[The algorithm for morphological assessment of malignant potential of adrenocortical tumors using mathematical modeling method]. / Algoritm morfologicheskoi otsenki zlokachestvennogo potentsiala adrenokortikal'nykh opukholei s ispol'zovaniem metoda matematicheskogo modelirovaniya.

OBJECTIVE: To develop the mathematical model with high sensitivity and specificity to assess the malignant potential of adrenal cortical tumors, which can be used to diagnose adrenocortical carcinoma (ACC) in adults. MATERIAL AND METHODS: Pathomorphological examination of surgical and consultative material of adrenocortical neoplasms was carried out. All cases were verified according to the WHO Classification of adrenal gland tumors (5th ed., 2022), the tumor's histogenesis was confirmed by immunohistochemical examination. Statistical analysis of the histological and immunohistochemical factors in terms of their value in relation to the diagnosis of ACC was carried out on Python 3.1 in the Google Colab environment. ROC analysis was used to identify critical values of predictors. The cut-off point was selected according to the Youden`s index. Logistic regression analysis using l1-regularisation was performed. To validate the model, the initial sample was divided into training and test groups in the ratio of 9:1, respectively. RESULTS: The study included 143 patients divided into training (128 patients) and test (15 patients) samples. A prognostic algorithm was developed, which represent a diagnostically significant set of indicators of the currently used Weiss scale. The diagnosis is carried out in 3 stages. This mathematical model showed 100% accuracy (95% CI: 96-100%) on the training and test samples. CONCLUSION: The developed algorithm could solve the problem of subjectivity and complexity in the interpretation of some of the criteria of current diagnostic algorithms. The new model is unique in that, unlike others, it allows verification of all morphological variants of ACC.

[Machine learning methods in differential diagnosis of ACTH-dependent hypercortisolism].

AIM: To develop a noninvasive method of differential diagnosis of ACTH-dependent hypercortisolism, as well as to evaluate the effectiveness of an optimal algorithm for predicting the probability of ectopic ACTH syndrome (EAS) obtained using machine learning methods based on the analysis of clinical data. MATERIALS AND METHODS: As part of a single-center, one-stage, cohort study, a retrospective prediction of the probability of EAS among patients with ACTH-dependent hypercortisolism was carried out. Patients were randomly stratified into 2 samples: training (80%) and test (20%). Eleven machine learning algorithms were used to develop predictive models: Linear Discriminant Analysis, Logistic Regression, elastic network (GLMNET), Support Vector machine (SVM Radial), k-nearest neighbors (kNN), Naive Bayes, binary decision tree (CART), C5.0 decision tree algorithms, Bagged CART, Random Forest, Gradient Boosting (Stochastic Gradient Boosting, GBM). RESULTS: The study included 223 patients (163 women, 60 men) with ACTH-dependent hypercortisolism, of which 175 patients with Cushing's disease (CD), 48 - with EAS. As a result of preliminary data processing and selection of the most informative signs, the final variables for the classification and prediction of EAS were selected: ACTH level at 08:00 hours, potassium level (the minimum value of potassium in the active stage of the disease), 24-h urinary free cortisol, late-night serum cortisol, late-night salivary cortisol, the largest size of pituitary adenoma according to MRI of the brain. The best predictive ability in a training sample of all trained machine learning models for all three final metrics (ROC-AUC (0.867), sensitivity (90%), specificity (56.4%)) demonstrated a model of gradient boosting (Generalized Boosted Modeling, GBM). In the test sample, the AUC, sensitivity and specificity of the model in predicting EAS were 0.920; 77.8% and 97.1%, respectively. CONCLUSION: The prognostic model based on machine learning methods makes it possible to differentiate patients with EAS and CD based on basic clinical results and can be used as a primary screening of patients with ACTH-dependent hypercortisolism.

[Association between preoperative cholecalciferol therapy and hypocalcemia after parathyroidectomy in patients with primary hyperparathyroidism].

