Current dissociation methods for solid tissues in scRNA-seq studies do not guarantee intact single-cell isolation, especially for sensitive and complex human endocrine tissues. Most studies rely on enzymatic dissociation of fresh samples or nuclei isolation from frozen samples. Dissociating whole intact cells from fresh-frozen samples, commonly collected by biobanks, remains a challenge. Here, we utilized the acetic-methanol dissociation approach (ACME) to capture transcriptional profiles of individual cells from fresh-frozen tissue samples. This method combines acetic acid-based dissociation and methanol-based fixation. In our study, we optimized this approach for human endocrine tissue samples for the first time. We incorporated a high-salt washing buffer instead of the standard PBS to stabilize RNA and prevent RNases reactivation during rehydration. We have designated this optimized protocol as ACME HS (ACetic acid-MEthanol High Salt). This technique aims to preserve cell morphology and RNA integrity, minimizing transcriptome changes and providing a more accurate representation of mature mRNA. We compared the ability of enzymatic, ACME HS, and nuclei isolation methods to preserve major cell types, gene expression, and standard quality parameters across 41 tissue samples. Our results demonstrated that ACME HS effectively dissociates and fixes cells, preserving cell morphology and high RNA integrity. This makes ACME HS a valuable alternative for scRNA-seq protocols involving challenging tissues where obtaining a live cell suspension is difficult or disruptive.

IntroductionEndocrine system disorders are a serious public health burden and can be caused by deleterious genetic variants in single genes or by the combined effects of multiple variants along with environmental and lifestyle factors.MethodsThe EndoGene database presents the results of next-generation sequencing assays used to genetically profile 5,926 patients who were diagnosed with 450 endocrine and concomitant diseases and were examined and treated at the National Medical Research Center for Endocrinology between November 2017 and January 2024. Among them, 494, 1,785, 692, and 1,941 patients were profiled using four internally developed genetic panels including 220, 250, 376, and 382 genes, respectively, selected based on a literature analysis and clinical recommendations, and 1,245 patients were profiled by whole exome sequencing covering 31,969 genes.Results2,711 genetic variants were reported as clinically relevant by medical geneticists and are presented here along with genomic, technical, and clinical annotations.DiscussionThis publicly accessible database will be useful to those interested in genetics, epidemiology, population statistics, and a better understanding of the molecular basis of endocrine disorders.

Analyzing the genetic architecture of hereditary forms of diabetes in different populations is a critical step toward optimizing diagnostic and preventive algorithms. This requires consideration of regional and population-specific characteristics, including the spectrum and frequency of pathogenic variants in targeted genes. As part of this study, we used a custom-designed NGS panel to screen for mutations in 28 genes associated with the pathogenesis of hereditary diabetes mellitus in 506 unrelated patients from Russia. The study identified 180 pathogenic or likely pathogenic variants across 13 genes (GCK, HNF1A, HNF1B, HNF4A, ABCC8, INS, INSR, KCNJ11, PAX4, PDX1, ZFP57, BLK, WFS1), representing 46.44% of the analyzed cohort (235 individuals). The glucokinase gene (GCK) had the highest number of identified variants, with 111 variants detected in 161 patients, 20 of which were identified for the first time. In the tissue-specific transcription factor genes HNF1A, HNF4A, and HNF1B, 34 variants were found in 38 patients, including 13 that were previously unreported. Seventeen variants were identified in the ABCC8 gene, which encodes the ATP-binding cassette transporter 8 of subfamily C, each found in a different patient; four of these were novel discoveries. Nine pathogenic or likely pathogenic variants were identified in the insulin gene (INS) and its receptor gene (INSR), including four previously unreported variants. Additionally, we identified 10 previously unreported variants in six other genes among 11 patients. Variants in the genes GCK, HNF1A, HNF1B, HNF4A, ABCC8, INS, and INSR were the main contributors to the genetic pathogenesis of hereditary diabetes mellitus in the Russian cohort. These findings enhance our understanding of the molecular mechanisms underlying the disease and provide a solid basis for future studies aimed at improving diagnostic accuracy and advancing personalized therapeutic strategies. This knowledge provides a foundation for developing region-specific genetic testing algorithms and personalized therapeutic strategies, which are critical for future initiatives in precision medicine.

