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

Introduction

The terminal hyperparathyroidism (PGPT) was contacted by the rough endocrine diseases, which is accompanied by a violation of phosphorous calcium exchange by the combination of urolithiasis (ICD), defeat bone system Spacetic (low-alcohol) fractures.

Until recently, the primary hyperparathyroidism (PGPT) was spoken as one of the rare endocrine diseases, which is accompanied by a violation of phosphorus-calcium exchange with the development of urolithiasis (ICD), the lesion of the bone system with pathological (low-alcoholum) fractures.

Changes in the presentation of the true prevalence of this disease occurred after widespread introduction into the standard biochemical study of the blood definition of general and ionized calcium. This made it possible to talk about PGPT as a more common endocrine disease. According to epidemiological studies, the prevalence of PGPT varies from 3.2 cases per 100 thousand inhabitants in Switzerland to 7.8 cases per 100 thousand inhabitants in the United States. The prevalence of PGPT among young men and women is almost the same, while with age in women exposure to this disease becomes 3 times higher compared to men. According to the Endocrinological Dispensary (ED) of the Moscow Department of Health, PGPT is distributed in all population groups, but its predominance is noted in the older age group. Most often, PGPT is diagnosed in women over the age of 55. Among 302 patients who applied to ED with the first time detected by PGPT, there were 290 women and 12 men.

Diagnosis of primary hyperparathyroidism

The development of PGPT in 80-85% of cases is due to the adenoma of one of the four stovered glands (ADD), in 10-15% of cases there is a hyperplasia of one or several degree or multiple adenoma. The topical diagnosis of adenoma Aception is carried out using ultrasound research (ultrasound). The informativeness of this method reaches 95%, but at weight of the gland less than 0.5 g decreases to 30%. As a rule, adenoma Association is visualized during scintigraphy using technetrile. The sensitivity of this method with the adenoma of the resistant reaches 100%, and with the hyperplasia of the accommodation - 75%. Extoped adenoma of the gentleman can be observed in 20% of cases and is not always detected on scintigraphy. In this case, it is additionally carried out by multispiral computed tomography of the heads of the head and neck to detect adenoma in the anterior mediastinum, pericardia, possessed space.

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

Pathogenesis and clinical manifestations of bone-visceral complications of primary hyperparathyroidism

The main target bodies that are affected with the PGPT due to excessive secretion of PTH and hypercalcemia are bone-muscular, urinary systems, gastrointestinal tract (gastrointestinal tract). The direct relationship between PTH and calcium levels and increasing morbidity and mortality from cardiovascular pathology has been revealed.

The damage to the musculoskeletal apparatus at the PGPT is manifested by a decrease in the mineral density of bone tissue (ICT) and the formation of secondary osteoporosis. The development of osteoporosis is directly related to the influence of PTH on bone tissue. PTH is involved in the differentiation and proliferation of osteoclast processes. Under the action of lysosomal enzymes and hydrogen ions produced by mature osteoclasts, the dissolution and degradation of the bone matrix occurs. Under the conditions of PGPT, bone resorption processes prevail over the processes of formation of new bone tissue and are the cause of the development of low-strata fractures.

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

Osteoporotic changes in the bones of the spine varies from a minor deformation of the bones up to compression fractures. The greatest changes are found in bones having a cortical structure. As a rule, patients impose complaints of muscle weakness, pains in the bones, frequent fractures, a decrease in growth during the disease. The risk of fractures during the PGPT is 2 times higher in bones that have both cortical and trabecular structure.

To identify bone complications of PGPT, two-energy X-ray absorption of the distal dice of the radial bone, the lumbar spine, is carried out, proximal departments femoral bones. The need to include in the study of the distal radiation dice is due to the most significant reduction in the ICT in this area with PGPT.

With severe manifest flow of PGPT, X-ray study allows you to identify heavy bone disorders: cystic fibrous osteodistrophiy, subperiodal resorption of bone tissue. The main cause of the development of visceral violations against the background of the PGPT is hypercalcemia. Increasing excretion of calcium with urine leads to a decrease in the sensitivity of the renal tubules to antidiuretic hormone, which is manifested in a decrease in the renal reabsorption of water and the concentration ability of the kidneys. Long-term hypercalcemia leads to the development of nephocalcinosis and, as a result of this, to a decrease in the speed of glomerular filtration and the development of CPNs. Reducing SCF less than 60 ml / min is an indication to operational treatment PGPT. The recurrent ICD in patients with PGPT is found in more than 60% of cases. The detection of nephrolithiasis is also an absolute indication to the operational removal of the adenoma of the ADC. Despite the treatment radically conducted, the risk of nephrolithiasis is maintained over the next 10 years.

All patients with PGPT carry out ultrasound kidneys, determine the speed of glomerular filtration (SCF) to detect visceral disorders.

Structural changes in coronary vessels in the absence of symptoms of damage to the cardiovascular system are available in patients with a soft form of PGPT. Arterial hypertension (AG) is detected at PGPT in 15-50% of cases. With more severe course PGPT The defeat of the cardiovascular system is accompanied by calcification coronary arteries And heart valves, left ventricle hypertrophy. Along with hypercalcemia, an increase in the content of intracellular calcium, an increase in the activity of renin plasma, hypomagnemia, and reduced glomerular filtration rates with the development of CPNs also participate in the AG development mechanism. Several population studies have confirmed the direct relationship between the increased morbidity and mortality from cardiovascular diseases and the level of PTH and calcium in the blood.

The diseases of the gastrointestinal tract are also directly related to hypercalcemia, which leads to an increase in the secretion of gastrin and of hydrochloric acid. In 50% of patients with PGPT, the development of the peptic ulcers of the stomach and duodenal gut. The course of ulcerative disease in patients with PGPT is accompanied by nausea, vomiting, anorexia, pain in the epigastric area. To identify the visceral gastrointestinal complications, the PGPT is carried out with esophagogastroduodenoscopy (EGDS).

Maintaining and treating patients with different forms of primary hyperparathyroidism

Depending on the level of calcium, the presence of bone, visceral or bone-visceral complications allocate the manifest and soft forms of PGPT. The soft form of PGPT, in turn, is divided into low-almptomatic and asymptomic forms.

The soft form of PGPT can be diagnosed:

• with normocalcemia or level of calcium in serum, exceeding the upper boundary of the norm by no more than 0.25 mmol / l;
• in the absence of visceral manifestations of PGPT;
• according to the results of densitometry, the IPT is reduced by the T-criterion of no more than 2.5 SD;
• in history there are no indications of low-alcohol fractures.

Recently, the frequency of identification of patients with a soft form of PGPT has increased to 80%.

In 40% of patients with a normocalcemic form of PGPT for a 3-year observation period, severe hypercalciuria was detected with the development of nephrolithiasis, a decrease in the IPT with the development of low-leveling fractures was noted. At the same time, most of the patients observed for 8 years have not been the development of bone and visceral complications of PGPT. Thus, the decision on the operational treatment of the patient should be taken for each specific case. Under the progression of the ICD, the decrease in SCF is less than 60 ml / min, the development of osteoporosis or low-alcoholic fractures, as well as with the negative dynamics of laboratory indicators (raising the level of calcium and PTH in serum) recommended operational treatment.