BACKGROUND: Primary hyperparathyroidism (PHPT) is a endocrine disorder characterized by excessive secretion of parathyroid hormone (PTH) from parathyroid gland tumors. Parathyroidectomy (PTE) is the main treatment for PHPT, but it can lead to hypocalcemia in up to 46% of cases. Hypocalcemia is associated with seizures and life-threatening cardiac arrhythmias, and vitamin D deficiency can exacerbate PHPT severity and contribute to «hungry bones syndrome,¼ resulting in severe and persistent postoperative hypocalcemia. AIM: To evaluate the association and determine the strength of the relationship between preoperative cholecalciferol therapy and the occurrence of hypocalcemia within 1-3 days after PTE in patients with PHPT. MATERIALS AND METHODS: The study was conducted at the Endocrinology Research Centre, during the periods of 1993-2010 and 2017-2020. The inclusion criteria consisted of patients diagnosed with PHPT who required PTE, had a serum 25-hydroxyvitamin D (25(OH)D) level below 20 ng/mL, and a serum total calcium level below 3 mmol/L. The exclusion criterion was the use of medications that affect calcium-phosphorus metabolism, including cinacalcet, denosumab, or bisphosphonates, either as monotherapy or as part of combination therapy. RESULTS: There were 117 patients, including 110 (94%) females and 7 (6%) males. The median age and interquartile range were 58 [49; 65] years. Among the participants, 21 (18%) received cholecalciferol supplementation for a duration of 2 weeks to 2 months prior to PTE, aiming to address vitamin D deficiency. The remaining 96 (82%) participants did not receive -cholecalciferol supplementation. Both groups, i.e., participants receiving cholecalciferol and those who did not, were similar in terms of anthropometric factors (sex and age at the time of surgery), preoperative clinical characteristics (BMD decrease), and laboratory parameters (PTH, total calcium, phosphorus, ALP, OC, CTX-1, and 25(OH)D levels). The occurrence of postoperative hypocalcemia was significantly lower in participants who received cholecalciferol supplementation (10% vs. 63%, p<0,001, FET2). Cholecalciferol intake showed a negative association with hypocalcemia development (RR=0,15, 95% CI (0,03; 0,51)). CONCLUSION: Preoperative cholecalciferol supplementation for 2 weeks to 2 months before PTE reduces the risk of postoperative hypocalcemia in patients with PHPT by 2-33 times.

[Comparative analysis of bone complications/manifestations in sporadic and MEN1-related primary hyperparathyroidism].

BACKGROUND: Multiple endocrine neoplasia type 1 (MEN1) - is a rare syndrome with an autosomal dominant inheritance pattern caused by a mutation in the tumor suppressor gene (MEN1). Parathyroid involvement is the most common MEN1 manifestation resulting in primary hyperparathyroidism (mPHPT). Data on the prevalence and structure of bone disease in mPHPT compared to sporadic one (sPHPT) are often incomplete and contradictory. AIM: The purpose of this study was to compare the severity of bone involvement between mPHPT and sPHPT. MATERIALS AND METHODS: A single-center retrospective study was conducted among young patients in the active phase of PHPT and without prior parathyroidectomy in anamnesis. The analysis included the main parameters of calcium-phosphorus metabolism, bone remodeling markers, as well as an assessment of disease complications. Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry (DXA) at sites of lumbar spine, femur and radius. Trabecular bone score (TBS) was applied to estimate trabecular microarchitecture. All patients included in the study underwent genetic testing. RESULTS: Group 1 (mPHPT) included 26 patients, and group 2 (sSHPT) included 30 age-matched patients: the median age in group 1 was 34.5 years [25; 39], in group 2 - 30.5 years [28; 36], (p=0.439, U-test). Within group 1, the subgroup 1A (n=21) was formed with patients without other hormone-produced neuroendocrine neoplasms (NEN) in the gastrointestinal tract (GI) and the anterior pituitary gland. The duration of PHPT was comparable in both groups: mPHPT - 1 year [0; 3] versus sPHPT - 1 year [0; 1], (p=0.533, U-test). There were no differences in the main parameters of calcium-phosphorus metabolism, as well as in the prevalence of kidney complications. In the mPHPT group, bone abnormalities were observed significantly more often compared to sPHPT: 54 vs 10% (p=<0.001; F-test). Statistically significant differences were revealed both in BMD and in Z-score values of the femoral neck and total hip, which were lower in the mPHPT group. These differences remained significant when comparing subgroup 1A with sPHPT. CONCLUSION: MEN1-associated PHPT may be accompanied by a more severe decrease in BMD in the femoral neck and total hip compared to sPHPT regardless of the other hormone-producing NEN. Clarifying the role of mutation in the MEN1 gene in these processes requires further study.

