Primary hyperparathyroidism. Hyperparathyroidism - symptoms, treatment, causes, recommendations Algorithms for diagnosis and treatment of hyperparathyroidism

For quotation: Antsiferov M.B., Markina N.V. Modern approaches to the diagnosis and treatment of primary hyperparathyroidism // Breast Cancer. 2014. No. 13. P. 974

Introduction

Until recently, primary hyperparathyroidism (PHPT) was considered to be one of the rare endocrine diseases, which is accompanied by a violation of phosphorus-calcium metabolism with the development of urolithiasis (KD), damage to the skeletal system and pathological (low-traumatic) fractures.

Until recently, primary hyperparathyroidism (PHPT) was spoken of as one of the rare endocrine diseases, which is accompanied by disturbances in phosphorus-calcium metabolism with the development of urolithiasis (UCD), damage to the skeletal system with pathological (low-traumatic) fractures.

Changes in the understanding of the true prevalence of this disease occurred after the widespread introduction of determination of total and ionized calcium into standard biochemical blood tests. This allowed us to talk about PHPT as a more common endocrine disease. According to epidemiological studies, the prevalence of PHPT ranges from 3.2 cases per 100 thousand inhabitants in Switzerland to 7.8 cases per 100 thousand inhabitants in the USA. The prevalence of PHPT among young men and women is almost the same, while with age, women's susceptibility to this disease becomes 3 times higher than men. According to the Endocrinological Dispensary (ED) of the Moscow Department of Health, PHPT is common in all groups of the population, but its predominance is noted in the older age group. PHPT is most often diagnosed in women over 55 years of age. Among the 302 patients who applied to the ED with newly diagnosed PHPT, there were 290 women and 12 men.

Diagnosis of primary hyperparathyroidism

The development of PHPT in 80-85% of cases is caused by an adenoma of one of the four parathyroid glands (PTG), in 10-15% of cases there is hyperplasia of one or more PTG or multiple adenomas. Topical diagnosis of parathyroid adenoma is carried out using ultrasound examination (ultrasound). The information content of this method reaches 95%, however, when the mass of the gland is less than 0.5 g, it decreases to 30%. As a rule, parathyroid adenomas are visualized during scintigraphy using technetril. The sensitivity of this method for PTG adenoma reaches 100%, and for PTG hyperplasia - 75%. Ectopic parathyroid adenoma can be observed in 20% of cases and is not always detected on scintigraphy. In this case, an additional multislice computed tomography of the head and neck organs is performed to identify adenomas in the anterior mediastinum, pericardium, and retroesophageal space.

Laboratory methods for diagnosing PHPT are based on the determination of parathyroid hormone (PTH), free and ionized calcium, phosphorus, alkaline phosphatase, creatinine, vitamin D in the blood, calcium and phosphorus in daily urine.

Pathogenesis and clinical manifestations of osteovisceral complications of primary hyperparathyroidism

The main target organs that are affected in PHPT due to excessive secretion of PTH and hypercalcemia are the musculoskeletal, urinary systems, and the gastrointestinal tract (GIT). A direct relationship has been identified between PTH and calcium levels and increased morbidity and mortality from cardiovascular pathology.

Damage to the musculoskeletal system in PHPT is manifested by a decrease in bone mineral density (BMD) and the formation of secondary osteoporosis. The development of osteoporosis is directly related to the effect of PTH on bone tissue. PTH is involved in the processes of differentiation and proliferation of osteoclasts. Under the influence of lysosomal enzymes and hydrogen ions produced by mature osteoclasts, the bone matrix dissolves and degrades. In conditions of PHPT, the processes of bone tissue resorption prevail over the processes of formation of new bone tissue and are the cause of the development of low-traumatic fractures.

The indirect effect of PTH on bone tissue is associated with its effect on the renal tubules. PTH, by reducing the reabsorption of phosphate in the renal tubules, increases phosphaturia, which leads to a decrease in the level of phosphate in the blood plasma and the mobilization of calcium from the bones.

Osteoporotic changes in the bones of the spine range from minor bone deformities to compression fractures. The greatest changes are found in bones with a cortical structure. As a rule, patients complain of muscle weakness, bone pain, frequent fractures, and decreased height during the course of the disease. The risk of developing fractures with PHPT is 2 times higher in bones that have both a cortical and trabecular structure.

To identify bone complications of PHPT, dual-energy X-ray absorptiometry of the distal radius, lumbar spine, and proximal femurs is performed. The need to include the distal radius in the study is due to the most significant decrease in BMD in this area in PHPT.

