Neurofibromatosis type 1 is a hereditary disease with a wide variability of clinical manifestations, from the almost complete absence of typical symptoms to a multisystem lesion of the body. One of the possible clinical manifestations of this pathology is a pheochromocytoma - a tumor of the adrenal gland with the possible development of considerable cardiovascular complications. The article describes four cases of patients with pheochromocytoma as part of familial neurofibromatosis type 1, differing in clinical course from asymptomatic form to vivid paroxysmal manifestations. At the same time, the presence and degree of arterial hypertension did not correlate with the level of metanephrines and the size of the pheochromocytoma. 3 out of 4 patients have a hereditary history of neurofibromatosis type 1. In 1 out of 4 cases, simultaneous bilateral damage to the adrenal glands was noted, while the radiation characteristics of pheochromocytomas, both with computed tomography and CT/PET with 18-FDG, differed from the "classic" ones. An objective examination with the identification of "erased" signs of neurofibromatosis type 1 made it possible to establish the diagnosis of bilateral pheochromocytoma even with questionable laboratory and imaging data. Knowledge of clinical manifestations, timely diagnosis of neurofibromatosis type 1, comprehensive treatment and subsequent regular monitoring of patients, as well as examination of blood relatives can significantly improve prognosis and survival.

Pituitary adenomas (PA) are the most common lesions of hypothalamic-pituitary region. Clinical presentations of PA depend on both hormonal activity and tumor growth characteristics. Despite the fact that PA are mostly benign, they can grow invasively and mechanically affect adjacent structures. With invasive growth of PA, radical removal is difficult and associated with a higher risk of surgical complications. Pathogenesis of PA invasiveness is not fully understood. Tumor cell invasion depends on both intercellular interactions within the tumor and interaction with extracellular matrix components (ECM). Major factors that play an important role in these processes include matrix metalloproteinase (MMP) family and tissue inhibitors of matrix metalloproteinases (TIMPs). Two MMPs were mostly studied in PA - types 2 and 9. These molecules are of interest, as they participate in degradation of type IV collagen, which is a key component of the ECM in hypothalamic-pituitary region. This review discusses the general concept of PA invasiveness, the characteristics of MMPs, and research of the relationship between these molecules and PA invasiveness.

Thyroid nodules in children are relatively rare; the risk of malignancy is considerably higher compared to adults. The optimal extent of surgery, the indications for radioactive iodine therapy (RAI), and the role of molecular genetic testing in children with thyroid carcinoma remain a matter of debate.

The basis of the vital activity of each cell of the body is energy metabolism, necessary for the implementation of physiological needs in norm and pathology. The most important pathways for the synthesis of adenosine triphosphate are glycolysis, the tricarboxylic acid cycle and oxidative phosphorylation. Glucose, free fatty acids and amino acids can be used as a substrate for obtaining energy. As the disease develops, reprogramming occurs in cells with the ability to switch between energy pathways and the choice of its sources, forming a specific metabolic phenotype that ensures cell survival and the formation of clinical characteristics of the disease. The availability of information on pathophysiological changes at the level of cell metabolism is of scientific and practical interest in relation to the development of methods for accurate diagnosis and the choice of personalized tactics in each specific case. This review describes the characteristics of energy metabolism in normal and tumor cells. It also provides information on modern methods for assessing energy metabolism in the body.

Neurofibromatosis type 1 (NF1) is a multisystem genetic disorder associated with a lifelong increased risk of tumor development. Comprehensive monitoring of patients with NF1, involving a multidisciplinary team of specialists and the implementation of screening programs, is crucial for the early detection of associated pathological conditions that contribute to disability and reduced life expectancy. This article presents a clinical case of an adolescent female patient with tumor manifestations of NF1, in whom both diagnosed neoplasms - plexiform neurofibroma and pheochromocytoma, had a symptomatic course, significantly affecting her physical health and quality of life. A multidisciplinary approach and correct treatment led to favorable outcomes, enabling the patient to resume a normal lifestyle, despite the continuation of targeted therapy.

