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

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

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

ACROMEGALIC CARDIOMYOPATHY WITH DYNAMIC OBSTRUCTION OF THE LEFT VENTRICLE OUTFLOW TRACT

Aim. To explore genesis of the left ventricle hypertrophy in acromegaly patient, with the method of next generation sequencing.Material and methods. Standard clinical and laboratory minimum was done, with electrocardiography, 24 hour ECG monitoring, echocardiography, magnete resonance tomography of the heart, new generation sequencing on the IlluminaHiSeq 2000 equipment with simultaneous analysis of 108 genes associated with idiopathic hypertrophic cardiomyopathy (HCMP) and phenocopies of HCMP.Results. At the age 59 y. o. the female patient had beed first time diagnosed with asymmetric HCMP, non-obstructive type (interventricular septum 19 mm, posterior wall 11 mm, pressure gradient in outflow tract of the left ventricle (OTLV) — 25 mmHg). At the age 62 y. o. she developed HCMP with dynamic obstruction of OTLV (pressure gradient in OTLV up to 80 mmHg) with progressing dyspnea on exertion, and required non-surgical reduction of interventricular septum. By the computed tomography data, at the age 63 y. o. the patient was diagnosed with endocellar hypophysis microadenoma (a tumor 6,7*7,3 mm), somatotropic hormone — 53,39 mU/L (normal: 0,1-20 mU/L), insulin-like growth factor 1 — 359 ng/mL (normal: 118-314 ng/mL). However, with retrospective analysis of her photos, even from the age 40 y. o. there were enlarged hands, feet, nasal cartilages, ears, lips and eyebrow arcs that witness for long lasting disease course. With the new generation sequencing, there were no pathological mutations revealed.Conclusion. The case represents hypertrophic cardiomyopathy as a leading clinical sign in acromegalic cardiomyopathy that imitated idiopathic HCMP. Patient management in such case should include on-time etiopathogenetic therapy that works against disease progression, and in some cases even for regression of the left ventricle hypertrophy

Association of gestational free and total triiodothyronine with gestational hypertension, preeclampsia, preterm birth and birth weight: an individual-participant data meta-analysis

CONTEXT: Triiodothyronine (T3) is the bioactive form of thyroid hormone. In contrast to TSH and FT4, we lack knowledge on the association of gestational T3 with adverse obstetric outcomes. METHODS: We collected individual participant data from prospective cohort studies on gestational free and/or total T3 (FT3 or TT3), adverse obstetric outcomes (preeclampsia, gestational hypertension, preterm birth and very preterm birth, small for gestational age (SGA) and large for gestational age (LGA)) and potential confounders. We used mixed-effects regression models adjusting for potential confounders. RESULTS: Final study population comprised of 33,118 mother-child pairs of which 27,331 had data on FT3 and 16,164 on TT3. There was a U-shaped association of FT3 with preeclampsia (P = 0.0069) and a J-shaped association with the risk of gestational hypertension (P = 0.029). Higher TT3 was associated with a higher risk of gestational hypertension (OR per SD of TT3 [95% CI]: 1.20 [1.08 to 1.33]; P = 0.0007). A lower TT3 but not FT3 was associated with a higher risk of very preterm birth (OR [95% CI]: 0.72 [0.55 to 0.94]; P = 0.018). TT3 but not FT3 was positively associated with birth weight (Mean difference per 1-SD increase in TT3 [95% CI]: 12.8 [6.5 to 19.1] grams, P < 0.0001) but there was no association with SGA or LGA. CONCLUSION: This study provides new insights on the association of gestational FT3 and TT3 with major adverse pregnancy outcomes which form the basis for future studies required to elucidate the effects of thyroid function on pregnancy outcomes. Based on the current study, routine FT3 or TT3 measurements for the assessment of thyroid function during pregnancy do not seem to be of added value in the risk assessment for adverse outcomes.Published version, accepted version (12 month embargo), submitted versionThe article is available via Open Access. Click on the 'Additional link' above to access the full-text

Medullary Thyroid Cancer: Management Guidelines

Представленные клинические рекомендации объединяют мнения членов рабочей группы по ключевым и наиболее спорным проблемам диагностики и лечения МРЩЖ, которые сложились в отечественной клинической практике. В рабочую группу вошли специалисты, работающие в различных лечебных и научно-исследовательских учреждениях.Этот документ не является официально утвержденным различными структурами Министерства здравоохранения и социального развития РФ. Представленные в нем положения носят рекомендательный характер.Основные предпосылк