Course of Cushing`s disease and treatment outcomes in correlation with pituitary MRI in children.

BACKGROUND: Cushing's disease (CD) is a rare disorder of a persistent cortisol excess caused by ACTH-secreting pituitary tumor (corticotropinoma). Transsphenoidal surgery (TSS) is a treatment of choice for СD, which effectiveness range is from 70 to 90%. Recurrence rate after successful treatment is about 25%. If surgical treatment is unsuccessful or recurrence appear, radiation treatment is the next therapeutic option, which effectiveness range is also 90%, but the hypopituitarism rate as side effect of treatment is higher. Preoperative predictors of remission and recurrence are still unexplored what leads to further investigations. AIM: Analysis of remission and recurrence rates of pediatric CD after successful treatment according to preoperative MRI and therapeutic option. MATERIALS AND METHODS: We conducted a retrospective analysis of 90 pediatric patients with CD who were observed between 1992 and 2020 at the Endocrinology Research Centre. RESULTS: The most common clinical symptoms of CD were weight gain [94%] and growth retardation [72%]. Pituitary tumor was detected on radiological imaging in 53/90 patients [59%], there were no signs of visible adenoma in 37/90 of patients [41%]. 63 of 90 patients underwent TSS (70%), 27 patients underwent radiosurgery (30%). Remission rate after TSS was 71% [45/63], after radiosurgery - 85% [23/27]. There were no significant differences in remission rates after radical treatment according to preoperative MRI results (P=0.21 after TSS and P=0.87 after radiosurgery, х2 analysis). Recurrence after successful treatment was diagnosed in 10 patients. There were no significant differences in time to recurrence according to preoperative MRI results (P=0.055, х2 analysis). Time to recurrence was statistically different after TSS compared to radiosurgery (P=0.007, Kaplan-Meier analysis) and in the group with developed adrenal insufficiency in the early postoperative period (P=0.04, Kaplan-Meier analysis). Analysis of side effect of treatment showed that the frequency of growth hormone and gonadotrophin deficiency was statistically higher after radiosurgery (р<0.01, Kruskel-Wallis ANOVA test). Diabetes insipidus was diagnosed only after TSS. CONCLUSION: Results of our study didn`t allow to use MRI-results as predictor of effectiveness treatment in pediatric CD. Therapeutic option has an impact on time to recurrence, not on recurrence rates. The frequency of growth hormone and gonadotrophin deficiency was statistically higher after radiosurgery compared to TSS. Further studies are needed to identify predictors of remission and recurrence in CD.>< 0.01, Kruskel-Wallis ANOVA test). Diabetes insipidus was diagnosed only after TSS. CONCLUSION: Results of our study didn`t allow to use MRI-results as predictor of effectiveness treatment in pediatric CD. Therapeutic option has an impact on time to recurrence, not on recurrence rates. The frequency of growth hormone and gonadotrophin deficiency was statistically higher after radiosurgery compared to TSS. Further studies are needed to identify predictors of remission and recurrence in CD.

[Clinical and radiological diagnosis of hypophysitis: a review of literature and own data].

This article presents a literature review of the various forms of hypophysitis, its varieties, as well as the problem of radiation diagnosis and treatment of this pathology. Hypophysitis is a poorly understood and multifactorial disease which the difficulty of diagnosing is not only to a variety of nonspecific clinical manifestations and hormonal research data, but also the ambiguous results of MRI studies, the lack of clear MR patterns. The article reflects the main histological types of hypophysitis, the peculiarities of diagnosis in connection with general clinical symptoms, outlines the features of each type of hypophysitis with their own clinical observations. This review is devoted to modern ideas about the clinical course of hypophysitis, presented a set of characteristic diagnostic signs of the disease according to MRI and the treatment algorithms recommended today are also highlighted. The article summarizes data from foreign literature and our own clinical observations in order to develop an optimal protocol for MRI studies in patients with suspected hypophysitis, to develop recommendations for radiologists and endocrinologists for the correct results interpretation. The uniqueness of this review is the lack of data on the clinic, diagnosis and treatment of hypophysitis in the Russian literature today.

