Hyperparathyroidism and hypoparathyroidism: diseases of the parathyroid glands

Hyperparathyroidism and hypoparathyroidism are two names for a disease condition consisting of altered production of parathyroid hormone, a hormone of the parathyroid glands. What do they mean, why do they occur, and how are they manifested or treated?

Parathyroid hormone is a hormone secreted by the parathyroid glands. It is crucial for regulating the balance of two minerals in the body - calcium and phosphorus.

Hypoparathyroidism is a condition where the body produces too low levels of parathyroid hormone. This leads to abnormally low levels of calcium in the blood and increased levels of phosphorus. The most common manifestation is increased neuromuscular irritability called tetany.

Hyperparathyroidism is the opposite condition, where the parathyroid glands produce too high levels of parathyroid hormone. This causes increased blood calcium levels, decreased bone density leading to osteoporosis, and high levels of calcium in the urine, which manifests as urinary stone formation and renal colic.

What are parathyroid glands and where can we find them? What are they for?

The parathyroid glands are 4 small endocrine glands located on the back of the thyroid gland. Their physiological size and shape resemble a lens.

These small glands maintain balanced calcium and phosphorus levels in the body by "turning off" or "turning on" parathyroid hormone secretion.

The very important vitamin D is also involved in this regulation and control of calcium and phosphorus levels.

Under physiological circumstances, this system is in harmony and functions well.

When blood calcium levels fall below a certain norm, the parathyroid glands release sufficient parathyroid hormone to restore normal calcium levels.

Parathyroid hormone releases calcium from the bones,
improves the ability to absorb calcium from the small intestine, and
reduces the amount of calcium excreted in the urine.

When blood calcium levels are too high, the parathyroid glands restrict the secretion of parathyroid hormone and the concentration of calcium in the blood begins to gradually decrease.

In addition to maintaining healthy teeth and bones, calcium helps in the transmission of nerve impulses in nerve and muscle cells. This contributes to proper nerve function and muscle contraction.

Along with calcium, another mineral, phosphorus, acts in these areas.

To ensure the harmony of these substances in the body and blood, an opposite regulator is also needed to act "against" the parathyroid hormone. This is the hormone calcitonium, secreted by the thyroid gland in the human body.

A reasonable daily dose of calcium should be between 800 and 1500 mg. Of this, 100-250 mg is absorbed in the small intestine.

During periods such as growth, pregnancy or lactation, the need for calcium increases significantly.

The importance of calcium in the human body:

• Important for bone and tooth structure
• Found in all body fluids
• Regulates the transmission of neuromuscular impulses
• Important for proper muscle contraction
• Activates enzymes in metabolic processes
• Proper functioning of the heart
• Involved in the blood clotting process
• Helps in the absorption of vitamin B12

Phosphorus and its importance:

• Helps in tissue and cell regeneration
• Involved in the filtration of waste products
• Important for proper bone and tooth structure
• Maintains muscle, kidney and blood vessel function
• Involved in the transmission of signals in the nervous system

Hypo/hyper - Decrease/increase

Hypoparathyroidism is a condition in which there is a decreased secretion of parathyroid hormone by the parathyroid glands. Because the body lacks a major regulator of calcium and phosphorus levels, there is a disharmony of these substances. It manifests itself with characteristic symptoms.

Hyperparathyroidism is an increased production of parathyroid hormone. It may result from primary hyperparathyroidism or secondary hyperparathyroidism.

Hyperparathyroidism/hypoparathyroidism = increase/decrease in parathyroid function.

There are several known causes of both conditions. They are divided into several forms.

Causes of hypoparathyroidism/decreased function include...

Iatrogenic causes

Iatrogenic cause means a condition that is caused as a side effect after a medical intervention:

• Surgical removal of the parathyroid glands (called subtotal parathyroidectomy), in which more than 50% of the parathyroid tissue is removed. These procedures are either therapeutic (in the treatment of hyperparathyroidism) or the parathyroid glands are removed incidentally (in thyroid surgery).

• Interruption of the blood supply. In this case, the blood vessel that supplies the parathyroid glands with nutrients is damaged. This condition can occur again accidentally during thyroid surgery or other operations on the neck near the parathyroid glands.

• Another cause of parathyroid gland dysfunction is damage following radiation exposure, e.g. as a result of treatment for Graves-Basedow disease with radioactive iodine or following external irradiation in the treatment of thyroid cancer.