Bone Health ECHO (Extension of Community Healthcare Outcomes) is a virtual community of practice that has been connecting healthcare professionals online once weekly for the past 10 years. A key component of each ECHO session is presentation and discussion of patient cases with diagnostic and treatment dilemmas. Here we present two wheelchair-bound female patients aged 47 years (Patient 1) and 34 years (Patient 2), both with type 1 diabetes mellitus (T1DM). They were admitted to our hospital due to multiple fractures and muscle weakness. Since age 8 years, both women suffered from T1DM. Patient 1 had extremely poor glycemic control over the whole period of diabetes with frequent cases of ketoacidosis (glycated hemoglobin [HbA1c] varied 10.0-14.2 %), with multiple end-stage complications of DM including anuria requiring hemodialysis from age 37 years. Patient 2 had minimal DM complications and maintained HbA1c within an individual goal (5.0-6.1 %). Both patients had low fasting phosphate and elevated alkaline phosphatase on laboratory evaluation. In the patient with anuria (Patient 1), after careful evaluation of all possible causes of hypophosphatemia, we found the most likely cause to be the effects of constantly repeated intracellular phosphate depletion due to poorly compensated T1DM. While achieving stable glucose control in hospital care, her phosphate levels gradually returned within the reference range. In the younger patient (Patient 2), tumor-induced osteomalacia (TIO) was diagnosed. After tumor removal her symptoms and laboratory results normalized. These cases illustrate two different causes of hypophosphatemia in patients with similar skeletal presentations in association with T1DM.

Background: Phosphaturic mesenchymal tumours secreting fibroblast growth factor 23 (hereinafter referred to as FGF23+ PMT) are rare neoplasms that can cause hypophosphataemic osteomalacia, owing to excessive FGF23 production. Mast cells (MCs) play a key role in tumour biology by modulating proliferative activity of atypical cells, resistance to innate and acquired immunity, angiogenesis, and metastatic behaviour. However, MCs associated with FGF23+ PMT have not previously been investigated. This study, to our knowledge, is the first to characterise features of the tumour microenvironment through spatial phenotyping of the immune and stromal landscape, together with histotopographic mapping of intercellular MC interactions with other subcellular populations in FGF23+ PMT. Methods: Histochemical staining (haematoxylin and eosin, toluidine blue, Giemsa solution, picro-Mallory protocol, silver impregnation), as well as monoplex and multiplex immunohistochemical staining with spatial phenotyping, were performed to detect atypical FGF23-secreting cells, immune cells (CD3, CD4, CD8, CD14, CD20, CD38, CD68, or CD163), stromal components (CD31, α-SMA, or vimentin), and specific MC proteases (tryptase, chymase, or carboxypeptidase A3). Bioinformatics analysis using artificial intelligence technologies was applied for spatial profiling of MC interactions with tumour, immunocompetent, and stromal cells in the tumour microenvironment. Results: Bioinformatic analysis of the entire tumour histological section, comprising over 70,000 cells stained using monoplex and multiplex immunohistochemical protocols, enabled identification of more than half of the cell population. The most abundant were CD14+ (30.7%), CD163+ (23.2%), and CD31+ (17.9%) cells. Tumour-associated MCs accounted for 0.7% of the total pool of immunopositive cells and included both mucosal and connective tissue subpopulations, predominantly of the tryptase + chymase-CPA3-specific protease phenotype. This pattern reflected combined multidirectional morphogenetic processes in the patient’s FGF23+ PMT. More than 50% of MCs were colocalized with neighbouring cells of the tumour microenvironment within 20 μm, most frequently with monocytes (CD14+CD68+), M2 macrophages (CD68+CD163+), and endothelial cells (CD31+). In contrast, colocalization with atypical FGF23-secreting cells was rare, indicating minimal direct effects on tumour cell activity. Interaction with T lymphocytes, including CD8+, was also infrequent, excluding their activation and the development of antitumour effects. Mapping of MC histotopography validated the hypothesis of their inductive role in monocyte differentiation into M2 macrophages and probable polarisation of macrophages from M1 into M2, thereby contributing to slow tumour growth. MCs were further involved in extracellular matrix remodelling and participated in the formation of pro-osteogenic niches within the FGF23+ PMT microenvironment, leading to pathological osteoid development. Conclusions: This study demonstrated active MC participation in the evolution of the FGF23+ PMT microenvironment. The findings may be applied in translational medicine to develop novel algorithms for personalised therapy in patients with FGF23-secreting tumours, offering an alternative when surgical removal of the tumour is not feasible.

