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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 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.

Primary hyperaldosteronism (PA) - is the clinical syndrome, results from autonomous of the major regulators of secretion, aldosterone overproduction by a tumorous or hyperplastic tissue in adrenal cortex. Being the most frequent cause of secondary hypertension, PA may be represented by disorders with unilateral or bilateral aldosterone overproduction and differential diagnosis between them is crucial for choosing a right therapeutic approache: lifelong medical therapy with mineralocorticoid receptor antagonists or unilateral adrenalectomy. Adrenal venous sampling (AVS) is currently the «gold standard» test for identifying laterality of excess hormone production, unlike imaging tests, sensitivity and specificity of which is not enough, due to inability to evaluate functional activity with confidence, and also to limitations in detecting tiny abnormalities of adrenals, such as microadenoma or hyperplasia. Excluding certain cases, AVS is recommended to patients with confirmed PA, planning surgical treatment, to determine the lateralization of aldosterone hypersecretion. Described clinical case of patient with confirmed lateralization from adrenal without any detected lesions on CT-imaging and nonfunctioning tumour on contralateral side, highlights the importance of using AVS for decision to refer patients for surgery.Первичный гиперальдостеронизм (ПГА) - клинический синдром, развивающийся в результате избыточной секреции альдостерона функционально автономным от ренин - ангиотензин - альдостероновой системы опухолевым или гиперпластическим процессом в коре надпочечника. Являясь крайне распространенной формой вторичной артериальной гипертензии, ПГА может быть представлен нозологиями как с односторонней, так и с двусторонней гиперпродукцией альдостерона, дифференциальная диагностика между которыми является ключевым моментом для определения лечебной тактики и показаний к оперативному лечению, целесообразному лишь при одностороннем варианте ПГА. В настоящее время сравнительный селективный венозный забор крови (ССВЗК) из надпочечниковых вен является «золотым стандартом» в дифференциальной диагностике нозологических форм ПГА, в отличие от визуализирующих методов, не обладающих достаточной чувствительностью и специфичностью. За исключением определенных случаев, ССВЗК рекомендован к проведению всем пациентам с подтвержденным ПГА, планирующим оперативное лечение. На примере представленного клинического наблюдения пациентки с подтвержденной односторонней гиперпродукцией альдостерона, картиной неизмененного надпочечника по данным визуализирующих исследований и наличием гормонально - неактивного образования контралатерального надпочечника подчеркивается важность проведения ССВЗК для решения вопроса об оперативном лечении.

Background: The high incidence of cervical lymph nodes metastasis in highly differentiated thyroid carcinoma (DTC) and insufficient of existing diagnostic methods determines the urgency of finding reliable and more effective tests. Aims: The aim of our study is to determine the prognostic significance of the thyroglobulin measurement in washout fluid from fine-needle aspiration biopsy (FNA-Tg) and the cut-off value in the diagnosis of DTC lymph nodes metastasis. Materials and methods: 245 patients evaluated for suspicious cervical lymph nodes were retrospectively reviewed. All patients underwent FNA-Tg, serum thyroglobulin (sTg) levels, thyroglobulin antibodies (Tg-Ab), thyroid-stimulating hormone (TSH) were measured. 125 patients with malignant changes according to FNA and/or high FNA-Tgvalues underwent surgical treatment. Patients were divided into 2 groups with reactive (n = 23) and metastatic (n = 102) changes. FNA-TG was assayed on automated system Cobas 601 (Roche, France). Results: All patients were comparable by sex, age and levels of TSH, sTG, Tg-Ab. The FNA-Tg median in metastatic group was 537.0 [0.1; 1000], and in benign group – 17.9 [0.5; 158.0], p = 0.003. The sensitivity of isolated FNA was 85%, specificity 57%, AUC = 0.618, 95% CI 0.516–0.713. The sensitivity and specificity of FNA-Tg was 73% and 100%, respectively, AUC = 0.865, 95% CI 0.78–0.92. The optimal cut-off point for malignancy was >9.2 ng/ml (sensitivity 75%, specificity 100%), Youden Index 0.73. Conclusions: Additional FNA-Tg may increase the sensitivity of isolated FNA in evaluation of DTC lymph node metastasis. The optimized cut-off value >9.2 ng/ml can be proposed as a diagnostic threshold for the definition of malignancy.

