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Обоснование. Болезнь Иценко–Кушинга (БИК) – тяжелое многосимптомное заболевание гипоталамо-гипофизарно-надпочечниковой системы. Причиной заболевания является наличие аденомы гипофиза (кортикотропиномы). Увеличение секреции адренокортикотропного гормона (АКТГ) аденомой гипофиза приводит к повышенной секреции кортизола корой надпочечников и развитию тотального эндогенного гиперкортицизма. Золотым стандартом лечения данного заболевания является хирургическое удаление кортикотропиномы. Однако аденомэктомия не во всех случаях бывает эффективной, и примерно в 20% случаев после проведенного радикального лечения не удается достичь ремиссии заболевания и возникает рецидив. Цель. Целью нашей работы являлась оценка факторов, оказывающих влияние на результат аденомэктомии у пациентов с болезнью Иценко–Кушинга, и выявление предикторов рецидива. Методы. В исследование было включено 84 пациента (80 женщин и 4 мужчин) в возрасте от 18 до 58 лет с БИК до и после трансназальной аденомэктомии. Период наблюдения от 3 до 15 лет, начиная с 2001 г. (в среднем 9,0 лет). Была проведена ретроспективная оценка клинических и гормональных факторов (АКТГ и кортизола) до операции и через 1–3 и 8–13 дней после операции. Результаты. У 54 (64,3%) из 84 пациентов с БИК после проведенной трансназальной аденомэктомии развилась ремиссия заболевания. Оперативное лечение было неэффективно у 30 (35,7%) пациентов, и им была проведена повторная аденомэктомия. По данным МРТ головного мозга, среди пациентов с ремиссией заболевания чаще встречались микроаденомы гипофиза (54%) по сравнению с пациентами, у которых операция оказалась неэффективна, а на МРТ чаще встречались макроаденомы (63%). У всех больных с БИК независимо от исхода нейрохирургической операции наблюдалось достоверное снижение уровня кортизола и АКТГ в раннем послеоперационном периоде. Заключение. Показателями эффективности аденомэктомии и длительной ремиссии у пациентов с БИК являются уровень утреннего кортизола менее 100 нмоль/л и уровень АКТГ менее 10,0 пг/мл на ранних сроках после операции (1–13-й дни). Наличие надпочечниковой недостаточности после аденомэктомии является предиктором эффективности операции, но не исключает вероятности развития рецидива.

Purpose: To describe the clinical findings of two patients with reversible ocular hypertension secondary to endogenous hypercortisolism. Design: Retrospective, observational case series. Subjects: A 65-year-old man (patient 1) and a 21-year-old woman (patient 2) were both found to have Cushing's syndrome after presentation to our clinic with elevated intraocular pressures (IOP). Methods: Clinical histories, ophthalmic examinations including IOP measurements, optical coherence tomography of the retinal nerve fiber layer, visual field testing, magnetic resonance imaging and computerized tomography of two patients were reviewed between 2007 and 2019. Observations: Patient 1 demonstrated elevated IOP (maximum 26 mmHg OD and 22 mmHg OS) and bilateral disc edema. Following diagnosis of Cushing's syndrome, the patient underwent two pituitary resections and bilateral adrenalectomy, with subsequent resolution of his hypercortisolism and ocular hypertension (OHT). Patient 2 presented with blurred vision and found to have OHT (maximum 32 mmHg OU). Following diagnosis of Cushing's disease and two resections of her adrenocorticotropic hormone (ACTH) producing pituitary adenoma, her IOPs normalized. Both patients maintained normal IOPs after resolution of their endogenous hypercortisolism and discontinuation of topical IOP-lowering medication. Conclusions and Importance: Ocular hypertension induced by endogenous hypercortisolism is, in some cases, fully reversible following normalization of cortisol levels. These findings suggest that the physiologic changes to the trabecular meshwork induced by endogenous hypercortisolism may be fully reversible. Keywords: Ocular hypertension, Endogenous hypercortisolism, Glaucoma, Trabecular meshwork, Glucocorticoid, Cushing's syndrome