In severe manifest course of PHPT, X-ray examination reveals severe bone disorders: cystic fibrous osteodystrophy, subperiosteal bone resorption. The main cause of the development of visceral disorders against the background of PHPT is hypercalcemia. Increased urinary calcium excretion leads to a decrease in the sensitivity of the renal tubules to antidiuretic hormone, which is manifested in a decrease in renal water reabsorption and the concentrating ability of the kidneys. Long-term hypercalcemia leads to the development of nephrocalcinosis and, as a consequence, to a decrease in glomerular filtration rate and the development of chronic renal failure. A decrease in GFR of less than 60 ml/min is an indication for surgical treatment of PHPT. Recurrent urolithiasis in patients with PHPT occurs in more than 60% of cases. Detection of nephrolithiasis is also an absolute indication for surgical removal of the parathyroid adenoma. Despite radical treatment, the risk of developing nephrolithiasis remains over the next 10 years.

All patients with PHPT undergo renal ultrasound and glomerular filtration rate (GFR) is determined to identify visceral disorders.

Structural changes in the coronary vessels in the absence of symptoms of damage to the cardiovascular system are present in patients with a mild form of PHPT. Arterial hypertension (AH) is detected with PHPT in 15-50% of cases. In more severe cases of PHPT, damage to the cardiovascular system is accompanied by calcification of the coronary arteries and heart valves, and left ventricular hypertrophy. Along with hypercalcemia, the mechanism of development of hypertension also involves an increase in intracellular calcium content, an increase in plasma renin activity, hypomagnesemia and a decrease in glomerular filtration rate with the development of chronic renal failure. Several population-based studies have confirmed a direct relationship between increased morbidity and mortality from cardiovascular disease and blood levels of PTH and calcium.

Gastrointestinal diseases are also directly related to hypercalcemia, which leads to increased secretion of gastrin and hydrochloric acid. 50% of patients with PHPT develop peptic ulcers of the stomach and duodenum. The course of peptic ulcer disease in patients with PHPT is accompanied by nausea, vomiting, anorexia, and pain in the epigastric region. To identify visceral gastrointestinal complications of PHPT, esophagogastroduodenoscopy (EGDS) is performed.

Management and treatment of patients with various forms of primary hyperparathyroidism

Depending on the level of calcium, the presence of bone, visceral or osteovisceral complications, manifest and mild forms of PHPT are distinguished. The mild form of PHPT, in turn, is divided into oligosymptomatic and asymptomatic forms.

The mild form of PHPT can be diagnosed:

• with normocalcemia or serum calcium levels exceeding the upper limit of normal by no more than 0.25 mmol/l;
• in the absence of visceral manifestations of PHPT;
• according to the results of densitometry, BMD is reduced according to the T-criterion by no more than 2.5 SD;
• There is no indication in the anamnesis of low-traumatic fractures.

Recently, the detection rate of patients with mild forms of PHPT has increased to 80%.

In 40% of patients with the normocalcemic form of PHPT, during the 3-year observation period, severe hypercalciuria with the development of nephrolithiasis was detected, and there was a decrease in BMD with the development of low-traumatic fractures. At the same time, the majority of patients observed for 8 years did not develop bone and visceral complications of PHPT. Thus, the decision to surgically treat a patient must be made on a case-by-case basis. With the progression of urolithiasis, a decrease in GFR less than 60 ml/min, the development of osteoporosis or low-traumatic fractures, as well as negative dynamics of laboratory parameters (increased levels of calcium and PTH in the blood serum), surgical treatment is recommended.

Management of patients with a mild, asymptomatic form of PHPT with osteopenia without a history of fractures is usually conservative. All patients are recommended to follow a diet limiting calcium intake to 800-1000 mg/day and increasing fluid intake to 1.5-2.0 l. If during dynamic observation there is a decrease in BMD with the development of osteoporosis, patients are prescribed drugs from the group of bisphosphonates. Bisphosphonates (BPs) are analogues of inorganic pyrophosphates. The phosphate groups of BF have two main functions: binding to cellular minerals and cell-mediated antiresorptive activity. The main target cell for the action of BP is the osteoclast. When they enter the osteoclast by endocytosis, BPs affect the mevalonate pathway - they block the enzyme farnesyl pyrophosphate synthase, which leads to inhibition of the modification of signaling proteins necessary for the normal function of the osteoclast and a decrease in its resorptive activity. The tactics of active monitoring of patients must necessarily include monitoring of indicators such as PTH, total and ionized calcium, creatinine, daily calcium excretion in urine (once every 3 months, then once every 6 months). Every 12 months Kidney ultrasound and densitometry must be performed.