Currently, due to the lack of clear criteria for predicting the aggressive course of pituitary adenomas (APA), the search for diagnostic markers is highly relevant. Genetic markers, among others, may serve as such markers since their identification is possible at early stages of the pathological process.

DICER1 syndrome is a rare monogenic disease with autosomal dominant inheritance. DICER1 protein is involved in the regulation of gene expression by microRNAs. Changes in the expression of DICER1 can be associated with various cancers. A 13,8-year-old girl with a history of embryonal rhabdomyosarcoma (ERMS) of uterine cervix and vagina excised at 6 months of age is presented with a thyroid follicular nodular disease (TFND). Molecular genetic examination revealed a heterozygous pathogenic variant p.Arg1003Ter in the DICER1 gene (NM_030621.4). The presented case emphasizes the importance of molecular genetic diagnosis of DICER1 syndrome in a diagnostic algorithm in the management of patients with TFND and history of malignancy. Considering ERMS of genital tract as a probable component of DICER1 syndrome it is necessary to screen for other manifestations of the disease as well.

Medullary thyroid carcinoma is a rare aggressive tumor of thyroid gland. Due to its neuroendocrine origine medullary thyroid carcinoma can be the source of ectopic production of different peptides and hormones. We describe a unique case of severe ACTH-dependent Cushing's syndrome due to ectopic corticotropin production by medullary thyroid carcinoma in a male patient of 39 years old with calcitonin level more than 4000 pg/ml (<11,8), thyroid nodule, multiple neck jugular and central lymphnodes. The potassium level was 1,34 mmol/l (3,5-5,1), hypercortisolemia up to 1613,2 nmol/l (185-624) with elevated level of ACTH up to 24,7 pmol/l (1,03-10,74). After the correction of water and electrolytes disorders an operation was performed - thyroidectomy, central and lateral neck dissection. Postoperative calcitonin decreased to 126 pg/ml (<11,8), calcium and parathormone blood levels remained normal. The potassium level didn't decrease without any pharmacological treatment. There was a sharp fall in postoperative blood levels of cortisol and ACTH. The hormonal replacement treatment with hydrocortisone was induced. Morphological examination showed medullary carcinoma with ACTH production in tumor nodule, with metastatic neck lymph nodes. Thus this is a rare case and successful treatment of patient with severe hypercortisolism by thyroidectomy and neck lymphnodes dissection.

 Analysis and assessment of the role of convolutional neural networks in the cytological diagnosis of the thyroid pathology, exploring their potential for increasing the accuracy and automation of diagnostic processes.

Primary hyperparathyroidism (PHPT) is a common endocrine disorder characterized by autonomous secretion of parathyroid hormone by altered parathyroid glands. In most cases PHPT is a sporadic disease, 5-10% of observations are genetically determined syndromal and non-syndromal forms. Studies of families with hereditary forms of PHPT have led to the discovery of key oncosuppressor genes and proto-oncogenes whose somatic mutations underlie the development of many sporadic parathyroid tumors. Another interest in the pathogenesis of primary hyperparathyroidism is studying mechanisms of epigenetic regulation in tumor tissue. In the first part of this review, we will discuss the classification, morphology, and etiology of PHPT. In the second part, we will present a summary of the most important studies using genetic analysis, classified according to the method used.

Pheochromocytoma (PHEO) currently is considered to be malignant due to metastatic potential. One of the most common familial forms of PHEO is multiple endocrine neoplasia syndrome (MEN) type 2. The penetrance of PHEO in MEN2 syndrome is up to 50% of cases. It may be one- or two-sided, but metastases occur extremely rare. The fact that in majority of cases of MEN2 syndrome the source of distant metastases is medullary thyroid carcinoma (MTC) complicates differential diagnosis in case of PHEO metastasis.Isolated cases of PHEO with metastases to the lymph nodes, lungs, liver, bones, brain in MEN2 patients were described. In the available literature, we have found a description of 31 cases of metastatic PHEO in MEN2 syndrome. The available data of those cases is presented as a table in the article.We present a description of a 40-year-old woman with MEN2A syndrome (mutation of the RET proto-oncogene p.Cys634Tyr), with a history of twice-performed surgical treatment of MTC, with daily crises of arterial hypertension accompanied by vegetative symptoms, with a giant bilateral PHEO (up to 200 m on the right and up to 150 mm on the left) with synchronous large metastasis (up to 50 mm) into the pubic bone with the destruction. The patient underwent several surgeries: bilateral adrenalectomy, then a bilateral revision of the neck, removal of the right upper and right lower parathyroid glands, residual thyroid tissue, then resection of the right pubic bone with a tumor.