Maintaining patients with a soft, small-axipput form of PGPT with osteopenia without fractures in history, as a rule, conservative. All patients recommended a diet with a limitation of calcium consumption to 800-1000 mg / day and an increase in fluid consumption up to 1.5-2.0 liters. If in the process of dynamic observation there is a decrease in the ICT with the development of osteoporosis, patients prescribe preparations from the bisphosphonate group. Bisphosphonates (BF) are analogues of inorganic pyrophosphates. Phosphate groups BF have two main functions: communication with cell mineral and cell-mediated antisorbative activity. The main target cell for the effects of BF is osteoclast. If in osteoclast, the BF endocytosis affects the MEVALONATE Path - block the fern-refinery phosphate-synthase enzyme, which leads to the braking of the modification of the signal proteins necessary for the normal function of osteoclast, and reduce its resorbative activity. The tactics of active observation of patients should necessarily include control of such indicators as PTH, general and ionized calcium, creatinine, daily excretion of calcium with urine (1 time in 3 months, then - 1 time at 6 months). Every 12 months. Be sure to conduct ultrasound kidneys, densitometry.

Recently, the possibility of treating secondary osteoporosis in patients with PGPT with the use of monoclonal human antibodies to RANKL (Denosuumab) has appeared. Unlike other anti-relative drugs (bisphosphonates), Denosuumab reduces the formation of osteoclasts without disturbing the function of mature cells. Denosuumab (60 mg x 1 time in 6 months) demonstrated the best result in terms of increasing the mineral density of cortical and trabecular bone tissue compared to alendronate (70 mg x 1 time per week). The purpose of the Denosuumab after therapy with bisphosphonates (alendronom) leads to a further increase in the ICT.

The PGPT manifest form is diagnosed if:

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

At calcium level above 3.0 mmol / l in patients, psychosis is possible in patients. The calcium level in the range of 3.5-4.0 mmol / l can cause the development of a hypercalcemic crime, in which mortality reaches 50-60%.

When detecting the manifest form of the PGPT with the definite localization of the adenoma, the Association recommended operational treatment. With negative results of the ultrasound and scintigraphy of the SCC, the MSCT of the mediastinal and neck organs in patients with a high level of calcium and PTH and in the presence of bone and visceral complications, it is possible to quickly interfere with the revisions of all zones of the possible arrangement of the SCC. To confirm the successful removal of the adenoma, an intraoperative determination of the PTH level is recommended.

The removal of the adenoma of the resistant is the most radical method of treating PGPT. Postoperative complication PGPT is a persistent or transient hypocalcemia. In connection with this, patients need a long time in the reception of active metabolites of vitamin D (alphacalcidol, calcitriol) and calcium preparations. IN postoperative period The average dose of alphaqalcidol can be 1.75 μg / day, the average calcium dose is up to 2000 mg / day. In the dose rate of drugs, the doses of preparations are gradually reduced to supporting - 1.0-1.5 μg of active metabolites of vitamin D and 1000 mg calcium per day. Surgical treatment and reception in the postoperative period of active metabolites of vitamin D and calcium preparations lead to a significant increase in the ICT for 12 months. Women in menopause with heavy osteoporosis phenomena after taking calcium and alpha cell drugs during the year it is necessary to prescribe drugs from the group of bisphosphonates.

Conservative maintenance of patients with a manifest form of PGPT is carried out:

• with the recurrent flow of hyperparathyroidism;
• after an inconsistent operation;
• in the presence of contraindications to surgical treatment (severe concomitant diseases);
• with an atypically located adenome of the SCC;
• if it is impossible to visualize adenomose on scintigraphy, the MSCT of the mediastinum and neck organs.

Patients are under dynamic observation, the visualizing studies of the adenoma are held 1 time in 12 months.

In the manifest form of the PGPT, there is a high level of calcium in the blood. In connection with these patients, a calcium-sensitive receptor (CASR) - cynakaltseet is prescribed (CASR). The initial dose of the drug is 30 mg / day followed by titration every 2-4 weeks. Prior to reaching the target level of calcium. The maximum dose of the drug is 90 mg x 4 r. / Day. The drug is assumed orally while eating or immediately after it. The dose of the drug is titrated under the control of the levels of general and ionized calcium, the excretion of calcium and phosphorus with urine.

Against the background of the 3-year-old application of cynaculzeta (30-90 mg / day), 65 patients with a manifest form of PGPT noted not only a decrease in blood calcium level during the first 2 months., But the retention of the result obtained during the entire observation period. The average level of total calcium in the blood before treatment was 2.91 mmol / l, after 3 years on the background of 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 a manifest form of PGPT with heavy bone complications to prevent further loss of bone mass and reducing the risk of fractures are prescribed with antisorbative therapy with preparations from the bisphosphonate group.

Primary hyperparathyroidism as part of multiple endocrine neoplasia syndrome (Men-syndrome)

It should be borne in mind that hyperparathyroidism caused by adenoma or hyperplasia of the SCC, in 1-2% of cases there may be part of multiple endocrine neoplasia syndrome (Men-syndrome).

The 1-th type Maine syndrome has an autosomal dominant type of inheritance and is associated with a mutation in the gin of the tumor growth suppressor in the long shoulder of the 11th chromosome. In 90% of cases, PGPT is the first manifestation of the disease that is asymptomatic for a long time. As a rule, with the syndrome of Maine 1 type, the ectopied arrangement of the adenoma of the degree or hyperplasia of all glands is detected. In the syndrome of Maine of the 1st type of PGPT, it is combined with multiple formations of other endocrine glands: in 70% - with the front lobes of pituitary gland (prolactinoma, somatostatinoma, corticotropinoma), in 40% of cases - with isle-cellular tumors (insulin, glucagon, gastric) .

2-type Maine Syndrome is an autosomal-dominant associated with the mutation of the gene, Ret-syndrome. The disease is characterized by hyperplasia of the generosity, the development of medullary cancer of the thyroid gland and feochromocytoma. In 50% of cases is inherited.

Conclusion

Thus, PGPT is a severe disabled disease. The detection of the PGPT in the early stages and the operational removal of the adenoma of the ASC make it possible to prevent the development of bone-visceral complications. At the same time, there is a group of patients who cannot be operated on a number of circumstances. Conservative maintenance of these patients includes cynaculzet therapy. In the presence of bone complications, preparations from the bisphosphonate group are long. Close attention should be paid to young patients with first identified PGPT, since it can be part of Maine's Syndrome of the 1st or 2nd types. Algorithms for differential diagnosis and maintenance of patients with PGPT are presented in diagrams 1 and 2.

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Primary hyperparathyroidism (PGPT) is a disease, the development of which is associated with excessive secretion of the parathyroid hormone (PTH) and as a result of this, with an increase in the content of calcium in the blood serum. PGPT is one of the causes of hypercalcemia - metabolic disorders manifested by an increase in the level of calcium in blood serum and accompanied by a varying degree of severity by a clinical picture. In addition to the PGPT hypercalcemia, malignant neoplasms are accompanied (osteolatic metastases of malignant tumors in the bone); pseudo-opporathyroidism; Family isolated hyperparathyroidism; Tertiary hyperparathyroidism; thyrotoxicosis; chronic adrenal insufficiency; Feochromocytoma; Vipoma; blood system diseases (leukemia, lymphoma, myeloma disease, lymphogranulomatosis); Medical hypercalcemia; bone fractures; long immobility; acute renal failure and family hypocalciuric hypercalcemia.