[Adrenal imaging: anatomy and pathology (literature review)].

This literature review focuses on the normal adrenal gland anatomy and typical imaging features necessary to evaluate benign and malignant lesions. In particular, adenoma, pheochromocytoma, metastases and adrenocortical carcinoma were discussed as some of the most common lesions. For this purpose, a review of relevant local and international literature sources up to January 2021 was conducted.In many cases, adrenal incidentalomas have distinctive features allowing characterization using noninvasive methods. It is possible to suspect a malignant nature and promptly refer the patient for the necessary invasive examinations in some cases. -Computed tomography, especially with intravenous contrast enhancement, is the primary imaging modality because it enables differential diagnosis. Magnetic resonance tomography remains a sensitive method in lesion detection and follow-up but is not very specific for determining the malignant potential. Positron emission computed tomography also remains an additional method and is used mainly for differential diagnosis of malignant tumors, detecting metastases and recurrences after surgical treatment. Ultrasound has a limited role but is nevertheless of great importance in the pediatric population, especially newborns. Promising techniques such as radiomics and dual-energy CT can expand imaging capabilities and improve diagnostic accuracy.Because adrenal lesions are often incidentally detected by imaging performed for other reasons, it is vital to interpret such findings correctly. This review should give the reader a broad overview of how different imaging modalities can evaluate adrenal pathology and guide radiologists and clinicians.

[Heart arrhythmias and conduction disorders in patients with acromegaly: the role of cardiac magnetic resonance imaging].

Cardiovascular complications including arrhythmias and cardiac conduction disorders are one of the main reasons of high mortality rate in acromegaly, while they have not been well explored. AIM: To estimate arrhythmias frequency in acromegaly, identify risk factors leading to the development of arrhythmia and cardiac conduction disorder, to determine the role of cardiac MRI in detecting structural and functional changes. MATERIALS AND METHODS: A single-center prospective cohort study, which included 461 patients (151 men and 310 women) with acromegaly, was conducted. All the patients underwent a standard medical examination, including hormonal blood test, electrocardiogram, echocardiography, electrocardiogram daily monitoring. 18 patients with arrhythmias (11 men and 7 women) had cardiac MRI with gadolinium-based contrast. RESULTS: The results of our research show high frequency of arrhythmias and cardiac conduction disorders in patients with acromegaly 42%. Most frequent kinds of arrhythmias and cardiac conduction disorders were sinus bradycardia 19.1% of the cases and conduction disorders of bundle branch blocks 14.5%. Men were more likely to suffer from arrhythmias and cardiac conduction disorders than women (54.2% and 37.4%, respectively,p=0.0005). Not acromegaly activity but duration of the disease was a main risk factor of arrhythmias and cardiac conduction disorders. Patients with arrhythmias had a long anamnesis of acromegaly (10 and 7 years, respectively, p=0.04). Meanwhile, cardiac conduction disorders were commonly observed in the patients who were treated with somatostatin analogs comparing to the patients who didnt undergo this therapy (50% and 38.6% respectively,p=0.004). We showed that 61% of patients with acromegaly and cardiac conduction disorders who underwent magnetic resonance imaging (MRI) had the signs of myocardial fibrosis. The value of the ejection fraction of the left ventricle according to MRI was higher than with echocardiography (p=0.04). CONCLUSION: Arrhythmias and cardiac conduction disorders are often observed in patients with acromegaly even with remission of the disease. High risk group need careful diagnostic and monitoring approaches. Cardiac MRI is the gold standard for visualization of structural and morphological changes in the heart. Use of cardiac MRI in acromegalic patients expands our understanding of arrhythmias and cardiac conduction disorders in this disease. There are no specific laboratory markers of diffuse myocardial fibrosis, and the role of myocardial fibrosis in the occurrence of cardiac arrhythmias and conduction disorders needs further studying.

[Multiple endocrine neoplasia type 1 syndrome with three classical components and chiasm glioma: specific features of target organ lesions and a clinical observation].