Recently, it has become possible to treat secondary osteoporosis in patients with PHPT using monoclonal human antibodies to RANKL (denosumab). Unlike other antiresorptive drugs (bisphosphonates), denosumab reduces the formation of osteoclasts without impairing the function of mature cells. Denosumab (60 mg x 6 months) demonstrated better results in terms of increasing cortical and trabecular bone mineral density compared to alendronate (70 mg x 1 week). The administration of denosumab after therapy with bisphosphonates (alendronate) leads to a further increase in BMD.

The manifest form of PHPT is diagnosed if:

• the level of total calcium in the blood is more than 0.25 mmol/l above the upper limit of normal;
• there are bone, visceral or osteovisceral complications of PHPT.

When calcium levels are above 3.0 mmol/l, patients may develop psychosis. Calcium levels in the range of 3.5-4.0 mmol/l can cause the development of a hypercalcemic crisis, in which mortality reaches 50-60%.

If a manifest form of PHPT with a specified localization of the parathyroid adenoma is detected, surgical treatment is recommended. If the results of ultrasound and scintigraphy of the parathyroid gland, MSCT of the mediastinal and neck organs are negative in patients with high levels of calcium and PTH and in the presence of bone and visceral complications, surgical intervention with revision of all areas of possible location of the parathyroid gland is possible. To confirm the successful removal of a parathyroid adenoma, intraoperative determination of PTH levels is recommended.

Removal of the parathyroid adenoma is the most radical method of treating PHPT. A postoperative complication of PHPT is persistent or transient hypocalcemia. In this regard, patients need to take active metabolites of vitamin D (alfacalcidol, calcitriol) and calcium supplements for a long time. In the postoperative period, the average dose of alfacalcidol can be 1.75 mcg/day, the average dose of calcium can be up to 2000 mg/day. With persistent normocalcemia, the dose of drugs is gradually reduced to maintenance - 1.0-1.5 mcg of active metabolites of vitamin D and 1000 mg of calcium per day. Surgical treatment and postoperative administration of active vitamin D metabolites and calcium supplements lead to a significant increase in BMD over 12 months. Menopausal women with symptoms of severe osteoporosis after taking calcium and alfacalcidol for a year need to be prescribed drugs from the group of bisphosphonates.

Conservative management of patients with manifest form of PHPT is carried out:

• with recurrent hyperparathyroidism;
• after a non-radical operation;
• if there are contraindications to surgical treatment (severe concomitant diseases);
• with an atypically located adenoma of the parathyroid gland;
• if it is impossible to visualize the adenoma on scintigraphy of the parathyroid gland, MSCT of the mediastinal and neck organs.

Patients are under dynamic observation; imaging studies of the adenoma are carried out once every 12 months.

In the manifest form of PHPT, there is a high level of calcium in the blood. In this regard, patients are prescribed an allosteric modulator of the calcium-sensing receptor (CaSR) - cinacalcet. The initial dose of the drug is 30 mg/day, followed by titration every 2-4 weeks. until target calcium levels are reached. The maximum dose of the drug is 90 mg x 4 times / day. The drug is taken orally during or immediately after meals. The dose of the drug is titrated under the control of the levels of total and ionized calcium, calcium and phosphorus excretion in the urine.

Against the background of 3 years of use of cinacalcet (30-90 mg/day) in 65 patients with a manifest form of PHPT, not only a decrease in the level of calcium in the blood was noted during the first 2 months, but also retention of the obtained result throughout the entire observation period. The average level of total calcium in the blood before treatment was 2.91 mmol/l, after 3 years during treatment - 2.33 mmol/l (p<0,001; норма — 2,15-2,57 ммоль/л). Также отмечалось уменьшение уровня ионизированного кальция с 1,50 ммоль/л до 1,22 ммоль/л (р<0,001; норма — 1,02-1,30 ммоль/л).

Patients with manifest PHPT with severe bone complications are prescribed antiresorptive therapy with drugs from the bisphosphonate group to prevent further bone loss and reduce the risk of fractures.

Primary hyperparathyroidism as part of multiple endocrine neoplasia syndrome (MEN syndrome)

It must be taken into account that hyperparathyroidism caused by adenoma or hyperplasia of the parathyroid gland can be part of the syndrome of multiple endocrine neoplasia (MEN syndrome) in 1-2% of cases.