[Hyperparathyroidism of different genesis in young patients with Turner syndrome: case series and brief review].

Hyperparathyroidism is a syndrome characterized by an excessive secretion of parathyroid hormone. Etiologically, hyperparathyroidism is subdivided into primary hyperparathyroidism, which develops as a result of parathyroid adenoma, carcinoma or hyperplasia, and secondary hyperparathyroidism, which happens as a compensatory response to a hypocalcemia caused by condition outside the parathyroid glands. Turner syndrome may also be accompanied by mineral metabolism disorders of various etiology. An association of hyperparathyroidism and Turner syndrome is interesting because of multifactorial impact on bone mineral density, but only few cases of such coexistence have been previously described in the literature. This article describes two patients with Turner syndrome and hyperparathyroidism of different etiology. Hyperparathyroidism, normocalcemia, vitamin D deficiency, osteoporosis, parathyroid tumors were found in both cases. In one case a number of assays was performed to confirm the patient's normocalcemic primary hyperparathyroidism, and surgery was performed to achieve remission. In the second case, treatment of vitamin D deficiency resulted in normalization of serum concentration of parathormone, after which the patient was prescribed antiresorptive therapy. The pathogenetic association between Turner syndrome and hyperparathyroidism requires further investigation. Comprehensive approach to the diagnosis and treatment of mineral metabolism disorders are essential for patients with coexistence of these two diseases.

[Diagnostic value of bilateral inferior petrosal sinus sampling in various modifications and methods of radiation and radionuclide imaging in the diagnosis and differential diagnosis of ACTH-dependent endogenous hypercortisolism].

AIM: To analyze the diagnostic performance of bilateral inferior petrosal sinus sampling (BIPSS) with desmopressin as a stimulation agent and prolactin measurements to control catheter position with or without the ACTH/prolactin normalized ratio calculation in the differential diagnosis of ACTH-dependent endogenous hypercortisolism, and the diagnostics performance of ectopic ACTH-syndrome (EAS) visualization. MATERIALS AND METHODS: A single-center diagnostic study with a retrospective analysis of the data was carried out. The study included patients with ACTH-dependent endogenous hypercorticism with no visualization of pituitary adenoma on MRI or adenoma sizes less than 6 mm. All patients underwent BIPSS with and without calculation of the ACTH/prolactin normalized ratio. Visualization of an EAS included pituitary MRI (to exclude EAS), whole-body CT scan with contrast, and somatostatin receptor scintigraphy with 99mTc-Tectrotide and CT (99mTc-Tectrotide SPECT). The final verification was based on immunohistochemical confirmation of the tumor or stable remission of Cushing's disease (CD) after surgical treatment. Statistical data processing was carried out by using IBM SPSS Statistics 23. Confidence intervals were calculated using the JavaStat online calculator. RESULTS: 230 BIPSS were performed in 228 patients (166 women, 62 men), of which 178 patients were verified as CD and 50 cases were EAS of various localization. The effectiveness of catheterization of petrosal sinuses was 96.9%. The sensitivity of BIPSS without ACTH/prolactin ratio calculation (n=70) was 95.9% (95% CI 86.3-98.9), specificity was 92% (95% CI 75.0-97.8), for the BIPSS with additional determination of ACTH/prolactin-normalized ratio (n=51) - 97.3% (95% CI 86.2-99.5) and 93.8% (95% CI 71.7-98.9), respectively. The use of the MRI method for this sample of patients had a sensitivity of 60.2% (95% CI 52.6-67.5), specificity of 59.2% (95% CI 44.2-73.0), the total body CT with contrast has a sensitivity of 74% (95% CI 59.7-85.4), specificity of 100% (95% CI 97.95-100). The diagnostic accuracy for 99mTc-Tectrotide SPECT in NET visualization has a sensitivity of 73.3% (95% CI 44.9-92.2), specificity of 100% (95% CI 95.3-100). CONCLUSION: BIPSS with desmopressin stimulation and prolactin measurements to control catheter position, as well as the additional calculation of the ACTH/prolactin-normalized ratio, is an optimal method for the differential diagnosis of EAS. Patients who are identified an EAS on BIPSS may be further referred for 99mTc-Tectrotide SPECT and CT for tumor visualization.

[Predicting the presence of MEN1 gene mutation based on the clinical phenotype of patients with primary hyperparathyroidism].