Obesity is a chronic metabolic disease characterized by excessive accumulation or uneven distribution of fat in the body, which poses a serious threat to health. Obesity significantly increases the risk of developing сonditions such as type 2 diabetes, coronary heart disease, hypertension, obstructive sleep apnea, and some types of cancer. The prevalence of obesity, especially in childhood, has increased significantly worldwide over the past few decades. The World Health Organization predicts that 250 million children and adolescents aged 5-19 years will be obese by 2030, which indicates a global problem with far-reaching consequences. Advances in genomic technologies have led to the identification of multiple genetic loci associated with the disease ranging from severe cases with early onset to common multifactorial polygenic forms. Epigenetic changes driven by dietary and lifestyle factors are now recognized as crucial contributors to obesity. These modifications can alter gene expression and thereby link environmental influences to the observable clinical features of the disease. Significant progress has been made in deciphering the genetic architecture of obesity, particularly in pediatric populations. However, further advancement requires integrative multiomics analyses that encompass genomic, epigenomic, transcriptomic, proteomic, metabolomic, and microbiome data. To better understand the complex molecular underpinnings and clinical variability of obesity, researchers are increasingly applying methods from machine learning and artificial intelligence. These technologies help analyze large-scale genomic and phenotypic datasets, allowing for the identification of biological pathways involved in weight regulation. In the future, this may support the design of individualized diagnostic tools and targeted treatment plans that reflect a patient's genetic profile, lifestyle, and environmental exposures. To implement the principles of personalized and precision medicine in the treatment of obesity, it is crucial to identify risk profiles by assessing multiple contributing factors. This approach not only enables the prediction of an individual's risk of obesity and its associated diseases but also facilitates the optimization of treatment based on the patient's genetic profile. This study provides a comprehensive overview of the current understanding of childhood obesity, including its prevalence, genetic determinants, and pathophysiological mechanisms. It highlights the contribution of genetic factors to hereditary and syndromic forms, the role of gene-environment interactions (including nutrition and environmental pollutants), and the influence of epigenetic modifications on metabolic disturbances associated with polygenic obesity.

Early detection of aggressive pituitary neuroendocrine tumors (PitNETs) remains challenging due to the absence of reliable markers that can predict disease progression. Aggressive tumors are typically identified through long-term observation. Tumor immune microenvironment (TIME) is crucial for understanding PitNETs' heterogeneity and identifying potential predictors of tumor aggressiveness. In this study, we analyzed immune profile of micro- and macroenvironment in two somatotropinomas (aggressive and non-aggressive) using flow cytometry. We observed lymphopenia and elevated neutrophil levels in the periphery in the patient with tumor recurrence. The aggressive TIME showed greater leukocyte infiltration, with lymphoid cells predominating over myeloid cells along with a higher proportion of CD4 + T cells over CD8 + T cells. We detected double-positive CD4 + CD8 + population, high level of regulatory T cells and a sharp increase in PD-1 + expressing T cells over six months during recurrence. In the blood of the patient with tumor recurrence, we observed reduced granule-mediated cytotoxicity of CD8 + T cells and NK-cells. In the aggressive TIME the number of effector cells producing perforin and granzyme B—both independently and simultaneously was significantly lower. The proportion of CD3-CD20- NK cells and CD3-CD56 + NK cells was low after the first recurrence but increased sharply after six months. The ratio of monocyte subpopulations in tumor differed from that in blood, with CD16 + expressing monocytes predominating in the TIME of both patients. M2 macrophages in TIME rose sharply to 60.8% over six months during recurrence. In several immunological parameters, the patient with tumor recurrence exhibited a more pronounced immunosuppressive profile.

Endogenous Cushing’s syndrome (CS) is a rare neuroendocrine disorder characterized by either secondary cortisol increases due to an adrenocorticotropic hormone (ACTH)-secreting pituitary tumor (Cushing’s disease (CD)), an ACTH-secreting neuroendocrine tumor (NET) of non-pituitary origin (ectopic ACTH syndrome (EAS)), or by the primarily adrenal autonomous overproduction of cortisol [...]

