RU2844726C1 - Diagnostic technique for primary and secondary hyperparathyroidism - Google Patents

Abstract

FIELD: medical science.

SUBSTANCE: invention refers to medicine, namely to endocrinology, and may be used for diagnosing primary and secondary hyperparathyroidism. Patient’s blood is sampled to determine the concentration of parathormone, calcium and phosphorus in blood serum. Parathormone, calcium and phosphorus coefficient is determined by formula PCP=PTH×Ca/P, where PCP is the coefficient of parathormone, calcium and phosphorus; PTH is parathormone concentration, pg/ml; Ca is concentration of calcium, mmol/l; P is concentration of phosphorus, mmol/l. If PCP is 194.65 and more, primary hyperparathyroidism is diagnosed. If PCP is 122.94-194.64, secondary hyperparathyroidism is diagnosed.

EFFECT: method provides the possibility of optimizing the diagnosis of hyperparathyroidism, the ability to sort out the differential diagnosis of the form of hyperparathyroidism and determine the optimal therapeutic approach to patients by diagnosing disturbed calcium and phosphorus metabolism by determining the concentration of parathormone, calcium and phosphorus in the patient's blood.

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Description

The invention relates to medicine, namely to endocrinology, and can be used as a method for diagnosing primary (PHPT) and secondary (SHPT) hyperparathyroidism.

There is a known method for diagnosing hyperparathyroidism by ultrasound examination (US) [1 - Clinical guidelines. Primary hyperparathyroidism. Developer of the clinical guideline: Russian Association of Endocrinologists, Association of Endocrine Surgeons. 2020. pp. 9-11.] This method is accepted as an analogue.

A method for diagnosing primary and secondary hyperparathyroidism is known, by scintigraphy of the parathyroid glands (PTG) [2 - Clinical guidelines. Primary hyperparathyroidism. Developer of the clinical guideline: Russian Association of Endocrinologists, Association of Endocrine Surgeons. 2020. pp. 13-14.]. This method is adopted as a prototype. However, the prototype method provides diagnostics only by contrast examination.

The goal is to increase the efficiency of diagnostics of primary and secondary hyperparathyroidism, due to the possibilities of non-contrast examination methods.

The technical result consists in the fact that in the method of diagnosing primary and secondary hyperparathyroidism, including taking blood from a patient, determining the concentration of parathyroid hormone, calcium and phosphorus in the blood serum, characterized by the fact that the coefficient of parathyroid hormone, calcium and phosphorus is determined according to the formula

PCF=PTG×Ca/P, where

PCF - parathyroid hormone, calcium and phosphorus coefficient;

PTH - parathyroid hormone concentration, pg/ml;

Ca - calcium concentration, mmol/l;

P - phosphorus concentration, mmol/l,

and with a PCF value of 194.65 or more, primary hyperparathyroidism is diagnosed, with a PCF value of 122.94-194.64 - secondary hyperparathyroidism."

The method is carried out as follows

Primary hyperparathyroidism (PHPT) in 85-90% of cases is caused by a solitary adenoma of the parathyroid glands (PTG), in 5-10% of cases - by multiple adenomas or hyperplasia of several/all PTG; in 1% - by PTG cancer. In 90-95% of cases, PHPT is sporadic, about 5-10% are hereditary forms that manifest as isolated pathology of the PTG or occur in combination with other components of genetically determined syndromes.

The pathogenesis of PTG tumors has not been sufficiently studied; the literature discusses the influence of some proto-oncogenes and tumor suppressor genes on the development of PTG tumors. Chronic vitamin D deficiency and increased inactivation of vitamin D in the liver are considered as putative mechanisms for triggering hyperplasia with subsequent transformation into PTG adenoma. The constant need for PTH hypersecretion presumably causes the conversion of proto-oncogenes into oncogenes or inactivation of proliferation suppressor genes. Tumor formation is often a multi-stage process during which cells acquire mutations/deletions in one or more genes; the involvement of epigenetic factors is not excluded. Most neoplasms are monoclonal, which implies their origin from a single abnormal cell. In some cases of sporadic forms of primary hyperparathyroidism (PHPT), key somatic oncogenic events may occur - somatic mutations in the genes MEN1, CDC73, CASR or inhibitors of cyclin-dependent kinases CDKIs, which leads to the formation of tumor tissue. According to the results of studies using high-throughput sequencing (NGS), it was shown that the formation of sporadic PTG adenomas is based on somatic mutations of MEN1 in 35% of cases, and only in 10% are somatic mutations in other genes determined, for example, EZH2, POT1.