MEN type 1 syndrome has an autosomal dominant pattern of inheritance and is associated with a mutation in the tumor suppressor gene in the long arm of chromosome 11. In 90% of cases, PHPT is the first manifestation of the disease, which remains asymptomatic for a long time. As a rule, with MEN type 1 syndrome, an ectopic location of the parathyroid adenoma or hyperplasia of all glands is detected. In type 1 MEN syndrome, PHPT is combined with multiple formations of other endocrine glands: in 70% - with tumors of the anterior pituitary gland (prolactinoma, somatostatinoma, corticotropinoma), in 40% of cases - with islet cell tumors (insulinoma, glucagonoma, gastrinoma) .

MEN type 2 syndrome is an autosomal dominant RET syndrome associated with a gene mutation. The disease is characterized by parathyroid hyperplasia, the development of medullary thyroid cancer and pheochromocytoma. In 50% of cases it is inherited.

Conclusion

Thus, PHPT is a severely disabling disease. Detection of PHPT in the early stages and surgical removal of the parathyroid adenoma can prevent the development of osteovisceral complications. At the same time, there is a group of patients who cannot be operated on for a number of reasons. Conservative management of these patients includes therapy with cinacalcet. In the presence of bone complications, drugs from the bisphosphonate group are prescribed for a long time. Careful attention should be paid to young patients with newly diagnosed PHPT, since it may be part of the MEN type 1 or 2 syndrome. Algorithms for differential diagnosis and management of patients with PHPT are presented in Schemes 1 and 2.

Literature

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Hyperparathyroidism is a disease caused by endocrinological disorders that provoke an increase in the secretion of parathyroid hormones. It is characterized by a significant disruption of the metabolic processes of calcium and phosphorus. As a result of this disorder, the bones become fragile, increasing the risk of damage and fractures.

There are primary, secondary, and tertiary forms of the disease. Nutritional hyperparathyroidism occurs only in veterinary practice.

Let's talk on the www.site about how hyperparathyroidism manifests itself, what is its treatment, what are its causes, what are the recommendations of specialists on the disease - our conversation today will focus on all this:

Causes, symptoms of the disease

Primary hyperparathyroidism (Recklinghausen's disease):

Causes

The most common cause of this form is considered to be the presence of a solitary adenoma of the parathyroid gland or, in other words, parathyroma. Less commonly, the cause of the primary form is called multiple adenomas. Even less common is parathyroid cancer. This form of the disease is most often diagnosed in adults, but can sometimes occur in children and the elderly.

It should be noted that primary hyperparathyroidism is observed in multiple endocrine neoplasia syndromes.

How primary hyperparathyroidism manifests itself (symptoms)

The disease may not manifest itself for a long time, as it develops asymptomatically. This is typical for the initial stage, when calcium levels are slightly elevated. As the disease progresses, characteristic symptoms appear. Severe complications, such as hypercalcemic crisis, may develop.

However, most often this form manifests itself with the following symptoms:

Changes in bone tissue: bone fragility increases, frequent fractures occur. Sometimes there may be a decrease in the patient's height;

Urolithiasis, nephrolithiasis;

Increased level of ionized calcium, severe calciuria, manifestations of severe hypercalcemia;

Visceral complications of the primary form of hyperparathyroidism: fibrous periostitis, nephrocalcinosis;

Secondary and tertiary hyperparathyroidism

Secondary hyperfunction and hyperplasia of the parathyroid glands, occurring against the background of prolonged hypocalcemia, hyperphosphatemia, is called secondary hyperparathyroidism.

Tertiary is characterized by the development of adenoma of the parathyroid glands, which occurs against the background of secondary hyperparathyroidism lasting a long time.

Causes of secondary hyperparathyroidism

The main causes of the secondary form of the pathology are chronic renal failure, as well as some diseases of the digestive system.

How do tertiary and secondary hyperparathyroidism manifest (symptoms)?

Clinical signs of the secondary and tertiary forms are similar to those of the underlying disease. The most common diagnosis is chronic renal failure (CRF).

Specific signs include:

Bone soreness;

Muscle weakness, arthralgia;

Frequent injuries, fractures, bone deformations;

Calcification of the arteries may also be a characteristic symptom. This condition provokes ischemic changes. Manifested by the formation of periarticular calcifications on the arms and legs.

It is also possible to develop calcification of the conjunctiva. When this pathology is combined with recurrent conjunctivitis, a condition occurs that experts refer to as red eye syndrome.

How is tertiary and secondary hyperparathyroidism corrected (treatment)?

Treatment of secondary and tertiary forms of hyperparathyroidism is quite complex. In severe cases, hemodialysis is prescribed and kidney transplantation is performed, which prolongs the patient's life by about 10-15 years.

When prescribing drug treatment, the drug Rocaltrol is used. At the same time, careful monitoring of calcium excreted in the urine is carried out. Vitamin D metabolites are prescribed, for example, Calcitriol, and aluminum phosphate binders are used.