Insulinoma is a neuroendocrine tumor, the main manifestation of which is hypoglycemia. However, the symptoms of hypoglycemia can be non-specific for a long time, especially outside provocative conditions, and quite often the tumor manifests from a life-threatening condition - hypoglycemic coma. In this regard, timely laboratory diagnosis of insulinoma and determination of its aggressive course is one of the priorities in modern researches.

Cowden disease (Cowden syndrome) refers to PTEN-associated hamartoma tumor syndromes. It arises due to a mutation in the phosphatase and tensin homolog gene, one of the main functions of which is cell cycle regulation. The presence of a mutation in the gene leads to uncontrolled cell growth, and patients have a lifelong increased risk of neoplasms of various degrees of malignancy. This article presents a clinical case of Cowden syndrome with an early debut at the age of 7 years. The combination of macrocephaly (SDS of head circumference >2) with various skin manifestations (facial trichilemmomas, acral keratosis, papillomatous papules) and the presence of benign and/or malignant neoplasms are pathognomonic for Cowden syndrome. Of the malignancies, breast and thyroid cancer, colorectal cancer, renal cell carcinoma, and endometrial cancer are the most common. Thyroid carcinoma has been shown to have an earlier age of manifestation and often occurs already in childhood. This determines the need to screen patients with a proven mutation in the PTEN gene for nodal neoplasms from an early age. If surgical treatment is necessary, thyroidectomy remains preferable due to the frequent recurrence of nodules, as well as the uncertain potential for malignancy due to the low study of thyroid nodules in patients with mutations in the PTEN gene.

Metastatic lesion of pituitary is a rare condition and is diagnosed in 1.8-4% of cases. Monitoring and treatment of such patients is a complex task and requires increased attention from a multidisciplinary team of specialists. The authors represent three patients with metastatic pituitary lesion who underwent neurosurgical treatment at the National Research Center of the National Research Institute of Endocrinology with subsequent pathomorphological confirmation of the diagnosis. The primary tumors were breast cancer, lung carcinoid, and clear cell kidney cancer. Two patients had distant metastases other than the pituitary gland. The clinical manifestation consisted in the appearance of symptoms of panhypopituitarism, chiasmal syndrome and mass effect in all cases. The follow-up period after surgical treatment was 0.25-2.5 years. Progression of the underlying disease was noted in two patients. One of them carried out stereotactic radiosurgical treatment and stereotactic oriented irradiation. One patient has a stable condition.

Pituitary carcinoma (metastatic neuroendocrine tumor of the pituitary gland) is the pituitary tumor with confirmed craniospinal and/or systemic metastases. These tumors are extremely rare accounting for only 0.1% to 0.5% of all pituitary tumours and are characterized by high mortality. In the presented case, pituitary carcinoma with intracranial metastasis was diagnosed in a young patient 25 years after manifestation of an aggressive recurrent prolactin-secreting pituitary tumor. Standard therapy (removal of metastasis, radiation therapy, cabergoline therapy) resulted in a long-term remission of the disease.