PHPT accompanied by hyperplasia of the parathyroid gland or multiple adenomas is usually associated with hereditary syndromes and can be caused by mutations in various genes. Multiple endocrine neoplasia syndrome type 1 (MEN-1) is associated with mutations in the tumor suppressor gene MEN1; MEN-2 syndrome - with mutations in the RET proto-oncogene; MEN-4 syndrome develops due to mutation of the cyclin-dependent kinase inhibitor CDNK1B. Hyperparathyroidism syndrome with tumor of the jaw (HPT-JT) is associated with mutations in the CDC73 gene, encoding the parafibromin protein. Familial isolated hyperparathyroidism (FIHP) is a rare disease with an autosomal dominant type of inheritance, characterized by the development of tumors of one or more PTG and the absence of other neoplasms of endocrine and non-endocrine organs, and can sometimes be an incomplete version of other syndromes (MEN-1, HPT-JT). FIHP can be associated with mutations in the MEN1, CASR, and CDC73 genes. Familial hypocalciuric hypercalcemia (FHH) is a genetically heterogeneous disease caused by mutations in the CASR, Gα11, AP2S1 genes, and requires differential diagnosis with PHPT. Mutations in the CDC73 genes (about 50% of cases) and PRUNE2 mutations in 18% of cases have been described for PTG carcinomas.

Until the mid-1970s, PHPT was considered a rare pathology of phosphorus-calcium metabolism, manifested by severe clinical symptoms with damage to the kidneys (recurrent nephrolithiasis), skeletal system (pathological fractures, skeletal deformation, fibrocystic osteitis) and gastrointestinal tract (GIT, recurrent ulcers of the stomach and duodenum). According to the results of the largest epidemiological study conducted in 1965-1974 at the Mayo Clinic in Rochester (USA), the incidence of PHPT averaged 7.8±1.2 cases per 100,000 residents.

Over the past decades, there have been significant changes in the understanding of the epidemiology of the disease. A sharp increase in the detection of PHPT has been noted, including asymptomatic forms not accompanied by high hypercalcemia. These changes are primarily due to the advent of automated biochemical analyzers and the active introduction of widespread calcium level determination in North America, Western Europe, and China. In the general population, the prevalence of PHPT averages 0.86-1%. It should be noted that the results of epidemiological studies remain variable, which is due to differences in the diagnostic criteria for PHPT and the methodology of biochemical screening for calcemia. PHPT can occur in all age groups, including children and adolescents. However, the totality of factual data indicates that the incidence of PHPT increases with age, and the average age at diagnosis is 54-59 years. Most patients with sporadic PHPT are postmenopausal women with disease onset within the first decade after menopause. The male to female ratio is 1:3 on average.