Primary aldosteronism (PA) is the most common form of secondary arterial hypertension. In patients with PA, more so than in the general population, there is a prevalence of insulin resistance, diabetes mellitus, metabolic syndrome, osteoporosis, and symptoms of depression; these conditions are more likely to manifest a gluco- rather than mineralocorticoid excess. This fact is of particular importance in light of recent studies that have shown that PA is often associated with glucocorticoid excess. Since the first reports of cases of combined secretion of aldosterone and cortisol in 1979, the number of cases of so-called Connshing syndrome has increased. An analysis of data from recent studies suggests that hypercortisolism in PA is closely associated with an increased risk of cardiovascular complications, metabolic disorders and post-surgical adrenal insufficiency. The most important diagnostic problem in adenomas with combined secretion is the risk of false interpretation of the results of adrenal venous sampling (AVS). The indications that suggest aldosterone-and-cortisol-co-producing adenoma are the lack of suppression of cortisol levels following a night test with 1mg of dexamethasone, and an adrenal tumo of over 2.5cm. As an alternative test capable of differentiating this type of tumor, a number of researchers have proposed measuring the level of so-called hybrid steroids in the peripheral plasma and urine. Taking into account the high prevalence and potential risks, ruling out of excess corisol secretion is obligatory in all cases of PA before AVS and when planning surgery.Первичный гиперальдостеронизм (ПГА) является самой частой формой вторичной артериальной гипертензии. У пациентов с ПГА чаще, чем в общей популяции, отмечаются инсулинорезистентность, сахарный диабет, метаболический синдром, остеопороз, симптомы депрессии и тревожности – состояния, скорее являющиеся проявлением избытка глюко-, а не минералокортикоидов. Этот факт имеет особое значение в свете недавних исследований, показавших, что ПГА нередко ассоциирован с синдромом гиперкортицизма. С момента первого указания на сочетанную секрецию альдостерона и кортизола (1979 г.) число описаний случаев так называемого синдрома Конншинга, увеличивалось. Анализ данных последних лет позволяет заключить, что гиперкортицизм при ПГА тесно связан с повышенным риском сердечно-сосудистых осложнений, метаболических нарушений и надпочечниковой недостаточности в исходе оперативного лечения. Самой важной диагностической проблемой при аденомах с сочетанной секрецией является риск ложной интерпретации результатов сравнительного селективного забора венозной крови из надпочечниковых вен (ССВЗК). Признаками, позволяющими заподозрить альдостерон- и кортизол-продуцирующую аденому, являются отсутствие подавления секреции кортизола на фоне ночного теста с 1 мг дексаметазона и размеры образования надпочечника более 2,5 см. В качестве альтернативного теста, способного дифференцировать данный тип опухолей, рядом исследователей предложено измерение концентрации так называемых гибридных стероидов в периферической плазме и моче. С учетом высокой распространенности и потенциальных рисков обязательное исключение гиперкортицизма рекомендуется во всех случаях ПГА перед ССВЗК и при планировании оперативного лечения.

Цель работы. Изучение динамического изменения интра- и ранних послеоперационных гормональных показателей (адренокортикотропного гормона (АКТГ) и кортизола) в качестве предикторов ремиссии гиперкортицизма. Материал и методы. Проведен сравнительный анализ результатов эндоскопической аденомэктомии у 50 пациентов с болезнью Иценко–Кушинга. Пациенты были разделены на три группы в зависимости от исхода операции. Первая группа – пациенты с вторичной надпочечниковой недостаточностью, подтвержденной клинической картиной и уровнем кортизола меньше 50 нмоль/л; вторая группа – с нормализацией уровней АКТГ и кортизола; третья – с персистенцией болезни Иценко–Кушинга. Оценена динамика снижения уровней АКТГ и кортизола во время операции и в раннем послеоперационном периоде. Группу составили 38 женщин и 12 мужчин в возрасте от 15 до 66 лет. Заборы крови для оценки уровней АКТГ и кортизола производились из периферической вены: первый – на этапе разреза твердой мозговой оболочки, второй – сразу после удаления опухоли и заключительный – через 20 мин после удаления аденомы. Затем исследование вышеуказанных гормонов проводилось всем пациентам через сутки после операции. Уровни АКТГ и кортизола определялись путем иммунохемилюминесцентного анализа на автоматизированной системе Сobas 6000 (Roche, Франция). Референсные интервалы АКТГ – 0–30 нг/мл, кортизола – 123–626 нмоль/л. Результаты. Не получено четкой зависимости между изменениями уровня исследуемых гормонов в интра- и раннем послеоперационном периоде (20 мин после удаления опухоли) и вероятностью наступления ремиссии заболевания (p > 0,0125). Результаты гормонального исследования через сутки коррелировали с частотой послеоперационной ремиссии (p < 0,0125). В послеоперационном периоде из 50 пациентов у 41 (82%) развилась надпочечниковая недостаточность, у 5 (10%) пациентов показатели нормализовались и у 4 (8%) пациентов наблюдалась персистенция гиперкортицизма. Заключение. Интраоперационное определение уровней АКТГ и кортизола не является целесообразным для оценки радикальности удаления опухоли.

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.