Epidemiology PGPT

PGPT is the most common cause of hypercalcemia. The frequency of occurrence of PGPT is approximately 25-28 cases per 100,000 population. The prevalence of PGPT is 0.05-0.1%, while in women it occurs 4 times more often than in men. Approximately half of all cases of the disease fall on the age group from 40 to 60 years, the peak of morbidity is 60-70 years. Thus, in the group of women older than 50 years, the prevalence of hyperparathyroidism is 1-2%. Over the past 50 years, the clinical picture of this disease has undergone significant changes. In the countries of Western Europe and North America, by 1965, the manifestic forms of PGPT prevailed: 60% - kidney pathology, 25% of the bone system and only 2% is the asymptomatic form of PGPT. By 1975, about 50% of kidney forms, 15% of bone and 20% of asymptomic or low-power; By 1990, 18% was the pathology of the kidneys, bone manifestations decreased to 2%, and the proportion of asymptomatic and soft forms of PGPT increased to 80%. In Russia, until 2000, the asymptomic and soft forms of PGPT were practically not treated and did not have been treated, while manifestic, often heavy forms of PGPT were diagnosed in 85-90% of cases. According to preliminary data obtained in the separation of neuroendocrinology and osteopathies of the Federal State Unitary Enterprise ENZ RosMedtechnology, among 340 patients observed about the PGPT, the proportion of manifest forms is comparable to the shares of small-mixed. Thus, a tendency towards an increase in the specific gravity of soft and asymptomatic forms of PGPT and in Russia is traced.

Etiology and pathogenesis of PGPT

The PGPT is due to adenoma or hyperplasia and, less likely, the carcinoma of the Pori-shaped glands (SCC). In most cases, solitary paratromes (80-89%) are detected, less often - multiple adenoma (2-3%), hyperplasia (2-6%) and Cancer ADC (0.5-3%). Hyperparathyroidism, accompanied by a hyperplasia of the alex or multiple adenomas, as a rule, is combined with hereditary syndromes: multiple endocrine neoplasia of the 1st type (Main-1), hyperparathyparatrosis syndrome with a tumor of the lower jaw, family isolated hyperparathyroidism and family hypercalcium. As for sporadic forms, in addition to age and gender, the irradiation of the neck area with a diagnostic or therapeutic goal is a significant risk factor.

Adenoma Associty is usually benign. In accordance with the modern data, the development of adenoma ADCH is associated with two types of mutations: I type - Mutation in mitotic control and type II - mutation of the finite control mechanism of PTH Calcium secretion. The monoclonal tumors are attributed to both the adenoma observed in the Meng-1, sporadic (incomarestic) hyperplasia and the secondary or tertiary hyperplasia of the Associty in chronic renal failure (CPN) and Uremia.

In other cases, under the influence of various factors (low calcium or calcitriol), there is a population of rapidly proliferating cells, which can cause hyperplasia or hyperplastic adenoma. In such cases, polyclonal adenoma is developing.

A specific role in the mutation of the gene encoding PTH belongs to a specific PRAD1-gene belonging to the proto-curved and localized chromosome 11Q13 on which the gene encoding PTH is also localized - 11p15. Subsequently, it was proved that oncogen Prad1 refers to cycles - cellular cycle regulators. Cyclin A is involved in the regulation of the S-phase, and Cycline B - in the regulation of the C2-M-phase of the cell cycle. The PRAD1 protein gene, or cyclin D1, is excessively expressed in the adenoma of the SCC.

In recent years, it has been established that, in addition to the above factors for the formation of tumors of the SCC, this contributes to microsatellite instability. Microsatellites are short tandem repeats in polymorphic DNA sites (usually sa-repetitions). Variations between tandem repeated nucleotides in tumors, but not in normal tissue is called microsatellite instability. Microsatellite instability L. A. LOEB determined as a marker of a mutagenic phenotype with cancer. Confirmation of this concept is a study conducted by M. Sarquis et al., In which it was first shown that a sporadic large adenoma of the Associty, removed from the girl at the age of 8.5 years, contained instability of 4 dinucleotide markers in three different loci 1st, 10 And the 11th chromosome.

It is suggested that the violation of the physiological action of vitamin D is one of the factors predisposing to the development of adenoma ADN. This assumption was confirmed by the study by T. Carling et al., Which believe that the level of mRNA receptor to vitamin D was significantly reduced with adenoma or hyperplasia of the ... 42 ± 2.8 and 44.0 ± 4.0%, respectively) compared to Its content in normal gentle. The reduced expression of the vitamin D receptor gene is probably worsens 1.25 (s) 2D3-mediated control of parathyroidic functions, and it has a value in the pathogenesis not only the secondary hyperparathyroidism at CPN, but also PGPT.

Clinical picture of PGPT

Clinically PGPT can manifest itself as a asymptomatic form, a soft shape, a clinically manifesting form without complications and a clinically manifesting form with the development of complications.

The development of clinical manifestations of PGPT is due to hypercalcemia, which is a consequence of PTG hypersection. With asymptomatic form of hypercalcemia, as a rule, moderate, and clinical manifestations Nonspecific.

Hypercalcemia is manifested by numerous symptoms and signs of the disease that can be submitted by the following groups:

1) manifestations of systemic nature (general weakness, dehydration, calcification of horny shell, soft and other tissues);
2) violations of the CNS activities (decline in the concentration of attention, depression, psychosis, changes in consciousness - from twilight consciousness to coma);
3) the pathology of the musculoskeletal system (osteoporosis, hyperparathyroid osteodistrophy, fractures, proximal myopathy);
4) function disorders gastrointestinal tract (nausea, vomiting, anorexia, constipation, abdominal pain in pancreatitis and peptic ulcers);
5) disorders of the kidney function (polyuria, polydipsee, isoostenuria, reduction of glomerular filtration, renal disease, nephrollociety);
6) Violations of the function of the cardiovascular system (hypertension, the shortening of the Qt interval, increasing sensitivity to Digitalis preparations).

There are several clinical (manifest) forms of PGPT:

• bone - osteoporotic, fibrous-cystic osteite, pedaloidal;
• burcepathic - with preferably damage to the kidneys, gastrointestinal tract, cardiovascular system;
• mixed.

The damage to the bone system is one of the permanent symptoms of hyperparathyroidism. Bone losses in the peripheral skeleton are first revealed in the end departments of tubular bones due to the prevalence of spongy bone here. Endostal resorption plays a dominant role in PGPT. The result of this process is to expand the bone marrow channel with the thinning of the cortical layer. It was previously believed that one of the most frequent lesions of the bone system in hyperparathyroidism is a generalized fibrous-cystic osteite, which was observed more than 50% of patients. In recent years, due to the earlier diagnosis of the disease, these lesions of bone tissue are revealed less often (10-15%). Cysts and giant tumors are arranged, as a rule, in long tubular bones and are detected during radiography. Cysts are also found in the bones of wrists, ribs, bones pelvis. Gigantaeer tumors on radiographs have a mesh structure and a characteristic view of bee honeycombs. With histological examination of bone lesions, a decrease in the trabecual number is revealed, an increase in multi-core osteoclasts and a substitution of cellular and bone marginal elements with a fibrovascular cloth. The osteoporotic variant is characterized by a progressive decrease in the bone mass in a unit of bone volume with respect to the normal indicator in individuals of the appropriate gender and age, disruption of bone microarchitectonics, leading to increased bone fragility and increasing the risk of fractures from minimal injury and even without such. At PGPT, a diffuse reduction of bone mineral density (IPC) is often fixed, which is difficult to distinguish from age or postmenopausal osteoporosis. It is believed that more frequent detection of osteoporosis is associated with the earlier diagnosis of hyperparathyroidism, when the processes characteristic of fibrous-cystic osteite were not fully formed. These data reflect the influence of low PTH concentration, which causes diffuse osteolysis, and not localized osteoclastic proliferation. Along with this, individual patients identify the characteristic subperiodal resorption of bone tissue, which is most often localized in the phalanges of the fingers of the brush. In this case, resorption prevails over oste formation, which is reflected in the change in levels of bone resorption markers.