If the level of calcium is very high, as well as in the presence of severe symptoms, the patient must be hospitalized, after which treatment is carried out in a hospital setting. If there is high fragility of bone tissue, strict bed rest and therapeutic nutrition are indicated.

If the calcium level is slightly elevated, characteristic symptoms are absent or mild, emergency medical intervention is not required. The patient can lead a normal life without limitations in performance. On the recommendation of a doctor, the patient may be prescribed therapeutic nutrition. Its principles are always developed individually.

In order to prevent hyperparathyroidism, chronic diseases of the kidneys and digestive system should be treated in a timely manner. Visit more, play sports, practice with sun and air baths. It is very important to avoid stressful conditions. Be healthy!

Hyperparathyroidism is a disease that affects women more than men, and it occurs 2-3 times more often. This disease is a disorder of the endocrine system and is caused by excessive production of parathyroid hormone (PTH) by the parathyroid glands. This hormone leads to the accumulation of calcium in the blood, which causes bone tissue and kidney damage. When diagnosed with hyperparathyroidism, symptoms and treatment in women - information that is necessary for everyone who has problems with the thyroid gland, especially if the girl is at risk - between the ages of 25 and 50 years.

Causes

A healthy thyroid gland produces a normal amount of parathyroid hormone, but when problems occur in it, the amount can either decrease or increase significantly. The functioning of the gland is affected by:

1. Tumors, appearing in the tissues of the thyroid gland or lymph nodes of the neck. In this case, disturbances are caused by both malignant and benign neoplasms.
2. Kidney failure which has passed into the chronic stage.
3. Hereditary autosomal dominant syndrome, which provokes tumors in one or more endocrine glands. Sometimes diseases cause hyperplasia instead of a tumor.
4. Diseases associated with gastrointestinal tract.
5. Secondary hyperparathyroidism against the background of vitamin D deficiency - one of the rare cases of the disease, usually has a chronic form, which leads to changes in the tissues of internal organs. Most often, a disorder in the thyroid gland is not its only symptom.
6. Nutritional hyperparathyroidism- a disease caused by poor nutrition. It can be present even with a varied and balanced diet, if the body does not absorb some of the nutrients.

Depending on the reasons that caused the disease, there are:

1. Primary hyperparathyroidism - the disorder is caused by diseases of the thyroid gland. Most often these are hereditary disorders that are diagnosed at an early age.
2. Secondary - appears as the body's response to a long-term lack of calcium caused by poor diet or lack of vitamin D. Another cause of secondary hyperparathyroidism is diseases of the bone tissue or digestive organs, and also when the kidneys remove calcium from the body too quickly.
3. Tertiary - appears only with a long course of secondary hyperparathyroidism, which, without proper treatment, provokes the appearance of adenomas in the parathyroid glands.

In addition to this disease caused by disorders in the thyroid gland, there is pseudohyperparathyroidism, caused by the production of a substance similar in function to parathyroid hormone. This disease occurs due to malignant tumors that produce this substance. In this case, neoplasms affect other glands in the body and do not directly affect the secretion of parathyroid hormone.

Symptoms

Hyperparathyroidism, the symptoms of which are not specific in the early stages, and in some cases the disease resolves without significant manifestations. Therefore, the disorder is rarely diagnosed in a mild form, unless there are significant changes in the thyroid tissue.

In the early stages appear:

• Headache and cognitive decline.
• Increased fatigue.
• Decreased muscle tone, which leads to difficulties with movement; it is especially difficult for the patient to climb stairs, even to a small height.
• Deterioration in the emotional sphere, the appearance of signs of neurasthenia, and sometimes depression. People with reduced immunity, as well as children and the elderly, may develop mental disorders that cannot be explained by genetic predisposition or external influences.
• Changes in skin color to pale, and with prolonged disturbance, it acquires an earthy tint.
• A change in gait, which becomes a “duck-like” waddle, due to decreased tone of the pelvic muscles or changes in the bone structure of the hips.

At a later stage, disorders occur in bone tissue:

1. Osteoporotic- developing decrease in bone mass, as well as disturbances in its structure.
2. Osteitis fibrocystis- inflammation in the bones, leading to the appearance of cystic tumors.

Due to a violation of the bone structure, patients often experience fractures during normal movements, which are not traumatic. So, a person can break an arm or leg while in bed. At this stage of the disease, pain occurs without a clear localization, and most often it is characterized as “bone aches.” Fractures that appear at this stage cause less pain than in a healthy person, but they heal less well and are more often accompanied by complications. Broken bones often heal incorrectly, causing limb deformities.

