Introduction: Secondary diabetes mellitus (DM) during glucocorticoid therapy (GT) is caused by insulin resistance (IR) and decreased insulin secretion but their contribution is insufficiently examined. Aim: to evaluate the particularity of carbohydrate metabolism in patients receiving GT. Materials and Methods: The study included 36 patients with interstitial lung diseases (ILD), 11 males, 25 females (age – 54[25-46] years, body mass index (BMI) - 28,3 [25,2-32,1] kg/m2), who received GT (methylprednisolone 8 mg per day) for more than 6 months. Control group (CG) included 19 healthy volunteers, 6 males, 13 females (age - 50[40-53] years, BMI - 31,1 [28,1-35,7] kg/m2). All underwent an oral glucose tolerance test (OGTT), with measurement of plasma insulin and blood glucose in the fasting state and every 30 minutes for 2 hours. We used the insulin resistance index (НОМА-IR) to estimate insulin sensitivity. Results: In GT group the level of glycated hemoglobin (HbA1c) was higher than those in CG: 5,9[5,5-6,3] to 5,6[5,2-5,9]% respectively,р=0,02. The fasting glucose on GT was lower than in CG: 5,0[4,4-5,5] to 5,5[4,8-5,9] mmol/l, р=0,08, while the 120 minute plasma glucose level of OGTT was higher in GT group: 6,7[5,1-8,2] to 5,3[4,4-7,4]mmol/l, р=0,1. НОМА-IR in patients receiving GT was lower than those in CG (1,6[0,9-2,3] to 2,6[1,6-2,3],р=0,02). Area under insulin curve at 30-60 minute in GT group was 1,4 times lower than in CG, p=0,09. Some results were non-significant due to the lack of data. Conclusion: GT in patients with ILD doesn’t lead to IR increase but it can cause postprandial glucose and HbA1c elevation due to the insulin decrease during the second phase.

Acromegaly is a rare disease with increased growth hormone secretion most often caused by pituitary adenoma. Not adequately treated acromegaly may lead to early death related to increased rates of acute cardiovascular events, sleep apnea, metabolic disorders and malignancies. Prevalence of malignancies in acromegaly is in the range of 4.5 to 25%, with some specifics in their pathogenesis, and their proportion as mortality cause is 9 to 50%. Overall and cancer-related mortality in acromegaly are associated with activity of the disease. There is a direct correlation between high levels of insulin-like growth factor 1 and the risk of malignancies. The most common types of cancer in patients with acromegaly are colorectal (1 to 20%) and thyroid cancer (7.8 to 11%). This review of literature describes the results of epidemiological studies on malignancies and some aspects of their pathogenesis in patients with acromegaly.

Rationale: Prevalence of neoplasms in patients with acromegaly and the effects of various risk factors on their development have been insufficiently studied.Aim: To assess the prevalence of thyroid, gastric and colon neoplasms in patients with newly diagnosed acromegaly, depending on their age, gender, duration and activity of the underlying disease.Materials and methods: We retrospectively analyzed data extracted from out- and in-patient medical files of 108 patients with acromegaly (25 male, 93 female). Their median age was 50.5 [range 39.3 to 59] years, median duration of acromegaly 5 [range 2 to 10] years (starting from the first appearance of the first physique abnormalities). Thyroid ultrasound was performed in 96 patients, gastroscopy in 92, and colonoscopy in 89.Results: Benign thyroid nodules were found in 50% (48/96) of patients, malignant thyroid nodules in 6.2% (6/96). Insulinlike growth factor 1 (IGF-1) levels (calculated as a percentage above upper limit of the normal range) in patients with thyroid cancer was 2.3-fold higher than in patients without nodular thyroid disease and 2-fold higher than in patients with benign thyroid nodules (р < 0.012 and p < 0.03, respectively). Malignant neoplasms were more often seen in the elderly (above 60 years of age), compared to younger adults (45 to 60 years) (30.8% and 4.3% of patients, respectively, p = 0.01). Male patients had higher prevalence of thyroid cancer than female (11.1% and 5.1%, respectively). Benign gastrointestinal neoplasms were observed in 51.7% of patients (18% had gastric polyps and 37% colon polyps). Age and duration of acromegaly in patients with gastric neoplasms were higher, than in those without them (р = 0.015 and p = 0.036, respectively). Colon neoplasms consisted of hyperplastic polyps (33.7%) and colon cancer (3% of patients). Patients with colon neoplasms were 11 years older than those without it (p = 0.015).Conclusion: Gastrointestinal tract and thyroid gland should be diagnostically assessed in all patients at diagnosis of acromegaly, because of the higher risk of the neoplasms in these patients. The association of higher IGF-1 levels with thyroid cancer indicates that this factor may contribute to carcinogenesis and requires further studies.