The article provides an overview of the main stages of work on the prevention of diseases associated with iodine deficiency in the USSR and the Russian Federation, highlights the current state of the problem, and presents data from studies of iodine provision of the population of the Russian Federation conducted in the period 2020–2023. Ways to solve the problem of diseases associated with iodine deficiency at the present stage are proposed in the context of the Health and Demography national projects at the federal and regional levels. Assessing the scale of the threat of uncompensated iodine deficiency to the health and intelligence of current and future generations, it is obvious that the law on population iodine prevention in Russia is necessary.

Due to its effect on insulin resistance, ease of administration and favorable safety profile, metformin has been included in the recommendations of foreign medical communities for the management of pregnant women with hyperglycemia since 2008. However, in Russia, the use of any oral hypoglycemic agents during pregnancy is still contraindicated. However, recent studies demonstrate the safety and positive effects of metformin on pregnancy in patients with pregestational diabetes mellitus, polycystic ovary syndrome and gestational diabetes mellitus. In 2023, the Federal Service for Surveillance in Healthcare of the Ministry of Health of Russia updated the instructions for the medical use of Glucophage® and Glucophage®Long: pregnancy was excluded from the “Contraindications” section and moved to the “With caution” section. This resolution is intended to evaluate studies of the effectiveness and safety of metformin, as well as to study the experience of foreign colleagues and Russian legal aspects of prescribing metformin in the stages of preparation for pregnancy, during it and in the post-gravid period.

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.

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.

The molecular mechanisms underlying adrenal and thyroid neuroendocrine tumors, including their tumorigenesis, progression, and metastasis, involve unique pathways regulating cell cycle progression. To better understand these mechanisms and pathways, extensive in-depth research on cell cycle-related genes is necessary. This review aims to describe and interpret current single-cell RNA sequencing studies on neuroblastoma, medullary thyroid cancer, and pheochromocytoma tumors. Our review summarizes differentially expressed cell cycle-related genes with distinct functions, highlighting their potential as therapeutic targets and components of panels used to determine tumor type or aggressiveness. Although some insights have been gained, there is still limited information on these topics, and further research is required to explore the regulatory mechanisms of these tumors.

Pituitary neuroendocrine tumors (PitNETs) are common, most likely benign tumors with complex clinical characteristics related to hormone hypersecretion and/or growing sellar tumor mass. PitNET types are classified according to their expression of specific transcriptional factors (TFs) and hormone secretion levels. Some types show aggressive, invasive, and reoccurrence behavior. Current research is being conducted to understand the molecular mechanisms regulating these high-heterogeneous neoplasms originating from adenohypophysis, and single-cell RNA sequencing (scRNA-seq) technology is now playing an essential role in these studies due to its remarkable resolution at the single-cell level. This review describes recent studies on human PitNETs performed with scRNA-seq technology, highlighting the potential of this approach in revealing these tumor pathologies, behavior, and regulatory mechanisms.

Steroid hormones take an active part in a whole complex of physiological processes that are fundamental for the normal development and functioning of the human body. In the bloodstream steroid hormones are bind with specific transport proteins, in particular with transcortin. The matter of changes in hormone-protein complex in various conditions were actively studied in the second half of the twentieth century, but currently this issue has been taken a back seat by the development of high-precision diagnostic methods of steroid hormones determining. This literature review presents accumulated data on the physicochemical properties of transcortin, genetic factors affecting its synthesis and secretion. Published data on its physiological significance in the human body are analyzed in detail within the framework of not only the “free hormone” hypothesis, but also the reservoir hypothesis. Research results have shown that the synthesis of transcortin has been detected in some extrahepatic tissues, including the adrenal glands, however, its role is unknown.

Hypoparathyroidism is an endocrine disease characterized by reduced production of parathyroid hormone by the parathyroid glands or tissue resistance to its action. This is accompanied by disturbances in phosphorus-calcium metabolism. The main cause of hypoparathyroidism is damage or removal of the parathyroid glands during surgery on the neck organs. Autoimmune hypoparathyroidism is the second most common form of the disease, which occurs, as a rule, within the autoimmune polyglandular syndrome type 1. The development of chronic hypoparathyroidism of any etiology requires lifelong appointment of multicomponent therapy, as well as careful monitoring and an individual approach. In the absence of adequate dynamic monitoring, multiple complications develop from vital organs, in particular calcification of the urinary system, soft tissues and the brain; cardiovascular pathology; visual disturbances; muscle and bone diseases leading to decreased quality of life of patients. Thus, timely diagnosis, rationally selected drug therapy and competent patient management will reduce the risks of complications, improve the prognosis, and reduce the frequency of hospitalizations and disability of patients with chronic hypoparathyroidism. The article presents the main recommendations of the new project of clinical guidelines for patients with hypoparathyroidism, approved by the Ministry of Health of the Russian Federation in 2021. They include the algorithms of diagnosis, treatment and dynamic monitoring of hypoparathyroidism, as well as management of postsurgical hypocalcemia and medical care of and the disease during pregnancy.