Autoimmune diseases

In autoimmune diseases, the immune system attacks its own tissues, in this case parathyroid tissue, as if they were foreign pathogens.

Autoimmune inflammation causes extensive damage to the parathyroid glands, which stop producing their hormone.

Familial hypoparathyroidism

This is a hereditary form of the disease. A child is born with either no parathyroid glands or with glands that have significantly reduced function. Some types of hereditary hypoparathyroidism occur in conjunction with other inherited disorders of the hormone-producing endocrine glands.

The disorder of the development of the parathyroid glands is called congenital aplasia or so-called De-George syndrome. It is associated with defective development of the thymus, congenital developmental defects of the cardiovascular system and other defects. It is diagnosed immediately after the birth of the child.

Pathological processes in the body

This includes conditions and diseases in which there is secondary damage or reduction of the parathyroid glands.

These include, for example:

• Haemochromatosis, i.e. high iron content in the blood
• Hemosiderosis, high iron content in the blood, e.g. after repeated blood transfusions
• Wilson's disease, a disorder in which there is a high level of copper in the blood
• Metastasis in cancer, e.g. breast cancer
• Sarcoidosis

Transient hypoparathyroidism

This condition can occur after parathyroid adenoma surgery that was performed as a treatment for previous hyperparathyroidism. The gland that is left is inhibited by the previous long-term hypercalcemia. Therefore, it does not secrete sufficient amounts of parathyroid hormone. The second type of transient hypoparathyroidism is in newborns delivered by hypercalcemic mothers, that is, mothers with high blood calcium levels.

The causes of hyperparathyroidism/increased production are...

Primary hyperparathyroidism

Primary hyperparathyroidism is the name given to a pathological condition in which the glands themselves, the parathyroid glands, are directly damaged.

The most common cause of primary hyperparathyroidism is a benign tumor of the gland - an adenoma.

In other cases, the common cause is hyperplasia, i.e. enlargement of two or more parathyroid glands.

A rarer cause of primary hyperparathyroidism is an oncological process, i.e. a tumor.

Primary hyperparathyroidism occurs sporadically in most cases. However, some patients have a gene that predisposes them to the disease.

Secondary hyperparathyroidism

Secondary hyperparathyroidism is the result of another disease in which there is a decrease in the level of calcium in the blood. This subsequently affects the function of the parathyroid glands.

Low blood calcium levels are a signal for the parathyroid glands to start producing large amounts of parathyroid hormone to maintain or restore calcium levels.

Factors that lead to the development of secondary hyperparathyroidism include:

• Severe calcium deficiency caused by inadequate calcium intake from the diet or after small bowel or stomach surgery (bariatric surgery), when absorption of this mineral from the diet is impaired.
• A severe deficiency of vitamin D, which helps maintain normal blood calcium levels and promotes the absorption of dietary calcium in the intestines. Vitamin D can be synthesised by the body when the skin is exposed to sunlight. The body also receives it in the diet or in various supplements.
• Chronic kidney failure is the most common cause of secondary hyperparathyroidism. Healthy kidneys convert vitamin D into a form that the body can use. Damaged kidneys are unable to produce this form of vitamin D. This causes a drop in blood calcium and subsequently increased production of parathyroid hormone.

Tertiary hyperparathyroidism

In some cases, the parathyroid glands begin to enlarge spontaneously and produce increased amounts of parathyroid hormone. This is particularly the case when a patient suffers from long-term secondary hyperparathyroidism, most often in the final stages of kidney failure.

This stage no longer responds to any conservative treatment and blood calcium levels cannot be reduced.

Patients with tertiary hyperparathyroidism require surgical removal of the parathyroid glands.

Both conditions differ in their manifestations.

Symptoms of hypoparathyroidism

Hypoparathyroidism is manifested by low levels of calcium in the blood, which is associated with the symptoms of the disease.

A disorder of calcium metabolism that is caused by a reduction in urinary excretion of phosphate and reduced mobilization of calcium from the bones:

• Hypocalcemia (low blood calcium levels)
• Hypocalciuria (reduced excretion of calcium by the kidneys and urine)
• Hyperphosphatemia (high blood phosphorus levels)
• Hypophosphatasuria (reduced urinary excretion of phosphorus)

Neurological symptoms are a manifestation of disturbed calcium concentrations within the cell and in the intercellular space. Calcium transport across cell membranes ensures the transmission of signals between cells, especially in nervous tissue and muscle.

