[Ectopic acromegaly due to bronchial neuroendocrine tumors: the first description in Russia of three clinical cases].

 Acromegaly is a neuroendocrine disorder caused by excessive production of growth hormone (GH). In the majority of cases the cause of acromegaly is a pituitary tumor producing GH. Cases of ectopic acromegaly are much rarer. Ectopic acromegaly occurs in cases of tumors which produce growth hormone-releasing hormone (GHRH) or extrapituitary tumors which produce GH. The main sources of excessive GHRH production are neuroendocrine tumors (NETs) of the lung or pancreas. Treatment of ectopic acromegaly consists of surgical removal of the source of GHRH hyperproduction and in cases where surgery is not an option, somatostatin analogues, pegvisomant, chemotherapy, immunotherapy or radiation therapy are used.In this article three cases of ectopic acromegaly due to GHRH-producing lung NETs are presented, each of them being notable for a number of features. In the first two cases, clinical symptoms were mild, besides in the second case ectopic acromegaly was accompanied by primary hyperparathyroidism. In the third case ectopic acromegaly was accompanied by pituitary macroadenoma, and after surgical removal of the lung NET remission of acromegaly was not achieved. In all three cases, lung NETs were detected incidentally on radiologic chest screening for other conditions.

[Diagnostic value of bilateral inferior petrosal sinus sampling in various modifications and methods of radiation and radionuclide imaging in the diagnosis and differential diagnosis of ACTH-dependent endogenous 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.

[Cyclic Cushing's syndrome: difficulties of diagnostic search and choice of treatment tactics. A clinical case].

Cyclic Cushing's syndrome is a pathological condition characterized by alternating periods of excessive cortisol secretion with corresponding clinical manifestations and periods of spontaneous remission of the disease.To diagnose Cyclic Cushing's syndrome it is necessary to record at least three episodes of excessive cortisol secretion alternating with periods of normalization of its production.In most cases, this pathology is diagnosed in patients with ACTH-secreting pituitary tumor, however, there are rare cases of cyclic hypercorticism with ectopic ACTH secretion by tumors of different localization and without verification of pathological hormonal secretion focus. In addition, cyclic hyperproduction of cortisol can be also observed in ACTH-independent Cushing's syndrome associated with the presence of corticosteroma or adrenal hyperplasia. The exact causes and mechanisms of the cyclic hypercorticism are currently insufficiently studied.Due to the atypical course of the disease, the unpredictability of the occurrence of a new «cycle¼, the variability of its duration and manifestations (not only in different patients, but also in the same patient), verification of the diagnosis and determination of treatment tactics may be difficult in the daily practice of specialists, and the prevalence of this condition can be undervalued.

[Thyrotropin-secreting pituitary adenomas: clinical features and results of treatment in 45 patients].

BACKGROUND: Thyrotropin-secreting pituitary adenomas (TSH-PA) are a rare cause of thyrotoxicosis and account for 0.5-2% of all pituitary adenomas. Taking into account the rarity of the disease, it is extremely important to analyze each case of TSH-PA. AIM: To analyze the clinical characteristics and treatment outcomes of patients with TSH-PA, as well as to determine preoperative and early postoperative factors that predict long-term remission. MATERIALS AND METHODS: In a single-center retrospective study we analyzed clinical signs, laboratory and instrumental studies, as well as the treatment outcomes of patients with TSH-PA from 2010 to 2023. Preoperative factors, as well as TSH level measured on day 3 postoperatively, were evaluated for their ability to predict long-term remission when comparing groups of patients with and without remission. RESULTS: The study included 45 patients with TSH-PA (14 men, 31 women), with a median age of 45 years [30; 57]. The most common clinical manifestations of TSH-PA were: cardiac arrhythmia in 37 (82.2%) patients, thyroid pathology in 27 (60%), neurological disorders in 24 (53.35%). Most PAs were macroadenomas (n=35, 77.8%). Preoperatively, 28 (77.8%) patients received somatostatin analogs, and 20 (71.4%) patients were euthyroid at the time of surgery. Surgical treatment was performed in 36 (80%) patients, postoperative remission was achieved in 31 cases (86.1%). Administration of somatostatin analogues to patients with no remission/relapse after surgery lead to the remission in 100% of cases (4/4). A 1 mm increase in PA size raised the odds of recurrence/no remission by 1.15-fold,and PA invasion during surgery - by  5.129 fold. A TSH level on day 3 postoperatively above 0.391 mIU/L (AUC, 0.952; 95% CI 0.873-1.000; standard error 0.04; p<0.001) identifies patients with relapse/absence of remission after surgical treatment (sensitivity = 100%, specificity = 88.9%). CONCLUSION: The TSH-PA in the structure of PAs is extremely rare, and as a result, most of them are misdiagnosed and detected already at the stage of macroadenoma. The most effective method of treatment is transnasal transsphenoidal adenomectomy. Somatostatin analogues can be used as second-line therapy if surgical treatment is ineffective. We have proposed a possible model for postoperative TSH levels (>0.391 mU/l) to predict recurrence of TSH-PA, which requires validation on an expanded number of cases.

