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

Clinical guidelines ‘Hyperprolactinemia’ (draft)

Hyperprolactinemia is a persistent excess of the blood serum prolactin. The syndrome contains various symptoms, the most characteristic is a violation of the reproductive system. There are multiple endogenous and exogenous causes of hyperprolactinemia. The main treatment method is dopamine agonist therapy, in case of prolactinoma existence, surgical and radiation methods can be applied. About 15% of patients are resistant to dopamine agonist therapy, which determines creation of individual management tactics. The article presents a draft of clinical guidelines for the diagnosis and treatment of hyperprolactinemia, which provides a modern examination algorithm, discusses the basic principles of diagnostics and treatment approaches

ACTH-producing neuroendocrine tumor of thymus with recurrences. Clinical case

One of the most difficult in diagnostic and treatment options for endogenous Cushing is the ectopic ACTH syndrome, which causes the development of tumors of different histogenesis localization producing adrenocorticotropic hormone (ACTH), and much less - corticotropin hormone (CRH). ACTH-secreting tumors varied in location, morphological structure and the degree of malignancy. Most of these tumors are characterized by an aggressive course with a propensity to metastasize and relapse. The article presents data of the prevalence, pathogenesis of ectopic ACTH tumors localized in the thymus, analyzis of clinical, morphological features, the methods of diagnosis and treatment. Based on the current literature, the world and our own experience on the diagnosis and treatment of patients with ectopic ACTH syndrome with localization of hormone production in the thymus, we want to highlight the current state of the problem in order to create the most efficient algorithm for diagnostic search and treatment of this difficult group of patients

Clinical and morphological characteristic of ACTH producing tumors of various localization and the ectopic Cushing’s syndrome

Background: Ectopic adrenocorticotropic hormone (ACTH)-dependent Cushing's syndrome is a type hypercorticism caused by ectopic production of ACTH and/or its precursors by neuroendocrine tumors (NET) of various localization, such as lung and thymus carcinoids, less frequently those of pancreas and gastrointestinal tract, medullary thyroid cancer, pheochromocytoma, small cell lung cancer, as well as some other tumor types. The wide spectrum of tumors associated with the ectopic ACTH syndrome (EAS) makes their diagnosis and treatment a complicated issue.Materials and methods: The study was done with surgical and diagnostic biopsy samples from 60 patients who had tumors with EAS, 36 (60%) of them being bronchopulmonary carcinoids, 10 (16.7%) thymus carcinoids, 5 (8.3%) pancreatic NETs, 3 (5%) medullary thyroid cancers, 3 (5%) NETs of unknown primary localization, and NET of appendix, cecum and pheochromocytoma (one case of each, i.e. 1.7%, 1.7%, 1.7%). There were 38 female and 22 male patients (1.72:1), with their mean age of 39 ± 14 years (range, 16 to 77 years). We analyzed their clinical data, as well as the results of morphological and immunohistochemical examination of the tumors.Results: According to the World Health Organization classification (2015), typical carcinoids (TC) of the lung were found in 77.8% (28/36) of the bronchopulmonary tumors. 22.2% (8/36) of the bronchopulmonary tumors and all thymus tumors (100%, n = 10) were classified as atypical carcinoids (ATC). Four pancreatic NETs were classified as Grade 2 (G2), 1 as G3, and NETs of the cecum and appendix as G1 and G2, respectively. At present, 29 (48%) patients are living with no relapse (mean age 39 ± 13.5 years), whereas 22 (37%) of patients developed a relapse (mean age 35 ± 13 years), and 15 (25%) of them died, regardless of the age of the patients The history of the disease was not traced in 4 cases. 5-year relapse-free survival of patients with TC of the lung was 85.7% (24/28), of those with ATC 25% (2/8), with ATC of the thymus and medullary thyroid cancer 0%. Mortality from to TC of the lung for the entire follow-up period was 3.6% (1/28), to ATC 12.5% (1/8), to ATC of the thymus and for medullary thyroid cancer 62.5% and 100%, respectively. The patients with NET of the cecum, appendix and pheochromocytoma are alive without progression for 4, 5 and 6 years, respectively. Therefore, the lowest 5-year survival of patients with EAS was observed in medullary thyroid cancer, pancreatic NET and thymus carcinoids: in 100% (3/3), 75% (3/4), and 57.1% (4/7), respectively.Conclusion: The most unfavorable prognostic factors in the EAS are the localization of tumors in the thymus, pancreas and thyroid gland. This indicates the necessity of a differentiated treatment approaches to patients with this syndrome