BACKGROUND: Timely referral of patients for genetic testing to rule out MEN1-associated primary PHPT is important factor in determining treatment strategy and prognosis. In the context of the limited availability of genetic testing, the search for clinical markers indicative of MEN1 gene mutations remains an extremely relevant task. AIM: To determine the diagnostic value of clinical features of primary PHPT in young patients for predicting the presence of MEN1 gene mutations. MATERIALS AND METHODS: A single-center, prospective study was conducted at the Endocrinology Research Centre, involving 273 patients with PHPT in the period 2015-2022. Based on the results of genetic and laboratory tests, patients were divided into three groups: those with MEN1 gene mutations (MEN+ group, n=71), those without MEN1 gene mutations - isolated sporadic PHPT (MEN- group, n=158), and patients with PHPT and associated endocrine gland disorders - MEN-1 syndrome phenocopies (PHEN group, n=32). Subgroups of patients younger than 40 years of age were also identified. Comparative analysis was performed among the independent groups and subgroups, and logistic regression analysis was used to develop a mathematical model for predicting the probability of the presence of MEN1 gene mutation. RESULTS: Patients in the MEN+ and MEN- groups were comparable by gender and age at manifestation, as well as calcium-phosphorus metabolism parameters and PHPT complications. In the PHEN group, PHPT manifested at older age compared to the other groups (p<0.001 for all), with lower total calcium levels and a trend toward lower iPTH concentrations. The MEN+ group had a significantly higher frequency of multiglandular parathyroid (PG) involvement, PHPT recurrence, and positive family history compared to the MEN- and PHEN groups. Histologically, adenomas predominated in the PHEN and MEN- groups (92% and 94%, respectively), whereas hyperplasia of PGs were more common in the MEN+ group (49%). None of the PHEN patients had all three «classic¼ components of the MEN-1 syndrome, and the clinical course of PHPT was similar to that of the MEN- group. These differences were also observed in the subgroups of patients younger than 40 years, which formed the basis for the development of a mathematical model. The logistic regression equation for predicting the probability of the presence of the MEN1 gene mutation included eight predictors, with a diagnostic sensitivity of 96% and specificity of 98%. CONCLUSION: Based on the analysis performed, eight hereditary predictors of PHPT within the MEN-1 syndrome were identified. A mathematical model was developed to predict the presence of the MEN1 gene mutation in patients, which demonstrated high classification performance on the training dataset. Further refinement of the model will help improve the quality of medical care for patients with PHPT.

[Clinical features, diagnostics and treatment of FGF23 secreting tumors: series of 40 clinical cases].

INTRODUCTION: Tumor-induced osteomalacia is an acquired rare disease manifested by hypophosphatemic osteomalacia due to excessive secretion of fibroblast growth factor 23 (FGF23). FGF 23 is a non-classical hormone secreted by bone tissue (osteocytes) and regulates phosphorus metabolism.The aim of this work is to present clinical experience in the diagnosis, treatment and rehabilitation of patients with tumor-induced osteomalacia. MATERIALS AND METHODS: 40 patients with clinically-confirmed tumor-induced osteomalacia were included in the study, 34 of whom had the tumor localized, 27 underwent surgical treatment and 21 achieved stable remission. RESULTS: The median age was 48 [41; 63] years, 43% were men, the time left from the the onset of the disease was 8 [4; 10] years. Biochemical findings were hypophosphatemia 0.47 [0.4; 0.53] mmol/l, a decrease in the tubular reabsorption phosphate 62 [52; 67]%, and an increase in alkaline phosphatase of 183 [112; 294] units/l. At the time of diagnosis, 100% had multiple pathological fractures, only 10% could move independently, and 77.5% classified the pain as unbearable (8-10 points according to the 10-point pain syndrome scale ). Among the methods used to detect tumors, the most sensitive were scintigraphy with tectrotide with SPECT/CT 71.4% (20/28) and MRI 90% (18/20). In 35% of cases, the tumor was localized in soft tissues and in 65% in bone tissue; The tumor was most often detected in the lower extremities, followed by the head in frequency of localization. 18 patients currently have no remission and they receive conservative treatment (phosphorus and alfacalcidol n=15 and burosumab n=3). In case of achieving remission (n=21), regression of clinical symptoms and restoration of bone and muscle mass was observed. Extensive excision of the tumor without prior biopsy resulted in the best percentage of remission - 87%. CONCLUSION: Tumor-induced osteomalacia is characterized by severe damage to bone and muscle tissue with the development of multiple fractures, muscle weakness and severe pain syndrome. In laboratory diagnostics, attention should be paid to hypophosphatemia, a decrease in the tubular reabsorption phosphate index and increased alkaline phosphatase. The use of functional diagnostic methods with a labeled somatostatin analogue to the subtype 2 receptor and MRI with contrast enhancement are the most accurate methods of topical diagnostics. In case of localization of the tumor, a wide excision without a preliminary biopsy is recommended.

