Prediction of the transsphenoidal endoscopic adenomectomy results in patients with cushing’s disease

Introduction. Transsphenoidal adenomectomy (TSA) is the method of choice in the treatment of Cushing’s disease (CD), but remission of hypercorticism cannot be achieved in all patients. The search for predictors of CD remission after TSA remains to be an important challenge in the endocrinology today.Aim. To study the preoperative and postoperative data of patients with CD to identify the predictors of hypercorticism remission after TSA.Materials and methods. 101 patients with confirmed CD after TSA were included. One year after operation all patients were examined for the presence of hypercorticism remission and divided into two groups: with CD remission and its absence. In both groups’ preoperative pituitary magnetic resonance imaging (MRI) data, the results of preoperative high dose dexamethasone suppression test (HDDST) and the results of serum cortisol collected in the morning 2–3 days after surgery were compared.Results. One year after TSA, CD remission was confirmed in 63 patients (62.4%), whereas in 38 patients (37.6%) hypercortisolism persisted. Favorable predictors of CD remission were: the adenoma size > 3 mm without the invasive growth according to pituitary MRI (specificity 82.4%, sensitivity 82.8%), serum cortisol suppression ≥ 74% in preoperative HDDST (specificity 81.5%, sensitivity 86.3%), morning serum cortisol level in 2–3 days after surgery ≤ 388 nmol/l (specificity 79.3%, sensitivity 97.4%).Conclusions. Pituitary MRI data, the results of preoperative HDDST and morning serum cortisol in the 2–3 days after surgery can be used as predictors of CD remission

КЛИНИКО-МОРФОЛОГИЧЕСКОЕ ИССЛЕДОВАНИЕ РОЛИ ФАКТОРА ТРАНСКРИПЦИИ NEUROD1 В РАЗЛИЧНЫХ ТИПАХ АДЕНОМ ГИПОФИЗА

The role of transcription factors in the pathogenesis of pituitary adenomas is extremely controversial.The aim of the study was to investigate the role of the transcription factor Neuro D1 in various types of pituitary adenomas.Materials and methods. A comparative clinico-morphological study was carried out with immunohistochemical analysis and confocal microscopy of the expression of the transcription factor NeuroD1, six adenohypophysis hormones and Ki-67 in 40 pituitary adenomas and 9 normal pituitary glands.Results. NeuroD1 was expressed in all cases and types of adenomas. The expression level of the transcription factor in adenomas was significantly different from that in the normal pituitary gland (p = 0.006). The average number of cells with expression of NeuroD1 in all tumors was higher than in the normal pituitary gland.Conclusion. NeuroD1 plays one of the key roles in the pathogenesis of pituitary adenomas, regardless of their hormonal status.Сведения о роли факторов транскрипции в патогенезе аденом гипофиза крайне противоречивы.Целью исследования явилось изучение роли фактора транскрипции NeuroD1 в различных типах аденом гипофиза.Материал и методы. Выполнено сравнительное клинико-морфологическое исследование с иммуногистохимическим анализом и конфокальной микроскопией экспрессии фактора транскрипции NeuroD1 6 гормонов аденогипофиза и Ki-67 в 40 различных аденомах гипофиза и 9 нормальных аденогипофизах.Результаты исследования. NeuroD1 экспрессировался во всех случаях и типах аденом, уровень его экспрессии в 40 аденомах достоверно отличался от такового в нормальном гипофизе (р=0,006), при этом NeuroD1 во всех опухолях был выше, чем в норме.Заключение. NeuroD1 играет одну из ключевых ролей в патогенезе аденом гипофиза вне зависимости от их гормонального статуса

Comparison of Pheochromocytoma-Specific Morbidity and Mortality among Adults with Bilateral Pheochromocytomas Undergoing Total Adrenalectomy vs Cortical-Sparing Adrenalectomy

