Metastatic lesion of pituitary is a rare condition and is diagnosed in 1.8-4% of cases. Monitoring and treatment of such patients is a complex task and requires increased attention from a multidisciplinary team of specialists. The authors represent three patients with metastatic pituitary lesion who underwent neurosurgical treatment at the National Research Center of the National Research Institute of Endocrinology with subsequent pathomorphological confirmation of the diagnosis. The primary tumors were breast cancer, lung carcinoid, and clear cell kidney cancer. Two patients had distant metastases other than the pituitary gland. The clinical manifestation consisted in the appearance of symptoms of panhypopituitarism, chiasmal syndrome and mass effect in all cases. The follow-up period after surgical treatment was 0.25-2.5 years. Progression of the underlying disease was noted in two patients. One of them carried out stereotactic radiosurgical treatment and stereotactic oriented irradiation. One patient has a stable condition.

Currently, the treatment of pituitary adenomas is inextricably linked with transsphenoidal neurosurgical intervention. Modern technologies used in surgery for this pituitary pathology, such as endoscopy using angled optics, as well as the use of specialized instruments, sealing and hemostatic materials, increase the effectiveness of surgical treatment of pituitary adenomas and reduce the incidence of intraand postoperative complications. The development of radiation methods of diagnostics, such as MRI, makes it possible to more accurately identify the formation of the pituitary gland, assess its size, direction of growth, and the degree of invasion of surrounding tissues. The authors of the article described in detail the modern technique of transsphenoidal removal of pituitary adenoma using an endoscope. Each stage of the operation is described step by step, taking into account various anatomical features and illustrated. This article discusses the MRI characteristics of pituitary adenomas: size of the tumor, the direction of its growth, the degree of invasion of the cavernous sinuses, the compression effect on the structures of the chiasmal-sellar region. The use of treatment methods, knowledge of the features of MRI diagnostics described in this article greatly increase the effectiveness of the treatment of patients with pituitary adenomas and reduce the risk of complications after neurosurgical intervention in such patients.

Background: Currently, there is an increase in the incidence of chiasmosellar neoplasms and respective neurosurgical interventions. The postoperative period may be complicated by vasopressin synthesis and secretion disorders. Both the development and abortion of the fluid and electrolyte disorders can be delayed. Due to a tendency for an earlier discharge of the patients, a proportion of the disorders remain unaddressed. There is no data on the evolution and time to regress of transient abnormalities in the published studies with a long-term postoperative follow-up. Aim: To assess the incidence, evolution and regression trends, clinical and laboratory characteristic of postoperative central diabetes insipidus (CDI). Materials and methods: The single center retrospective comparative study included 150 patients who had undergone transnasal adenomectomy for Cushings disease, acromegaly, prolactinomas, and hormonally inactive pituitary adenomas. Clinical and laboratory assessments were performed pre- and postoperatively. In the event of CDI, treatment with desmopressin was administered. Ninety six (96) patients aged 20 to 65 years (median age 43 [35; 54] years) were followed for at least 60 months after the procedure. Results: Median time to the onset of permanent CDI (pCDI) was Day 5 [1; 9.5] after surgery, that of transient CDI (tCDI) Day 1 [1; 4.5] with its remission by Day 30 [1.5; 199]. The maximally delayed onset was on Day 86 for the pCDI and Day 61 for tCDI; that to the remission of tCDI, 738 days. At discharge from the hospital, postoperative CDI was present in 34/150 patients (23%; 95% CI 1730), and in 25/150 of the patients (16%; 95% CI 1224) the disorder resolved. At 5 to 7 years after surgery, the prevalence of pCDI was 16% (95% CI 1024), that of tCDI 35% (95% CI 2745), 49% (95% CI 3959) of the patients had no abnormalities (respective absolute patient numbers being 15, 34, and 47 of 96 followed for at least 60 months). At Days 1 to 7 after surgery, the patients with pCDI and tCDI had more frequent complaints of dry mouth and thirst than those without the disorder. These complaints were verified by higher 24-hour fluid intake and diuresis at the day of surgery and Days 5 to 7 thereafter, compared to those in the patients without the disorders. At Days 57 after surgery, urine sodium and urine specific gravity were significantly lower, as was urine osmolality at all postoperative stages, compared to those in the patients without the disorders. Conclusion: Within 2 years after transnasal adenomectomy, the incidence of postoperative CDI is gradually decreasing (from 23% to 16%). Due to potentially delayed manifestation of water and electrolyte imbalance, it is recommended that these parameters should be monitored at least for 2,5 months after the discharge from hospital. Due to potentially delayed remission (12 months and more), follow-up and monitoring for 1.5 years is reasonable, with periodic assessment of sodium levels, fluid intake and excretion, and attempts to withdraw desmopressin.