[Acromegaly in the differential diagnosis of hearing loss].

Acromegaly is a multifactorial neuroendocrine disease caused by hyperproduction of growth hormone (GH). In more than 95% of cases the reason of acromegaly the GH-secreting pituitary adenoma. In patients with this neuroendocrine disease, a slowly developing complex of symptom can manifest with concomitant pathological conditions, including auditory function disordersDiagnostic difficulties of acromegaly at the ambulatory stage determine the importance of doctor`s awareness in different medical specialties.Here we demonstrate a clinical case of the improvement of the auditory function due to combined surgical and medical treatment of a patient with the pituitary macroadenoma, acromegaly and hearing loss.Anamnesis features: a patient with an active stage of acromegaly and a pituitary macroadenoma measuring 57x35x32 mm with ante-, supra-, infra-, parasellar spread, (Knosp III(D), Knosp IV(S) noted a violation of auditory function. She was consulted by an otolaryngologist, sensorineural hearing loss on the right of the 3rd degree was diagnosed, on the left of the 1st degree. The patient underwent surgical treatment of pituitary adenoma, noted a significant improvement in auditory function in the early postoperative period. Six months later, repeated audiometry was performed, marked regression of hearing damage was noted.The case described by us indicates the reversibility of a rare complication of acromegaly - hearing loss and the importance of an interdisciplinary approach in the management of patients with this pathology.

[Features of steroidogenesis and arterial hypertension in men in different types of "physiological" male hyperandrogenism].

AIM: To reveal the peculiarities of steroidogenesis and arterial hypertension in «physiological¼ hyperandrogenism in men. MATERIALS AND METHODS: One-stage simultaneous study. The groups of men with hyperandrogenism caused by increased total testosterone (n=34) and those with hyperandrogenism caused by increased dihydrotestosterone (DHT) (n=66) were compared. In determining the type of hyperandrogenism and allocating patients to groups, DHT and total testosterone levels were determined by enhanced chemiluminescence. Subgroups of men with and without arterial hypertension were compared in the group of patients with hyperandrogenism due to an increase in total testosterone. Body mass index, waist circumference, systolic and diastolic blood pressure, pulse, and LH, SBHG, estradiol, blood multisteroid levels by isotope dilution liquid chromatography/tandem mass spectrometry, glucose, blood lipid spectrum, uric acid, creatinine, renin, potassium, sodium, and blood chloride were assessed in all patients. Patients with arterial hypertension additionally underwent daily BP monitoring, albuminuria assessment, electrocardiography, ocular fundus examination. The baseline threshold level of significance was p<0.05. For multiple comparisons, the p significance level was calculated using the Bonferroni correction. RESULTS: Statistically significant differences were found in the levels of 17-hydroxypregnenolone, 17-hydroxyprogesterone, and androstenedione, which were higher in men with elevated levels of total testosterone. No statistically significant differences in other laboratory parameters were found. No cases of increased blood pressure were detected in the group of men with elevated DHT. In the group of men with elevated total testosterone, 23,5% of men with arterial hypertension without targetorgan lesions were identified, while hyperandrogenism was associated with 17,6% of cases. Arterial hypertension associated with hyperandrogenism was characterized by a rise in blood pressure in the early morning hours. Estradiol levels, while remaining within normal limits, were statistically significantly lower in patients with arterial hypertension compared with men with elevated testosterone but without hypertension. CONCLUSION: No cases of arterial hypertension were observed in «physiological¼ hyperandrogenism due to elevated DHT levels, whereas its incidence in «physiological¼ hyperandrogenism due to elevated total testosterone was 23,5%. The features of steroidogenesis were increased production of 17-hydroxypregnenolone, 17-hydroxyprogesterone, and androstenedione in men with testosterone hyperandrogenism and decreased estradiol production in patients with arterial hypertension compared with patients without testosterone hyperandrogenism.