Primary hyperparathyroidism (PHPT) is a common disorder often associated with reduced bone mineral density (BMD) and osteoporosis. The main goal in treating patients who refuse surgery is the correction of bone complications. The aim of this study is to evaluate safety and efficacy of alendronate treatment in patients with PHPT and osteoporosis. Eligible patients were postmenopausal women suffering from PHPT who did not meet surgical guidelines or ignored surgery due to different reasons. 55 osteoporotic or osteopenic women received alendronate 70 mg weekly and 43 were leaved under medical observation for the reasons of not being osteoporotic or financial unable to comply with treatment/ Results: After 2 years of treatment alendronate group showed statistically significant gain in BMD at L24 +4,0±4,2%, Neck +2,2±4,4%„ TH +2,3±4,5%. At the same time observational group showed decrease in BMD at L24 -4,2±4,0%, TH -3,5±3,8%, R33% -4,0±6,5%, [95% CI -7,6; -0,4]. On the whole BMD dynamics in groups differed at the following sites: L2 (p=0,00004), Neck (p=0,005), TH (p=0,001), R33% (p=0,006). ' Alendronate intake was accompanied by serum Ca decrease (at 1 year point -4,3±5,4%, p=0,00005, at 2 year -2,7±6,4%, p=0,04), 24 hours'Ca excretion decrease from (Me) 8,5 to 6,3 mmol/day at 1 year point, (p=0,007) without PTH elevation. As well as CTx fell at Me: 66% at 1 year and at 60% at 2 year point and OK at 39% and at 27%, correspondingly, p

Introduction. In patients with obesity coronary atherosclerosis and chronic heart failure (CHF) progress rapidly and have a worse long-term prognosis than those with normal weight. Objective: To investigate the prognostic significance of GH and IGF-1 in the evaluation of cardiovascular risk in patients with obesity. Materials and Methods. The study included 75 men (mean age 55.31±6.32 years), which are overweight or have mild obesity (body mass index (BMI) 28.69±3.6 kg/m 2 ). Group 1 included 45 patients (age 56.4±6.29 years, BMI 28.69±3.69 kg/m 2 , blood pressure 124±10.18/80±4.59 mm Hg) who underwent coronary angiography. Group 2 included 30 patients (mean age 53.6 ± 6.1 years, BMI 28.68±3.52 kg/m 2 , blood pressure 128±9/83±6.81 mm Hg), CAD who are excluded by treadmill test. The coronary artery calcium score was assessed in group 2. All participants were evaluated impaired glucose tolerance (IGT), triglycerides (TG), IGF-1 and GH, LPHD, LPLD, geometry of the heart chambers was assessed by echocardiography. Results. Patients in both groups did not differ in age, BMI, blood pressure. IGF-1 levels were not significantly different among the study groups. High circulating IGF-1 levels were frequently observed in group 1 (р=0.018). A statistically significant association of high IGF-1 observed with obesity (p=0.033), smoking (p=0.049), hypertension (p=0.002), end-diastolic dimension (p=0.045). GH was lower in group 1 compared with group 2 (p=0.046). Serum levels of GH are positively associated with EF (p=0.023) and E/A (p=0.043) and negatively associated with left atrial wall thickness (p=0.025) and coronary artery calcium score (p=0.005). Conclusion: 1. IGF-1 may be a useful indicator to assess the prognosis of CAD and CHF in patients with obesity. 2. Relative GH deficiency was more often associated with severe CAD in patients with obesity.

The high prevalence of diseases associated with the disturbances in the renin-angiotensin-aldosterone system (RAAS) including those affecting the children dictates the necessity of the development and application of highly specific, accurate, and sensitive indices. One of them widely used at present is plasma renin activity (PRA). Meanwhile, foreign researchers have demonstrated significant correlation between PRA and direct renin concentration that can be determined by a technically simpler and readily available method. We are unaware of the studies with the application of this approach reported in the Russian-language publications. The present work was designed to consider the possibility of using direct rennin levels and PRA for monitoring health conditions of the children presenting with congenital adrenal cortical hyperplasia. PRA and direct rennin concentrations were determined with the use of the relevant assay kits in 72 patients admitted to the Pediatric Department of Endocrinological Research Centre. Group 1 was comprised of 44 patients presenting with congenital adrenal cortical hyperplasia (CAH), group 2 consisted of 28 patients with the presumably unaffected adrenal function. Direct rennin concentrations and PRA are known to have virtually identical diagnostic value, i.e. they can equally well be used to diagnose disorders of RAAS functions including those in the patients with CAH. However, the measurement of direct rennin permits to more precisely detect hyperaldosteronism and identify children exhibiting symptoms of mineralocorticoid overdose. The patients with the supposedly normal functioning adrenal glands were also found to show high percentage of abnormal PRA values and direct rennin levels which suggests the relationship between the functions of RAAS and other endocrine organs.