[Molecular genetic abnormalities in ACTH-secreting pituitary tumors (corticotropinomas): fundamental research and prospects for use in clinical practice].

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.

[Unification of pathomorphological examination of patients with neuroendocrine tumors of the pituitary gland. Controversial issues of the new classification].

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 adenoma¼ to «neuroendocrine tumor¼ 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.

[A clinical Case and brief literature review of Icenko-Cushing's Disease in a pediatric patient with atypical onset of the disease].

Itsenko-Cushing's disease is a rare, multisystem disease characterized by the presence of endogenous central hypercortisolism due to an ACTH-secreting brain tumor. The frequency of Itsenko-Cushing's disease in adulthood is 0.7-2.4 per 1 million population, and only 10% of all cases occur in childhood. The age of onset of the disease in children is on average 12.0-14.8 years. A typical manifestation of the disease in children, along with obesity and arterial hypertension, is a decrease in growth rates. The gold standard for diagnosing central hypercortisolism is MRI of the brain, however, the effectiveness of this method in children is only 50%. The main method of treatment is neurosurgical transnasal transsphenoidal removal of endosellar pituitary adenoma, which makes it possible to achieve remission in more than 65% of cases. This article describes a clinical case of Itsenko-Cushing's disease in a 6.5-year-old child with obesity, arterial hypertension, atypically «high¼ stature, average velocity and non-visualizable corticotropinoma. The article presents the stages of diagnostic search, the complexity of differential diagnosis and surgical treatment, the results of follow-up after the treatment and a brief review of the literature.

[Short-term and long-term remission after endoscopic transnasal adenomectomy in patients with acromegaly].

BACKGROUND: Neurosurgery is the most effective treatment for acromegaly. As most of the patients present with macroadenomas, surgical treatment is not always successful, even with the expert level of a neurosurgeon. Assessment of the postoperative remission rates in acromegaly preoperative predictors of treatment efficacy is an urgent task of modern research. AIM: To assess the short-term and long-term remission of acromegaly after endoscopic transnasal adenomectomy in a tertiary medical center and assess preoperative predictors of the treatment effectiveness. MATERIALS AND METHODS: A single-center, prospective, uncontrolled study was conducted. We included patients with active acromegaly who did not receive medical therapy with somatostatin analogues and were referred for endoscopic transsphenoidal adenomectomy. Plasma miRNA expression was assessed by quantitative reverse transcription PCR. Postoperative samples of adenomas were sent for study, with the determination of the immunohistochemical staining for somatostatin receptors 2 and 5 subtypes and morphology was performed on postoperative adenoma samples. RESULTS: The study included 44 patients: 32.8% men, median age 47.0 [34.0; 55.0], IGF-1 744.75 ng/ml [548.83;889.85], growth hormone 9.5 ng/ml [4.94; 17.07]. Tumor volume 832 mm3 [419.25; 2532.38]. Early postoperative remission was achieved in 35 patients (79.5%). Patients who achieved short-term remission had higher IGF-1 and basal growth hormone levels. Median follow-up was 19.0 months [12.5;29.0]. Long-term remission was achieved in 61.4% (27 patients), no remission in 9 (20.5%), recurrency in 2 patients (4.5%), 6 patients were to follow-up (13.6%). In patients with long-term remission, we observed lower growth hormone and IGF-1 levels. No differences in miRNA expression was observesd. The predictive value of basal GH before surgery for long-term remission was assessed: area under the curve 0.811 (95% CI: 0.649; 0.973). A cut-off value of 15.55 ng/mL corresponded to a sensitivity of 70.0% (34.8%; 93.3%), a specificity of 85.7% (67.3%; 96.0%), an accuracy of 81.6% (65 .7%; 92.3%), PPV 63.6% (39.3%; 82.5%), NPV 88.9% (75.4%; 95.4%). CONCLUSION: Rates of short-term and long-term remission after endoscopic transsphenoidal adenomectomy in our cohort is 79,5% и 61,4%, respectively, and is comparable with literature data for expert pituitary centers. Preoperative GH shows potential value in predicting the long-term remission of acromegaly, but further studies in a larger sample are needed to obtain more accurate cut-off values.

