Nurana Nuralieva

Ministry of Health of the Russian Federation

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ЕА

Е. А. Трошина

Ministry of Health of the Russian Federation

M. Yu. Yukina

Ministry of Health of the Russian Federation

Marina Yukina

Ministry of Health of the Russian Federation

Elena Savvateeva

Engelhardt Institute of Molecular Biology

НМ

Н. М. Платонова

Endocrinology Research Center

Dmitry Gryadunov

Engelhardt Institute of Molecular Biology

ГА

Г. А. Мельниченко

Endocrinology Research Center

НГ

Н. Г. Мокрышева

Endocrinology Research Center

M.Yu. Yukina

Endocrinology Research Center

O. Yu. Rebrova

Pirogov Russian National Research Medical University

Cooperative Institutions

Endocrinology Research Center

Ministry of Health of the Russian Federation

Faculdades Guarulhos

Sechenov University

Lomonosov Moscow State University

National Medical Research Center of Cardiology

Pirogov Russian National Research Medical University

Russian Academy of Sciences

State Research Center for Dermatovenereology and Cosmetology

Engelhardt Institute of Molecular Biology

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Diagnosis of artificial hypoglycemia due to oral hypoglycemic drugs by high-performance liquid chromatography with tandem mass spectrometric detection

Diabetes Mellitus (2024)

M. Yu. Yukina Е. А. Трошина Nurana Nuralieva В. А. Иоутси O. Yu. Rebrova

BACKGROUND: Artificial hypoglycemia (ArH) is a decrease of blood glucose levels less than 3 mmol/l due to the deliberate use of hypoglycemic drugs by a patient outside of medical appointments. Timely diagnosis of this kind of hypoglycemia avoids unnecessary numerous examinations and hospitalizations. However, the detection of ArH still remains an extremely difficult task for both the healthcare facility and the attending physician. The foreign literature describes cases of successful detection of deliberate intake of oral hypoglycemic drugs (OHD) using high-performance liquid chromatography with tandem mass spectrometric detection (HPLC-MS/MS). Thus, it is relevant to develop and validate a method for determining OHD using HPLC-MS/MS. AIM: To optimize the diagnosis of ArH due to the use of OHD. MATERIALS AND METHODS : A total of 92 patients were examined. The development of the HPLC-MS/MS method for the detection of the studied OHD (sOHD; n=1-glibenclamide, n=1-gliquidone, n=1-gliclazide, n=1-glimepiride, n=1-glipizide, n=1-nateglinide and n=1-repaglinide) in the blood was carried out in a group of patients with diabetes mellitus type 2 (n=7) who received sOHD, and a group of conditionally healthy people who did not receive any medications (n= 7). To validate the method, the determination of sOHD substances was carried out on groups of patients with hyperinsulinemic nondiabetic hypoglycemia (NDH) of unknown origin (n=11) and with insulinoma (n=67). RESULTS: In the study of blood samples by HPLC-MS/MS in the group of patients with diabetes mellitus type 2, was confirmed in 100% of the cases the use of the drug that the patient received, in the group of conditionally healthy — sOHD were not detected. A false positive result was not obtained in any conditionally healthy and in any patient with insulinoma. ArH was diagnosed in 5 out of 11 patients in the group with hyperinsulinemic NDH of unknown origin, the method identified sOHD glibenclamide and gliclazide in the patients’ blood samples. In the remaining 6 patients of this group, examinations were continued and other causes of NDH were diagnosed. The sensitivity of the method was 100% [74%; 100%], specificity — 100% [95%; 100%]. CONCLUSION: The HPLC-MS/MS method has high diagnostic accuracy in the detection and identification of sOHD (glibenclamide, gliquidone, gliclazide, glimepiride, glipizide, nateglinide and repaglinide) in blood samples of patients receiving these drugs. Currently, due to the low availability of the method, this study is advisable to use in patients with hyperinsulinemic hypoglycemia with negative results of first-line insulinoma imaging methods (computed tomography with contrast enhancement, ultrasound and magnetic resonance imaging of the abdominal cavity).