Therapy with bisphosphonates (BP) is recognized to be "the golden standard" for the treatment of osteoporosis of different etiology. However, the data on the use of BP by the women during pregnancy and lactation are scarce. This paper reports a case of gestation, labour, and lactation in a patient treated with ibandronic acid (Bonviva) for severe steroid-induced osteoporosis attributable to Cushing's disease. To our knowledge, the application of ibandronic acid during pregnancy has never been described in the literature before. The present study has demonstrated that therapy with ibandronic acid does not necessarily require the interruption of pregnancy or cessation of birth feeding. Nevertheless, the treatment of the women of reproductive age with BP can be prescribed only upon strict indications.

This study included the patients presenting with neuroendocrine tumours (NET) and the clinical picture of hypercoticism caused by excessive ACTH secretion from the tumour. The overwhelming majority of the patients (85%) suffered Cushing's disease (CD) associated with a pituitary tumour. The remaining 15% of the patients presented with ACTH-ectopic syndrome (ACTH-ES). The clinical picture of CD and ACTH-ES was very similar. The latter condition was associated with the higher plasma ACTH and cortisol levels as well as the free cortisol content in 24 hour urine and saliva samples collected in the evening compared with CD even though the differences were insignificant due to data scattering. Decompressin administration and catheterization of inferior petrosal sinuses caused a much greater enhancement of the ACTH level in the patients with CS in comparison with those suffering ASTH-ES.

The objective of the present study was to estimate the informative value of the measurements of aldosterone level, direct renin, and plasma renin activity as well as the relationships between these characteristics for differential diagnostics of various forms of hypertension and, first and foremost, of primary aldosteronism. We have examined a total of 162 patients. The results of differential tests were used to allocate them to a few groups including 41 patients presenting with primary aldosteronism, 52 ones with incidentalomas, 26 with essential hypertension, and 43 with various endocrine diseases and normal arterial pressure (control groups). The aldosterone levels, direct renin, and plasma renin activity were measured in blood samples taken in morning hours from the patients in the supine position. The aldosterone to plasma renin activity (A/PRA) and aldosterone to direct renin (A/DR) ratios were calculated. The elevated blood aldosterone level is currently believed to be the principal criterion for primary aldosteronism in the patients suffering arterial hypertension. The RIA technology is the method of choice for the measurement of aldosterone levels. The determination of the A/PR ratio significantly improves the detectability of the disease. The use of direct renin level instead of kinetic renin ensures the high efficacy of screening for primary aldosteronism and its early diagnostics. The cut-off point for the calculation of the A/PRA ratio to differentiate between primary aldosteronism and incidentalomas is 2160 pmol/mcg/hr (sensitivity 100%, specificity 97.8%) in comparison with the analogous cut-off point for the discrimination between primary aldosteronism and endocrine pathology without hypertension is 49 pmol/mU (sensitivity 100%, specificity 95%). The cut-off point for the calculation of the A/PR ratio to differentiate between primary aldosteronism and incidentalomas is 2160 pmol/mcg/hr (sensitivity 89.5%, specificity 99%) in comparison with the analogous cut-off point for the discrimination between primary aldosteronism and endocrine pathology without hypertension is 1432 pmol/mcg/hr (sensitivity 89.5%, specificity 100%). It is concluded that the results of determination of direct renin level in the blood plasma are independent of the endogenous angiotensinogen level, less variable and more reproducible than than the results of the measurement of plasma renin activity. The aldosterone to direct renin ratio may be used for the screening of primary aldosteronism.

Primary hyperaldosteronism is known to be one of the commonnest causes of arterial hypertension. The authors propose a diagnostic protocol for primary hyperaldosteronism and a method for comparative selective blood sampling from adrenal veins. This method is described as the sole tool for differential diagnostics of different nosological forms of primary hyperaldosteronism. A clinical case of idiopathic hyperaldosteronism is presented.

The objective of the present study was to estimate the prevalence and and characterize clinical phenotypes of PCOS. A total of 312 women from 18 to 45 years of age working engaged in Moscow enterprises were examined in 2009. All of them were interviewed by questionnaire, underwent routine medical examination, anthropometry and blood sampling for the measurement of Prl, TSH, FSH, testosterone, 17-OP, and DHEAS levels. The degree of hirsutism was assessed using the modified Ferriman-Galway scale. Women with fewer than eight cycles during a year were regarded as having menstrual problems. All women presenting with disturbances were invited for verification of the diagnosis. PCOS was diagnosed based on the Rotterdam (2003) criteria (the presence of oligo-/amenorrhea and clinically manifest hyperandrogenism (hirsutism), with all other disorders simulating the clinical picture of PCOS being excluded). All patients with clinical signs of PCOS were examined at the Endocrinological Research Centre. They were divided into the following groups: 1. Regular menstrual cycles in the absence of hirsutism. 2. Menstrual dysfunction (oligo-/amenorrhea) without hirsutism. 3. Hirsutism without menstrual disturbances. 4. Menstrual dysfunction plus hirsutism. Mean age of the women was 30,2±7,4 years, their BMI 24±5,5, overweight patients comprised 17,3% of the total (n=54), obesity occurred in 14.7% (n=46), oligoamenorrhea in 12.8%, hirsutism in 9.3%, acne in 6.4%, infertility in 2.6%, obesity in 14%. Menstrual dysfunction without hirsutism was documented in 17/312 (5.4%) cases. The prevalence of PCOS in this phenotypical group was estimated at 17.6%. Hirsutism in the absence of menstrual dysfunction was diagnosed in 8/312 (2.6%) women (prevalence of PCOS 62.5%), menstrual dysfunction plus hirsutism in 21/312 (6.7%) patients (prevalence of PCOS 85.7%). The study has demonstrated that the overall prevalence PCOS in the given population was 6,4%, but individual symptoms of this condition were manifest much more frequently than that. It is concluded that the diagnosis of PCOS is most reliably confirmed by the presence of combination of oligo-/amenorrhea and hirsutism.