[Algorithm for morphological diagnosis of neoplasms in the chiasmal-sellar region]. / Algoritm morfologicheskoi diagnostiki novoobrazovanii khiazmal'no-sellyarnoi oblasti.

In the Turkish saddle area, there is a wide variety of pathological processes, the vast majority of which present as tumors of various origins (up to 90%). For a clear morphological verification of the diagnosis, it is proposed to use a diagnostic algorithm that includes the stages of differential diagnosis of normal adenohypophysis and neurohypophysis with tumors in the anterior and posterior lobes of the pituitary gland, non-pituitary origin neoplasms, as well as with non-tumor pathological processes (inflammation, cystic masses, and hyperplasia). For morphological diagnosis, histochemical and immunohistochemical methods are recommended using various staining techniques (silver impregnation, periodic acid Schiff reaction) of tissue specimens and antibody panels (pituitary hormones, low-molecular cytokeratins, pituitary transcription factors, neuroendocrine markers, etc.).

[Morphological characteristics of pituitary adenomas in the phenocopy of multiple endocrine neoplasia type 1].

BACKGROUND: Multiple endocrine neoplasia type 1 (MEN 1) is a rare autosomal dominant disorder caused by mutations in the MEN1 gene, which encodes the menin protein. If a patient has the MEN 1 phenotype in the absence of mutations in the MEN1 gene, the condition is classified as a phenocopy of this syndrome. Although significant progress has been made in understanding the function of menin, its role in the oncogenesis of the endocrine glands is still being elucidated. Due to its key role in physiological and pathological processes, the assessment of the menin expression can provide valuable information. AIM: to determine whether there are any differences in the expression of menin in the pituitary adenomas (PA) in patients with phenocopy of MEN 1 (phMEN 1) and genetically confirmed MEN 1 (gMEN 1) compared with their sporadic forms. MATERIALS AND METHODS: immunohistochemical assessment of the menin expression was carried out in PA of patients with gMEN 1, phMEN 1 and sporadic acromegaly (SA), surgically treated in 2008-2020. IHC was performed using antibodies to menin, PRL, GH, ACTH, FSH, TSH, Pit-1, T-box, ERA on previously prepared histological section. RESULTS: The study included 35 samples of PA: gMEN 1 - 9 samples, phMEN 1 - 12 (somatotropinomas + PHPT); CA - 14  samples. The patients were comparable by gender, adenoma size, and drug intake. The gMEN  1 group differed from phMEN 1 and SA by age (p = 0.0005). In patients with gMEN 1, the expression of menin varied from no staining (5/9) to intense cytoplasm staining. Cytoplasmic expression of menin was mainly present (11/12) in the phMEN 1. In the SA group, there was no staining in 1 case; nuclear expression was detected in 6/14 cases. The phMEN  1 group showed significantly higher cytoplasmic expression of menin than the gMEN  1 group (p = 0.006). The gMEN 1 group also differed from the SA group (p = 0.012). There were no statistically significant differences between the phMEN 1 and SA groups (p = 0.049). CONCLUSION: It was revealed that the menin expression, in general, is retained in phMEN 1 and SA groups, although with different localization in the cell structure (nucleus and / or cytoplasm). At the same time, the expression of menin varies greatly in patients with gMEN 1. According to the data obtained, it can be assumed that the pathogenesis of PA in phMEN 1 and SA may have similarities; however, there could be factors contributing to the appearance of several tumors of the endocrine glands in one person with phMEN 1. To understand this process, it is necessary to further study the genes associated with MEN 1, epigenetic factors, signaling pathways in which menin is involved.

[Differences in plasma miRNA levels in inferior petrosal sinus samples of patients with ACTH-dependent Cushing's syndrome].