The article briefly reviews the specific features of target-organ lesions in multiple endocrine neoplasia type 1 (MEN1) syndrome and a clinical case of genetically confirmed MEN1 syndrome in a young female patient. Despite the relative rarity of this disease, timely diagnosis, treatment and screening for its main components are very important for the overall prognosis of patients with MEN1 and their first-degree relatives who are MEN1 gene mutation carriers. The described case is noteworthy for a number of specific features. The authors could find no account of optic chiasm glioma within the framework of MEN1 in the literature. Moreover, therapy-resistant somatoprolactinoma engages attention, which points to its aggressive nature with pituitary adenoma that is not been clearly visualized on magnetic resonance imaging. Of interest is the order of detection of neoplasms, in particular the manifestation of hypoglycemic episodes as a sign of organic hyperinsulinism. which have been initially regarded as epileptic seizures, after the use of sustained-release somatostatin analogues for the treatment of acromegaly.

[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.

Inactivation and mineralization of aerosol deposited model pathogenic microorganisms over TiO2 and Pt/TiO2.

Air disinfection from bacteria and viruses by means of photocatalytic oxidation is investigated with microorganisms loaded over photocatalysts' films from aerosols. Deposition method and equipment have been developed to load Mycobacterium smegmatis , Bacillus thuringiensis , vaccinia virus, and influenza A (H3N2) virus on slides with undoped TiO(2) and platinized sulfated TiO(2) (Pt/TiO(2)). Inactivation dynamics was measured under UVA irradiation and in the dark. About 90% inactivation is reached in 30 min irradiation on TiO(2) and from 90 to 99.8% on Pt/TiO(2). The first-order inactivation rate coefficient ranged from 0.18 to 0.03 min(-1), over Pt/TiO(2) being higher than on TiO(2) for all microorganisms except Bacillus thuringiensis. The photocatalytic mineralization of Bacillus thuringiensis was performed on TiO(2) and Pt/TiO(2) with different photocatalyst and microorganism loadings. Completeness of mineralization depended on the TiO(2) to bacteria mass ratio. The rate of the photocatalytic carbon dioxide production grows with both the cell mass increase and the photocatalyst mass increase. Pt/TiO(2) showed increased rate of mineralization as well as of the inactivation likely due to a better charge carrier separation in the doped semiconductor photocatalyst. The results demonstrate that photocatalytic filters with deposited TiO(2) or Pt/TiO(2) are able to inactivate aerosol microorganisms and completely decompose them into inorganic products and Pt/TiO(2) provides higher disinfection and mineralization rates.

Air detoxification with nanosize TiO2 aerosol tested on mice.

A method for fast air purification using high concentration aerosol of TiO(2) nanoparticles is evaluated in a model chemical catastrophe involving toxic vapors of diisopropyl fluorophosphate (DFP). Mice are used as human model in a closed 100 dm(3) chamber. Exposure of mice to 37 ppm of DFP vapor for 15 min resulted in acute poisoning. Spraying TiO(2) aerosol in 2 min after the start of exposure to DFP vapors resulted in quick removal of DFP vapors from the chamber's air. Animals did not show signs of poisoning after the decontamination experiment and exposure to TiO(2) aerosol alone. Reactive oxygen species (ROS) and antioxidant activity (AOA) of mice blood plasma were measured for animals exposed to sound of aerosol generator, DFP vapors, TiO(2) aerosol and DFP vapors+TiO(2) aerosol. Reduced ROS and increased AOA were found for mice exposure to sound, DFP and TiO(2) aerosol. Exposure to DFP and decontamination with TiO(2) nanoparticles resulted in decreased AOA in 48 h following the exposure. The results suggest that application of TiO(2) aerosol is a powerful method of air purification from toxic hydrolysable compounds with moderate health aftermaths and requires further study and optimization.

[New mutation in the CYP17 gene: description of a case].

Deficiency of 17α-hydroxylase is a rare variant of congenital adrenal cortical dysfunction. The defect was first described by E. Biglieri et al. in 1966 in patients with sexual infantilism, pronounced excess mineralocorticoids with salt retention and arterial hypertension. Currently, several variants of the nonclassical course of the disease are described (with an increased level of aldosterone and without the development of hypertension and hypokalemia), the pathophysiological mechanism of which could not be explained. Cases of isolated deficiency of 17,20-lyase activity associated with mutations of R347H and R358Q in the CYP17 gene are also described. Here is the observation of a patient with a new mutation in the CYP17 gene with 17α-hydroxylase/17,20-lyase deficiency.