The present paper deals with late results of the treatment of patients with Cushing's disease by proton beam irradiation of the pituitary gland. Retrospective analysis included results of hormonal assays in 197 patients (161 women and 36 men) with verified Cushing's disease who had undergone proton therapy at the Endocrinological Research Centre. The age of the patients prior to irradiation varied from 17 to 54 years (mean 29±12.1). Duration of the follow up period ranged from 1 to 24 years. Each patient was first examined 6 month after irradiation, then annually for 5 years, and thereafter during episodic visits to the clinic of Endocrinological Research Centre. Trophic hormones (ACTH, GH, prolactin, LH, FSH, TSH) as well as cortisol, estradiol, testosterone, and free thyroxin were determined in peripheral blood; in addition, free cortisol was measured in daily urine. ACTH and cortisol were measured twice daily (at 8 a.m. and 11 p.m.) to characterize diurnal dynamics of these hormones. Complete remission of the primary disease was documented based on the results of hormonal assays in 164 (83.6%) patients 0.5-3 (mean 1.5±1.8) years after irradiation; remission without subsequent impairment of the pituitary trophic activity was achieved in 43 (21.8%) patients. Different combinations of post-treatment side effects (hypopituitarism) were recorded in 100 (50.1%) patients while 54 (27.4%) others had only one function affected by radiation. The following disorders of hormonal function of the pituitary and peripheral glands developed: adrenal insufficiency in 58 (29.7%) patients, secondary hypothyroidism in 66 (22.8%), hypogonadism in 93 (47.4%), and hyperprolactinemia in 72 (36.7%). Adrenal insufficiency was the first adverse event to develop after proton therapy (within 0.5-12.0, mean 2.5±2.3, years). It was followed by elevation of prolactin levels and decrease of gonadotropins (within 1.0-7.2, mean 3.0±2.9, years and 0.8-11.8, mean 3.0±3.1, years respectively). Secondary hypothyroidism was the last to develop (within 1.3-12.3, mean 5.0±3.2, years after treatment). It is concluded that biochemical monitoring hormonal changes coupled to the evaluation of the patient's clinical conditions is a very important component of long-term (throughout the lifespan) dynamic observation of patients with Cushing's disease necessary for the timely detection of manifestations of hypopituitarism and initiation of relevant treatment.

The reported clinical case represents an example of characteristic traits in lipid metabolism and fat tissue deposition in hypercorticosolism. Probable causes for fat mass expansion in glucocorticosteroid excess, its distinctive cushingoid distribution, role of 11β-HSD1 and glucocorticoid receptors and reversibility of specific abnormalities after correction of hypercortisolism are discussed in the context of physiological and pathological aspects of glucocorticosteroid action.

Hypogonadism is the most popular cause of BMD decreasing not only in women, but also in men. There are several studies showed a correlation between duration of hypogonadism and BMD reducing degree. Despite wide light exposure of osteoporosis problem at women with hyperprolactinemia, there are a few researches devoted to the same question at men. The aim of our study was to assess the biochemical parameters of bone metabolism and the bone mineral density (BMD) in men with tumoral and not tumoral hyperprolactinemia. In 24 men with hyperprolactinemia and 17 healthy controls we evaluated BMD, serum osteocalcin (OK) and C-terminal telopeptide of type I collagen (CTX), as well as calcium total, ionized calcium and alkaline phosphatase. All men with hyperprolactinemia were also studied after 24 months of cabergoline treatment. The results showed significant differences between study groups in BMD of vertebra and femur bone (p = 0,000052 up = 0,002718). We confirm increasing of BMD in vertebra and femur bone after cabergoline treatment (p = 0,003 и p = 0,027).