Problems with the bone structure cause not only fractures, but also changes in the spine, which can cause a person to become shorter or have a sharp deterioration in their posture. A common case is a violation of the integrity of the teeth, in which they begin to become loose due to disturbances in the alveolar bone and gum tissue. Often in such cases, even healthy molars begin to fall out.

Hyperparathyroidism, the symptoms of which are nonspecific, is called visceropathic. It is very rare. This case of the disease develops gradually, which makes diagnosis difficult. Initially, a person develops signs of intoxication, frequently recurring vomiting or diarrhea, increased flatulence, as well as decreased appetite and rapid weight loss.

Ulcers may appear in the gastrointestinal tract, which are accompanied by bleeding, while treatment of the mucous membrane is ineffective, which is why frequent exacerbations and relapses occur. Possible damage to the pancreas, liver or gallbladder. They also often record an increase in the amount of urine excreted above the daily norm, which is why patients develop a constant thirst that cannot be quenched. As the disease develops, calcium salts are deposited in the kidney tissues, which causes their changes and, over time, kidney failure.

Diagnostics

Initially, the disease has no specific symptoms, which makes it difficult to diagnose. But there are a number of general tests that can show an increase in calcium levels in the body:

1. General urine analysis - the liquid becomes more alkaline, while calcium salts are found in it, and the amount of phosphorus also increases. Sometimes protein is found in the urine, which indicates inflammation in the kidneys. At the same time, the density of the secretions decreases, but their quantity increases.
2. Biochemical blood test - allows you to find out the composition of the blood and accurately determine the imbalance of proportions. With hyperparathyroidism, the amount of total and ionized calcium in the blood is increased, and phosphorus is decreased.

Specific tests:

1. Chemiluminescent immunoassay- collection of venous blood to determine the amount of parathyroid hormone.
2. Ultrasound of the thyroid gland- allows you to determine changes in tissues, as well as detect abnormalities in the lymph nodes.
3. X-ray, CT or MRI- carried out both in the neck and limbs if the patient complains of pain, unexpected fractures, or changes in mobility.
4. Scintigraphy of the gland- makes it possible to determine how normally the parathyroid glands are located, as well as what tissues are part of them, whether there are pathological changes, and how the organ functions.

In addition to general and specific tests, the doctor may prescribe additional tests to identify the cause of the disease. This is especially important if the disease is secondary.

Treatment

If hyperparathyroidism is detected, treatment should be comprehensive; it will depend on the root cause of the disease. Because tumors or other abnormalities of the thyroid gland are often present, a combination of surgery and drug therapy is considered optimal.

When hyperparathyroidism is initially diagnosed, doctors’ clinical recommendations most often include removal of the tumor or dysplasia of the parathyroid glands. If the size of the altered tissues is small, then special endoscopic equipment is used, which reduces interference in the body, which has a beneficial effect on the speed of recovery.

In addition, doctors prescribe various measures to help reduce calcium in the blood. To do this, a sodium chloride solution can be administered intravenously, and furosemide, potassium chloride and a 5% glucose solution can also be prescribed. But such measures are necessary only if the calcium content is too high, which can provoke a crisis. This increases the load on the kidneys, so all medications should be taken only under the supervision of a doctor to reduce the likelihood of pathological changes.

If the disease is caused by malignant tumors, then after their removal a course of radiation or chemotherapy is administered, selected individually, depending on the course of the disease.

If the disease is diagnosed in the early stages, and there are no serious chronic diseases in the body, then the prognosis for treatment is quite favorable. When the disease begins to affect bone tissue, but has not gone too far, therapy takes from 4 to 24 months. A more severe case is kidney damage due to pathological changes in the organs.

The disease hyperparathyroidism, symptoms and treatment in women do not differ from those typical for men, but due to unstable hormonal levels, the endocrine glands are more susceptible to changes. Therefore, it is important for sexually mature women to monitor the health of the thyroid gland and regularly check the amount of calcium in the blood.

RCHR (Republican Center for Health Development of the Ministry of Health of the Republic of Kazakhstan)
Version: Clinical protocols of the Ministry of Health of the Republic of Kazakhstan - 2018

Primary hyperparathyroidism (E21.0)

Endocrinology

general information

Short description

Approved
Joint Commission on Healthcare Quality
Ministry of Health of the Republic of Kazakhstan
from April 18, 2019
Protocol No. 62

Primary hyperparathyroidism- primary disease of the parathyroid glands, manifested by hyperproduction of PTH and damage to the skeletal system and/or internal organs (primarily the kidneys and gastrointestinal tract).