PROSPECTS AND PROBLEMS OF USING THE EFFECT OF SURFACE-ENHANCED RAMAN SCATTERING IN THE DIAGNOSIS OF VIRAL INFECTIONS

This review presents the latest advances in the use of surface-enhanced Raman scattering (SERS) immunoassay, which can be used to detect viral markers. As in the case of conventional immunoassays, these methods are often based on «sandwich-type» solid phase immunoassay. In recent years the necessary components of the immunochemical methods with SERS detection is SERS-active substrates to create a variety of approaches have been developed. Despite the difficulty of achieving high sensitivity and specificity in the analysis of clinical samples, a number of successful examples with promising results have been demonstrated

Difficulties in the Diagnosis of ACTH-ectopic Tumors. Case Report

At the present time topical diagnosis of ACTH-producing neuroendocrine tumors of different localization is the most challenging problem for endocrinologists around the world. Despite the significant improvement of existing diagnostic techniques, in 9-19% localization of the source of ectopic secretion ACTH re-mains undetected throughout life. Thus even regular using of routine laboratory tests and visual methods of diag- nosis do not allow to reveal the primary tumor. This article describes a case report, that is particular by a long period of ectopic ACTH syndrome detection. However, this demonstrates the importance of inten-sive and prolonged diagnosis of primary tumor, that can significantly reduce the morbidity and mortality of these patients and improve their prognosis

ACTH-Secreting Pheochromocytoma. Case report

Ectopic hormone-secreting pheochromocytomas are rare. Only case reports exist in the literature. Despite the large number of guides on diagnosis and treatment of pheochromocytoma, and Cushing syndrome, the extreme rarity of ectopic ACTH-syndrome caused by pheochromocytoma, and complexity of clinical cause numerous diagnostic errors leading to treatment failure. Therefore, we belive it appropriate to share our experience of this group of patients

ACTH-Secreting tumor of cecum. Case report

Ectopic hormonesecreting of cecum are rare. We report the case of a 52yearold woman with a typical clin ical picture of Cushing disease. Diagnostic tests confirmed ACTH dependent Cushing’s syndrome, which is caused by neuroendocrine tumor of the cecum. Due to the rarity of the disease, we believe it appropriate to share our experience of this group of patients

Khirurgicheskoe lechenie patsientov s bolezn'yu Itsenko-Kushinga

Болезнь Иценко-Кушинга является редким и тяжелым нейроэндокринным заболеванием, причиной которого, в большинстве случаев, является аденома гипофиза, развивающаяся из адренокортикотропных клеток. Это, в свою очередь, приводит к повышенной выработке адренокортикотропного гормона (АКТГ), с последующей активацией коры надпочечников и развитием гиперкортицизма с соответствующей клинической и лабораторной картиной [5, 8, 11]. Впервые заболевание было описано в 1912 г. американским нейрохирургом Г. Кушингом и впоследствии независимо от него в 1924 г. русским неврологом Н.М. Иценко. В настоящее время существует два патогенетических метода лечения БИК: хирургический (трансназальное или транскраниальное удаление опухоли) и лучевой (протонотерапия, «гамма-нож» и др.). По данным разных авторов [4, 9, 10] эффективность этих методов сопоставима друг с другом и достигает порядка 80-90%. Каждый метод имеет свои преимущества и недостатки, показания и противопоказания. Так, например, при наличии аденомы гипофиза отдается предпочтение хирургическому методу лечения, а при ее отсутствии лучевому [2, 3]. Современный уровень развития микрохирургической техники, в частности развитие эндоскопии, позволил в значительной степени повысить эффективность оперативного вмешательства, практически свести к нулю число серьезных осложнений и летальных исходов, а также минимизировать частоту развития таких осложнений, как несахарный диабет, пангипопитуитаризм, назальная ликворея и др