Omics technologies accumulated an enormous amount of data that advanced knowledge about the molecular pathogenesis of type 1 diabetes mellitus and identified a number of fundamental problems focused on the transition to personalized diabetology in the future. Among them, the most significant are the following: (1) clinical and genetic heterogeneity of type 1 diabetes mellitus; (2) the prognostic significance of DNA markers beyond the HLA genes; (3) assessment of the contribution of a large number of DNA markers to the polygenic risk of disease progress; (4) the existence of ethnic population differences in the distribution of frequencies of risk alleles and genotypes; (5) the infancy of epigenetic research into type 1 diabetes mellitus. Disclosure of these issues is one of the priorities of fundamental diabetology and practical healthcare. The purpose of this review is the systemization of the results of modern molecular genetic, transcriptomic, and epigenetic investigations of type 1 diabetes mellitus in general, as well as its individual forms. The paper summarizes data on the role of risk HLA haplotypes and a number of other candidate genes and loci, identified through genome-wide association studies, in the development of this disease and in alterations in T cell signaling. In addition, this review assesses the contribution of differential DNA methylation and the role of microRNAs in the formation of the molecular pathogenesis of type 1 diabetes mellitus, as well as discusses the most currently central trends in the context of early diagnosis of type 1 diabetes mellitus.

Hyperandrogenism syndrome (HA) is a large group of endocrine diseases that occur due to various pathogenetic mechanisms, but are united by the principle of similar clinical symptoms due to excessive quantity and/or quality (activity) of male sex hormones in the female body. HA is one of the most common pathologies of the endocrine system in women of reproductive age. Patients with HA seek help from various specialists: cosmetic defects — to a cosmetologist, menstrual irregularities and infertility — to a gynecologist, pediatricians (congenital dysfunction of the adrenal cortex), therapists and endocrinologists — remote consequences: dyslipidemia, arterial hypertension and carbohydrate metabolism disorders. Testosterone (T) occupies a key position in the hypothalamus-pituitary-gonads system. In women, it is synthesized by the adrenal cortex, ovarian cells, and is also formed in peripheral tissues. Russian clinical diagnostic laboratories have various diagnostic systems for determining all sorts of biochemical parameters and markers. The accuracy and correctness of the determination depend on the availability of an adequate and accessible method, as well as the characteristics of the woman’s somatic status, for example, the presence of obesity. The emergence and development of modern technology of high-performance liquid chromatography with tandem mass spectrometric detection, which provides high productivity, almost 100% selectivity, the necessary sensitivity and reproducibility, allows using HPLC-MS/MS as a method recommended by clinical guidelines for diagnosing biochemical hyperandrogenism, which allows excluding false diagnoses in routine clinical practice.

Multiple endocrine neoplasia type 1 (MEN1) and congenital adrenal hyperplasia (CAH) are rare monogenic hereditary endocrinopathies with a prevalence of 1–9 cases per 100,000 and 9–15 cases per 100,000, respectively. MEN1 is characterized by the development of multiple endocrine and nonendocrine organ tumors, including parathyroid, pituitary, and duodenopancreatic neuroendocrine tumors (NETs), which constitute the classical triad of the disease. CAH is associated with genetic defects in enzymes and transport proteins involved in the synthesis of adrenal cortical steroid hormones. Overall, cases of the combination of two hereditary diseases in one patient are extremely rare. In this article, we describe a clinical case of the combination of MEN-1 with all three classical components and CAH, which, taking into account the low prevalence of both diseases, represents scientific interest. To date, only one similar case has been described in the literature. In addition, the paper discusses the pathogenetically determined combination of CAH and Ehlers-Danlos syndrome, known as the CAH-X syndrome.