The aim of this review is to summarize the data available in the literature on the causes of headache in patients with acromegaly, as well as on the effect of various methods of acromegaly treatment on headache. Publications were searched in the PubMed database using the keywords «Headache in patients with acromegaly», «Headache in patients with pituitary adenomas», «Tension-type headache», «Migraine». Headache in patients with pituitary adenomas secreting somatotropic hormone (STH) is not uncommon: according to various authors, cephalgic syndrome occurs in 30-70% of patients with acromegaly and can worsen their quality of life, along with other factors, up to disability. By the nature of development, headache with acromegaly is classified into primary (migraine, tension headache, trigeminal autonomic cephalgia, for example, SUNCT syndrome and cluster headaches), and can also be caused by various causes directly related to the tumor. All this requires differential diagnosis. The factors causing headaches in somatotropinomas have not yet been well studied and require further research. These include the mass effect of the tumor, hormonal hypersecretion, pathology of the temporomandibular joint, sodium and fluid retention in the body, psychological factors, etc. The authors evaluated the effect on headache of various methods of acromegaly treatment: transnasal transsphenoidal adenomectomy, radiation therapy and drug therapy with somatostatin analogues, dopamine agonists and growth hormone receptor antagonist. However, even when normal levels of STH and insulin-like growth factor 1 (IGF-1) are reached, cephalgic syndrome may persist, therefore patients should be warned about this in advance and referred to a cephalgologist to select adequate headache therapy.

According to numerous studies, the most common pituitary tumors are prolactinomas, reaching 60% of all clinically significant adenomas, the next in order are non-functional pituitary adenomas, somatotropinomas, corticotropinomas and thyrotropinomas. Plurigormonal tumors occur in less than 1% of all pituitary adenomas. The most common form of mixed secretion adenoma in this patient population, derived from the Pit-1 cell line, produces various combinations of hormones: growth hormone (GH), prolactin (PRL), thyroid-stimulating hormone (TSH). This article presents a patient with a plurihormonal two-component pituitary macroadenoma with a rare and exceptional combination of secreted hormones - GH / adrenocorticotropic hormone (ACTH) / TSH / follicle-stimulating hormone (FSH) / luteinizing hormone (LH) with minimal nonspecific clinical manifestations such as diabetes mellitus and poorly controlled arterial hypertension.

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.

The progressive improvement of the classification using modern analytical methods is an essential tool for the development of precise and personalized approaches to the treatment of pituitary adenomas. In recent years, endocrinologists have witnessed evolutionary changes that have occurred in the histopathological identification of pituitary neoplasms, revealing new possibilities for studying tumorigenesis and predicting biological behavior.The paper considers the historical aspects of the gradual improvement of the classification of pituitary adenomas, as well as the new international 2022 WHO classification, according to which pituitary adenomas are included in the list of neuroendocrine tumors (PitNETs) to reflect the biological aggressiveness of some non-metastatic pituitary adenomas. The characteristics of pituitary adenoma are presented, as well as a list of histological subtypes of aggressive neuroendocrine tumors of the pituitary gland, marked by the main potentials for invasive growth, an increased risk of recurrence and a negative clinical prognosis.The expediency of changing the definition of «pituitary adenoma» to «neuroendocrine tumor» is discussed. It is emphasized that the introduction of a unified clinical, laboratory and morphological protocol into national clinical practice will help provide comparable comparative studies on the prognosis of the disease and the effectiveness of secondary therapy and also contribute to adequate management of potentially aggressive PitNETs.

In recent years, a large number of studies have been carried out to research molecular genetic abnormalities in ACTH--secreting pituitary tumors. This review presents a comprehensive analysis of exome studies results (germline and somatic mutations, chromosomal abnormalities in corticotropinomas which developed as part of hereditary syndromes MEN 1, 2, 4, DICER1, Carney complex etc., and isolated tumors, respectively) and transcriptome (specific genes expression profiles in hormonally active and inactive corticotropinomas, regulation of cell cycles and signal pathways). Modern technologies (next-generation sequencing - NGS) allow us to study the state of the microRNAome, DNA methylome and inactive chromatin sites, in particular using RNA sequencing. Thus, a wide range of fundamental studies is shown, the results of which allow us to identify and comprehend the key previously known and new pathogenesis mechanisms and biomarkers of corticotropinomas. The characteristics of the most promising molecular genetic factors that can be used in clinical practice for screening and earlier diagnosis of hereditary syndromes and isolated corticotropinomas, differential diagnosis of various forms of endogenous hypercorticism, sensitivity to existing and potential therapies and personalized outcome determination of Cushing`s disease.