In most cases, patients with PGPT occur in the spinal bones, characterized by varying degrees of osteoporosis from a slight deformation of the vertebrae to the characteristic "fish vertebral", sometimes with fractures of the vertebral bodies. In these cases, patients indicate a decrease in growth during the disease. Many patients have complaints against back pain, increasing after exercise, with a long stay in the same position (standing or sitting). Often, when the PGPT is observed the lesion of the joints - chondroalcinosis (calcium phosphatehydrate crystals).

Visceral shape with a predominant kidney damage is found in more than 60% of cases of primary manifestic hyperparathyraratroposis, sometimes kidney damage can be the only manifestation and more often in the form of urolithiasis. In 13-15% of cases, single stones are detected, in 25-30% - multiple and in 30-32% of cases - concrections in both kidneys. In cases of visceral manifestations of hyperparathyroidism, for example, in the form of urolithiasis, the surgical removal of the stone does not lead to recovery, the concrections may be formed in another kidney, and often in the operated one. However, the forecast of the urolithiasis after removing the adenoma is favorable, if CPN has not developed. Conductors in the kidneys with hyperparathyroidism consist of oxalate or calcium phosphate.

With a visceral form with a predominant lesion of the Cardiovascular system, the PGPT is accompanied by hypertension, calcification of coronary arteries and heart valves, left ventricular hypertrophy and the deposition of calcium salts in the heart muscle and others. The deposition of calcium salts in the heart muscle can cause myocardial necrosis with a clinic of acute myocardial infarction. In a prospective study by T. Stefenelli et al. It was established that PTH PER SE plays an important role in maintaining myocardial hypertrophy. After parathyroidectomy and normalization of the level of calcium in the blood serum for 41 months, the authors observed the regression of hypertrophy of the partition, the back wall and left ventricle by 6-21%.

Gastrointestinal symptoms are detected by half of patients with PGPT. Patients impose complaints against anorexia, constipation, nausea, flatulence, weight loss. The peptic ulcers of the stomach and / or duodenum are found in 10-15% of cases, pancreatitis - at 7-12%, less often pancreaticalculcosis and pancreaticity. The development of the gastric ulcers in hypercalcemia is associated with an increase in gastroin and hydrochloric acid, which returns to the norm after removing the adenoma of the resolution. The course of the gastric ulcer with PGPT is characterized by a more pronounced clinical picture (frequent exacerbations with strong pain syndrome, perforations are possible) than with a stomach peppercan disease due to other factors.

In addition to the above-described symptoms in PGPT, it is observed in rare cases, skin necrosis due to the deposition of calcium salts, the calcification of the ears of the sinks, the rod keratitis (linear keratopathy), developing due to the deposition of calcium salts in the corneal of the cornea of \u200b\u200bthe eye.

One of the serious complications of PGPT is hypercalcemic crisis. An increase in calcium content above 3.49-3.99 mmol / l (14-16 mg / 100 ml) leads to the development of signs of intoxication, characteristic of hypercalcemia.

Hypercalcemic crisis is a severe complication of PGPT arising against the background of fractures, infectious diseases, pregnancy, immobilization, intake antacids (calcium carbonate). It develops suddenly, while nauseous, indomitable vomiting, thirst, acute abdominal pain, pain in muscles and joints, high fever, convulsions, confusion, stupor, coma. Mortality in hypercalcemic crisis reaches 60%. Against the background of Anuuria, cardiovascular failure appears. If hypercalcemia increases to 4.99 mmol / l (20 mg / 100 ml), then the activities of the CNS with the braking of the function of the respiratory and vascular centers are oppressed and an irreversible shock is developing.

Diagnostics and Differential PGPT

The diagnosis of hyperparathyroidism is based on anamnesis data, patient complaints, clinical picture (peptic ulcer of the stomach, urolithiasis, pancreatitis, chondroalcinosis, bone changes - osteoporosis, bone cysts) and the results of laboratory studies.

Laboratory research

During the laboratory research, the cardinal sign in suspected of the PGPT is an increase in the level of PTH, which in most cases is accompanied by hypercalcemia. The permanent sign of hyperparathyroidism is hypercalcemia; Hypophosphatemia is less constant than the increase in calcium in serum. The content of alkaline phosphatase in the blood serum is increased. Less often occurs hypomagnesiamia. Along with this, the excretion of calcium, phosphorus with urine.

In some patients with elevated PTH level, the concentration of general calcium in serum is normal. This state is called a normocalcemic variant of PGPT.

Causes of the normocalcemic version of the PGPT:

• renal failure (violation of Calcium tubular reabsorption);
• calcium absorption disorder in the intestine;
• avitaminosis D.

To distinguish the hyperparathyroidism with vitamin D from the isolated Avitaminosis d, vitamin D is carried out. Against the background of vitamin D replacement therapy in patients with hyperparathyroidism, hypercalcemia occurs, and in patients with insulated avitaminosis D is restored by normocalcemia. Transient normocalcemia may occur on early stages Development of PGPT. In order to confirm the diagnosis of hyperparathyroidism in patients with recurrent urolithiasis and normocalcemia, a provocative test with thiazide diuretics is carried out.

For bone and mixed PGPT forms, a significant increase in bone metabolism is characterized with an increase in the frequency of activation and the predominance of resorption processes. In the manifest form of the PGPT, the average osteokalcin level exceeded the normative values \u200b\u200bof 2.6-20 times, and a reliable correlation between alkaline phosphatase activity and PTH (R \u003d 0.53, P< 0,01), между уровнем остеокальцина и ПТГ (r = 0,68, p < 0,01). У больных ПГПТ отмечается повышение общей щелочной фосфатазы крови, остеокальцина крови и оксипролина мочи, а также дезоксипиридинолина мочи и тартратрезистентной кислой фосфатазы крови . В исследовании пациентов с ПГПТ были выявлены статистически значимые корреляции между дезоксипиридинолином мочи и сывороточной костной щелочной фосфатазой, а также остеокальцином сыворотки. Кроме того, отрицательные корреляции высокой степени были выявлены между дезоксипиридинолином мочи и минеральной плотностью костной ткани как в позвоночнике, так и в лучевой кости .

The effect of PTH on the products of osteoprothyterine (HGG) and the Ligand of the NF-KAPPAB receptor of the NF-KAPPAB (RANKL) is not fully installed. It has been demonstrated that PTH reduces the GDG products and increases RANKL products. It was noted that in front of the surgical treatment of hyperparathyroidism Rankl and osteoprothyterine correlated with serum osteocalcin. The ratio of Rankl / osteoprothyterin decreased after surgical treatment, which indicates the possibility of their use as markers of the state of bone tissue with PGPT.

Speaking about the role of the N-terminal Telopeptide, it should be noted that according to the researchers, the high level of this marker is a factor indicating the greatest effectiveness of surgical treatment.

The diagnosis of hyperparathyroidism is confirmed by determining the content of PTH in serum. Sensitive methods for determining PTH in the blood are developed: immunoradiometric (IRMA) and immunohemyluminometric (ICMA). Thus, the bases for the diagnosis of PGPT is a resistant hypercalcemia and an increase in the level of PTH in serum.