Tandem

10.14341/dm13119

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Atypical and typical course of neurofibromatosis type 1 in combination with pheochromocytoma

Endocrine Surgery (2022)

M. Yu. Yukina Ekaterina Avsievich Antonina Pushkareva Nurana Nuralieva E. V. Bondarenko

Neurofibromatosis type 1 is a hereditary disease that has a multisystem character of organism damage, a wide variability of clinical manifestations, up to the almost complete absence of typical symptoms. Phenotypic manifestations, their expressiveness and heaviness can be varied even among members of the same family with identical mutations. One of the possible clinical manifestations of this pathology is pheochromocytoma, the development of which is associated with a high risk of developing life-threatening conditions. Timely diagnosis of the disease, the choice of treatment tactics for the patient, genetic testing of blood relatives can significantly improve the survival rate and prognosis of the disease. In this article, on the presented clinical examples of patients with a typical and atypical course of type 1 neurofibromatosis in combination with pheochromocytoma, the issues of managing patients with this pathology are outlined.

10.14341/serg12730

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Анализ распространенности и заболеваемости надпочечниковой недостаточностью в мире

Ateroscleroz (2023)

М. Ю. Юкина Nurana Nuralieva Е. А. Трошина

10.52727/2078-256x-2022-18-4-426-429

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Clinical and Genetic Diagnosis of Pheochromocytoma and Paraganglioma

Nurana Nuralieva

Background: Pheochromocytomas are rare tumors of the adrenal medulla and extra-adrenal sympathetic chromaffin tissues. This study investigates the clinical and genetic features of pheochromocytoma. Methods: We analyzed records of 167 patients diagnosed with pheochromocytomas. Patients were divided into three groups, as follows: group 1 – patients with multiple endocrine neoplasia type 2; group 2 – patients with von Hippel-Lindau Syndrome; group 3 – patients with sporadic pheochromocytoma. Findings: The average age at the time of initial diagnosis was 25 years in group 1, 18 years in group 2 and 47 years in group 3. The predominant secretion of epinephrine was associated with the multiple endocrine neoplasia type 2, the predominant secretion of norepinephrine was associated with von Hippel-Lindau syndrome and the mixed secretion was associated with sporadic pheochromocytoma. There was a positive relationship between the tumor sizes and excretion of methylated metanephrines in group 1. All tumors of this group were localized in adrenals (82% of pheochromocytomas were bilateral and 58% of pheochromocytomas were multifocal). In group 2 16.4% of patients had extraadrenal tumor localization, at 6.6% of patients had metastases. In groups 1 and 3 no metastases were found. Conclusion: These data suggest that genetic testing should be recommended in patients younger than 40 years, in patients with bilateral and multifocal tumors and in patients with family history of pheochromocytoma. The predominant production of norepinephrine makes the diagnosis of multiple endocrine neoplasia type 2 unlikely. In patients with multiple endocrine neoplasia type 2 and the predominant production of epinephrine the search for the metastases and extra-adrenal tumor localization is inappropriate.

Metanephrines

Group B

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Promising immunohistochemical and circulating markers of insulinoma

Endocrine Surgery (2020)

M. Yu. Yukina Л С Селиванова Nurana Nuralieva Е. А. Трошина Natalya S. Izmailova

Insulinoma is the most common functioning pancreatic neuroendocrine tumor. The review examines the currently used immunohistochemical and circulating markers for its diagnosis, and discusses the sensitivity and specificity of these parameters. At the same time, the relevance of searching for new biochemical indicators of the presence of insulinoma and its characteristics, as well as studying the mechanisms of tumor growth and hormonal hypersecretion is emphasized. One of the primary methods for solving these problems is immunohistochemical testing with the determination of circulating markers. The results of recent studies of alternative secretory products, in particular, cocaine - and amphetamine - regulated transcript (CART), chromogranin B, and neuroendocrine secretory protein 55 (NESP55) are presented. In addition, the question of expression of various receptors in the insulinoma tissue is considered, including in the context of determining molecular targets for its visualization or radiotherapy. In particular, the expression of receptors for glucagon-like peptide 1 in the tumor tissue is characterized. The possible role of melatonin receptors MT1 (MTNR1a) and MT2 (MTNR1b) in the pathogenesis of insulinoma is clarified. The article also discusses the possible use of tumor protein D52 (TPD52) as a new predictive biomarker for the differential diagnosis of benign and malignant insulinoma.