Importance: Large studies investigating long-term outcomes of patients with bilateral pheochromocytomas treated with either total or cortical-sparing adrenalectomies are needed to inform clinical management. Objective: To determine the association of total vs cortical-sparing adrenalectomy with pheochromocytoma-specific mortality, the burden of primary adrenal insufficiency after bilateral adrenalectomy, and the risk of pheochromocytoma recurrence. Design, Setting, and Participants: This cohort study used data from a multicenter consortium-based registry for 625 patients treated for bilateral pheochromocytomas between 1950 and 2018. Data were analyzed from September 1, 2018, to June 1, 2019. Exposures: Total or cortical-sparing adrenalectomy. Main Outcomes and Measures: Primary adrenal insufficiency, recurrent pheochromocytoma, and mortality. Results: Of 625 patients (300 [48%] female) with a median (interquartile range [IQR]) age of 30 (22-40) years at diagnosis, 401 (64%) were diagnosed with synchronous bilateral pheochromocytomas and 224 (36%) were diagnosed with metachronous pheochromocytomas (median [IQR] interval to second adrenalectomy, 6 [1-13] years). In 505 of 526 tested patients (96%), germline mutations were detected in the genes RET (282 patients [54%]), VHL (184 patients [35%]), and other genes (39 patients [7%]). Of 849 adrenalectomies performed in 625 patients, 324 (52%) were planned as cortical sparing and were successful in 248 of 324 patients (76.5%). Primary adrenal insufficiency occurred in all patients treated with total adrenalectomy but only in 23.5% of patients treated with attempted cortical-sparing adrenalectomy. A third of patients with adrenal insufficiency developed complications, such as adrenal crisis or iatrogenic Cushing syndrome. Of 377 patients who became steroid dependent, 67 (18%) developed at least 1 adrenal crisis and 50 (13%) developed iatrogenic Cushing syndrome during median (IQR) follow-up of 8 (3-25) years. Two patients developed recurrent pheochromocytoma in the adrenal bed despite total adrenalectomy. In contrast, 33 patients (13%) treated with successful cortical-sparing adrenalectomy developed another pheochromocytoma within the remnant adrenal after a median (IQR) of 8 (4-13) years, all of which were successfully treated with another surgery. Cortical-sparing surgery was not associated with survival. Overall survival was associated with comorbidities unrelated to pheochromocytoma: of 63 patients who died, only 3 (5%) died of metastatic pheochromocytoma. Conclusions and Relevance: Patients undergoing cortical-sparing adrenalectomy did not demonstrate decreased survival, despite development of recurrent pheochromocytoma in 13%. Cortical-sparing adrenalectomy should be considered in all patients with hereditary pheochromocytoma

EXPERIMENTAL STUDY OF THE DEFORMATION PROPERTIES OF WATER-SATURATED LEATHER SEMI-FINISHED PRODUCTS

The paper presents the results and analysis of experimental studies of the deformation properties and characteristics of moisture-saturated leather semi-finished product on topographic areas and coatings of working rolls

TRANSSPHENOIDAL SURGERY OF NASAL LIQUORRHEA AS A COMPLICATION AFTER TREATMENT OF PROLACTINOMAS WITH DRUGS

The objective of the research is to optimize the method of transnasal endoscopic plasty of liquor fistulas in patients with prolactinomas, who got nasal liquorrhea against the background of treatment with dopamine agonists.Material and methods. Transnasal endoscopic approach was performed in 7 cases with prolactinomas. There were 9 operations including 2 interventions caused by liquorrhea relapse. Plasty with Tachocomb and biological adhesives were used in 2 cases. The other 7 cases demanded additional use of an adipose tissue fragment.Results. Complete arrest of liquorrhea was achieved in 5 cases. It resumed in 2 patients who had undergone plasty with Tachcomb and biological adhesives. They needed into the reoperations with use of autoadipose tissue.Conclusion. Using of CTcisternography is necessary for revealing exact localization of liquor fistula. It is expedient to apply Tachocomb and a fragment of autoadipose tissue fixed with biological adhesives. Discontinuation of treatment with Cabergoline for a month is recommended after the operation