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Распространенность сахарного диабета (СД) и ранних нарушений углеводного обмена (РНУО) при эндогенном гиперкортицизме (ЭГ) по данным различных исследований достигает 70%. Распространенность СД при ЭГ в Московской области (МО) изучена недостаточно. Цель исследования: оценить распространённость РНУО и СД у пациентов с ЭГ Московской области в зависимости от пола и возраста. Материал и методы: были обследованы 42 пациента (5 мужчин, 37 женщин) с ЭГ (32 с кортикотропиномой, 7 - с кортикостеромой, 3 - с АКТГ-эктопированным синдромом), возраст 42,0 [33,7–49,2] лет, длительность заболевания – 36 [24-70] месяцев. Всем больным, за исключением лиц с ранее выявленным СД, проводился пероральный глюкозотолерантный тест. Больные с ЭГ в зависимости от возраста были разделены на 3 группы: моложе 45 лет, 45-55 лет, старше 55 лет. В качестве групп сравнения использовались данные скрининга, проведенного среди случайной выборки взрослого населения МО (838 человек, возраст 47,0 [39,0 – 50,0] лет) и в группе риска (ГР) развития СД (604 человека, возраст 46,0 [39,0 – 52,0] лет) МО. Сравниваемые группы были сопоставимы по возрасту и индексу массы тела. Результаты: Общая распространенность СД среди больных ЭГ составила 62%, что в 7 раз превышает распространенность СД в случайной выборке населения МО (8,9%). Распространённость впервые выявленного СД была вдвое выше в группе ЭГ по сравнению с группой риска развития СД (38,1% и 16,1% соответственно, p<0,05). Распространённость РНУО не различалась в группе ЭГ, в случайной выборке МО и группе риска развития СД (17%, 15.2% и 23,7% соответственно). Среди женщин с ЭГ СД встречался в два раза чаще, чем у мужчин (64,8% и 40,0%, p<0,05), причем распространённость впервые выявленного СД также была выше у женщин, чем у мужчин (40% и 20%, p<0,05). Распространенность СД при ЭГ увеличивалась с возрастом: с 57 % у пациентов моложе 45 лет до 88% у пациентов старше 55 лет. Выводы: Распространенность СД при эндогенном гиперкортицизме значительно превышает таковую как в популяции, так и в группе риска развития СД. Распространенность сахарного диабета увеличивается с возрастом, а также в 2 раза чаще встречается у женщин.

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Background: Somatostatin analogues therapy is an important part of the acromegalic patients’ treatment. Aim: Assessment of treatment efficiency for patients with acromegaly using different doses of somatostatin analogues. Materials and methods: The data of 128 acromegaly patients registered in Moscow Region were analyzed, 79 (61.7%) of them were treated with somatostatin analogues. The treatment was started with a dose of 20 mg. If the target levels of growth hormone (GH) and type 1 insulin-like growth factor (IGF-1) were not achieved within 6-12 months, the dose was increased to 30 mg, and then to 40 mg. If GH and IGF-1 levels fell under the target values, the dose was decreased to 10 mg. The rate of achievement of optimal GH and IGF-1 levels was analyzed depending on the somatostatin analogue doses used. Results: The percentage of the acromegalic patients who were under the first and the second lines of drug therapy, was almost similar: 55.7 and 44.3%, respectively. Sandostatin LAR in dose of 10 mg was given to 4 (5.1%) of 79 patients, 20 mg – to 33 (41.8%), 30 mg – to 11 (13.9%), and 40 mg – to 31 (39.2%) patients. The target levels of GH and IGF-1 were achieved in 57.6, 54.5, and 32.2% of patients, who received preparation in doses 20, 30, and 40 mg, respectively. Achievement of, at least, one planned criterium (GH or IGF-1) was additionally noted in 10 of 33 (30.3%), 4 of 11 (36.2%), and 9 of 31 (29%) patients within these study groups. The rate of side effects didn’t increase with the raising of оctreotide dose. Conclusion: Application of long-acting release octreotide (Sandostatin-LAR) in doses of 30 and 40 mg is safe and allows to increase percentage of acromegalic patients who achieve a biochemical control over acromegaly.