INTRODUCTORY PART

ICD-10 code(s):
Date of protocol development/revision: 2013 (2018 revision)

Abbreviations used in the protocol:
Protocol users: endocrinologists, general practitioners, therapists.

Level of evidence scale:

Table 1. Relationship between strength of evidence and type of research

Classification

Classification

Table 2. Clinical classification of primary hyperparathyroidism:

Diagnostics

METHODS, APPROACHES AND PROCEDURES FOR DIAGNOSIS AND TREATMENT

Complaints: for bone pain, weakness, decreased appetite, decreased growth.

Anamnesis: the presence of frequent, inadequate load-bearing and poorly consolidating fractures, urolithiasis, depressive states, polyuria, polydipsia

Physical examination:
Inspection: skeletal deformations, bone growths in the area of ​​the facial bones, large joints, long bones, lethargy, pallor, dry skin.

Main clinical manifestations :
- Musculoskeletal system: bone pain, bone deformities, pathological fractures, gout, pseudogout, muscle atrophy, soft tissue calcifications.
- Recurrent nephrolithiasis, nephrocalcinosis,
- Chronic pancreatitis, peptic ulcer of the stomach and duodenum
- Dyspeptic disorders, weight loss.
- Mental changes - depression, asthenic syndrome
- Insipid syndrome
- Heart rhythm disturbances, arterial hypertension

Laboratory research:
Table 3. Biochemical parameters in blood and urine during PHPT

Differential diagnosis

Differential diagnosisand rationale for additional research:

Table 7. Differential diagnosis of PHPT

Treatment abroad

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Treatment

Drugs (active ingredients) used in treatment

Treatment (outpatient clinic)

OUTPATIENT TREATMENT TACTICS

Goal of treatment PGPT:
- Elimination of the source of PTH hyperproduction
- Normalization or reduction of Ca and PTH levels in the blood
- Elimination and/or prevention of progression of osteovisceral disorders
Conservative management in patients with PHPT is used when there is a medical contraindication for parathyroidectomy; the patient's refusal to undergo surgical treatment; in patients with asymptomatic forms of the disease without sufficient indications for parathyroidectomy.

Non-drug treatment:
Diet therapy: table No. 9, adequate rehydration.
Physical activity: Limiting physical activity, preventing fractures.

Drug treatment
Indicated for:
- the presence of mild bone abnormalities and mild hypercalcemia or
normocalcemia
- absence of remission after surgical treatment
- manifest hyperparathyroidism and the presence of contraindications to surgical treatment or if the patient refuses surgery.

Table 9. Drug treatment for PHPT

Treatment (inpatient)

TREATMENT TACTICS AT THE INPATIENT LEVEL

Patient observation card, patient routing: No.

Non-drug treatment: see Outpatient level

Drug treatment: see Outpatient level

Surgical intervention : parathyroidectomy, effectiveness 95-98%.
The gold standard for surgical treatment of PHPT is considered to be parathyroidectomy using local anesthesia. Depending on the extent of damage to the parathyroid gland, partial, subtotal or total parathyroidectomy is performed.

Absolute indications for surgical treatment:
- Age less than 50 years
- Impossibility of long-term observation under medical supervision
- Excess of total calcium in the blood by more than 0.25 mmol/l above the upper limit of normal
- Urinary calcium excretion of more than 400 mg per day with a normal diet
- Decrease in GFR less than 60 mg/min
- Presence of nephrocalcinosis
- Bone mineral density - T-score less than -2.5 in any area and/or history of fracture
- Parathyroid cancer

Complications after surgical treatment
- Damage to the recurrent laryngeal nerve
- Transient or persistent hypocalcemia, hypomagnesemia, “hungry bone syndrome.”

Treatment of hypocalcemic crisis:
1. 1500-2000 mg Ca and alfacalcidol 1-3 mg/day;
2. For seizures - calcium gluconate 80 ml with 0.9% NaCl solution daily.

Further management: In the postoperative period, restoration of calcium metabolism does not occur immediately, and patients require additional intake of calcium and vitamin D3.
Upon reaching remission:
- Clinical observation by an endocrinologist, treatment of osteoporosis.
- Monitoring the activity of alkaline phosphatase in the blood serum once every 3-6 months.
- X-ray control once every 3 years
In case of relapse, repeat courses of treatment.
Relapse rate:
Sporadic hyperparathyroidism - 5-10%
For hyperparathyroidism as part of MEN syndromes - 15-25%
For parathyroid cancer - 32%

Indicators of treatment effectiveness:
- Normalization of PTH, Ca and blood phosphorus levels, alkaline phosphatase, absence of relapses.

