[Clinical and laboratory characteristics and results of treatment of patients with ACTH-producing neuroendocrine tumors of various localization].

AIM: To study the clinical, biochemical characteristics, treatment results and follow-up of patients with ectopic ACTH syndrome EAS (ACTH adrenocorticotropic hormone ). MATERIALS AND METHODS: A retrospective, observational, single-center study of 130 patients with EAS. Demographic information of patients, medical history, results of laboratory and instrumental investigations at the pre- and postoperative stages and follow-up of EAS were analyzed. RESULTS: The mean age at the diagnosis ranged from 12 to 74 years (Me 40 years [28; 54]). The duration of the disease from the onset of symptoms to the verification of the diagnosis varied from 2 to 168 months (Me 17.5 months [7; 46]). Eighty-one (62,3%) patients had bronchopulmonary NET, 9 thymic carcinoid, 7 pancreatic NET, 5 pheochromocytoma, 1 cecum NET, 1 appendix carcinoid tumor, 1 medullary thyroid cancer and 25 (19.2%) had an occult source of ACTH. The median follow-up period of patients was 27 months [9.75; 61.0] with a maximum follow-up of 372 months. Currently, primary tumor was removed in 82 (63.1%) patients, bilateral adrenalectomy was performed in 23 (18%) patients, in 16 of them there was an occult source of ACTH-producing NET and in 7 patients in order to control hypercortisolism after non-successful surgical treatment. Regional and distant metastases were revealed in 25 (19.2%) patients. At the time of the last observation 59 (72%) patients were exhibited a full recovery, 12 (14.6%) had relapse of the disease and 26 (20%) died from multiple organ failure (n=18), pulmonary embolism (n=4), surgical complications (n=2), disseminated intravascular coagulation syndrome (n=1) or COVID-19 (n=1). CONCLUSION: In our cohort of patients bronchopulmonary NET are the most frequent cause of EAS (62.3%). Surgical treatment leads to remission of hypercortisolism in 72% cases; the proportion of relapse (14.6%) and fatal outcome (20%) remains frequent in EAS.

[Expression of plasma microRNA in patients with acromegaly].

BACKGROUND: microRNA is a class of small non-coding RNA molecules involved in posttranscriptional regulation of gene expression. MicroRNAs are detectable in blood in stable concentrations, which makes them promising biomarkers for various diseases. AIM: to assess plasma microRNA expression in patients with active acromegaly compared with healthy controls. MATERIAL AND METHODS: single-center, case-control study: assessment of plasma microRNA in patients with acromegaly compared with healthy controls. Fasting blood samples were drawn and centrifuged at +5С temperature and 3000 rpm for 20 minutes, then aliquoted and frozen at 80C until further analysis. MicroRNA extraction and library preparation was done according to manufacturers instructions. Expression analysis was performed on NextSeq sequencer. Bioinformatic analysis using atropos (adapted deletion), STAR (aligning), FastQC (quality control), seqbuster/seqcluster/miRge2 (microRNA annotation, isomiR and new microRNA search, expression analysis). Primary endpoint of the study differential expression of plasma microRNA in patients with acromegaly compared with healthy controls. RESULTS: we included 12 patients with acromegaly age 33.1 [20; 47], BMI 29.3 kg/m2 [24.0; 39.6], IGF-1 686.1 ng/mL [405.9; 1186.0] and 12 healthy subjects age 36.2 [26; 44], BMI 26.7 kg/m2 [19.5; 42.5], IGF-1 210.4 ng/mL [89.76; 281.90]; gender ratio for both groups 4 males, 8 females. The groups did not differ in gender (p=0.666), age (p=0.551) and BMI (p=0.378). We found decreased expression of four microRNAs in patients with acromegaly: miR-4446-3p 1.317 (p=0.001), miR-215-5p 3.040 (p=0.005), miR-342-5p 1.875 (p=0.013) and miR-191-5p 0.549 (p=0.039). However, none of these changes were statistically significant after adjustment for multiple comparisons (q 0.1). CONCLUSION: we found four microRNAs, which could potentially be downregulated in plasma of patients with acromegaly. The result need to be validated using different measurement method with larger sample size.

[Role of microRNA in oncogenesis of pituitary tumors and their practical significance]. / Rol' mikroRNK v onkogeneze opukholei gipofiza i ikh prakticheskaia znachimost'.

Microribonucleic acids (miRNAs) are a class of noncoding RNAs that regulate posttranscriptional gene expression. These molecules are regulators of cell proliferation, metabolism, apoptosis, and differentiation. MiRNAs are not degraded by RNAases and their concentrations can be measured in different body fluids, including serum. The expression of miRNAs varies in intact tissues and tumors, including pituitary adenomas. Pituitary tumors are encountered in 22.5% of the population and, in a number of cases, may be asymptomatic, but in case of invasion or/and hormone overproduction, their clinical presentation is severe with multiple symptoms leading to disability and even death. The mechanisms for the development and progression of pituitary tumors and the markers for remission and recurrence have not been adequately investigated. This literature review discusses the biological significance of miRNAs in pituitary tumors and the potential value of circulating miRNAs as biomarkers.