The most objective data on the prevalence of PHPT are provided by large epidemiological studies conducted in Sweden from 1976 to 2002 and a ten-year prospective study of one county in Scotland among all residents over 20 years of age. According to the Swedish studies, the prevalence of PHPT among adults of both sexes over 18 years of age was approximately 1% of the total adult population, increasing to 2.1% in the group of menopausal women (55-75 years). As a result of the study of the Scottish population, 2709 new cases of PHPT were registered over 10 years: 1918 women (71%) and 791 men (29%). In the overwhelming majority of cases, the disease was diagnosed in people over 40 years of age. The peak incidence occurred in the period of 60-70 years, which confirmed the increase in the risk of developing the disease with age. The female/male ratio increased from 2 (at the age of 40-49 years) to 4 (at the age of over 80 years). As a result, the incidence of PHPT in different years ranged from 4.13 to 11.3 cases per 10,000 person-years. One of the latest studies on the epidemiology of PHPT in California analyzed data on 15,234 patients with chronic hypercalcemia and found that in 87% of cases, the cause of the increase in serum calcium was PHPT. The prevalence of PHPT fluctuated on average within 34-120 cases per 10,000 among women and 13-36 cases among men. With age, a significant increase in the incidence in general and prevalence among women were determined, in addition, the authors revealed a reliable difference in the frequency of disease development depending on the ethnicity of patients (the maximum prevalence was noted for African Americans, p < 0.0001). Thus, primary lesion of the parathyroid gland remains the main etiologic factor of hypercalcemia. It should be noted that malignant neoplasms are the second most common cause of hypercalcemia. In more than 50% of cases, paraneoplastic hypercalcemia is caused by breast cancer with distant metastases to the bones. Hypercalcemia is observed in malignant tumors of the lungs and kidneys, hemoblastoses (myeloma, lymphomas, lymphogranulomatosis, leukemia). An increase in serum calcium develops as a result of metastatic skeletal damage, as well as local activation of bone resorption processes due to the production of cytokines such as tumor necrosis factor and interleukin-1 or humoral activators of osteoclasts, especially PTH-like peptide, by metastases.

In the majority of patients in the Russian Federation, hypercalcemia is diagnosed late, since calcium levels are not included in the general therapeutic biochemical blood test. This creates the preconditions for late detection of hyperparathyroidism. According to the results of the analysis of 1914 patients with PHPT (Russian registry of patients with primary hyperparathyroidism), as of December 2017, an increase in the prevalence of the disease in Moscow is observed. In 2017, it was 13 cases per 100,000 adults (in 2016 - 5.6 cases, in 2010 - 4 cases per 100,000 adults). In the Moscow region, the prevalence of PHPT as of December 2017 was 3.4 cases per 100,000 adults (compared to 2014 - 0.25 cases). Despite the increase in prevalence, the data obtained do not correspond to the frequency of hypercalcemia detected according to the data of pilot screening of calcium levels among the adult population. In general, manifest forms of PHPT prevailed - in 67% of cases, asymptomatic course of the disease was determined in 33%, while in the countries of Europe and North America by 2004 the frequency of manifest forms did not exceed 20%.

The development of the clinical picture of PHPT is caused, first of all, by the pathological effect of elevated levels of PTH and calcium in the blood. In most cases, symptomatic PHPT is accompanied by "classic" manifestations, which include disorders of the musculoskeletal system (osteoporosis, fibrocystic osteitis, bone deformities, fractures, gait disturbances), kidney pathology (nephrolithiasis/nephrocalcinosis, decreased filtration and concentration function of the kidneys), less often the gastrointestinal tract (recurrent defects of the mucous membrane of the duodenum and stomach, pancreatitis, pancreatic calcifications - pancreatic calculus). In addition, changes in the cardiovascular system (arterial hypertension, left ventricular myocardial hypertrophy and left ventricular diastolic dysfunction, cardiac rhythm and conduction disturbances) are detected, which are directly dependent on the level of intact PTH (iPTH), disturbances in phosphorus-calcium metabolism and the state of the renal filtration function, as well as neurocognitive disorders. However, there is no convincing data to consider neurocognitive and cardiovascular disorders as characteristic clinical manifestations of PHPT, despite the fact that a number of studies have shown an improvement in these symptoms after parathyroidectomy.

According to the literature, PHPT may be an additional risk factor for the development of obesity, leading to an increased risk of developing insulin resistance and type 2 diabetes mellitus, proatherogenic disorders of the blood lipid spectrum, and secondary hyperuricemia.

Primary hyperparathyroidism is the third most common endocrine disease, second only to diabetes mellitus and thyroid pathology in the number of cases detected. In recent years, special attention has been paid to the study of the role of vitamin D deficiency in the pathophysiology of phosphorus-calcium metabolism disorders. Vitamin D deficiency is widespread in the modern population. Low vitamin D levels are a risk factor for endocrine pathology, leading to the development of secondary hyperparathyroidism. Vitamin D deficiency can promote proliferation of parathyroid gland cells and the progression of primary hyperparathyroidism due to decreased expression of the vitamin D receptor and calcium-sensitive receptor in hyperplastic and adenomatous cells of the parathyroid gland. Secondary hyperparathyroidism is the result of a compensatory increase in parathyroid hormone production in response to a decrease in serum calcium levels.