Hospitalization

INDICATIONS FOR HOSPITALIZATION, INDICATING THE TYPE OF HOSPITALIZATION

Indications for planned hospitalization:
1. In case of severe hypercalcemia and in cases of refusal of surgical treatment, hospitalize the patient for rehydration and treatment of cardiovascular and neurological complications of PHPT. Rehydration is carried out by introducing a 0.9% sodium chloride solution to reduce the toxic effect of hypercalcemia on target organs and increase calcium excretion in the urine.
2. Carrying out a planned operation to remove adenoma or carcinoma of the parathyroid gland

Indications for emergency hospitalization: hypercalcemic crisis.
Hypercalcemic crisis- an acute complication of PHPT, is severe, life-threatening calcium intoxication. Develops when plasma calcium levels exceed 3.5 mmol/l.
Provoked:
- rough palpation of the thyroid gland and parathyroid gland
- pregnancy
- taking thiazide diuretics, calcium and vitamin D supplements
- fractures
- infections
- long bed rest
The clinical picture develops very quickly, with increasing symptoms of dehydration, damage to the central nervous system (psychosis, stupor, coma) and gastrointestinal tract (nausea, uncontrollable vomiting, thirst, epigastric pain, often simulating the picture of an “acute abdomen”). Hyperthermia up to 40 °C, thrombosis of various localizations, disseminated intravascular coagulation syndrome, acute renal, respiratory and cardiovascular failure are noted. Symptoms increase like an avalanche, anuria develops, and coma develops.
Treatmenthypercalcemic crisis:
- restoration of bcc (infusion therapy with a 0.9% NaCl solution in a volume of 3000-4000 ml/day while maintaining plasma osmolality at 280-290 mOsm/kg in combination with diuretics).
- At the same time, the level of calcemia is normalized (bisphosphonates are used).
- After normalization of the patient’s condition, parathyroidectomy of pathologically altered parathyroid glands is recommended.

Information

Sources and literature

1. Minutes of meetings of the Joint Commission on the Quality of Medical Services of the Ministry of Health of the Republic of Kazakhstan, 2018
   1. 1. Dedov I.I., Melnichenko G.A., Endocrinology national guide, Moscow, “GEOTAR - Media”, 2018, pp. 817-832. 2. Primary hyperparathyroidism: clinical picture, diagnosis, differential diagnosis, treatment methods. Clinical protocol. FSBI "Endocrinological Research Center" of the Ministry of Health of Russia, Moscow. Problems of endocrinology, No. 6, 2016, pp. 40-77 3. Primary hyperparathyroidism: Modern approaches to diagnosis and treatment. Educational and methodological manual, Minsk BSMU 2016, 21 p. 4. Primary hyperparathyroidism: review and recommendations on evaluation, diagnosis, and management. A Canadian and international consensus. Osteoporos Int., 2017; 28(1): P.1–19. 5. The American Association of Endocrine Surgeons Guidelines for Definitive Management of Primary Hyperparathyroidism. JAMA Surg. 2016;151(10): P.959-968. 6. Guidelines for the Management of Asymptomatic Primary Hyperparathyroidism: Summary Statement from the Fourth International Workshop. The Journal of Clinical Endocrinology & Metabolism, V, 99, Issue 10, 1 October 2014, P.3561–3569.

Information

ORGANIZATIONAL ASPECTS OF THE PROTOCOL

List of protocol developers with qualification information:

1. Nurbekova Akmaral Asylovna - Doctor of Medical Sciences, Professor of the Department of Endocrinology of JSC National Medical University;
2. Rimma Bazarbekovna Bazarbekova - Doctor of Medical Sciences, Professor, Head of the Department of Endocrinology of JSC “Kazakh Medical University of Continuing Education”, Chairman of the RPO “Association of Endocrinologists of Kazakhstan”.
3. Taubaldieva Zhannat Satybaevna - Candidate of Medical Sciences, Head of the Department of Endocrinology, JSC National Scientific Medical Center.
4. Kalieva Sholpan Sabataevna - Candidate of Medical Sciences, Associate Professor, Head of the Department of Evidence-Based Medicine and Pharmacology of Karaganda Medical University JSC.

Disclosure of no conflict of interest: No.

Reviewer:
Ainur Kasimbekovna Dosanova - Candidate of Medical Sciences, Associate Professor of the Department of Endocrinology of the Kazakh Medical University of Continuing Education JSC, Secretary of the Regional Educational Institution AVEC.

Indication of the conditions for reviewing the protocol: review of the protocol 5 years after its publication and effective date or if new methods with a level of evidence are available.

Attached files

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