OBJECTIVE: The purpose of this study was to evaluate the direct action of desmopressin (agonist of vasopressin) on the hypophysis and the three zones of the adrenal cortex in patients with different forms of hypercortisolism. DESIGN: Forty-three patients with hypercortisolism—21 with Cushing’s disease (14 females, 7 males), 11 with extrapituitary, ectopic tumours (5 females, 6 males), and 11 with ACTH-independent Cushing’s syndrome (6 females, 5 males)—were evaluated. The response of the pituitary and adrenal glands was assessed by measuring plasma levels of Adrenocorticotropic Hormone (ACTH), cortisol, aldosterone, and dehydroepiandrosterone sulfate (DHEAS) at baseline and at 15, 30, 60, 90, and 120 min after the administration of desmopressin. RESULTS: We observed two main modes of secretory response: (1) elevation of the ACTH level followed by a rise of one, two or all three adrenal steroids, and (2) ACTH-independent elevation of adrenal steroids in various combinations. CONCLUSION: In a number of patients with hypercortisolism, the adrenal cortex responded to desmopressin administration by enhanced synthesis and secretion of glucocorticoids (cortisol), mineralocorticoids (aldosterone), and adrenal androgens (DHEAS) without a concomitant rise in ACTH. These findings suggest the presence of “ectopic” vasopressin receptors in the human adrenal cortex.

The aim was to estimate the effects of treatment with alendronate (Fosomax 35 mg) in postmenopausal women with osteoporosis and subclinical hyperthyroidism. Thirty postmenopausal women (64 (60-69) years old) with osteoporosis (T-score ≤ -2,5) and subclinical hyperthyroidism (77% with endogenous subclinical hyperthyroidism and 23% on L-thyroxine suppres-sive therapy after thyroidectomy due to differentiated thyroid cancer) were randomly assigned into two groups: 1-14 women received Fosamax 35 mg a week in combination with 500 mg of calcium and 400 UI of Vitamin D3 (VD) daily; 2-16 women received 1000 mg of calcium and 800 UI of VD daily. Euthyroidism was achieved in all women with endogenous subclinical hyperthyroidism. An increase in physical activity was recommended to all patients and a hypolipidemic diet was given to those who had had high cholesterol level. Biochemical parameters (calcium (Ca), phosphorous (P), creatinine (Cre), alkaline phosphatase (ALP), cholesterol, low density lipoprotein (LDL), high density lipoprotein (HDL), triglycerides (TG), cholesterol/HDL ratio) in fasting serum as well as calcium/creatinine ratio in fasting urine (U-Ca/U-Cre); biochemical markers of bone metabolism: osteocalcin (OC) and C-terminal telopeptide of type I collagen (b-CTx) serum ("ECLIA", Roche Elecsys 1010/2010), BMD (DXA; Prodigy, Lunar) at the lumbar spine (L1-L4), femoral neck (FN), total hip (TH) and radius total (RT) were measured at the baseline visit and after 1 year of treatment. At the baseline visit there were not found any differences between the 1 and the 2 groups. After 12 months of treatment the markers of bone metabolism as well as ALP decreased significantly in both groups, though the decreases were significantly greater (p

The papers examines the specific features ofsteroidogenesis in the adrenal cortex ofpatients with different types of tumors and analyzes the ratio of ∆4- to ∆5-pathways of corticosteroid biosynthesis, which is a governing factor in the development of adrenal cortical hyperfunction. The levels of all major corticosteroids (cortisol, aldosterone, androgens of the adrenals) and their precursors were studied in the peripheral blood of patients with corticosteroma, aldosteroma, androsteroma, and hormonally inactive tumors (in the morning and in the evening). Based on the calculation of the mean daily concentration of steroids and the ratio of product/substrate of an enzymatic reaction in the biosynthesis of corticosteroids, the authors determined the activity of some enzymes and analyzed the changes found in this activity as compared with the normal values. The findings indicate that in corticosteroma, the higher activity of 11β-hydroxylase and the lower activity of 17,20-desmolase leads to a biosynthesis shift to ∆4-pathway; in virilizing tumor, the enhanced activity of Зβ-olsteroid dehydrogenase results in the same shift; in aldosteroma, the ratio of biosynthesis pathways does not differ from the normal values. The significant scatter in the individual values when the blood concentrations were determined in patients with hormonally inactive tumors fails to make an unambiguous conclusion about the activity of steroidogenic enzymes and about the direction of biosynthesis in these patients.

Sixty-nine males aged 18-57 years, who had different impaired reproductive function and the body mass index (BMI) in the range of 20 to 40 kg/m2, were examined. In the patients, the baseline values of leptin, cortisole, corticosterone, dehydroepiandrosterone (DHA) and dehydroepiandrosterone sulfate (DHAS), progesterone, 17-hydroxyprogesterone, testosterone, and insulin were measured by using current radioimmunoassay and enzyme immunoassay. In the examinees, the mean values of all the hormones varied in the physiological normal range with deviations being in some patients. The patients with higher leptin levels were found to have also elevated adrenal hormones, such as corticosterone, cortisole, DHA and DHAS vice versa. This was not accompanied by differences in BMI and in the levels of insulin and testosterone. Analysis of the content of hormones in relation to the level of insulin indicated that there is a positive correlation of the level of insulin and leptin. However, this relationship was multifactorial, which had a possible modifying effects of BMI and the level of testosterone.