BACKGROUND: For the last decades microRNAs (miR) have proven themselves as novel biomarkers for various types of diseases. Identification of specific circulating microRNA panel that differ patient with Cushing's disease (CD) and ectopic ACTH syndrome (EAS) could improve the diagnostic procedure. AIM: to evaluate the differences in miR levels in plasma samples drained from inferior petrosal sinuses in patients with CD and EAS. MATERIALS AND METHODS: single-center, case-control study: we enrolled 24 patients with ACTH-dependent Cushing's syndrome (CS) requiring bilateral inferior petrosal sinus sampling (BIPSS).  Among them 12 subjects were confirmed as CD (males=2, females=10; median age 46,5 [IR 33,8;53,5]) and 12 as EAS (males=4, females=8, median age 54 [IR 38,75;60,75]). BIPSS was performed through a percutaneous bilateral approach. Once catheters were properly placed, blood samples were withdrawn simultaneously from each petrosal sinus and a peripheral vein. Plasma samples from both sinuses were centrifuged and then stored at -80 C. MiRNA isolation from plasma was carried out by an miRneasy Plasma/Serum Kit (Qiagen, Germany) on the automatic QIAcube station according to the manufacturer protocol. To prevent degradation, we added 1 unit of RiboLock Rnase Inhibitor (Thermo Fisher Scientific, USA) per 1 µL of RNA solution. The concentration of total RNA in the aqueous solution was evaluated on a NanoVue Plus spectrophotometer (GE Healthcare, USA). The libraries were prepared by the QIAseq miRNA Library Kit following the manufacturer standard protocols. MiR expression was then analyzed by sequencing on Illumina NextSeq 500 (Illumina, USA). RESULTS: 108 miRNAs were differently expressed (p <0,05) in inferior petrosal sinus samples of patients with CD vs EAS. We divided these miRNAs into 3 groups based on the significance of the results. The first group consisted of samples with the highest levels of detected miR in both groups. Four miRNAs were included: miR-1203 was downregulated in CD vs EAS - 36.74 (p=0,013), and three other were upregulated in CD vs EAS: miR-383-3p 46.36 (p=0,01), miR-4290 6.84 (p=0,036), miR-6717-5p 4.49 (p=0,031). This miRs will be validated in larger cohorts using RT-qPCR. CONCLUSION: Plasma miR levels differ in inferior petrosal samples taken from patients with CD vs EAS. These miRs need to be validated by different methods and in peripheral plasma samples in order to be used as potentially non-invasive biomarkers to differentiate ACTH-dependent CS.

A standardised diagnostic approach to pituitary neuroendocrine tumours (PitNETs): a European Pituitary Pathology Group (EPPG) proposal.

The 2017 World Health Organization (WHO) classification proposes to type and subtype primary adenohypophyseal tumours according to their cell lineages with the aim to establish more uniform tumour groups. The definition of atypical adenoma was removed in favour of high-risk adenoma, and the assessment of proliferative activity and invasion was recommended to diagnose aggressive tumours. Recently, the International Pituitary Pathology Club proposed to replace adenoma with the term of pituitary neuroendocrine tumour (PitNET) to better reflect the similarities between adenohypophyseal and neuroendocrine tumours of other organs. The European Pituitary Pathology Group (EPPG) endorses this terminology and develops practical recommendations for standardised reports of PitNETs that are addressed to histo- and neuropathologists. This brief report presents the results of EPPG's consensus for the reporting of PitNETs and proposes a diagnostic algorithm.

[An ovarian hyperstimulation syndrome caused by gonadotropinoma in a young woman].

From 14 to 54% of all pituitary adenomas are nonfunctioning pituitary adenomas (NPAs), their prevalence is estimated as 7.041.3 cases per 100 000 population. The most common type of NPAs (73% of cases) are gonadotropinomas. In most cases, gonadotropinoma is characterized by secretion of biologically inactive hormones, so the release of gonadotropins does not lead to the development of any clinical symptoms. For this reason the diagnosis of gonadotropinomas is most often performed on the basis of immunohistochemical analysis. However, in rare cases, gonadotropinomas secrete biologically active hormones, most often follicle-stimulating (FSH). Ovarian hyperstimulation syndrome due to gonadotropin-secreting pituitary tumors occurs in about 3% of women with hormonally inactive pituitary adenomas at reproductive age and in 8% of patients with verified gonadotropinomas. This clinical case describes a young patient with a rare pathology: FSH/LH-secreting macroadenoma of the pituitary, which led to the development of ovary hyperstymulation symdrome. The diagnosis of pituitary adenoma was performed due to the identified hyperprolactinemia one month before the development of visual impairment, which can be considered a late diagnosis. Surgical treatment of gonadotropinomy was carried out successfully and without complications, remission of the disease was achieved, visual function was restored, the patient successfully became pregnant.