Patients with both secondary hyperparathyroidism and primary hyperparathyroidism have high PTH levels. In practice, it is not always easy to differentiate primary hyperparathyroidism from secondary hyperparathyroidism caused by D deficiency, which is essential for determining the tactics of further treatment. In patients with secondary hyperparathyroidism caused by D deficiency, primary hyperparathyroidism can be misdiagnosed, since there is no clear topical difference between adenoma and hyperplasia of the PTG.

Vitamin D deficiency is common among patients with primary hyperparathyroidism, and normocalcemic form of the disease may be observed. Evaluation of the situation in patients with elevated blood PTH levels and normal serum calcium levels in the absence of PTG imaging is a significant clinical problem. This combination of symptoms is possible both with the normocalcemic variant of PHPT and with vitamin D deficiency, as well as a number of other conditions.

The PTH×Ca/P index (PCF index) (serum PTH (pg/ml) x serum calcium concentration (mmol/l) / serum phosphate concentration (mmol/l) reflects the relationship between PTH and the main targets of this hormone in mineral metabolism - calcium and phosphorus and is of interest to physicians of various specialties who encounter calcium-phosphorus metabolism disorders in practice. The PTHxCa/P index is an informative indicator in the differential diagnosis of hyperparathyroidism, which allows distinguishing primary hyperparathyroidism from secondary, using available laboratory parameters and determining the tactics of patient management: making a decision on vitamin D therapy or surgery for primary hyperparathyroidism. In addition, it does not require large economic costs.

The method for diagnosing primary and secondary hyperparathyroidism includes

blood sampling from a patient, determination of the concentration of parathyroid hormone, calcium and phosphorus in the blood serum and is characterized by the fact that the parathyroid hormone coefficient is determined,

calcium and phosphorus according to the formula

PCF=PTG×Ca/P, where

PCF - parathyroid hormone, calcium and phosphorus coefficient;

PTH - parathyroid hormone concentration, pg/ml;

Ca - calcium concentration, mmol/l;

P - phosphorus concentration, mmol/l,

and with a PCF value of 194.65 or more, primary hyperparathyroidism is diagnosed, with a PCF value of 122.94-194.64 - secondary hyperparathyroidism.

We present clinical examples demonstrating the practical significance of the PTHxCa/P index as a method for differential diagnosis of primary and secondary forms of hyperparathyroidism.

Example No. 1.

Patient X. 76 years old. Complaints of weakness, fatigue, pain in the lower back, in the bones of the skeleton. History of the disease.

For about 2-3 years, I have been bothered by pain in the lumbar region and diffuse pain in the bones of the skeleton of a periodic nature. I was observed in a polyclinic at my place of residence with a diagnosis of osteochondrosis, the therapy (chondroprotectors, non-steroidal anti-inflammatory drugs, calcium preparations) did not give an effect.

Objective research data.

Weight 77 kg, height 168 cm, BMI 28 kg/ ^m2 . Skin is clean. No clinical signs of thyroid dysfunction. No peripheral edema. Chvostek's syndrome is negative. Peripheral lymph nodes are not palpable. Respiratory rate is 17 per minute. Vesicular breathing in the lungs. Heart sounds, regular rhythm. HR 78 beats per minute. BP 140/84 mmHg. Tongue is moist. Abdomen is soft and painless on palpation. Liver is at the edge of the costal arch. Spleen is not palpable. No constipation. Percussion symptom is negative on both sides, urination is not difficult, painless. Diuresis is 2.0 l.

Results of laboratory and instrumental studies.

Examination of phosphorus-calcium metabolism revealed: PTH - 78.45 pg/ml (15.0-74.0 pg/ml), total calcium - 2.63 mmol/l (2.15-2.55 mmol/l), ionized calcium - 1.44 mmol/l (1.05-1.30 mmol/l), organic phosphorus - 1.06 mmol/l (0.74-1.42 mmol/l), 25(OH)D - 21 ng/ml (target level 30-60 ng/ml).

