoms can be very mild and thus be a "chance finding."

 

In primary hypoparathyroidism, blood calcium is low and phosphorus high, with absent or low PTH. In magnesium deficiency, calcium and phosphorus in the blood are low and PTH is low or absent. In pseudohypoparathyroidism, there is little calcium and little phosphorus in the blood and PTH is high; furthermore, hypophosphatemia is more marked than hypocalcemia due to the increased secretion of PTH, which is only partially effective in raising calcium in the blood, but favors the excretion of phosphorus by the kidney. In hypoparathyroidism due to magnesium deficiency, the levels of magnesium in the blood are, of course, low.

 

There should be abundant calcium and low phosphorus values ​​in the urine in primary hypoparathyroidism. In pseudohypoparathyroidism, urine calcium is high and phosphorus is generally low.

 

If there is a suspicion of a vitamin D deficiency as a cause of hypoparathyroidism, it will be useful to test your blood levels, which will be low in most cases.

 

The history and medical examination will help to find the origin of the hypoparathyroidism and to request other studies. For example, the recent onset of hypocalcemia in an adult suggests nutritional deficiency, kidney failure, or intestinal disorders that lead to vitamin D deficiency or ineffectiveness. Neck surgery, even old, can be associated with the development of hypoparathyroidism by over time. A history of a seizure disorder points to antiepileptic drugs as the cause. Developmental defects, especially in childhood and adolescence, sometimes guide the diagnosis of pseudohypoparathyroidism. Rickets and various neuromuscular syndromes and deformities may indicate an ineffective action of vitamin D, either due to a lack of it or due to defects in its metabolism.

 

In primary hypoparathyroidism, imaging and functional techniques of the parathyroid glands should be used in search of a partial or total lack of them. They include ultrasound, tomography (CT), and magnetic resonance imaging of the neck. The scintigraphy with labeled technetium (99Tc) allows us to know if these glands work or not.

 

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

Treatment

Treatment is primarily medical and will consist (in primary hypoparathyroidism) in giving the patient calcium supplements to correct any symptoms that may exist. Patients with hypoparathyroidism should take 2 to 3 g / day of elemental calcium by mouth. In severe cases with tetany, intravenous calcium treatment is required with the patient admitted to hospital.

 

Along with oral calcium, vitamin D (or its active form, calcitriol) will be administered, since this favors the absorption of calcium at the intestinal level and prevents its renal loss.

 

In general, treatment with calcium and vitamin D (or calcitriol) are sufficient to normalize calcium and phosphorus in the blood, although it does not allow correcting the excessive elimination of calcium in the urine and the risk of kidney stones that this entails; we add a treatment with diuretics like hydrochlorothiazide to prevent this problem.

 

On the other hand, if phosphorus levels in the blood persist high, it is necessary to restrict the phosphorus in the diet and, if necessary, add aluminum hydroxide to the treatment (which binds phosphorus in the intestine and prevents its absorption).

 

The treatment of pseudohypoparathyroidism is similar to that of primary hypoparathyroidism, except that the doses of calcium and vitamin D are usually lower than those needed in primary or "true" hypoparathyroidism.

Hypocalcemia associated with hypomagnesemia includes correction of magnesium levels in the blood.

 

In vitamin D deficiencies, treatment consists of administering vitamin D (or calcitriol) and calcium until the blood calcium normalizes and then continuing with vitamin D (or calcitriol) exclusively.

Precautionary measures

There are no specific measures to prevent the development of hypoparathyroidism, but it can be suspected in cases of alterations of the skeleton in a child, or in cases of previous surgery or radiotherapy on the neck. It will also be suspected in cases of relatives with decreases in calcium.

 

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 the disease, and which will be confirmed with the PTH values.

Conclusions.

Hypoparathyroidism is a rare disorder and can appear in both children and adults. It is characterized by low levels of calcium and variable levels of phosphorus in the blood and, on occasions, by alterations of the skeleton. The symptoms are variable, depending on the calcium levels and their evolution time.

 

The diagnosis is made by a decrease in calcium levels in a blood test requested by nonspecific symptoms or by clear symptoms of hypocalcemia. The diagnosis of primary hypoparathyroidism should involve the study of the glands by imaging or functional techniques to detect their absence or lack of development.

 

Treatment is never surgical. It is usually controlled with calcium and vitamin D in primary hypoparathyroidism and with vitamin D in defects of this substance.