Thyrotoxicosis, which characteristics are increased excitability, emotional lability, tachycardia episodes, increasing of free fractions of tetraiodothyronine (T4) and triiodothyronine (T3) is one of the most common endocrinological syndromes. However, during the interpretation of thyroid status it is very important to take into account the possibility that a patient has TSH-secreting pituitary adenoma. Timely diagnosis of TSH-secreting adenomas plays prominent role in guiding the treatment course since it is associated with an improvement of long-term prognosis and an increase of the patient’s total life expectancy. Needed to underline that in some patients with TSH-secreting adenomas manifestations of the other pituitary hormones hypersecretion (first of all — somatotropin and prolactin) come to the fore, that lead to the development of acromegaly and hyperprolactinemia accordingly. Our work basing on two clinical cases presents main principles of diagnosis and specific clinical manifestations of TSH-secreting pituitary adenomas and demonstrates efficacy of somatostatin analogues in the treatment of this pathology.

Acromegaly is a severe neuroendocrine disease caused by chronic excessive production of somatotropic hormone (STH), characterized by specific changes in appearance, metabolic disorders. In 95% of cases, the cause of pathology is STH-producing pituitary adenomas. The priority method of treatment for acromegaly is transnasal transsphenoidal adenomectomy. If it is impossible to carry out neurosurgical intervention, in order to prevent the progression of the disease and the development of complications, patients are recommended drug therapy with long-acting somatostatin analogues, and if their effectiveness is low, additional radiation therapy may be applied to the neoplasm area. The usage of a relatively new group of drugs, antagonists of STH receptors, namely Pegvisomant for the purpose of drug treatment of acromegaly demonstrates high efficacy even in cases of aggressive forms resistant to other types of treatment. In this article we present two clinical cases of hereditary acromegaly, when the initiation of Pegvisomant therapy led to the achievement of clinical and laboratory remission of acromegaly in patients with an aggressive form of the disease, accompanied by continued growth of residual neoplasm tissue and preservation of its secreting ability even after surgical interventions, radiatiotherapy and long-term drug treatment with somatostatin analogues. The results of the above clinical cases confirm the success of mono- or combined (in cases with continued growth of the neoplasm) therapy with a growth hormone receptor antagonist, Pegvisomant, especially in the case of aggressive acromegaly.

Objective: To evaluate the effectiveness and conduct a comparative analysis of consumer qualities of desmopressin intranasal drops 0.01% 5ml ("Biopharm", Georgia) in patients with central diabetes insipidus (CDI). Materials and Methods: The study included 9 patients (3 men and 6 women, mean age 44 ± 12 years) diagnosed with CDI. Patients for 7 days were switched to desmopressin intranasal drops 0.01% (JSC "Biopharm" Georgia) from there basal desmopressin preparations by means of recalculating daily dose by proposed formular: 10 mg (2 drops) of desmopressin intranasal drops = 0.2 mg of desmopressin tableted = 10 micrograms (one dose) of intranasal spray metered desmopressin = 120 mcg sublingual tablets of desmopressin. Safety biochemical parameters, efficiency to control of the main manifestations of CDI, increase in urine specific gravity, quality of life, basic consumer properties of different desmopressin preparation were evaluates at baseline and after treatment period. Results: Desmopressin nasal drops 0.01% showed to be an effective drug for the treatment of patients with CDI. Dose calculation algorithm daily was adequate in most patients. Hyponatremia was detected in 2 out of 9 patients during the study period but has been related to study drug alone in one case. The investigational drug was marked convenient to use by less than 25% of patients which may be associated with the pharmacological form of the drug as intranasal drops with special storage conditions (refrigerator). Conclusions: The drug desmopressin intranasal drops can be recommended as a second line (reserve) therapy in the treatment of patients CDI. Sodium levels should be checked during initiation of therapy.