Instrumental research

To detect bone changes, it is conducted by radiography of tubular bones, pelvic bones, the chest and lumbar spine, osteodensitometry of lumbar vertebrae, proximal departments of the thigh, radiation bone.

Finding out the nature of hypercalcemia and the diagnosis of hyperparathyroidism should be carried out comprehensively, including studies in order to determine the localization of adenoma or hyperplasia: ultrasound examination (ultrasound), arteriography, scintigraphy, selective vein catheterization and determination of the content in the Blood Iron PTH, computed tomography (CT) , magnetic resonance tomography (MRI).

Ultrasound Joints. The sensitivity of the method is from 34% to 95%, specificity reaches up to 99%. The results of the study depend on the experience of a specialist in ultrasound diagnostics, the mass of the mind (with a mass of gland less than 500 mg, sensitivity is significantly reduced to 30%). The method is not informative with atypical localization of the resistant - behind the sternum, in the possession of the space.

Scintigraphy. As a rule, it is carried out with the 201TL Tallium, the pesthote technicia of 99 MTS, which accumulate in thyroid gland and in increased gentlemen. One of the latest methods is scintigraphy using Tehnetrile-99Ts (99MTC-SESSIBI-scintigraphy) - the complex Technetium 99m and methoxyisobutylinitrile. Compared to 201t, scintigraphy with techneteril-99ts is characterized by a significantly lower radial load and more accessibility, the sensitivity of the method reaches 91%. It should be noted that if there are gigantaic tumors in the bones, which are with heavy forms of PGPT and are detected x-ray, the accumulation of 99MTC in the lesions of the damage to these bones can give a false positive result of topical diagnostics, which should be borne in mind when evaluating the SCINTIGRATIGRATIGRATIGRATIGRATIGRAY data to compare The results of the X-ray study of the corresponding skeleton department.

CT allows you to reveal the adenoma of a decrease in 0.2-0.3 cm. The sensitivity of the method is from 34% to 87%. The disadvantages of the method are the load in the form of ionizing radiation.

Some authors consider MRI with one of the most effective methods of visualization of the Assignment, but due to the high cost and time spent time spent to obtain an image, it does not apply quite widely. It is believed that the gentlemen located in the tissues of the thyroid gland is much more difficult to differentiate with MRI than with an ultrasound, but, focusing on the latest data, we can assume that MRI is a fairly sensitive method (50-90%).

Invasive research methods include puncture of the Association under the control of ultrasound, selective arteriography, veins catheterization and taking from the blood from the gland to determine PTH. Invasive methods are used in the case of PGPT recurrence or after an unsuccessful audit of the ADD while maintaining the signs of PGPT.

However, sometimes, despite the use of all research methods, it is not possible to confirm the presence of adenoma, and the course of the disease does not allow continuing conservative therapy. In these cases, an operation is recommended during which all the Audit revision is conducted. More often (60-75%) adenoma is located in the lower detection, and the detection of the tumor in one of them, as a rule, eliminates the adenomose in the other gentlemen. Nevertheless, the revision of the rest of the glands is obligatory.

Treatment of primary hyperparathyroidism. Selection of therapy

The choice of the treatment method depends on the presence or absence of the adenoma of the ASH, on the degree of expression of hypercalcemia and the presence of complications, such as nephroalcinosis, ulcerative illness of the stomach, etc. If there is a confirmed tumor, hypercalcemia and complications are recommended operation. According to the consensus on the diagnosis and maintenance of patients with PGPT, surgical intervention is shown in the following cases:

1) the concentration of general calcium in the blood serum by 0.25 mmol / l (1 mg%) exceeds the rate set in this laboratory for this age group;
2) reducing the glass filtration rate by more than 30% compared with the norm established in this laboratory for this age group;
3) visceral manifestations of PGPT;
4) Daily excretion of calcium more than 400 mg;
5) Reducing the IPC of the cortic bones by more than 2.5 SD on the T-criterion;
6) Age less than 50 years.

Surgical treatment methods

As a rule, during operations on the SCC about the PGPT, there are revision of all four wells, since not always a preoperative topical diagnosis reveals multiple adenoma and hyperplasia, the adenoma of the extension.

According to J. N. Attie, from 1196 patients operated on for hyperparathyroidism, a single adenoma (including one patient with Men-2 syndrome) was discovered in 1079 patients; In 41 patients - two adenomas; 4 - three adenomas; In 23 - primary hyperplasia; In 30 - secondary hyperplasia; in 6 - tertiary hyperplasia; At 12 - Cancer Association and in 1 patient - in one degree of cancer and in the second - adenoma. Interestingly, out of 1158 patients operated on by the author on the PGPT, in 274 (23.7%) were simultaneously identified and thyroid diseases were identified: in 236 patients, changes in the tissues of the thyroid gland were benign and 38 - a papillar or follicular thyroid cancer was found. glands. Of the 38 patients with malignant tumors The thyroid gland in 26 tumors were palpable before the operation; In 2 patients, they were found on the ultrasound and 10 - revealed randomly during surgery about the removal of the adenoma of the SCC.

In the case of diagnosis of PGPT during pregnancy, parathyroidectomy is permissible in the II trimester of pregnancy.

Specific peculiarities are characterized by operational tactics against the Cancer ADC. Cancer Associty, as a rule, slowly grows and rarely gives metastases. With full gland removal without damage to the capsule, the forecast is favorable. In some cases, cancer is more aggressive, and at the first operation, metastases in the lungs, liver and bones are found. It is not always possible to immediately determine that the primary tumor is precisely cancer; With histological examination of the non-invasive tumor, it is possible to detect an increase in the number of figures of mitosis and fibrosis of stroma gland. Cancer Associty is often diagnosed retrospectively. Hyperparathyroidism due to the cancer of the gentleman, it is often impossible to distinguish from other forms of PGPT. At the same time, it is known that Cancer Associty is often accompanied by severe hypercalcemia. Therefore, at the level of calcium in the blood, more than 3.5-3.7 mmol / l, the surgeon should be particularly attentive to prevent damage to the capsule when the affected gland is removed.

The frequency of complications and mortality in the surgical treatment of PGPT is not large, and recovery occurs in more than 90% of cases. With successful intervention, the postoperative period proceeds, as a rule, without complications. It is necessary 2 times a day to determine the content of calcium in the blood; With its rapid decline, calcium preparations are recommended. Permanent ECG controls.

The most common postoperative complications include: damage to the return gastriced nerve, transient or resistant hypocalcemia, very rarely hypomagnation, in patients suffering from heavy hypercalcemia, can develop "hungry bone syndrome".

Treatment of postoperative hypocalcemia ("hungry bone syndrome")

Most clinical symptoms of PGPT after successful operational intervention are exposed to reverse development. After surgical treatment PGPT, i.e., after eliminating PTH hyperproduction, there is a fairly rapid reverse development of clinical symptoms and biochemical indicators. After adequately conducted surgical treatment in some cases, hypocalcemia occurs, which requires the use of vitamin D or its active metabolites and calcium preparations. To eliminate the "hungry bones" syndrome in the bone form of the hyperparathyroidism in the postoperative period, calcium preparations are prescribed at a dose of 1500-3000 mg (by calcium-element) in combination with alpha calcidol (etylph, alpha d3-teva) by 1.5-3.0 μg per day and / or dihydroitachisterol (dihydrootahsterol, A.T. 10) at 20-60 drops per day. In the rate of normocalcemia, the dose is gradually decreasing to supporting: 1000 mg of calcium and 1-1.5 μg of alpha cellsidol by 0.5-2 years. In our practice, calcium-d3 is prescribed more often (in 1 chewing tablet 500 mg of calcium and 400 mg vitamin D3) in combination with alpha cellsidol. These drugs are well transferred, convenient to use and safe.