[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.

[Evaluation of the biological behavior of ACTH-secreting pituitary tumors using various methods].

This literature review is aimed at studying markers obtained by various research methods to assess the biological behavior of ACTH-secreting pituitary tumors. This paper presents the clinical, laboratory, instrumental. histological, and immunohistochemical aspects of ACTH-secreting pituitary tumors. Histological method allows assessing the structures of a tumor and differential diagnosis of other pathological process in the sella turcica. Immunohistochemical method enables determining the expression of multiple markers (fibroblast growth factors, matrix metalloproteinases, apoptotic factors, pituitary tumor transforming gene, and vascular markers), which reflect various processes of oncogenesis of studied tumors, and according to the authors, are promising with regard to predicting biological behavior using corticotropin. Epigenetic investigations including the study of micro-RNA expression, proteomics, and transcriptomics are the new methods in this area, which are expected to provide additional details regarding the prediction using corticotropin. Thus, the cumulative assessment using laboratory and instrumental methods, the study of immunoexpression of malignant potential markers in the tissue using corticotropin and micro-RNA allow predicting the future biological behavior of ACTH-secreting pituitary tumors.

[Histological and immunohistochemical characteristics of ACTH-secreting tumors].

The histological and immunohistochemical characteristics of pituitary (corticotropinomas) and nonpituitary adrenocorticotropic hormone (ACTH)-secreting neuroendocrine tumors (NET) were comparatively analyzed. The study included 46 corticotropinomas and 37 ectopic ACTH-secreting tumors. Removed NET tissue was investigated using routine histological and immunohistochemical techniques. A study of the morphofunctional characteristics of removed NETs yielded the following data: their ability to express ACTH, growth hormone, luteinizing hormone, follicle-stimulating hormone, and prolactin in both in pituitary and nonpituitary NET tumors. Angiogenic markers (CD31 and VEGF) were found in equal frequency. The histological structure of all corticotropinomas suggested their benign origin while nonpituitary NETs had different morphological structures, malignancy and invasiveness grades, and metastatic properties. The highest cell proliferation potential (Ki-67) was discovered in NET in ectopic ACTH syndrome as compared to corticotropinomas.

Comparative Analysis of Clinical, Hormonal and Morphological Studies in Patients with Neuroendocrine ACTH-Producing Tumours.

This paper highlights the problem of neuroendocrine tumours (NETs) with clinical symptoms of hypercorticism caused by hypersecretion of adrenocorticotropic hormone (ACTH) by tumour cells. In most cases (85%), the tumours were localized in the pituitary gland (Cushing's disease); 15% of the patients had an extrapituitary tumour that manifest as an ectopic ACTH secretion (EAS). Comparative analysis of clinical, hormonal, histological, and immunohistochemical characteristics of pituitary and extrapituitary ACTH-secreting NET was performed. It included 46 patients with CD and 38 ones exhibiting ectopic ACTH secretion (EAS). Results of the study suggest differences between CD and EAS in terms of the severity of clinical manifestations and duration of the disease. Hormonal studies showed that EAS unlike CD was associated with high plasma ACTH and cortisol levels, late-evening salivary cortisol and daily urinary free cortisol, the absence of a 60% or greater reduction of cortisol in the HDDST test, and the presence of a low (less than 2) ACTH gradient in response to desmopressin administration with catheterization of cavernous sinuses. The study of morphofunctional characteristics of the removed NET demonstrated the ability of both pituitary and extrapituitary NETs to express ACTH as well as GH, PRL, LH, and FSH. The angiogenic markers (CD31 and VEGF) were detected with equal frequency regardless of the NET localization. The histological structure of all corticotropinomas suggested their benign origin, but extrapituitary NETs were represented by different morphological types with varying malignancy, invasiveness, and metastatic properties. A higher cell proliferation potential (Ki-67) was documented for NET in patients presenting with an ectopic ACTH secretion compared to those having corticotropinomas.

[Recurring secondary hyperparathyroidism: case report].

The authors report a rare case of persistently recurring secondary hyperparathyroidism concomitant with chronic renal insufficiency. The patient underwent multiple surgical interventions (parathyroidectomy, implantation of parathyroid autograft into a forearm muscle, removal of hyperplastic autograft tissue). Results of clinical, laboratory, instrumental, and morphological studies are presented. Possible causes of relapses and problems of morphological diagnosis are discussed.