Background : At present, surgical intervention is a major treatment strategy for pituitary adenomas. It is commonly complicated with water and electrolyte imbalance. The prevalence of post-surgical central diabetes insipidus (CDI) may amount to 30%; however, its risk factors have not been established. Aim : To assess the rates and nosological distribution of CDI after transnasal adenomectomy and to identify its risk factors. Materials and methods : This retrospective study included 96 patients aged 20 to 65 years (median [Q1; Q3] 43 [34.5; 53.5]), who had transnasal adenomectomy in 2010-2011 due to Cushing's disease, acromegaly, prolactinoma, non-functioning pituitary adenoma. All patients underwent clinical examination and laboratory work-up before and after surgery. Their post-surgical course was assessed for 5 to 7 years. Depending on identified manifestations, the patients were categorized into the permanent CDI (n = 15) and transient CDI (n = 34); 47 patients had no CDI. Results : Cushing's disease (odds ratio (OR) 6.1, 95% confidence interval (CI) 2.3-16.1), secondary adrenal insufficiency (OR 6.8, 95% CI 2.618.3) and adrenocorticotropic hormone levels of < 15.8 pg/mL (OR 5.0, 95% CI 1.9-13.5), microadenoma (OR 4.5, 95% CI 1.7-11.5) promote transient postoperative CDI, whereas macroadenoma decrease this risk (OR 0.2, 95% CI 0.1-0.5). The transient CDI was also more common in patients with secondary hypothyroidism, cortisol level of<200 nmol/L, adenoma's volume at magnetic resonance imaging of < 0.83 cm 3 at trend level and more rare in patients with acromegaly and loss of tropic hormones before surgery at trend level as well. No significant risk factors were identified for permanent CDI, but it could be more often associated with secondary hypothyroidism, absence of any adenoma at magnetic resonance imaging and pituitary injury during the surgery and less frequent in patients with macroadenomas at trend level. Conclusion : The proportion of permanent postoperative CDI was 16% (95% CI 9-24), and that of the transient form 35% (95% CI 25-45). Cushing's disease, microadenoma, development of secondary adrenal insufficiency and adrenocorticotropic hormone levels of < 15.8 pg/mL after surgery increase the probability of transient CDI, whereas macroadenoma does decrease this risk. No significant risk factors were identified for permanent CDI.

The study objective is to compare pre- and intraoperative characteristics, and the results of neurosurgical treatment in patients with Cushing’s disease, non-visualized adenoma and microadenoma of the pituitary gland.Materials and methods. The results of transsphenoidal adenomectomy were analyzed in 102 patients with non-visualized corticotropinomas and 360 patients with microcorticotropinomas. The pituitary genesis of endogenous ACTH-dependent hypercorticism in 182 patients was proved by the results of selective blood sampling from inferior petrosal sinus with stimulation desmopressin. The study included 369 women and 93 men aged 16 to 64 years. All patients were operated by transnasal approach using endoscopic techniques.Results. The group with non-visualized adenoma was dominated by men (p = 0.005) and patients with severe hypercorticism (p = 0.021). When comparing intraoperative characteristics in this group, invasive growth was statistically significantly more frequent (53 % vs 39 %) (p = 0.017), which in turn led to more aggressive intraoperative tactics (p <0.001) and more frequent development of hypothyroidism (11 % vs 4 %) (p = 0.028) in the early postoperative period. Early postoperative remission occurred in 73 (72 %) of 102 patients with non-visualized adenoma and in 314 (87 %) of 360 patients with microadenoma (p <0.001).Conclusion. Early results of primary transsphenoidal adenomectomy in patients with non-visualized pituitary adenoma were significantly worse in comparison with patients with microadenoma detected by 1.5 T magnetic resonance imaging, which have more frequently invasive growth, what leads to an increase in the volume of surgery and a possible increase in postoperative hypopituitarism.

Background Some laboratory and clinical features are associated with a probability of recurrence after transnasal adenomectomy for Cushing disease (CD). However, there is no consensus on a set of predictors. Rules for prediction of recurrence were not proposed earlier. Aim To develop prediction model of recurrence/remission after successful neurosurgical treatment for CD. Methods Retrospective single-site comparative study included 349 patients (52 men and 297 women) with a verified diagnosis of CD who underwent effective endoscopic transsphenoidal adenomectomy between 2007 and 2014. Clinical and laboratory parameters were evaluated. Laboratory tests were performed using immunochemiluminescent method. Time-to-event analysis and ROC-analysis were applied. Multivariate models were developed using logistic regression and artificial neural network (ANN). Results Postoperative cortisol and ACTH levels and their combinations cannot be used for prediction of recurrence. ANN for prediction of recurrence within 3 years after successful surgery was developed. Input variables are age, duration of the disease, MRI data on adenoma, morning postoperative levels of ACTH and cortisol, output variable is binary (recurrence/remission). Predictive value for remission is 93%, 95% CI [89%; 96%], and predictive value for recurrence is 85%, 95% CI [71%; 94%]. Web-calculator based on the model is developed and free for use. Conclusion Effective method for prediction of recurrence and long-term remission within 3 years after successful endoscopic transsphenoidal adenomectomy is proposed.