Aims: this study evaluates the most common associations of symptoms and complications in patients with Cushing’s syndrome (CS) in order to choose a potential population to be screened for CS and estimates the diagnostic accuracy of first line screening tests (cortisol, ACTH) to differentiate ACTH-ectopic CS from Cushing’s disease. Materials and Methods: The clinical data of 259 patients with proven CS during 2001–2011 was analyzed. The clinical presentations of 197 patients (159 Cushing’s disease, 28 ACTH-ectopic CS and 10 cases of benign cortisol-secreting adrenal adenoma) were compared according to the cause of hypercortisolism. ROC-analysis was performed to estimate the diagnostic accuracy of the first line tests (cortisol, ACTH) to suggest ACTH-ectopic CS. A threshold for the test with the highest area under the curves was chosen based on the maximum sum of the sensitivity and specificity. Results: The most frequent complaints were related to fatigue, muscle weakness, weight gain and changes in appearance (facial plethora and fullness, striae). Among the complications of CS the most frequent were being overweight or obese (71%), hypertension (63%), dislipoproteinemia (41%), low traumatic fractures (43%) and steroid-induced diabetes (31%). In women, 16% were older than 50, in those who were younger amenorrhea was registered in 43%. The patients with ACTH-ectopic CS had higher rate of low traumatic fractures (p=0.04), increased serum late-night cortisol, 24 hours urinary free cortisol, morning and evening ACTH and lower levels of potassium (p0.01 for all parameters). Plasma late-night ACTH measurements showed the highest AUC (0,811 (95% CI 0,712–0,909)) to differentiate ACTH-ectopic CS from Cushing’s disease. A cut off value of 108.9 pg/ml for late-night ACTH yielded a sensitivity of 60,7% and a specificity of 79%. Conclusions: patients with a coexistence of obesity, muscle weakness, fatigue, some components of metabolic syndrome and especially low traumatic fractures should be screened for CS. High plasma late night ACTH values in patients with proven CS value suggest ACTH-ectopic syndrome.

Pasireotide is the first pituitary-directed drug approved for treating patients with Cushing's disease (CD). Our 10-year experience with pasireotide in CD is reported here. Twenty patients with de novo, persistent, or recurrent CD after pituitary surgery were treated with pasireotide from December 2003 to December 2014. Twelve patients were treated with pasireotide in randomized trials and 8 patients with pasireotide sc (Signifor(®); Novartis AG, Basel, Switzerland) in clinical practice. The mean treatment duration was 20.5 months (median 9 months; range, 3-72 months). Urinary free cortisol (UFC) levels mean percentage change (± SD) at last follow-up was-40.4% (± 35.1; range, 2-92%; median reduction 33.3%) with a normalization rate of 50% (10/20). Ten patients achieved sustained normalized late night salivary cortisol (LNSC) levels during treatment. LNSC normalization was associated with UFC normalization in 7/10 patients. Serum cortisol and plasma ACTH significantly decreased from baseline to last follow-up. Body weight decrease and blood pressure improvement during pasireotide treatment were independent from UFC response. Glucose profile worsening was observed in all patients except one. The frequency of diabetes mellitus increased from 40% (8/20) at baseline to 85% (17/20) at last follow-up requiring initiation of medical treatment only in 44% of patients. Pasireotide treatment was associated with sustained biochemical and clinical benefit in about 60% of CD patients. Glucose profile alteration is a frequent complication of pasireotide treatment; however, it seems to be easy to manage with diet and lifestyle intervention in almost half of the patients.

The aim of the study was to determine peculiarities of protein and lipid metabolism as well as platelet-coagulation hemostasis depending on the pathogenesis of the endogenous hypercortisolism and assessment of the impact of chronic hyperglycemia on studied parameters. Materials and methods. The study included 19 patients with pituitary microadenomas with median age of 45,0 (41; 49) years and 9 patients with nodular adrenal gland hyperplasia aged 49,5 (42; 57) years, 14 of whom had diabetes mellitus. Results. Biochemical and coagulation parameters in patients with endogenous hyperpercortisolism regardless of ethiology Cushing`s syndrome differed from the control group in increased concentration of total cholesterol, high-density lipoproteins, low-density lipoproteins, alpha2-globulins and decreased gamma globulins, as well as in increased average volume of platelets and enhanced aggregation properties. Carbohydrate metabolism disorders were not characterized by significant differences in metabolic parameters and platelet hemostasis, but were accompanied by the reduction of APTT.

Avascular necrosis (AVN) of the femoral head is a well-recognized complication of steroid treatment. Exogenous glucocorticoids’ administration and alcoholism are the most common nontraumatic etiologies. AVN secondary to endogenous hypercortisolism (HC) is rare; very few case reports are available on this complication. We describe a 28-year-old female that has presented an AVN with Cushing's syndrome. Biochemical investigations confirmed HC. Magnetic resonance imaging (MRI) showed a pituitary adenoma that was resected transsphenoidally. The postoperative failure directed to radiosurgery treatment. Then, the patient then expressed a significant clinical improvement while developing adrenocorticotropic deficiency; hence, steroids were indicated. During the discovery of Cushing disease, the patient presented also limping and progressive pain in right hip. The pelvis MRI showed an AVN of the right femoral head. The patient underwent a total replacement of the right hip sine presenting an extensive AVN. This case elucidates that AVN could be an early manifestation of Cushing's disease.