An excess of endogenous GC in humans suppresses bone formation through the upregulation of Wnt-signaling antagonists and dysregulation of miRs involved in mesenchymal stem-cell commitment. Both Wnt-signaling antagonists and miRs seem to be promising targets for further research in therapeutic intervention in glucocorticoid-induced osteoporosis.

Corticotropinomas and adrenocorticotropic hormone (ACTH)-secreting neuroendocrine tumors exhibit differential levels of some microRNAs (miRs) compared to normal tissue. Because miRs can be released from tissues into circulation, they offer promise as novel disease biomarkers. Objective: To evaluate whether miRs are differentially detected in plasma samples of patients with ACTH-dependent Cushing's syndrome (CS). Design: Case-control study. Methods: Morning fasting plasma samples were collected from 41 consecutive patients with confirmed ACTH-dependent CS and 11 healthy subjects and stored at −80 • C. Twenty-one miRs previously reported to be differentially expressed in ACTH-secreting tumors vs. healthy tissue samples were quantified in plasma by qPCR. Results: Among enrolled subjects, 28 were confirmed to have Cushing's disease (CD), 13 had ectopic ACTH secretion (EAS) and 11 were healthy controls. We found statistically significant differences in the circulating levels of miR-16-5p [45.04 (95% CI 28.77-61.31) in CD vs. 5.26 (2.65-7.87) in EAS, P < 0.001; q = 0.001], miR-145-5p [0.097 (0.027-0.167) in CD vs. undetectable levels in EAS, P = 0.008; q = 0.087] and differences in miR-7g-5p [1.842 (1.283-2.400) in CD vs. 0.847 (0.187-1.507) in EAS, P = 0.02; q = 0.14]. The area under the receiver-operator (ROC) curve was 0.879 (95% CI 0.770-0.987), p < 0.001, when using miR-16-5p to distinguish between CD and EAS. Circulating levels of miR-16-5p in the healthy control group differed from that of both the CD and EAS groups. Conclusions: Plasma miR levels differ in patients with CD and EAS. In particular, miR-16-5p, miR-145-5p and miR-7g-5p are promising biomarkers for further research to differentiate ACTH-dependent CS.

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Acromegaly had minimal effects on tested mRNAs specific to osteoblast or osteoclast function except for downregulated ALP expression. The expressions of miR known to be involved in mesenchymal stem cell commitment and downregulated TWIST1 expression suggest acromegaly has a negative effect on osteoblastogenesis.

Background. Cushing’s disease (СD) is а severe neuroendocrine disease that can rapidly progress with the development of severe complications of hypercorticism requiring immediate treatment. The main method of treatment is a neurosurgical operation, the effectiveness of which at the present time can reach 80% or more, however, about a quarter of patients after successful neurosurgical treatment experience reccurence. Aim. The analysis of prognostic factors potentially affecting the occurrence of recurrence of CD after successful primary transnasal adenomectomy. Material and methods. A retrospective monocenter comparative study of treatment outcomes in 219 patients (32 men, 187 women) with confirmed diagnosis of Cushing&apos;s disease who underwent endoscopic transsphenoidal adenomectomy between 2007 and 2014 was performed. The inclusion criteria were: the absence of previous pathogenetic treatment for this disease and the development of remission of the disease in the early postoperative period. The duration of follow-up period was three years and more. We used methods of statistical comparison of groups, including survival analysis and ROC-analysis. Results. Within 3 years the remission was preserved in 172 patients, the recurrence of Cushing&apos;s disease developed in 47 patients (21.5% [16%; 28%]). The probability of CD recurrence was associated with morning levels of ACTH and cortisol and evening ACTH in the early postoperative period. As a result of the ROC-analysis for morning ACTH and cortisol, the optimal cutting points were 7 pg/ml and 123 nmol/l respectively. In patients with ACTH level less than 7 pg/ml, three years recurrence appeared to be 7%, 95% CI [3%, 14%], while at the level of ≥7 pg/ml recurrence was observed in 31% [23%, 40%] cases, RR 0.22 [0.09; 0.51], ОR – 0.16 [0.06; 0.43]. In patients with cortisol level below 123 nmol/l the recurrence developed in 13% [9%, 20%] of cases, while in patients with cortisol level ≥123 nmol/l, recurrence was equal to 45% [32%, 59%], RR 0.29 [0.18; 0.50], ОR – 0.19 [0.09; 0.39]. Conclusion. The development of adrenal insufficiency (a decrease in ACTH level less than 7 pg/ml and cortisol level less than 123 nmol/l) statistically significantly reduces the probability of the recurrence of CD within three years after surgery.

За прошедший век хирургия аденом гипофиза претерпела несколько революций в хирургической технике и технологических достижениях, что привело к развитию современной эндоскопической транссфеноидальной хирургии. Несмотря на то что транссфеноидальная хирургия хорошо освещена в современной нейрохирургической литературе, исторический лабиринт, который привел к ее развитию, по-прежнему представляет интерес, так как позволяет оценить уникальные вклады и новаторства пионеров нейрохирургии. Клю че вые сло ва: аденома гипофиза, эндоскопическая хирургия аденом гипофиза. Over the past century pituitary surgery has undergone multiple revolutions in surgical technique and technological advancements that have resulted in what is now recognized as modern transsphenoidal surgery. Although the procedure is well established in the current neurosurgical literature, the historical maze that led to its development continues to be of interest because it allows us to appreciate better the unique contributions made by the pioneers of the technique as well as the innovative spirit that continues to fuel neurosurgery.

We do not recommend population screening for diabetes insipidus (DI) (B3). We recommend to perform diagnostic testing for central diabetes insipidus (CDI) in patients who underwent neurosurgery, after skull and brain trauma, subarchnoid hemorrhage (B3). We recommend excluding thirst impairment during all stages of diagnostic assessment (С3). We recommend excluding DI in cases of persistent hypotonic polyuria: excretion of more than 3 L. or more than 40 mL/kg of urine daily; urine osmolality less than 300 mOsm/kg or urinary specific gravity less than 1004 g/L in all urine samples or during Zimnitsky test (В3). After hypotonic polyuria is confirmed, we recommend excluding of the main causes of nephrogenic diabetes insipidus (NDI) (B3). We recommend simultaneous measurement of urine osmolality and blood osmolality/sodium level in order to confirm DI. Blood hyperosmolality (more than 300 mOsm/kg) and/or hypernatremia with low urine osmolality (less than 300 mOsm/kg) confirms DI (B2). If testing does not reveal these findings, we recommend performing a fluid deprivation test to exclude primary polydipsia (PP) (B2). Desmopressin test is recommended to distinguish CDI and NDI (B2). In cases of CDI we recommend to perform head MRI with contrast (B3). In cases of NDI we recommend assessing renal structure and function and possible electrolyte disturbances (C3). In cases of PP we recommend to refer a patient to psychiatrist (B3). We recommend treating CDI with synthetic vasopressin analogue – desmopressin (B1). We recommend an individual approach in choosing desmopressin dosage form (B2). As the initial dose is difficult to predict when starting desmopressin treatment, we recommend titrating the dosage using two approaches: “the average dose” and “as required” (C4). We recommend educating the patients to ensure knowledge of the features of various desmopressin dosage forms (C4). To decrease the risk of water intoxication, we recommend educating the patients to the water intake regimen adherence (С4). When CDI is accompanied by thirst impairment, we recommend titrating the dose in a clinical setting, with assessment of blood sodium, bodyweight and/or urine volume (C4).

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