[Casuistic cases of parathyroid carcinoma with a verified mutation in the MEN1 gene].

Parathyroid cancer (PTC) is usually sporadic; however, it could be presented as a component of hereditary syndromes. The prevalence of PTC among patients with primary hyperparathyroidism (PHPT) is about 1% cases. The lack of reliable preoperative predictors significantly complicates the diagnosis of PTC. The clinical course is non-specific and in most cases is determined by severe hypercalcemia. The final diagnosis can only be made on the basis of invasive histopathologic features, while an analysis immunohistochemical (IHC) one can be used only as an additional method. Given the rarity the diagnosis of MEN1-related PTC a challenge. We present two clinical cases of patients with PTC and a verified heterozygous mutation in the MEN1 gene. The described cases demonstrate the complexity of morphological diagnosis for PTC, the heterogeneity of clinical manifestations in patients with the MEN1 mutation, as well as the need for timely screening to identify other components of MEN1 syndrome and mutations of the MEN1 gene among first-line relatives.

[Severe bone complications of primary hyperparathyroidism in a young patient with the rare verified mutation of MEN1].

Multiple endocrine neoplasia type 1 syndrome (MEN1) is a rare inherited disorder that can include combinations of more than 20 endocrine and non-endocrine tumors. Unfortunately, none of the described MEN1 mutations has been associated with a peculiar clinical phenotype, even within members of the same family, thus a genotype-to-phenotype correlation does not exist. MEN1 syndrome is the most common cause of hereditary primary hyperparathyroidism (PHPT), the disease penetrance of which exceeds 50% by the age of 20 and reaches 95% by the age of 40. At the same time, PHPT with hyperplasia or adenomas of the parathyroid glands (PTG) is the most distinctive manifestation of the MEN1 syndrome. One of the main symptoms of PHPT, both in sporadic and hereditary forms of the disease, is bone damage. At the time of diagnosis in PHPT/MEN1, the bone mineral density is generally lower in comparison with the sporadic form of PHPT. This may be due to excessive secretion of parathyroid hormone during the period of peak bone mass, concomitant components of the syndrome, extended surgical treatment, and the direct effect of a mutation in the menin gene on bone remodeling. This clinical case describes a young patient with severe bone complications of PHPT and uncertain rare MEN1 mutation. PHPT was diagnosed five years later from the first onset of bone complications and repeated orthopedic operations. There was the «hungry bones¼ syndrome after successful surgery of PHPT, which was managed with vitamin D and calcium carbonate supplementation and there is a positive dynamic in increased bone mineral density in the main skeleton after 6 months.

[Case of clinically "aggressive" course of primary hyperparathyroidism, algorithm of differential diagnosis].

Primary hyperparathyroidism (PHPT) is a significant endocrine disease caused by increased production of parathyroid hormone (PTH) by altered parathyroid glands and violation of the mechanisms of regulation of serum calcium concentrations. These changes can lead to nephrolithiasis, osteoporosis, erosive and ulcerative lesions of the gastrointestinal tract, a number of less specific symptoms (nausea, vomiting, weakness, fatigue, etc.). Etiologically, in more than 85% of cases, PHPT is a consequence of sporadic solitary adenoma or hyperplasia parathyroid glands, however, in 1-3% of cases, the cause is carcinoma of parathyroid glands , including as part of various genetic syndromes. The importance of timely examination for PHPT of patients with characteristic clinical manifestations of this disease and - with an aggressive course - alertness towards carcinomas of parathyroid glands was noted. At the same time, the severity of the clinical picture and even the presence of suspicious signs characteristic of hereditary forms of carcinomas of parathyroid glands are not always a consequence of the malignant process. We present a description of a young patient with a severe course of PHPT, multiple fractures and a voluminous tumor of the upper jaw, developed as a result of a typical adenoma of parathyroid glands. Additionally, the algorithm of pre- and postoperative differential diagnosis for such patients is highlighted.

[Review of clinical practice guidelines for hypoparathyroidism].