Treatment of patients with soft forms of PGPT

Patients older than 50 years with light hypercalcemia, normal or slightly reduced bone weight and normal or slightly disturbed kidney function can be treated conservatively. In these cases, it is recommended:

• increase fluid intake;
• limit the reception of sodium, protein and calcium;
• take diuretics;
• take preparations that reduce the resorption rate of bone tissue.

According to a 10-year-old prospective study of 120 patients with PGPT, subjected to or not exposed to surgical treatment, the authors concluded that there are no significant differences in biochemical indicators and indicators of bone mineral density in non-eaten patients with a small-mixed and asymptomatic hyperparathyroidism. However, a number of patients were revealed, in whose surveillance process there were indications for surgical treatment (the occurrence or progression of the urolithiasis, the negative dynamics of the bone mineral density, small-acting fractures). At the same time, if patients with PGPT deterioration of signs of the disease is not noted, it is possible to refrain from surgical treatment.

With the soft forms of PGPT with a moderate decrease in the IPC in women during menopause, it is recommended that estrogen or bisphosphonate preparations are recommended to prevent osteoporosis progression. In recent years, bisphosphonates are prescribed more often. The purpose of the appointment of bisphosphonates for long-term use is the correction of osteoporosis, and not a decrease in the level of PTH, but it is possible to reduce hypercalcemia. For therapy with bisphosphonates, paminery acid (pamineroneate medal), risadronate, alendronate are used. S. A. Reasner et al. Used to treat patients with osteoporosis and PGPT risadronate, which for 7 days normalized the level of calcium in serum while reducing not only alkaline phosphatase in the blood, but also the excretion of hydroxyproline, as well as an increase in calcium renal tubular reabsorption. Good results were also noted when using alendronate.

It should be emphasized that the effectiveness of the methods of treatment varies greatly depending on the pathogenetic variety of hypercalcemia and the individual sensitivity of the patient to a particular preparation. In medicinal tactics, the dynamics of laboratory indicators and the possibility of reducing hypercalcemia should be taken into account.

Conclusion

Thus, the above review of literature dedicated to etiologies, pathogenesis, diagnosis and treatment of PGPT, indicates both significant achievements and a number of unresolved problems in this area. Due to the presence of difficulties in the early diagnosis of PGPT, normocalcemic breakers of PGPT against the background of vitamin D deficiency, the absence of the widespread determination of calcium in the blood and urine in routine clinical practice, patients with soft or asymptomatic forms are poorly revealed. The question of testimony for surgical treatment, on conservative therapy of patients with a soft form of PGPT continues to be discussed. All this determines the need for further study of clinical manifestations of the disease and improve the methods of differential diagnosis and optimizing the treatment of patients with PGPT.

For literature, please contact the editor.

L. Ya. Rorinskaya, doctor of Medical Sciences
Enz Rosmedtehnologiy, Moscow

RCRZ (Republican Center for Health Development MD RK)
Version: Clinical Protocols MOR RK - 2018

Primary hyperparathyroidism (E21.0)

Endocrinology

general information

Short description

Approved
Joint Commission for Medical Services
Ministry of Health of the Republic of Kazakhstan
from "18" April 2019
Protocol No. 62.

Primary hyperparathyroidism - the primary disease of the parachitoid glands, manifested by the PTG hyperproduction and the lesion of the bone system and / or internal organs (First of all, kidneys and gastrointestinal tract).

Input part

Code (s) μb-10:
Date of development / revision of the Protocol: 2013 (revision 2018)

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

The scale of the level of evidence:

Table 1. The ratio between the degree of persuasiveness of evidence and the type of scientific research

Classification

Classification

Table 2. Clinical classification of primary hyperparathyroidism:

Diagnostics

Methods, approaches and diagnostic and treatment procedures

Complaints: on pain in the bones, weakness, decline in appetite, reduction of growth.

Anamnesis:the presence of frequent, inadequate loads and poorly consolidated fractures, urolithiasis, depressive states, polyuria, polydipsy

Physical examination:
Inspection: Skeleton deformations, bone expansions in the area of \u200b\u200bfacial skull bones, large joints, tubular bones, lethargy, pallor, dry skin.

Main clinical manifestations :
- Muscular system: pain in the bones, bone deformation, pathological fractures, gout, pseudo-rope, muscle atrophy, soft tissue calcinates.
- recurrent nephrolithiasis, nephrollociety,
- chronic pancreatitis, ulcerative disease of the stomach and duodenum
- Dyspeptic disorders, weight loss.
- mental changes - depression, asthenic syndrome
- Insipidar syndrome
- Disturbance of the heart rhythm, arterial hypertension

Laboratory research:
Table 3. Biochemical indicators in blood and urine with PGPT

Differential diagnosis

Differential diagnosis and the rationale for additional research:

Table 7. Differential diagnosis of PGPT

Treatment abroad

Treat treatment in Korea, Israel, Germany, USA

Get advice on medical examination

Treatment

Preparations ( active substances) applied in the treatment

Treatment (ambulatory)

Tactics of treatment on an outpatient level

Purpose of treatment PGPT:
- liquidation of the source of hyperproduction of PTH
- Normalization or reduction of CA and PTH in blood
- Liquidation and / or preventing the progression of bone-visceral violations
Conservative maintenance in patients with PGPT is used in the presence of medical contraindications for parathyroidectomy; failure of the patient from surgical treatment; In patients with asymptomic forms of the disease without sufficient readings for parathyroidectomy.

Non-drug treatment:
Diet and therapy:table number 9, adequate rehydration.
Physical activity:Limitation physical Loads, Prevention of fractures.

Medicia treatment
Shown at:
- The presence of the lungs bone violations and insignificant hypercalcemia or
Normocalcemia
- the absence of remission after surgical treatment
- manifestic hyperparathyroidism and presence of contraindications to surgical treatment or with a patient failure.

Table 9. Medical treatment of PGPT

Treatment (hospital)

Tactics of treatment at the stationary level

Map of patient surveillance, patient routing:not.

Non-drug treatment:see outpatient level

Medicia treatment: See outpatient level

Surgical intervention :paratroidectomy, efficiency 95-98%.
The "golden" standard of surgical treatment of PGPT is considered parathyroidectomy with the use of local anesthesia. Depending on the volume of the damage, the pschch is performed by partial, subtotal or total parathyroidectomy.

Absolute testimony for surgical treatment:
- age less than 50 years
- the impossibility of long-term surveillance under the control of the doctor
- Exceeding of general calcium in blood in more than 0.25 mmol / l above the upper limit of the norm
- excretion of calcium with urine more than 400 mg per day with a conventional diet
- Reduced SCF less than 60 mg / min
- The presence of nephrollsinosis
- bone mineral density - T-criterion less -2.5 in any zone and / or fracture in history
- Cancer of the Poorish glands

Complications after surgical treatment
- damage to the return gentle nerve
- transient or resistant hypocalcemia, hypomagnemia, "hungry bone syndrome".