Creatinine - 78 μmol/l, glomerular filtration rate (according to the CKD-EPI formula): 64 ml/min/1.73 ^m2 . In the daily urine analysis, calcium excretion is within the reference values.

During the examination, the following changes were identified.

According to the thyroid gland (TG) and PTG ultrasound data: TG volume is 9.06 ^cm3 , structure is homogeneous, echogenicity is normal. In the right lobe, a node with a diameter of up to 0.4 cm with clear even contours and perinodular blood flow is determined. At the lower pole of the left lobe, an enlarged PTG of up to 42×27×29 mm is located with clear even contours, homogeneous structure, with two anechoic inclusions up to 14×13 mm.

According to thyroid scintigraphy data: The scintigraphic picture is characteristic of an adenoma of the left lower parathyroid gland.

According to ultrasound examination of the kidneys, there are no signs of nephrocalcinosis/nephrolithiasis.

During osteodensitometry, a decrease (according to the T-criterion) in bone mineral density (BMD) in the lumbar spine (L1-L4) to -3.1 SD was revealed. BMD according to the T-criterion in the proximal part of the left femur = -3.4 SD, right femur = -3.3 SD, according to the WHO criteria, BMD indicators correspond to osteoporosis.

When examining the thyroid gland function, an increase in PTH to 78.45 pg/ml (8.0-74.0 pg/ml) was revealed, which, together with the above-mentioned mineral metabolism disorders, indicates the presence of primary PHPT.

The calculated PTH×Ca/P index (PCF index) in the patient was 194.65.

Taking into account the listed data, the following diagnosis was made:

Primary hyperparathyroidism, manifest form. Adenoma of the left inferior parathyroid gland. Secondary osteoporosis. D-deficiency. Nodular nontoxic goiter stage 0 (WHO).

Example #2

Patient X. 64 years old. Complaints of weakness, periodic pain in the lower limbs.

Medical history. Diabetes mellitus type 2 was diagnosed 5 years ago, receives Vildagliptin/Metformin 50/1000 mg 2 times a day. Examination revealed an increase in PTH levels.

Data of objective examination: Weight 74 kg, height 160 cm, BMI 29 kg/ ^m2 . Skin is clean. No clinical signs of thyroid dysfunction. No peripheral edema. Chvostek's syndrome is negative. Peripheral lymph nodes are not palpable. Respiratory rate is 17 per minute. In the lungs, breathing is vesicular, no wheezing. Heart sounds are clear, the rhythm is regular. HR 70 beats per minute. BP 130/82 mmHg. Tongue is moist. The abdomen is soft and painless on palpation. The liver is at the edge of the costal arch, the lower edge of the liver is painless on palpation. The percussion symptom is negative on both sides, urination is not difficult, painless. Diuresis is 1.4 l.

Results of laboratory and instrumental studies.

In terms of mineral metabolism, the following was revealed: PTH-76.84 pg/ml (15.0-74.0 pg/ml), total calcium - 2.24 mmol/l (2.15-2.55 mmol/l), ionized calcium -1.19 mmol/l (1.05-1.30 mmol/l), organic phosphorus level - 1.4 mmol/l (0.74-1.42 mmol/l), 25(OH)D-18 ng/ml (target level 30-60 ng/ml).

Creatinine - 81 μmol/l, glomerular filtration rate (according to the CKD-EPI formula): 66 ml/min/1.73 ^m2 .

During the examination, the following changes were identified.

According to the ultrasound examination of the thyroid gland and parathyroid gland: The volume of the thyroid gland is 8.4 cm ³ . In the lower pole of the right lobe, an oval-shaped node measuring 8 × 4 mm is located. In the middle third of the right lobe, a node of similar echostructure, measuring 3 × 2 mm, is located. In the left lobe - a similar node measuring 4 × 2 mm and an enlarged follicle of 2.5 × 2 mm. Signs of hyperplasia of the right upper parathyroid gland: V = 0.98 mm ³ .

According to ultrasound examination of the kidneys, there are no signs of nephrocalcinosis/nephrolithiasis.