Hypoparathyroidism is a rare disorder characterized by the absent or inappropriately decreased serum parathyroid hormone in the parathyroid glands, which is accompanied by impaired calcium-phosphorus metabolism.The main etiology of hypoparathyroidism remains damage or removal of the parathyroid glands during neck surgery. In view of the incidence of thyroid cancer, primary hyperparathyroidism and other pathologies of the neck organs, which radical treatment can lead to the parathyroid gland impairment, an increased number of patients with hypoparathyroidism is expected. Autoimmune hypoparathyroidism is the second most common form of the disease, usually occurring as part of type 1 autoimmune polyglandular syndrome. Autoimmune hypoparathyroidism usually occurs in childhood and is characterized by a severe course of the disease, especially in the case of concomitant malabsorption syndrome.Chronic hypoparathyroidism of any etiology requires lifelong multicomponent therapy, as well as careful monitoring and an individual approach to choose the optimal treatment strategy. In the absence of adequate follow-up, the risks of long-term complications significantly increase, particularly in the renal, cardiovascular systems; in the soft tissues and in the brain, it could lead to visual disturbances; pathology of the musculoskeletal system with a decreased bone remodeling and a potential risk of fractures, as well as to the neurocognitive disorders and an impaired health-related quality of life.Timely diagnosis, rational medical therapy and management strategy may reduce the risks of short-term and long-term complications, frequency of hospitalizations and disability of patients, as well as improve the prognosis.This review covers the main issues of Russian guidelines for the management of chronic hypoparathyroidism, approved in 2021, including laboratory and instrumental evaluation, treatment approaches and follow-up. This guidelines also include the recommendations for special groups of patients: with acute hypocalcemia, hypoparathyroidism during pregnancy.

[The clinical practice guidelines for primary hyperparathyroidism, short version].

Primary hyperparathyroidism (PHPT) is an endocrine disorder of parathyroid glands characterized by excessive secretion of parathyroid hormone (PTH) with an upper normal or elevated blood calcium level. Classical PHPT refers to a symptomatic, multi-system disorder, wich can lead to a significant decrease in the quality of life, disability of patients, and even an increased risk of premature death. Hypercalcemia and the catabolic effect of PTH on various cells are considered as the main pathogenetic mechanisms of the PHPT associated complications. In the last two decades, there has been an increase in the incidence of PHPT, mainly due to the mild forms of the disease, primarily due to the routine calcium screening in North America, Western Europe and, Asia. High prevalence of the disease, as well as the variety of clinical manifestations, cause the attention of different specialists - physicians, rheumatologists, urologists, nephrologists, cardiologists and other doctors. This review cover the main issues of Russian guidelines for the management of PHPT, approved in 2020, including laboratory and instrumental methods, differential diagnosis, surgical and conservative approach, short-term and long-term follow-up. This guidelines also include the recommendations for special groups of patients with hereditary forms of PHPT, parathyroid carcinoma, PHPT during pregnancy.

[Sporadic primary hyperparathyroidism with multiple parathyroid adenomas].

Multiple lesions of the parathyroid glands (PTG) in primary hyperparathyroidism (PHPT) can be sporadic or develop as part of hereditary syndromes, manifesting at young age. There the description of a severe sporadic PHPT with big parathyroid neoplasms in the young patient is presented. Clinical data made it possible to suspect MEN-1 syndrome or parathyroid carcinomas; however, mutations CDKN, CDC73, MEN1 were excluded. The patient underwent removal of three identified tumors: benign adenomas of the left PTG and hyperplasia of the right one. Postoperative hypocalcemia and severe hungry bone syndrome required the administration of vitamin D and calcium carbonate preparations. However, a year after the operation, a «mild¼ recurrent disease was confirmed. Taking into account the patient's refusal to reoperation and a significant improvement of the target organs state, active observation was continued. The patient needs further careful dynamic monitoring by specialists in order to timely identify indications for repeated surgical treatment to improve the life quality and span.

[Dynamic changes of renin-angiotensin-aldosterone system parameters after surgery of primary hyperparathyroidism].