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

Further maintenance:In the postoperative period, the recovery of calcium exchange does not occur immediately, and patients need additional reception of calcium and vitamin D3 preparations.
Upon reaching remissions:
- Clinical observation in the endocrinologist, treatment of osteoporosis.
- Control of the activity of alkaline phosphatase in serum 1 time in 3-6 months.
- X-ray control 1 time in 3 years
When recurring - repeated courses of treatment.
Recurious frequency:
Sporadic hyperparathyroidism - 5-10%
With hyperparathyroidism in the Main Syndrome - 15-25%
When cancer of the parachitoid glands - 32%

Treatment Efficiency Indicators:
- normalization of the level of PTH, Ca and phosphorus of blood, alkaline phosphatase, the absence of relapses.

Hospitalization

Indications for hospitalization indicating the type of hospitalization

Indications for planned hospitalization:
1. With pronounced hypercalcemia in cases of refusal of surgical treatment, hospitalized patients for rehydrating and treating cardiovascular and neurological complications of PGPT. Rejustation is carried out by the introduction of 0.9% sodium chloride solution to reduce toxic action hypercalcemia on target organs, increase calcium excretion with urine.
2. Conduct planned adenoma removal operation or parasite gland

Indications for emergency hospitalization:hypercalcemic crisis.
Hypercalcemic crisis - acute complication of PGPT, is a heavy, threatening life intoxication by calcium. Developed at calcium level in a plasma exceeding 3.5 mmol / l.
Provoke:
- Rough palpation of thyroid gland and pschzh
- Pregnancy
- Reception of thiazide diuretics, calcium and vitamin D preparations
- Fractures
- infection
- Long bedding
The clinic develops very quickly, the symptoms of dehydration, the damage to the central nervous system (psychosis, stupor, coma) and the gastrointestinal tract (nausea, indomitable vomiting, thirst, pain in the epigastria, often imitating the picture of the "acute abdomen"). Hypertermia is noted up to 40 ° C, thrombosis of various localization, DVS syndrome, acute renal, respiratory and cardiovascular failure. The symptoms increase avalanche-like, anorya joins, a coma develops.
Treatmenthypercalcemic crisis:
- Restoration of the BCC (infusion therapy 0.9% NaCl solution in a volume of 3000-4000 ml / day with the maintenance of plasma osmolality at 280-290 mos / kg in combination with diuretics).
- In parallel, the normalization of the calchemia level is carried out (bisphosphonates are used).
- After the patient's state normalization, the parathyroidectomy of pathologically changed pschz is recommended.

Information

Sources and literature

1. Meeting Protocols of the Joint Commission on the Quality of Medical Services MR RK, 2018
   1. 1. Dedov I.I., Melnichenko G.A., Endocrinology National Guide, Moscow, "Gootar - Media", 2018, p.817- 832. 2. Primary hyperparathyroidism: clinic, diagnosis, differential diagnosis, treatment methods. Clinical Protocol. FGBU "Endocrinological science Center»Ministry of Health of Russia, Moscow. Problems of Endocrinology, No. 6, 2016, P.40-77 3. Primary hyperparathyroidism: Modern approaches to diagnosis and treatment. Educational and methodological manual, Minsk BGMU 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 qualifying data:

1. Nurbekova Akmaral Asylovna - Doctor of Medical Sciences, Professor of the Department of Endocrinology JSC "National Medical University"
2. Bazaarbekova Rimma Bazarbekovna - Doctor of Medical Sciences, Professor, Head of the Department of Endocrinology JSC "Kazakh Medical University of Continuing Education", Chairman of the ROO "Association of Doctors of Endocrinologists of Kazakhstan".
3. Taubaldieva Zhannat Satybaevna - Candidate of Medical Sciences, Head of Endocrinology, JSC "National Scientific Medical Center".
4. Kaliya Sholpan Sabatayevna is a candidate of medical sciences, associate professor, head of evidence-based medicine and pharmacology Medical University of Karaganda JSC.

Indication for the absence of conflict of interest:not.

Reviewer:
Dosanova Ainur Casimbekovna - Candidate of Medical Sciences, Associate Professor of the Department of Endocrinology JSC "Kazakh Medical University of Continuing Education", Secretary ROO AVEK.

Note Protocol Review Conditions:revision of the Protocol 5 years after its publication and the date of its entry into force or in the presence of new methods with the level of evidence.

Attached files

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Hyperparathyroidism is a disease caused by endocrinological disorders that provoke an increase in the secretion of the hormones of the parachitoid glands. Characterized by a significant violation exchange processes Calcium and phosphorus. As a result, the dice becomes fragile, the risk of their damage and fractures increases.

There are primary, secondary, as well as tertiary forms of the disease. Alimentary hyperparathyroidism occurs only in veterinary practice.

Let's talk on www.Site about how the hyperparathyroidism is manifested by the treatment of it, what is his reasons, what are the recommendations of disease professionals - about all this and our today's conversation will go:

Causes, Symptoms of Disease

Primary hyperparathyroidism (Recklinghausen disease):

The reasons

Most frequent cause This form is considered the presence of the solitar adenoma of the parachitoid gland or, otherwise, parastromates. It is less likely to cause multiple adenoma to the occurrence of the primary form. More often - cancer of parachitoid gland. This form of the disease is more often diagnosed in adults, but sometimes it can occur in children and the elderly.

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

How the primary hyperparathyroidism (symptoms) is manifested

Disease may not manifest itself for a long time, as it develops asymptomatic. It is typical for initial stageWhen the calcium level is raised slightly. With the development of the disease, characteristic symptoms appear. Heavy complications may develop, for example, hypercalcemic crisis.

However, this form is most often manifested by the following symptomatics:

Bone-tissue changes: bone fragility increases, frequent fractures occur. Sometimes there may be a decrease in the growth of the patient;

Urolled, renal disease;

Elevated level of ionized calcium, pronounced calciumuria, manifestations of severe hypercalcemia;

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

Secondary and tertiary hyperparathyroidism

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

For tertiary, the development of the adenoma of the parachitoid glands, which proceeds against the background of the secondary hyperparathyroidism for a long time is characteristic.

Causes of secondary hyperparathyroidism

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

How do tertiary and secondary hyperparathyroidism (symptoms) manifest?

The clinical signs of the secondary and tertiary form are similar to the symptoms of the main disease. Most often, chronic renal failure (CPN) is found.

Specific features include:

Soreness of bones;

Muscle weakness, arthralgia;

Frequent damage, fractures, bone deformations;

A characteristic symptom may also be the calcification of the arteries. This state provokes ischemic changes. It is manifested by the formation of periarticular calcinates on hand and legs.

Calcification of conjunctivations is also possible. With a combination of this pathology with recurrent conjunctivitis, a state occurs that specialists are denoted as a red-eye syndrome.

How is the tertiary and secondary hyperparathyroidism (treatment) corrected?

Therapy of the secondary and tertiary form of hyperparathyroidism is quite complicated. In severe cases, hemodialysis is prescribed, the kidney transplantation is carried out, which extends the life of the patient about 10-15 years.

When appointing medical treatment Use the drug Rockaltrol. At the same time, carefully controls the calcium allocated with urine. Vitamin D metabolites are prescribed, for example, calcitriol, phosphates binding aluminum preparations are used.

With very high level Calcium, as well as in the presence of pronounced symptoms, patient must be hospitalized, after which treatment is carried out under hospital. If there are high brittleness of bone tissue, it shows a strict bed mode, medical nutrition.

If the calcium level is increasingly increasing, characteristic symptoms No or expressed slightly, urgent medical intervention is not required. The patient can lead an ordinary life without restrictions. On the recommendation of the doctor, the patient may be shown the healing nutrition. Its principles are always developed individually.

In order to prevent hyperparathyroidism, it should be treated on time chronic diseases kidneys, digestive system. More to go, play sports, practicing with solar and air baths. It is very important to avoid stressful states. Be healthy!