According to osteodensitometry data: total BMD by T-score in the lumbar spine (L1-L4) is reduced to -3.6 SD. BMD by T-score in the proximal left femur = -2.6 SD, right femur = -2.5 SD, according to WHO criteria, BMD indicators correspond to osteoporosis.

When examining the thyroid function, an increase in PTH to 76.84 pg/ml (8.0-74.0 pg/ml) was revealed, which requires clarification of the genesis of hyperparathyroidism.

The calculated PTHxCa/P index in the patient was 122.94.

During further examination to clarify the cause of the increase in the functional activity of the thyroid gland, the level of 25(OH)D was determined to be 22.1 ng/ml, which indicated a lack of vitamin D.

Taking into account the listed data, the following diagnosis was made: Secondary hyperparathyroidism. D-deficiency. Multinodular nontoxic goiter stage 0 (WHO).

The patient was recommended to take a saturating dose of cholecalciferol.

Example No. 3.

Patient 3. 55 years old. Complaints of weakness, increased blood glucose.

History of the disease. Diabetes mellitus due to damage to the exocrine pancreas since 2019 after distal pancreatectomy with splenectomy. On insulin therapy since the onset of the disease. The examination revealed an increase in PTH levels.

Data of objective examination: Weight 58 kg, height 172 cm, BMI 19.6 kg/ ^m2 . Skin is clean. No clinical signs of thyroid dysfunction. No peripheral edema. Chvostek's syndrome is negative. Peripheral lymph nodes are not palpable. Respiratory rate is 16 per minute. In the lungs, breathing is vesicular, no wheezing. Heart sounds are clear, the rhythm is regular. HR 71 beats per minute. BP 127/79 mmHg. Tongue is moist. The abdomen is soft and painless on palpation. The liver is at the edge of the costal arch, the lower edge of the liver is painless on palpation. The percussion symptom is negative on both sides, urination is not difficult, painless. Diuresis is 1.8 l.

Results of laboratory and instrumental studies.

In terms of mineral metabolism, the following was revealed: PTH-81.571 pg/ml (15.0-74.0 pg/ml), total calcium - 2.41 mmol/l (2.15-2.55 mmol/l), ionized calcium -1.18 mmol/l (1.05-1.30 mmol/l), organic phosphorus level - 1.01 mmol/l (0.74-1.42 mmol/l), 25(OH)D 14 ng/ml (target level 30-60 ng/ml).

Creatinine - 80 μmol/l, glomerular filtration rate (according to the CKD-EPI formula): 72 ml/min/1.73 ^m2 .

During the examination, the following changes were revealed. According to the ultrasound data, the thyroid gland is located typically, the total volume is 11.9 cm3, the structure of the parenchyma is diffusely heterogeneous, echogenicity is increased.

According to ultrasound examination of the kidneys, there are no signs of nephrocalcinosis/nephrolithiasis.

According to osteodensitometry data: total BMD by T-score in the lumbar spine (L1-L4) is reduced to -1.2 SD. BMD by T-score in the proximal left femur = -1.4 SD, right femur = -1.3 SD, according to WHO criteria, BMD indicators correspond to osteopenia.

When studying the thyroid function, an increase in PTH to 81.571 pg/ml (8.0-74.0 pg/ml) was revealed, which requires clarification of the genesis of hyperparathyroidism.

The calculated PTHxCa/P index in the patient was 194.64.

During further examination to clarify the cause of the increase in the functional activity of the thyroid gland, the level of 25(OH)D was determined to be 21.4 ng/ml, which indicated a lack of vitamin D.

Taking into account the listed data, the diagnosis was: Secondary hyperparathyroidism. D-deficiency.

The patient was recommended to take a saturating dose of cholecalciferol.

Example #4

Patient L., 65 years old. Complaints of weakness, decreased vision, pain in the lower extremities, increased blood glucose to 11.0.

History of the disease. Type 2 diabetes mellitus for over 20 years. Since the onset of the disease, on OAS therapy. Due to the ineffectiveness of the therapy, in 2022 she was transferred to combination hypoglycemic therapy. The examination revealed an increase in PTH levels.