Hormonal and semen parameters in 416 men aged 25-45 years were examined: 328 were men who cleaned the territory around the Chernobyl nuclear reactor (called 'liquidators') and 88 were healthy age-matched controls. The dose of radiation received by the liquidators was 0.16 +/- 0.08 Gy. LH, FSH, prolactin, testosterone and cortisol levels were assayed using WHO-matched reagents. Semen analyses were performed according to the WHO Manual (1992). The mean concentration of all hormones in liquidators and controls were within the WHO-defined normal range. The mean levels of LH and cortisol in liquidators were significantly lower (p = 0.013 and p < 0.001, respectively) and testosterone significantly higher (p = 0.023) than in controls. The variations in hormone levels in liquidators were not correlated with the acquired doses of radiation as measured by personal dosimeters (film badges). Semen parameters in a subgroup of 70 liquidators were within the normal WHO-defined range. The percentage of normal forms of spermatozoa in liquidators (35.0 +/- 13.1%) was significantly lower (p < 0.015) than in a control group (42.8 +/- 8.9%). The study has shown that exposure of men to relatively short-term radiation did not cause long-lasting disruption of their endocrine status and spermatogenesis. The study was 7-9 years retrospective and it is therefore impossible to infer what the immediate effects of the radiation exposure were on these parameters.

The level of leptin production was measured in relation to the concentrations of adrenal androgens, testosterone, and gonadotropins in patients with various disorders of the male reproductive system and obesity. LH, FSH, prolactin, testosterone, estradiol, hydrocortisone, dihydroepiandrosterone (DHEA) and DHEA sulfate were radioimmunoassayed and leptin was measured by enzyme immunoassay. Body weight index (ВИД) in 66 examined patients varied from 20 to 40 kg/m2 and leptin content from 0.8 to 106 ng/ml. In general, the level of leptin directly correlated with the levels of BWI, LH, FSH, and DHEA sulfate and inversely with testosterone level. The highest levels of leptin were observed in patients with obesity combined with androgenic insufficiency, while in patients with obesity or androgenic insufficiency alone leptin levels were lower. No significant differences in leptin concentrations in relation to gonadotropin levels were detected. Normal fluctuations in the levels of adrenal androgens did not affect leptin production. These data indicate a possible involvement of testosterone in regulation of leptin production.

Adenomectomy was carried out in 41 patients with Icenko-Cushing’s disease. Before surgery, computer-aided tomography showed pituitary adenomas in all the patients. The patients were divided into 2 groups. Group 1 consisted of 31 patients in whom the disease was diagnosed for the first time and group 2 of 10 patients previously treated by other methods (proton ther- ару and unilateral adrenalectomy) without effect. Pituitary adenomas were removed in all patients. Histological study showed hormone-active pituitary adenomas in all cases. The levels of hydrocortisone and ACTH in the plasma and daily urine were increased in both groups before the operation. Ten-twenty days after surgery, the levels of hydrocortisone and ACTH in group 1 were significantly lower than in group 2. We consider that the lower are the levels of these hormones early after surgery, the lower is the probability of a relapse. Postoperative hypocorticalism (10-20 days postoperation) is a good prognostic sign indicating radical removal of pituitary adenoma. Adenomectomy is indicated for patients with Icenko-Cushing’s disease as primary method of treatment.

Thirty-two children with craniopharyngiomas aged 3.6 to 18.9 were examined. The patients were divided into 2 groups. Group 1 consisted of 16 children treated conservatively and group 2 of 16 children subjected to radical surgery. No release of growth hormone in response to clonidine stimulation (no more than 4,5 ng/ml) was observed in both groups; growth hormone release in response to administration of growth hormone releasing factor was reliably (p=0.003) higher in group 1 than in group 2 (7.5 3.9 and 2,5 5.1 ng/ml, respectively). At the same time, growth SDS was closer to the norm in group 2 than in group 1 (-1.27 1.3 and - 2.04 1.4, respectively), and growth rate in 8 out of 12 children in group 2, despite growth hormone insufficiency, was 6-12 cm/year. Comparison of the levels of serum prolactin in both groups showed no reliable differences, and the standard glucose tolerance test showed a high basal and stimulated level of insulin secretion in 8 children in group 2 and in 1 girl in group 1. The total, area under the curve representing insulin secretion (ACins) was 3016.0 4288.8 IU/l - min in group 1 and 5378.8 + 4511.2 IU/ 1 min in group 2, the correlation between ACins and growth SDS being 0.58 and between ACins and body weight index 0.61. Normal or high growth rate was observed in all the children with hyperinsulinism (ACins over 6000 IU/l min) and in 2 with normal insulin release after surgery, this permitting a conclusion on the principal role of insulin in growth stimulation in the presence of growth hormone insufficiency in these children.