[Cross-sectional controlled study of the morphometric parameters of the epiphysis in patients with hyperpolactinemia by magnetic resonance imaging].

A cross-sectional study of the cerebral epiphysis, by using brain magnetic resonance imaging was studied in 146 patients with hyper-prolactinemia and 141 persons without diseases of the endocrine or central nervous system. The purpose of the study was to compare the volume and structure of the pineal gland in hyperprolactinemic patients with the similar values in apparently healthy individuals. There was a significant increase in the volume of the epiphysis and a rise of the proportion of cysts and cystic changes in the structure of the epiphysis in patients with idiopathic hyperprolactinemia as compared with healthy individuals. The increased volume of the epiphysis and the change in its structure may be pathogeneticalfy associated with idiopathic hyperprolactinemia. To clarify this as-sumption, it is necessary to perform a larger study and to include hormonal tests characterizing epiphyseal function into the study protocol and to reveal a relationship between the changes in the sizes and structure of the epiphysis and the level of secretion of major hormones.

[The specific features of the course of acromegaly in old age and possibilities of somatulin treatment].

Acromegaly is a severe neuroendocrine disease caused by chronic excessive production of growth hormone. There are 50-70 cases of this disease per 1 million people. In the vast majority of cases, the cause of the disease is a pituitary adenoma from somatotrophic cells. With the advent in clinical practice of prolonged analogues of somatostatin, endocrinologists have new therapeutic options. In the article we present a clinical case of the patient with the diagnosis: acromegaly, active form; Endosuprasellar pituitary adenoma (somatotropinoma); Hypopituitarism (secondary adrenal insufficiency, secondary hypothyroidism); Chronic pyelonephritis in the acute phase; Hypertension of the II stage, ischemic heart disease, angina pectoris II functional class; Common atherosclerosis with a primary lesion of the aorta, coronary vessels and cerebral vessels.

[The efficacy of Sulodexide--a low-molecular heparin--in the therapy of diabetic nephropathy]. / Effektivnost' Sulodeksida--nizkomolekuliarnogo geparina--v terapii diabeticheskoi nefropatii.

A novel pathogenetic approach to treatment of diabetic nephropathy (DN) as a severe complication of diabetes mellitus is aimed at inhibiting DN progression or its involution by means of reestablishment of heparan sulfate synthesis by glycosaminoglycane drug. In the study of 9 patients with microalbuminuria and 9 with proteinuria this drug was low-molecular heparin-sulodexide (Alfa-Wasserman, Italy). The treatment course of 3 weeks resulted in albuminuria fall in 89% of patients. In patients with microalbuminuria protein excretion returned to normal values in a week of treatment. This effect was persistent after the drug discontinuation. This was not so for protein excretion in proteinuria patients which became low after 3 weeks of treatment, but the effect was not long-lasting. The authors believe that glycosaminoglycanes hold great promise in DN, especially at early stages of renal diabetic affection.

[Clinical and experimental bases for the use of Acryloxide in restorative surgery of the joints]. / Kliniko-éksperimental'noe obosnovanie primeneniia "Akriloksida" v vosstanovitel'noi khirurgii sustavov.

Experimental and clinical investigations showed good prospects of further studies of deformation characteristics of Akryloxide, particularly the elasticity module to judge of the degree of biological destruction of the plastics and possible prognosis of working efficiency of the polymer in individual endoprosthesis of joints.

[Individual endoprosthesis of the joints and bone defects of the extremities in the surgical treatment of patients with skeletal tumors]. / Individual'noe éndoprotezirovanie sustavov i defektov kostei konechnostei pri operativnom lechenii bol'nykh s opukholiami skeleta.

The authors describe results of the individual endoprosthesis of joints and defects of extremity bones in 84 patients treated for skeleton tumors. In 80 of them positive results were obtained. In three patients the results were unfavourable. There were no complications due to the construction of individual endoprostheses.