Objective examination data: Weight 94 kg, height 170 cm, BMI 32.5 kg/ ^m2 . Skin is clean. No clinical signs of thyroid dysfunction. No peripheral edema. Chvostek's syndrome is negative. Peripheral lymph nodes are not palpable. Respiratory rate is 16 per minute. In the lungs, breathing is vesicular, no wheezing. Heart sounds are clear, the rhythm is regular. Heart rate is 79 beats per minute. Blood pressure 138/84 mm Hg. Tongue is moist. The abdomen is soft and painless on palpation. The liver is at the edge of the costal arch, the lower edge of the liver is painless on palpation. The percussion symptom is negative on both sides, urination is not difficult, painless. Diuresis is 2.1 l.

Results of laboratory and instrumental studies.

In terms of mineral metabolism, the following was revealed: PTH-79.5 pg/ml (15.0-74.0 pg/ml), total calcium - 2.61 mmol/l (2.15-2.55 mmol/l), ionized calcium - 1.13 mmol/l (1.05-1.30 mmol/l), organic phosphorus level - 1.29 mmol/l (0.74-1.42 mmol/l), 25(OH)D 14 ng/ml (target level 30-60 ng/ml).

Creatinine - 118 μmol/l, glomerular filtration rate (according to the CKD-EPI formula): 42 ml/min/1.73 ^m2 .

During the examination, the following changes were identified.

According to thyroid ultrasound: The thyroid gland is typically located. The thyroid gland volume is 12.43 cm ^3. The echostructure of the parenchyma is diffusely heterogeneous due to connective tissue strands. Echogenicity is moderately reduced; no nodular formations were detected. The parathyroid glands are not visualized.

According to ultrasound examination of the kidneys, there are no signs of nephrocalcinosis/nephrolithiasis.

According to osteodensitometry data: total BMD (L1-L2) = 3.0 SD (which is 31% higher than peak bone mass values). According to WHO criteria, BMD values are within the age norm. BMD according to the T-score in the neck of the left femur = 0.2 SD (which is 3% higher than peak bone mass values). According to WHO criteria, BMD values are within the age norm.

When examining the thyroid function, an increase in PTH to 79.5 pg/ml (8.0-74.0 pg/ml) was revealed, which requires clarification of the genesis of hyperparathyroidism.

The calculated PTHxCa/P index in the patient was 160.8.

During further examination to clarify the cause of the increase in the functional activity of the thyroid gland, the level of 25(OH)D was determined to be 27.4 ng/ml, which indicated a lack of vitamin D.

Taking into account the listed data, the diagnosis was: Secondary hyperparathyroidism. D-insufficiency.

The patient was recommended to take a saturating dose of cholecalciferol.

Example No. 5.

Patient B., 63 years old. Complaints of frequent sweating, periodic rapid heartbeat.

History of the disease. During the staged examination, a nodular goiter was detected (the total volume of the thyroid gland according to ultrasound is 25.5 ^cm3 , the node in the left lobe is 32 mm). FIA was performed in February 2020 - TBS II. During laboratory diagnostics - hormonal status - euthyroidism. High expression of calcium in daily urine was detected, total calcium is more than 3 mmol / l, ionized calcium is not elevated. Additionally, during diagnostics on scintigraphy, an adenoma of the left lower parathyroid gland. Densitometry - mild osteopenia. No ICD.

Data of objective examination: Weight 72 kg, height 159 cm, BMI 28.4 kg/ ^m2 . Skin is clean. No clinical signs of thyroid dysfunction. No peripheral edema. Chvostek's syndrome is negative. Peripheral lymph nodes are not palpable. Respiratory rate is 16 per minute. In the lungs, breathing is vesicular, no wheezing. Heart sounds are clear, the rhythm is regular. Heart rate is 74 beats per minute. Blood pressure 123/71 mmHg. Tongue is moist. The abdomen is soft and painless on palpation. The liver is at the edge of the costal arch, the lower edge of the liver is painless on palpation. The percussion symptom is negative on both sides, urination is not difficult, painless. Diuresis is 3.6 l.

Results of laboratory and instrumental studies.