Chromogranin A

Synaptophysin

10.14341/serg12452

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The first experience of using of ultrasound with multimodal imaging technology for the diagnosis of pancreatic insulinoma

Endocrine Abstracts (2018)

T. V. Soldatova Marina Yukina Е. А. Трошина Nurana Nuralieva

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Ultrasound imaging

10.1530/endoabs.56.p154

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Prolonged oral glucose tolerance test in the diagnosis of postprandial non-diabetic hypoglycemia

Endocrine Abstracts (2022)

M. Yu. Yukina Nurana Nuralieva Е. А. Трошина

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Glucose tolerance test

10.1530/endoabs.81.ep1177

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Antibodies to insulin receptor in the diagnosis of non-diabetic hypoglycemia

Endocrine Abstracts (2020)

Marina Yukina Nurana Nuralieva Е. А. Трошина Н. М. Малышева Larisa Nikankina

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

10.1530/endoabs.70.aep314

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Insulin-producing tumor of pancreas in a young patient: the search for germline mutations. Clinical case

Consilium Medicum (2019)

M.Yu. Yukina Nurana Nuralieva Е. А. Трошина Ayrat Kaldarov Tatjana V. Soldatova

10.26442/20751753.2019.4.190335

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Autoantibodies to 21-hydroxylase as a diagnostic marker of primary autoimmune adrenal insufficiency, including at its potential and latent stages

Almanac of Clinical Medicine (2020)

Nurana Nuralieva M. Yu. Yukina Е. А. Трошина Н. М. Малышева Larisa Nikankina

Rationale : In Russia, assessment of anti-P450c21 antibodies (AB) in the diagnosis of autoimmune adrenal insufficiency (AAI) has not been commonly used, and the disease screening has not been implemented. Aims : 1) To determine the sensitivity and specificity of anti-P450c21 AB determination in the AAI diagnosis; 2) To estimate the prevalence of anti-P450c21 AB carriage in patients without AAI. Materials and methods : Anti-P450c21 AB were assessed in 40 patients (group 1) with manifest AAI; 171 patients without established diagnosis of AAI, including 113 subjects with autoimmune thyroid disorders or type 1 diabetes mellitus (AID, group 2); 25 carriers of AB markers of thyroid AID and/or type 1 diabetes mellitus without any target organ dysfunctions (group 3); 33 patients with non-autoimmune endocrine disorders (group 4), and 25 healthy individuals (group 5). Results : Determination of anti-P450c21 AB for the diagnosis of AAI had 95% sensitivity, with specificity of 100%, predictive value of a positive result of 100%, and predictive value of a negative result 92.6%. Anti-P450c21 AB were inversely correlated with the duration of glucocorticoid replacement therapy (r=-0.222, p<0.05). High levels of anti-P450c21 AB were found in 4 (3.5%) patients of group 2; based on the results of additional hormonal testing, 50% cases were diagnosed with the latent stage of the disease and 50% cases with the potential stage. Discussion : The sensitivity of the anti-P450c21 AB determination for AAI diagnosis in our study was higher, than in the works by other authors. We have confirmed a time-related reduction of anti-P450c21 AB levels, whereby the strength of the correlation was higher in the subgroups with autoimmune polyendocrine syndrome type II and, to a greater extent, autoimmune polyendocrine syndrome type I. This might be related to their different pathogenesis, with an abnormality of central immune tolerance in autoimmune polyendocrine syndrome type I and that of peripheral immune tolerance in autoimmune polyendocrine syndrome type II. According to our data, in 50% of cases, the development of AAI was preceded by the manifestation of other AIDs (in 15% of cases being multiple). Among all patients with no AAI diagnosis at the study entry, increased anti-P450c21 AB levels were found exactly in those with pre-existing AID. Thus, we have confirmed the feasibility of AAI screening primarily in a cohort of patients with other AID (especially multiple) belonging to the risk group. Conclusion : The determination of blood anti-P450c21 AB is a highly sensitive and highly specific method to diagnose AAI. The frequency of anti-P450c21 AB detection might depend on the duration of glucocorticoid treatment. Screening for early AAI stages is relevant primarily in the risk groups with multiple autoimmune disorders.

10.18786/2072-0505-2020-48-023

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