Hyperparathyroidism is a disease that is more susceptible to women than men, and it is 2-3 times more often. This disease refers to violations endocrine systemand caused by excessive generation of parachitoid glands of the parathgamon (PTH). This hormone leads to the accumulation of calcium in the blood, which is why bone tissues suffer, as well as the kidneys. During the diagnosis of hyperparathyroidism, symptoms and treatment in women - information that is necessary for everyone who has disorders in the work of the thyroid gland, especially if the girl is in the risk group - aged 25 to 50 years.

The reasons

Healthy thyroid gland produces a normal number of pararathgamon, but when there are violations, the quantity can arise both to decrease and grow significantly. The work of the gland affect:

1. Tumors, appeared in the tissues of the thyroid or lymph nodes of the neck. In this case, disorders cause malignant and benign neoplasms.
2. Renal failurehaving passed into the chronic stage.
3. Hereditary autosomal dominant syndromewhich provokes tumors in one or more glasses of internal secretion. 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 illness, usually has chronic formWhat leads to changes in the tissues of internal organs. Most often, the violation in the work of the thyroid gland is not the only symptom.
6. Alimentary hyperparathyroidism - disease caused by poor nutrition. It may be present even with a diverse and balanced diet if the body does not absorb part of the beneficial substances.

Depending on the reasons that caused the disease, distinguish:

1. Primary hyperparathyroidism - the cause of violations are diseases of the thyroid gland. Most often it is hereditary violations that are diagnosed at an early age.
2. Secondary - it appears as an answer of the body for a long-term lack of calcium caused by poor food or disadvantage of vitamin D. Another cause of secondary hyperparathyroidism are bone tissue diseases or digestive organs, as well as the kidneys too quickly derive calcium from the body.
3. Tertiary - appears only with a long flow of secondary hyperparathyroidism, which, without proper treatment, provokes the appearance in the parachitoid glands of adenoma.

In addition to the present disease caused by disorders in the thyroid gland, there are pseudo-opporathyroidism caused by the production of a substance similar to the functions with a pararathgamon. There is such diseases due to malignant tumors producing this substance. At the same time, the neoplasms are affected by other glands in the body, and do not directly affect the secretion of the parathgamon.

Symptoms

Hyperparathyroidism, the symptoms of which are not specific in the early stages, and in some cases the disease passes without significant manifestations. Therefore, the violation is rarely diagnosed in light formIf there are no significant changes in the tissues of the thyroid.

In the early stages appear:

• Headache and deterioration of cognitive functions.
• Increased fatigue.
• Reducing the tone of the muscles, which leads to difficulties with movement, especially seriously the patient climbs the stairs, even on a small height.
• The deterioration in the emotional sphere, the emergence of signs of neurasthenia, and sometimes depressed. In people with reduced immunity, as well as children and the elderly, may appear mental disorderswhich cannot be explained by genetic predisposition or external influence.
• Changes on the color of the skin on the pale, and with a long disturbance, it acquires an earthy tint.
• The change in the gait, which becomes the "duck", due to the reduction of the tone of the pelvic muscles or changes in the bone structure of the hip.

At the later stage, disorders arise in bone tissue:

1. Osteoporotic - Developing reduction in bone mass, as well as violations of its structure.
2. Fibrozno-cystic osteite - Inflammation in the bones leading to the appearance of cystic tumors.

Due to the disorder of the bone structure, patients often have fractures, with ordinary movements that are not traumatic. So, a person can break his hand or leg, being in bed. With this stage of the disease occur painfulness Without a clear localization, and most often they are characterized as "bone lomit". Fractures that appear in this stage are delivered less painful sensationsthan u healthy manBut at the same time they worse heal, and more often accompanied by complications. Broken bones are often incorrect, because of which the deformation of the limbs occurs.

The problems with the bone structure cause not only fractures, but also changes in the spine, because of which a person can be lower than the growth or the posture will deteriorate sharply. A frequent occasion is a violation of the integrity of the teeth, at which they begin to stagger, due to violations in the alveolar bone and tissues. Often in such cases, even healthy native teeth begin to fall out.

Hyperparathyroidism, the symptoms of which are nonspecific, is called bombcopathic. He meets very rarely. This case of the disease is developing gradually, due to which difficulties arise with diagnostics. Initially, a person appears signs of intoxication, often repeated vomiting or diarrhea, elevated meteorism, as well as a decrease in appetite and a quick loss of body weight.

Ulzes that are accompanied by bleeding can appear in the gastrointestinal tract, while the treatment of the mucous membrane is ineffective, which is why frequent exacerbations and relapses occur. Maybe damage to the pancreas, liver or gallbladder. And also often register an increase in the amount of urine released more than the daily rate, which is why patients appear constant thirst, which is impossible to quench. In the development of the disease in kidney tissues, calcium salts are minimized, which causes their change, and with time and renal failure.

Diagnostics

Initially, the disease does not have specific symptoms, which is why it is difficult to diagnose. But there are a number general analyzeswhich can show an increase in calcium content in the body:

1. The overall urine analysis - the liquid becomes more alkaline, while in it there are calcium salts, and the amount of phosphorus increases. Sometimes a protein occurs in the urine, which indicates inflammation in the kidneys. At the same time, the density of the discharge is reduced, but their number increases.
2. Biochemical blood test - allows you to find out the composition of the blood, to accurately determine the violation of proportions. With hyperparathyroidism, the number of general and ionized calcium in the blood is increased, and phosphorus is reduced.

Specific analyzes:

1. Chemiluminescent immunoassay - Fence venous blood To determine the number of parathgamon.
2. Ultrasound thyroid gland - Allows you to determine changes in tissues, as well as detect disorders in lymph nodes.
3. Radiography, CT or MRI - Conduct both in the neck and limbs, if the patient complains of pain, unexpected fractures, or a change in mobility.
4. Scyntigraphy gland - It makes it possible to determine how well the parathyroid glands are located, as well as which fabrics are included in their composition, there are pathological changes, and as an organ functions.

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

Treatment

When a hyperparathyroidism is detected, treatment must be complex, it will depend on the root cause of the disease. Due to the fact that tumors or other disorders of the thyroid structure are often present, the combination of surgical intervention and drug therapy is optimal.

For primary stage diagnosis of hyperparathyroidism clinical recommendations Doctors most often contain tumor removal or parathyroid gland dysplasia. If the size of the changed tissues is small, the special endoscopic equipment is used, which reduces the intervention in the body, which has a beneficial effect on the rate of recovery.

In addition, doctors prescribe different measures to reduce calcium in the blood. For this, the sodium chloride solution can be administered intravenously, as well as assign a furosemide, potassium chloride and a solution of glucose 5%. But such measures are needed only with too high calcium content, which can provoke crisis. It increases the burden on the kidneys, so all medicines must be taken only under the supervision of the 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 carried out, selected individually, depending on the occurrence of the disease.

If the disease is diagnosed in the early stages, there are no serious chronic diseases in the body, the treatment prediction is quite favorable. When the disease began to strike bone tissue, but did not go too far, therapy takes 4 to 24 months. The defeat of the kidneys is considered a more severe case due to pathological changes in the organs.

In the disease, hyperparathyroidism, symptoms and treatment in women do not differ from those that are characteristic of men, but due to an unstable hormonal background, the gland of the internal secretion is more susceptible to changes. Therefore, having sexual women are important to follow the health of the thyroid gland and regularly check the amount of calcium in the blood.