In terms of mineral metabolism, the following was revealed: PTH - 441 pg/ml (15.0-74.0 pg/ml), total calcium - 2.58 mmol/l (2.15-2.55 mmol/l), ionized calcium - 1.32 mmol/l (1.05-1.30 mmol/l), organic phosphorus level - 0.6 mmol/l (0.74-1.42 mmol/l), 25(OH)D 40.3 ng/ml (target level 30-60 ng/ml).

Creatinine - 118 μmol/l, glomerular filtration rate (according to the CKD-EPI formula): 42 ml/min/1.73 ^m2 .

During the examination, the following changes were identified.

Thyroid ultrasound: Total volume 16.3 cm3. Nodular formations: in both lobes, fluid spongy formations with clear contours, up to 5x4 mm in the right lobe - Ti-RADS 2, in the left lobe up to 10x9 mm - Ti-RADS 2. According to parathyroid scintigraphy data - adenoma of the left lower parathyroid gland.

According to ultrasound examination of the kidneys, there are no signs of nephrocalcinosis/nephrolithiasis.

According to osteodensitometry data: total BMD (L1-L2) = 2.7 SD (which is 31% higher than peak bone mass values). According to WHO criteria, BMD values are within the age norm. BMD according to the T-score in the neck of the left femur = -17 SD. Osteopenia was detected.

When studying the thyroid function, an increase in PTH to 441 pg/ml (8.0-74.0 pg/ml) was revealed, which requires clarification of the genesis of hyperparathyroidism.

The calculated PTHxCa/P index in the patient was 1896.3.

During further examination to clarify the cause of the increase in the functional activity of the thyroid gland, the level of 25(OH)D was determined to be 40.3 ng/ml.

Taking into account the listed data, the following diagnosis was made: Primary hyperparathyroidism. Mixed form. Hypercalcemic variant. Adenoma of the left lower parathyroid gland. Multinodular goiter stage 1. Euthyroidism.

The patient was recommended surgical treatment.

Additionally, a ROC analysis was performed to calculate the sensitivity and specificity of the PTH×Ca/P index when comparing between individuals without calcium-phosphorus metabolism disorders (n=173) and patients with primary (n=59) and secondary hyperparathyroidism (n=24):

- point for “Control vs Secondary hyperparathyroidism” = 122.94 (sensitivity = 1.0, specificity = 0.88);

- point for “Control vs Primary hyperparathyroidism” = 194.65 (sensitivity = 0.91, specificity = 1.0);

Primary and secondary hyperparathyroidism were diagnosed. 59 patients with primary hyperparathyroidism underwent surgical treatment, with follow-up observation - the patients are healthy; 24 patients were diagnosed with secondary hyperparathyroidism, treatment was carried out using Vitamin D, with follow-up observation the patients are in clinical remission.

Thus, the determination of the PTH×Ca/P index available for calculation - a new method for diagnosing disorders of phosphorus-calcium metabolism, allows us to optimize the diagnosis of hyperparathyroidism, understand the issues of differential diagnosis of the form of hyperparathyroidism and determine the optimal treatment tactics for patients.

The goal has been achieved.

Sources of information

1 - Clinical guidelines. Primary hyperparathyroidism. Developer of the clinical guideline: Russian Association of Endocrinologists, Association of Endocrine Surgeons. 2020. Pp. 9-11

2 - Clinical guidelines. Primary hyperparathyroidism. Developer of the clinical guideline: Russian Association of Endocrinologists, Association of Endocrine Surgeons. 2020. Pp. 13-14

Claims (7)

A method for diagnosing primary and secondary hyperparathyroidism, including taking blood from a patient, determining the concentration of parathyroid hormone, calcium and phosphorus in the blood serum, characterized by determining the coefficient of parathyroid hormone, calcium and phosphorus according to the formula PCF=PTH×Ca/P, where PCF is the coefficient of parathyroid hormone, calcium and phosphorus; PTH - parathyroid hormone concentration, pg/ml; Ca - calcium concentration, mmol/l; P - phosphorus concentration, mmol/l, and with a PCF value of 194.65 or more, primary hyperparathyroidism is diagnosed, with a PCF value of 122.94-194.64 - secondary hyperparathyroidism.