A decrease in the total calcium concentration in the blood causes a change in the balance of calcium inside and outside the cell. This results in hyperexcitability, i.e. increased cellular readiness and hypersensitivity to nerve stimuli.

The clinical manifestations are as follows:

• painful tonic spasms - muscle pain or spasms in the legs, feet or face, twitching of muscles, especially around the mouth, but also in the hands, arms and neck
• paresthesias - tingling or burning in the fingertips, feet and lips
• visceral tetany - cramps in the stomach and intestines
• fatigue or weakness

Tetany is the name given to the clinical manifestation of increased neuromuscular excitability. When tetany is caused by hypoparathyroidism and parathyroid damage, it is called parathyroid tetany.

The manifestation is painful spontaneous tetanic muscle spasms. Tetany is manifested and may be exacerbated by emotional stress, physical activity and hyperventilation. In these situations, respiratory alkalosis occurs, leading to an even more pronounced decrease in blood calcium concentration.

Other neurological symptoms of tetany include:

• severe headaches.
• epileptic seizures
• papiloedema with increased intracranial pressure, which may mimic an intracranial tumour
• islands of calcification in the skull, which are visible on the skull X-ray in about one fifth of patients

Other signs and symptoms associated with hypoparathyroidism may include:

• painful menstruation
• dry, eczematous skin
• slow hair growth, hair loss, and hair loss that can result in alopecia (baldness)
• transverse streaking of the nails, white spots on the nails (leukonychia) and brittle nails
• depression or anxiety

Symptoms of hyperparathyroidism

Primary hyperparathyroidism is diagnosed in most cases before the first symptoms of the disorder appear. This is because an elevated calcium level is detected during a routine blood test.

The appearance of symptoms is already a sign of damage or dysfunction of other organs. This organ damage or dysfunction is caused by high levels of calcium in the blood and urine and a lack of calcium in the bones.

Symptoms range from mild and non-specific to severe and severe:

• Sparse bones that break easily are a sign of osteoporosis
• Kidney stones are caused by excessive calcium in the urine. Calcium forms into small, hard deposits. A symptom of kidney stones is the tremendous pain caused by the passage of the stone through the urinary tract. This condition is called renal colic.
• Polyuria, or urinating large amounts of urine
• Stomach pain
• Fatigue syndrome and weakness
• Depression
• Memory disorders
• Arthralgia - joint pain
• Disease
• Nausea, vomiting, loss of appetite and weight loss
• Problems with the cardiovascular system, e.g. high blood pressure, cardiac arrhythmias, etc.
• Neonatal hypoparathyroidism - low calcium levels in newborns of mothers with untreated severe hyperparathyroidism during pregnancy

The basis of the diagnosis of any disease is a thorough history of the patient's difficulties.

The next step is a laboratory examination of the blood.

Low calcium, low parathyroid hormone and high phosphorus levels in the blood suggest that hypoparathyroidism might be involved. Also, low magnesium levels in the blood can cause low calcium levels.

The next laboratory test is a urinalysis. Parathyroid hormone acts on the kidneys to prevent excessive excretion of calcium in the urine. Therefore, when there is a deficiency of parathyroid hormone, we may pick up an increased amount of excreted calcium in the urine.

An auxiliary and quick test is an electrocardiogram (ECG), which checks the heart rhythm and picks up any rhythm disturbances - cardiac arrhythmias.

High blood calcium levels and elevated parathyroid hormone concentrations indicate hyperparathyroidism.

The diagnosis can be confirmed by other tests, including:

• X-ray densitometry - Dual-energy X-ray absorptiometry or DXA (dual-emission X-ray absorptiometry) is an examination to diagnose and monitor osteoporosis. Each of the two energies of radiation is absorbed differently by bone tissue and differently by muscle and fat. This helps to differentiate between bone and soft tissue. The examination provides information about bone density, i.e. the amount of calcium stored in the bones. At least two areas are examined, namely the hip bone and the femur.
• The 24-hour urine collection test provides information on kidney function. The amount of calcium excreted in the urine is monitored.
• MRI or CT scan of the abdomen and small pelvis focusing on the kidney area. Kidney stones or other pathologies affecting the kidneys may be seen.

The course of hypothyroidism depends mainly on the age of the patient and associated diseases.

Tetany as one of the main symptoms can have a creeping onset. A period of mild discomfort is replaced by a sharp tetanic attack, with significant emotional stress, hyperventilation or other decompensation of the organism.

Hyperparathyroidism is usually an incidental finding in patients with findings of high calcium on routine venous blood examination.

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