AIM: To study an activity of the Renin-Angiotensin-Aldosterone System (RAAS) components in patients with primary hyperparathyroidism (PHPT) before and after parathyroidectomy (PTE). MATERIALS AND METHODS: A comparative study of patients with PHPT and control group. The first stage of the study included 56 patients with PHPT (group 1) before and on the third day after PTE. The second stage was carried out in 27 patients with remission of PHPT (group 2). All patients and healthy volunteers were tested for the main parameters of phosphorus-calcium metabolism and the RAAS parameters (plasma renin activity PRA, serum aldosterone, angiotensin II AT II). RESULTS: Patients with active PHPT demonstrated changes in RAAS activity (lower PRA, higher AT II level) comparing to control group, that have statistical significance in group 1 (p0.001 for both parameters). There were no significant differences in aldosterone levels (p1=0.090;p2=0.140). On the third day after PTE (group 1), a decrease in aldosterone level (p=0.009) and a tendency to decrease in PRA (p=0.030) were detected. However, an increase in PRA (p=0.018), a decrease in AT II concentration (p=0.032) comparing to the initial values and their normalization were observed 12 months after surgery when permanent normal serum calcium and PTH levels had been achieved. There were controversial correlations between the parameters of phosphorus-calcium metabolism and RAAS. The influence of angiotensin-converting-enzyme inhibitors and AT II receptor blockers on phosphorus-calcium metabolism in patients with PHPT was not observed. CONCLUSION: In patients with PHPT, there were no сlear correlations of phosphorus-calcium metabolism parameters with RAAS, however an increase of AT II concentration was noted, that can take part in a development of hypertension for this endocrinopathy. PTE can have a positive effect on AT II level.

[Evaluation of chronic hypoparathyroidism course according to the Database of Endocrinology Research Centre].

BACKGRAUND: Currently high frequency of thyroid or parathyroid surgery is associated with significant increased incidence of hypoparathyroidism. Evaluation of the epidemiological and clinical features of chronic hypoparathyroidism is necessary to predict social-significant complications and to improve the quality of medical care. AIMS: To estimate clinical and demographic features, different regimens and efficacy of conventional therapy in patients with chronic postsurgical and nonsurgical hypoparathyroidism. MATERIALS AND METHODS: The cross-sectional, observational, continuous study was carried out based on Database of patients with chronic postsurgical and nonsurgical hypoparathyroidism of Endocrinology Research Centre, Moscow. 293 patients from 61 regions of the Russian Federation were included in this study. Statistical analysis was done on June 2020. The descriptive statistics are presented by medians (Ме) and the first and third quartiles (Q1; Q3) and by absolute and relative frequencies. RESULTS: Hypoparathyroidism was most often recorded in women (85%) at the age of 43 [32; 52] years, after thyroid surgery. Less than a half of the study group had target indicators of serum calcium and phosphate levels (31% and 47%, respectively) despite ongoing treatment. A complex instrumental examination for the disease complications was performed in 58% of cases (n = 169). Among them, kidney disorders were detected in 38%, visual disturbance in 14%, brain calcification in 10%, arrhythmias in 4% and neuropsychiatric symptoms in 6%. Conventional therapy with calcium supplements and activated vitamin D analogues was noted in 75% of patients. CONCLUSIONS: The analysis of large databases of patients with chronic hypoparathyroidism is a necessary tool for determining of optimal clinical and therapeutic approaches, as well as prognostic markers of disease complications.

[Neuroendocrine markers in parathyroid tumors]. / Neiroendokrinnye markery v opukholyakh okoloshchitovidnykh zhelez.

The parathyroid glands (PTGs) are a key regulator of calcium and phosphorus metabolism in the human body. In terms of their, morphological and immunophenotypic characteristics, PTGs are neuroendocrine organs, and their neoplasms are neuroendocrine tumors. These neoplasms include adenoma and cancer; in addition, glandular hyperplasia may develop, which is most characteristic of multiple endocrine neoplasia (MEN1, MEN2a, and MEN4) syndromes. The morphological characteristics of pathologically altered PTGs in MEN syndromes are variable. The analysis and generalization of knowledge about the features and expression of various immunohistochemical markers in PTG tissue in health and in diseases are useful in the practical work of not only pathologists, but also clinicians of various specialties.

[The use of confocal microscopy in experimental studies and clinical practice of an endocrinologist: modern opportunities].

Confocal microscopy is a modern imaging method that provides ample opportunities for in vitro and in vivo research. The clinical part of the review focuses on well-established techniques, such as corneal confocal microscopy for the diagnosis of diabetic neuropathy or endocrine ophthalmopathy; new methods are briefly described (intraoperative evaluation of tissues obtained by removing pituitary adenomas, thyroid and parathyroid glands). In the part devoted to fundamental research, the use of confocal microscopy to characterize the colocalization of proteins, as well as three-dimensional intracellular structures and signaling pathways in vivo, is considered. Indicators of intracellular calcium are analyzed.