Background: Disorders of water and electrolyte balance, hyper- and hyponatremia, are common postoperative complications of transsphenoidal neurosurgical interventions and are found in up to 30–40% of cases. At the same time, delayed hyponatremia is the main cause of repeated hospitalizations of patients, and the risk factors/pathogenetic mechanisms responsible for the development of postoperative hyponatremia have not been fully investigated. Aim: To determine the frequency of water-electrolyte disturbances and to identify predictors of dysnatriemia states in patients after transnasal adenomectomy. Materials and methods: A retrospective single-site study included an analysis of electronic medical records of patients who underwent transnasal neurosurgical interventions for benign tumors of the pituitary gland ( n = 416). The diagnostic and prognostic factors for the development of postoperative water-electrolyte disorders were evaluated. Results: The prevalence of hyponatremia in the total group of patients was 7.2%, and for hypernatremia it was 3 times higher – 24.3%, with these indicators being kept stable through the years of surgery ( p > 0.05; χ 2 with the Yeats correction). 66 (16%) of the operated patients, the sodium level in the early (0–5 day) and 157 (38%) patients in the later (6+ day) postoperative period was not determined, which may underestimate the identification of the most dangerous delayed postoperative hyponatremia. When analyzing the main clinical and laboratory characteristics of patients with hypo-, normo- and hypernatremia, no statistically significant differences were found between the parameters characterizing natremia, the osmolality of blood and urine, the frequency of determining blood sodium in different time intervals of the postoperative period. Complications of the main diagnosis (diabetes mellitus, coronary heart disease and arterial hypertension), selected parameters of pathological examination (identification of neurohypophysis cells, adenohypophysis, oxyphilic, basophilic or chromophobic cells, as well as other structures that are not part of the pituitary gland) and the operation protocol (bleeding, coagulation of sellar structures, liquorrhea, excision of the pituitary gland), did not differ between groups. In the hypernatremia group, the tumor volume in quantitative representation was lower than in the normo- and hyponatremia groups (1.0 ml vs. 1.5 and 1.5 ml, respectively). The number of neurosurgical interventions performed in a patient did not differ between the study groups. Conclusions: After transnasal adenomectomy, hypo- and hypernatremia occur in 7.2% and 24.3%, respectively, and do not depend on the presence of complications of the underlying disease, the parameters of the pathomorphological protocol, the appearance of postoperative hypopituitarism or the course of the operation itself. For the timely detection of disorders of water and electrolyte metabolism, the implementation of blood sodium testing in the early and late (6+ day) postoperative period is necessary in management of patients after transnasal adenomectomy.

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 Cushingas 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 Cushingas 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.

Objective : to popularization the knowledge about hemostasis in patients with chiasmosellar tumors during conduction of endoscopic transnasal transsphenoid neurosurgical operations. Material and methods . The analysis of literature data dedicated to mechanism of action and area of application of modern hemostatic materials to solve the problem of hemostasis on endonasal surgery; our own material including more than 2000 patients operated during 10 years. Results: nowadays the principles of surgery in patients with chiasmosellar tumors had been totally changed thanks to endoscopic technologies. The appearance of new hemostatic materials and new methods of their application allow recommending them in various clinical situations. Conclusion : the usage of modern hemostatic materials allows conducting endoscopic transnasal interventions with minimal blood loss as well as decreasing the numbers of complications and expenses involved in blood transfusion.

