[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.

[Adrenocortical cancer: late diagnosis of the disease on the example of a clinical case. Case report].

Adrenocortical carcinoma (ACC) is a rare malignant tumor originating in the adrenal cortex and characterized by poor 5-year survival. It occurs with a frequency of 2-4 cases per 2 million in the population. Women are more frequently affected than men and it is mostly detected in the fourth and fifth decades. In the most of cases, the cancerogenesis occurs sporadically because of gene driver mutations in somatic adrenocortical cells, in other cases it can be found as part of a genetically determined syndrome such as Li-Fraumeni syndrome or Wermer's syndrome (multiple endocrine adenomatosis type I). ACC most frequently happens occurs without symptoms in the initial stages leading to poor diagnoses. Because of this lack of early detection, the tumor is not considered malignant reducing the benefits of further treatment. Sometimes the fact that the resected tumor is indeed adrenocortical carcinoma becomes clear only after recurrence, or after the appearance of metastases. We present a case of adrenocortical carcinoma in a 46-year-old woman who went to the doctor in 1.5 year after symptoms were manfested. This clinical case illustrates the consequences of late diagnosis of a malignant tumor. We would like to emphasize the importance of timely detection of a neoplasm, using all of the potential of laboratory-instrumental and genomic analysis. Due to low oncological awareness, our patient was slow to seek medical help, which in turn led not only to metastases, but also to complications in the cardiovascular system.

[Primary bilateral macronodular adrenal hyperplasia: clinical and laboratory features].

BACKGROUND: Primary bilateral macronodular adrenal hyperplasia (PBMAH) is characterized by bilateral benign adrenocortical lesions, which in some cases lead to Cushing syndrome (CS). Due to the low detection, non-specific, erased clinical picture and slow, long-term progression, it is difficult to assess the true prevalence of PBMAH. This also leads to fairly limited literature data. A detailed analysis of biochemical, imaging parameters, the clinical presentations, in particular, an assessment of the course of comorbidities (arterial hypertension (AH), diabetes (DM), osteoporosis), is necessary to develop an algorithm for managing patients with PBMAH. AIM: Analysis of clinical and laboratory characteristics of patients with various forms of PBMAH. MATERIALS AND METHODS: A single-center, retrospective, observational, cross-sectional study was carried out. This study included 110 patients with PBMAH who got referred to the National Research Center for Endocrinology in the period from 2013-2023. We carried out comparative and correlation analysis of hormonal (plasma cortisol concentrations after 1 mg dexamethasone (1-mg DST), urinary free cortisol (СКМ), ACTH), biochemical (glycated hemoglobin), radiological data (nodular tissue volume), course of comorbidities (metabolic syndrome, DM, AH, osteoporosis) in three groups of patients: with overt CS, mild autonomous cortisol excess (MACE) and comorbid diseases, and patients with PBMAH without hormonal activity. RESULTS: Among 110 patients 79.1% were women, median age - 60 [51; 68]. The proportion of hormonally inactive forms of PBMAH was 37.3%, the overt CS and MACE was detected in 25.4 and 37.3% consequently. According to the hormonal -examination data: the cortisol level during 1-mg DST was 173.8 nmol/l [86.0; 441.0], ACTH - 3.35 pg/ml [1.00; 8.00], СКМ - 445.5 [249.0; 900.0]. Statistically significant positive moderate correlations were found between the volume of nodular tissue and the level of cortisol after PDT1 (r=0.40, p<0.001), СКМ (r=0.29, p<0.004), as well as a negative moderate correlation between the volume and the level of ACTH (r=-0.40, p<0.001). When analyzing the prevalence and clinical severity of comorbid conditions, DM was diagnosed in 22 (53.7%), AH in 36 (87.8%), obesity and osteoporosis - 23 (56%) and 3 (7.3%) patients. There was no statistically significant difference in the prevalence of CS-associated diseases among the above groups (p=0.56). CONCLUSION: PBMAH is a heterogeneous pathology with different clinical, hormonal, and imaging characteristics. A correlation was found between the volume of nodular tissue and the degree of hormonal activity of PBMAH. The obtained results emphasize the difficulty in determining clear indications for surgical treatment in the group of patients with MACE. The radicality of proposed surgical procedure should be weighed against its potential complications.

[Fulminant hypercorticism due to ACTG producing pheochromocytoma].

Endogenous hypercorticism (EH) is a severe symptom complex caused by hypercortisolemia; according to the etiology, ACTH-dependent and ACTH-independent variants are distinguished, which, according to the literature, occur in 70-80% and 20-30% of cases, respectively. A rare cause of ACTH-dependent endogenous hypercorticism is ACTH-ectopic syndrome (ACTH-ES) (about 15-20% of cases). ACTH-ES is a syndrome of adrenocorticotropic hormone (ACTH) hyperproduction by neuroendocrine tumors of extrahypophyseal origin. Various tumors can secrete ACTH: bronchopulmonary carcinoid, small cell lung cancer, less frequently, thymus carcinoid, islet cell tumors and pancreatic carcinoid, medullary thyroid cancer, carcinoid tumors of the intestine, ovaries, as well as pheochromocytoma (PCC).This publication presents a clinical case of rarely detected paraneoplastic ACTH production by pheochromocytoma. The patient had clinical manifestations of hypercorticism, therefore, she applied to the Russian National Research Center of Endocrinology of the Ministry of Health of Russia. During the examination Cushing's syndrome (CS) was confirmed, multispiral computed tomography (MSCT) of the abdominal cavity revealed a voluminous formation of the left adrenal gland. Additional examination recorded a multiple increase in urinary catecholamine levels. Subsequently, the patient underwent left-sided adrenalectomy. The diagnosis of pheochromocytoma was confirmed morphologically, immunohistochemical study demonstrated intensive expression of chromogranin A and ACTH by tumor cells.

[Immunohistochemical study on the expression/hyperexpression of aberrant/eutopic receptors in patients with bilateral macronodular adrenal hyperplasia].

Bilateral macronodular adrenal hyperplasia (BMAH) is a rare cause of Cushing's syndrome. In this case cortisol production can be regulated by both genetic factors and various molecular mechanisms. The presence of aberrant or overexpression of eutopic receptors on the membrane of adrenal cortex may lead to activation of cAMP/PKA signaling pathways and consequently, pathological stimulation of steroidogenesis. Since proving the effectiveness of unilateral adrenalectomy in BMAH by achievement of stable remission, preoperative clinical and laboratory tests (ligand-induced tests) are no longer of relevant. Nevertheless, in the absence of normalization of the level of cortisol in the postoperative period or its recurrence, subsequent specific targeted medical options can be offered only if expression/hyperexpression predominance of one or another receptor. Their detection becomes possible using more reliable diagnostic methods such as polymerase chain reaction (PCR) and immunohistochemical studies (IHC) than clinical laboratory tests. At the moment, PCR has gained a wider application. This article summarizes data on the use of immunohistochemical study in BMAH.