[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.

[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.

[Primary hyperaldosteronism: difficulties in diagnosis].

Primary hyperaldosteronism (PA) - is the clinical syndrome, results from autonomous of the major regulators of secretion, aldosterone overproduction by a tumorous or hyperplastic tissue in adrenal cortex. Being the most frequent cause of secondary hypertension, PA may be represented by disorders with unilateral or bilateral aldosterone overproduction and differential diagnosis between them is crucial for choosing a right therapeutic approache: lifelong medical therapy with mineralocorticoid receptor antagonists or unilateral adrenalectomy. Adrenal venous sampling (AVS) is currently the «gold standard¼ test for identifying laterality of excess hormone production, unlike imaging tests, sensitivity and specificity of which is not enough, due to inability to evaluate functional activity with confidence, and also to limitations in detecting tiny abnormalities of adrenals, such as microadenoma or hyperplasia. Excluding certain cases, AVS is recommended to patients with confirmed PA, planning surgical treatment, to determine the lateralization of aldosterone hypersecretion. Described clinical case of patient with confirmed lateralization from adrenal without any detected lesions on CT-imaging and nonfunctioning tumour on contralateral side, highlights the importance of using AVS for decision to refer patients for surgery.

[Hybrid vascular interventions on the peripheral arteries in the treatment of critical ischemia in elderly patients.]

Peripheral arterial disease has a huge contribution to the overall mortality rate of the population, especially in the group of patients of old and old age. The likelihood of an adverse outcome is increased against a background with other possible nosological forms. In particular, the combination of peripheral atherosclerosis with diabetes mellitus very often manifests itself in the form of a multilevel lesion of the lower limb arteries. The treatment of such patients is very difficult, since the use of only open or endovascular approaches has its own contraindications and limitations, and cannot be used throughout the course of the lesion. The way out of this situation is the use of a hybrid approach, which consists in the combination of an open surgical reconstruction on the upper floors of the lesion and balloon angioplasty on the arteries of the lower leg. This approach allows you to use the advantages of both methods and achieve good results of treatment. The article presents the experience of treatment using a hybrid approach in elderly and senile patients with multilevel lesion of the lower limb arteries on the background of diabetes mellitus.

[Embolization of prostate arteries - an alternative technology for treatmetment of prostatic adenoma in patients with diabetes mellitus.]

The article details the examination plan and recommendations for the endovascular treatment of patients with prostate adenoma with concomitant diabetes mellitus. The results of the work of the Department of Andrology and Urology at the Endocrinological Research Center for prostate artery embolization are also displayed. A clinical case of care for a patient with prostate adenoma and severe diabetes mellitus is presented.

[X-ray guided endovascular occlusion of prostate arteries--alternative innovative method of treatment for patients with large prostatic adenomas].

The choice of method of surgical treatment of prostatic adenoma depends on the size of prostate, but often it can be limited to the patients with anesthesia risk or somatic risk. The article presents an alternative method of treatment of large prostatic adenomas--x-ray guided endovascular occlusion of prostate arteries, through which 38 patients were treated. Effectiveness of x-ray guided endovascular occlusion was evaluated in comparison to open prostatectomy (40 patients) and the administration of 5alpha-reductase inhibitor (43 patients). In the first two months after surgery, significant reduction in prostate volume and increased urinary flow rate was observed. Length of stay in the group of x-ray guided endovascular occlusion of prostate arteries was significantly less than in the group of open prostatectomy--2.3 days versus 19.7, respectively (P < 0.001). Variants of use of x-ray guided endovascular occlusion of prostate arteries in clinical practice are presented.

[Application of methods of angiosurgery for the treatment of venogenic erectile dysfunction].

The article presents the results of the use of alternative method of treatment--endovascular occlusion of the prostatic plexus--in patients with isolated venogenic erectile dysfunction. The IIEF-5 and AMS questionnaires were used for the evaluation of results of the operation. Improvement of quality of erection in the first 3 months after surgery was achieved in the majority of patients. The use of this innovative technology provides secure, minimally invasive and pathogenetically justified treatment of ED caused by abnormal venous drainage from the cavernous bodies.

[Atypical clinical course of Cushing's disease].

Endogenous hypercorticism is a severe endocrine disease with clinical symptoms resulting from long-term action of corticosteroids. In this country, conditions caused by the excess pituitary ACTH production are called Itsenko-Cushing disease. In the absence of adequate treatment, half of the patients die within 5 years after the onset of the disease. Correct diagnosis prior to the development of severe complications significantly improves its prognosis and patients' quality of life. It is generally believed that endogenous hypercorticosm must be accompanied by pathognomonic symptoms that may be helpful in establishing the diagnosis. However, certain patients present with non-specific symptoms of little diagnostic value. We report a case of Itsenko-Cushing disease lacking in specific symptoms of hypercorticism.

[The first experience with selective blood collection from the inferior petrosal sinuses in Russia (case reports)].

This paper reports two clinical cases of ACTH-dependent hypercorticism. Difficulties encountered in differential diagnosis of this condition were due to poor informative value of routine diagnostic methods. The use of selective blood collection from the inferior petrosal sinuses (for the first time in Russia) greatly facilitated the choice of the adequate treatment strategy. A detailed description of clinical features of ACTH-dependent hypercorticism in two young women is presented along with the results of laboratory and instrumental studies. Technical aspects of selective blood collection from the inferior petrosal sinuses in conjunction with the desmopressin stimulation protocol are considered. Indications for the use of this diagnostic method under real clinical conditions are proposed. Results of the study are discussed with reference to the treatment strategy chosen for the management of ACTH-dependent hypercorticism and the outcome of surgical intervention.

[Significance of the method of selective blood collection from the inferior petrosal sinuses for differential diagnosis of ACTH-dependent hypercorticism].

This review paper was designed to discuss the accumulated worldwide experience with selective collection of blood from the inferior petrose sinuses for the purpose of differential diagnostics of ACTH-dependent hypercorticism. The history of the development of the method is described, principal indications and contraindications to its clinical application are considered with reference to the informative value of this diagnostic tool. Possible causes of false positive and false negative results as well as complications ever reported as associated with the diagnostic procedure are discussed. Much attention is given to the comparative analysis of advantages and disadvantages of alternative techniques for blood collection and to the use of pharmaceutical agents that may increase efficiency of the method under consideration.

[Endovascular closure of defects of the interatrial septum and patent foramen ovale].

Endovascular occlusion of defects of the interatrial septum and patent foramen ovale has increasingly been gaining ground in surgical practice. This is predetermined by a shortened hospital stay of the patients and the lack of any cosmetic defects left, as compared with the conventionally performed surgical management. The present review analyses both Russian and foreign literature related to the problem concerned. Indications for and contraindication to this type of operative treatment are determined herein. Also described is the technique of implantation for the present-day types of occluders. A comparative assessment of efficacy and safety of various occlusion systems is given.