Objectives. The aim of this research was to study the dynamic changes of intra- and early postoperative hormonal parameters (ACTH and cortisol) as predictors of hypercorticism remission. Material and methods. 50 patients with confirmed Cushing`s disease (CD) were sampled for this research. The patients were divided into 3 groups depending on the outcome of the operation. The first group – patients with secondary adrenal insufficiency confirmed by clinical picture and the level of cortisol less than 50 nmol/l; the second group – with normalization of levels of ACTH and cortisol; the third – with the persistence of the CD. The results of intraoperative studies during the transnasal adenomectomy were then studied. The group sample consisted of 38 women and 12 men, aged 15–66 years. To assess the levels of ACTH and cortisol blood sampling was performed from a peripheral vein. The first sample was taken during the incision of the Dura mater, the second – immediately after removal of the tumor and the last – 20 minutes after the removal of the adenoma. Then, 1 day after the surgery the hormones mentioned above were studied in all patients. The levels of ACTH and cortisol were measured by immunochemiluminescent analysis on the automated system Cobas 6000 (Roche, France). Reference intervals ACTH 0–30 ng/ml, cortisol123–626 nmol/l. Results. The analysis of the obtained data did not suggest a relationship between the changes of intraoperative indicators of hormonal status and the likelihood of disease remission (p > 0.125). In the postoperative period, of the 50 patients, 41 (82%) developed adrenal insufficiency, 5 (10%) showed normalization and in 4 patients (8%) adrenal insufficiency was not observed. The results of the hormonal research after 1 day had a correlation with the frequency of postoperative remission (p < 0.125). Conclusion. Intraoperative measurement of levels of ACTH and cortisol is not appropriate and cannot serve as guidance for further tactics of the surgeon to define the totality of tumor removal.

Postoperative diabetes insipidus is a common life-threatening morbidity after pituitary surgery. More frequent neurosurgeon interventions make drugs’ adjustment very important for higher life quality in the case of postoperative complications. We present the case of personalized adjustment of drug dosage to treat postoperative diabetes insipidus in patient undergoing reccurent transnasal adenomectomy.

Cushing's disease (CD) is a progressive neuroendocrine disease caused by a pituitary tumor producing excessive amounts of ACTH. In most cases (80-85%) the cause of the disease is a pituitary corticotroph microadenomas (located within the sella, measuring 3–10 mm, rarely multiple microadenomas) and only 15% of cases are presented as corticotroph hyperplasia or pituitary macroadenoma extending beyond the sella. The macroadenomas in CD usually extend suprasellar (10%), infrasellar tumor growth is relatively rare (5%). If the clinical picture is subtle, the symptoms are caused by the development "mass effect" of the tumor as it propagates to the surrounding pituitary structures. Suprasellar growth leads to compression of the optic chiasm with narrowing of visual fields, infrasellar growth destructs the bottom of the sella turcica and may cause nasal cerebrospinal fluid leak, which is dangerous due depressurization of the cranial cavity and its communication with environmental pathogens, development of life-threatening conditions such as meningitis, meningoencephalitis, ventriculitis. Leading life-threatening complications of the CD are infectious and cardiovascular. But in the case of nasal liquorrhea with expansion of the tumor in sphenoid sinus with destruction of the bottom of the sella, there is an immediate threat to the life of the patient. This article presents an example of a patient with morbid obesity and lack of specific clinical manifestations of CD, in whom the diagnosis of disease CD was made on the results of laboratory and instrumental examination, which experienced a spontaneous nasal cerebrospinal fluid leak.

Objective. To estimate the outcomes of repeated transsphenoidal adenomectomy (RTA) at patients with relapse and persistent course of Itsenko-Kushing disease and to optimize the limits of surgical intervention at such patients. Material and methods. The analysis of RTA results at 50 patients (42 women and 8 men at the age from 16 till 64 years old) with confirmed Itsenko-Kushing disease was conducted. The mean time of RTA performance was 36 months. All patients underwent endoscopic surgery. Results. The remission after RTA was seen at 28 (56%) patients, among them 20 (69%) suffered from developing adrenocortical insufficiency, the recovery of hormonal state was revealed at 8 (31%). The hypercorticoidism remained at 22 (44%) patient. Follow-up after RTA was 6 months with following examination at 30 patients which revealed remaining hypercorticoidism at 14 (47%) persons, complete remission - at 14 (47%) patients and disease relapse - at 2 (6%) patients. Conclusion. The repeated transsphenoidal adenomectomy is relatively safe and effective treatment method at patients with relapse and residual course of Itsenko-Kushing disease while performed under conditions of specialized department. The clear predictors for persistence development or relapse of ACTH-dependent hypercorticoidism were not revealed. The limits of repeated neurosurgical intervention are necessary to determine on a case by case basis.

In this article we describe a rare case of spontaneous remission of acromegaly as a consequence of hemorrhage to pituitary adenoma and subarachnoid space, followed after intraoperative bleeding during transnasal removal of somatoprolactinomas.