CLINICAL AND MORPHOLOGICAL RESEARCH INTO THE ROLE OF THE TRANSCRIPTION FACTOR NEUROD1 IN VARIOUS TYPES OF PITUITARY ADENOMAS

The role of transcription factors in the pathogenesis of pituitary adenomas is extremely controversial.The aim of the study was to investigate the role of the transcription factor Neuro D1 in various types of pituitary adenomas.Materials and methods. A comparative clinico-morphological study was carried out with immunohistochemical analysis and confocal microscopy of the expression of the transcription factor NeuroD1, six adenohypophysis hormones and Ki-67 in 40 pituitary adenomas and 9 normal pituitary glands.Results. NeuroD1 was expressed in all cases and types of adenomas. The expression level of the transcription factor in adenomas was significantly different from that in the normal pituitary gland (p = 0.006). The average number of cells with expression of NeuroD1 in all tumors was higher than in the normal pituitary gland.Conclusion. NeuroD1 plays one of the key roles in the pathogenesis of pituitary adenomas, regardless of their hormonal status

Alzheimers disease as a womens health challenge: a call for action on integrative precision medicine approaches.

Alzheimers Disease (AD) is marked by pronounced sex differences in pathophysiology and progression. However, the field has yet to fully recognize AD as a womens health issue, delaying the development of targeted preventative strategies and treatments. This perspective explores the elements impacting AD in women, identifying sex specificity in risk factors, highlighting new diagnostic approaches with electronic health records, and reviewing key molecular studies to underscore the need for integrative precision medicine approaches. Established AD risk factors such as advancing age, the apolipoprotein E4 allele, and poorer cardiovascular health affect women differently. We also shed light on sociocultural risk factors, focusing on the gender disparities that may play a role in AD development. From a biological perspective, sex differences in AD are apparent in biomarkers and transcriptomics, further emphasizing the need for targeted diagnostics and treatments. The convergence of novel multiomics data and cutting-edge computational tools provides a unique opportunity to study the molecular underpinnings behind sex dimorphism in AD. Thus, precision medicine emerges as a promising framework for understanding AD pathogenesis through the integration of genetics, sex, environment, and lifestyle. By characterizing AD as a womens health challenge, we can catalyze a transformative shift in AD research and care, marked by improved diagnostic accuracy, targeted interventions, and ultimately, enhanced clinical outcomes

PREVALENCE OF SLEEP DISORDERED BREATHING IN PATIENTS WITH NEWLY DIAGNOSED ACROMEGALY

Background: Obstructive sleep disordered breathing or obstructive sleep apnea (OSA) is the most common respiratory impairment in acromegaly. OSA is bound up with heightened cardiovascular mortality. Aim: Тo study frequency, features, and structure of sleep disordered breathing in patients with newly diagnosed acromegaly and to elucidate the factors influencing their development. Materials and methods: 38 patients (10 men, 28 women, median age 53 (28-76) years, median body mass index (BMI) 29 (19.9-44.3) kg/m²) with newly diagnosed acromegaly were recruited into the study. All subjects underwent full polysomnography (Embla N7000, Natus, USA) and Remlogica software (USA). Results: Sleep disordered breathing was found in 28 (73.7%) patients. OSA was revealed in all cases, in 11 (39.3%) subjects it was mixed. In 10 (35.7%) patients OSA was mild, in 8 (28.6%) moderate, and in 10 (35.7%) severe. BMI (р<0.01), disease duration (р=0.003), and insulin-like growth factor-1 (IGF-1) level (р=0.04) were different in patients without OSA and patients with moderate-to-severe OSA. No difference was found in sex (р=0.4), age (р=0.064), and growth hormone level (р=0.6). Frequency of arterial hypertension, diabetes mellitus, and other glucose metabolism impairments was the same in subjects without OSA and with severe-to-moderate OSA. Conclusion: All patients with newly diagnosed acromegaly should undergo polysomnography. BMI, disease duration, and IGF-1 level are significant risk factors for OSA development. Correlation OSA with arterial hypertension and glucose metabolism impairments needs to be further investigated