The efficacy and safety of recombinant growth hormone (GH) Norditropin (Novo Nordisk) for children suffering from somatotropic insufficiency have been assessed in clinical trials. Twenty-three children (8 girls and 15 boys) aged 6.3 to 17.5 (mean SD: 12.3 5.96 years) were followed up. The diagnosis was verified by clofelin and/or insulin stimulation tests (max. serum level of GH in the tests no more than 7 ng/ml) and by measuring GH concentration in the nocturnal portion of urine by U-hGH NordiTest TM (Novo Nordisk) kits. Norditropin was injected daily subcutaneously in the evening in a daily dose of 0.07 to 0.1 IU/kg b. w. The treatment was administered for 6 months. During the first 3 months of treatment growth SDS in relation to chronological age increased from -4.5 1.12 to -3.9 1.08 (p0.0001) and the velocity of growth increased from 2.8 1.05 to 18.1 4.73 cm/year (p0.0001). A further increment in body length was observed during the second trimester, although the change of growth SDS in relation to chronological age was less expressed than during the first trimester (0.5 0.19 vs. 0.35 0.19, p=0.012). The gain in height over 6 months of treatment was 7.6 1.01 cm (min. 6.2 cm, max. 9.8 cm), Bone age altered from 6.3 2.99 to 7.3 + 2.66 years (p=0.005) during 6 months; at the same time, despite acceleration of bone age, therapy was conducive to growth SDS increase in relation to bone age (from 1.1 2.87 to 1.7 2.0; Z=2.1, p=0.04), this indicating a better growth prognosis. The treatment caused virtually no side effects of any type. Hence, clinical trials demonstrated the efficacy and safety of GH Norditropin for children with somatotropic insufficiency.

This paper highlights the problem of neuroendocrine tumours (NETs) with clinical symptoms of hypercorticism caused by hypersecretion of adrenocorticotropic hormone (ACTH) by tumour cells. In most cases (85%), the tumours were localized in the pituitary gland (Cushing's disease); 15% of the patients had an extrapituitary tumour that manifest as an ectopic ACTH secretion (EAS). Comparative analysis of clinical, hormonal, histological, and immunohistochemical characteristics of pituitary and extrapituitary ACTH-secreting NET was performed. It included 46 patients with CD and 38 ones exhibiting ectopic ACTH secretion (EAS). Results of the study suggest differences between CD and EAS in terms of the severity of clinical manifestations and duration of the disease. Hormonal studies showed that EAS unlike CD was associated with high plasma ACTH and cortisol levels, late-evening salivary cortisol and daily urinary free cortisol, the absence of a 60% or greater reduction of cortisol in the HDDST test, and the presence of a low (less than 2) ACTH gradient in response to desmopressin administration with catheterization of cavernous sinuses. The study of morphofunctional characteristics of the removed NET demonstrated the ability of both pituitary and extrapituitary NETs to express ACTH as well as GH, PRL, LH, and FSH. The angiogenic markers (CD31 and VEGF) were detected with equal frequency regardless of the NET localization. The histological structure of all corticotropinomas suggested their benign origin, but extrapituitary NETs were represented by different morphological types with varying malignancy, invasiveness, and metastatic properties. A higher cell proliferation potential (Ki-67) was documented for NET in patients presenting with an ectopic ACTH secretion compared to those having corticotropinomas.

It was previously proposed that hyperprolactinemia in primary hypothyroidism is caused by enhanced release of hypothalamic TRH leading to elevation of both TSH and prolactin levels. Since the dopaminergic system is involved in regulation of prolactin and TSH secretion, we attempted to evaluate the origin of hyperprolactinemia in patients with primary hypothyroidism using tests with metoclopramide, a dopaminergic blocker (10 mg, i.v) and TRH. Two groups of patients were examined: 20 women with primary hypothyroidism and normal prolactin levels (group A) and 10 women with primary hypothyroidism and hyperprolactinemia (mean basal prolactin level 1514.8 + 300.8 mIU/ml). Prolactin reaction in metoclopramide test in group A was markedly increased vs. control group (1131 and 776%, respectively). In group В prolactin reaction in metoclopramide test was blurred (299%), similarly as in patients with microprolactinomas. We came to a conclusion that hyperprolactinemia in patients with primary hypothyroidism is unlikely to be caused by excessive TRH release, but possibly by the presence of subclinical microadenoma which manifests by the hypothyroid state or, possibly, by disturbed dopaminergic regulation of prolactin and TSH secretion in patients with primary hypothyroidism.