Background: Somatostatin analogues therapy is an important part of the acromegalic patients’ treatment. Aim: Assessment of treatment efficiency for patients with acromegaly using different doses of somatostatin analogues. Materials and methods: The data of 128 acromegaly patients registered in Moscow Region were analyzed, 79 (61.7%) of them were treated with somatostatin analogues. The treatment was started with a dose of 20 mg. If the target levels of growth hormone (GH) and type 1 insulin-like growth factor (IGF-1) were not achieved within 6-12 months, the dose was increased to 30 mg, and then to 40 mg. If GH and IGF-1 levels fell under the target values, the dose was decreased to 10 mg. The rate of achievement of optimal GH and IGF-1 levels was analyzed depending on the somatostatin analogue doses used. Results: The percentage of the acromegalic patients who were under the first and the second lines of drug therapy, was almost similar:  55.7 and 44.3%, respectively. Sandostatin LAR in dose of 10 mg was given to 4 (5.1%) of 79 patients, 20 mg – to 33 (41.8%), 30 mg – to 11 (13.9%), and 40 mg – to 31 (39.2%) patients. The target levels of GH and IGF-1 were achieved in 57.6, 54.5, and 32.2% of patients, who received preparation in doses 20, 30, and 40 mg, respectively. Achievement of, at least, one planned criterium (GH or IGF-1) was additionally noted in 10 of 33 (30.3%), 4 of 11 (36.2%), and 9 of 31 (29%) patients within these study groups. The rate of side effects didn’t increase with the raising of оctreotide dose. Conclusion: Application of long-acting release octreotide (Sandostatin-LAR) in doses of 30 and 40 mg is safe and allows to increase percentage of acromegalic patients who achieve a biochemical control over acromegaly.

There are many endocrine diseases accompanied by development of secondary diabetes mellitus (sDM). The features of the development and course of sDM in acromegaly, Cushing’s syndrome, and growth hormone (GH) deficiency are of particular interest as the prevalence of sDM associated with these pathologies is higher than that in the population. The main risk factors for sDM in acromegaly are age, female gender, arterial hypertension, family history of type 2 DM (T2DM), acromegaly activity, and duration and certain treatment methods of acromegaly. The differences of the sDM pathogenesis from pathogenesis of T2DM in the population are due to the opposite effect of GH and insulin-like growth factor 1 on glucose metabolism as well as to effect of acromegaly treatment on the mechanisms of diabetes development. The prevalence of diabetes in patients with GH deficiency, especially against the background of GH replacement therapy, is slightly higher than that in population. However, some studies have shown that GH replacement therapy may lead to normalization of the impaired glucose metabolism. High prevalence of metabolic syndrome (43%) and visceral obesity in the GH deficiency are the causes of the development of lipotoxicity (free fatty acids excess) and insulin resistance.In Cushing’s syndrome, the prevalence of early carbohydrate metabolism disturbances may reach 70%. In Cushing’s disease, chronic glucocorticoid excess determines insulin resistance and reduces insulin secretion, which results in hyperglycaemia. Currently, the recommendations for the treatment of sDM in acromegaly, hypercortisolism, and GH deficiency are the same as for the treatment of T2DM. However, as the pathogenesis is different in sDM and T2DM, the new algorithms for the diagnosis, prevention and treatment need to be developed. Prevention and timely treatment based on pathological principals will slow down the development of micro- and macrovascular complications leading to early disability and death of patients with neuroendocrine diseases.

Цель: оценка особенности механизмов развития нарушений углеводного обмена (НУО) при акромегалии в зависимости от лечения. Материалы и методы: обследовано 110 больных акромегалиeй (31 мужчина, 79 женщин; возраст 54,5 [46,8-60,3] лет. У 62 больных акромегалия была впервые выявлена (группа de novo), 25 получали терапию аналогами соматостатина (группа АСС), 23 человека перенесли транссфеноидальную аденомэктомию (группа ТСА). Оценка механизмов развития НУО при помощи исследования уровней инсулина плазмы натощак (ИПН), глюкозы плазмы натощак (ГПН), НвА1с, результатов перорального глюкозотолерантного теста (ПГТТ), индексов инсулинорезистентности (НОМА-IR), площадей под инсулинемической кривой в течение первых 30 минут ПГТТ (AUС инс. 30) и с 30 по 120 минуту ПГТТ (AUC инс 30-120). Показатели активности акромегалии представлены в виде СТГ, процента превышения ИРФ-1 верхней границы нормы (ИРФ-1ВГН). У 23 больных впервые выявленной акромегалией оценка метаболизма глюкозы представлена в динамике через 3 и 6 месяцев терапии АСС (13 больных) или после ТСА (10 больных). Результаты: распространенность НУО в группах de novo, АСС и ТСА составила 53,3%, 88% и 43,4%, соответственно. Уровни ИПН, индекс НОМА-IR не отличались у больных в группах АСС и ТСА и были более, чем в 1,5 раза ниже, чем в группе de novo (р 0,05). Выводы: несмотря на сопоставимое снижение инсулинорезистентности на фоне терапии АСС и после ТСА, снижение первой фазы секреции инсулина на фоне терапии АСС ведет к развитию НУО.

110 acromegalic patients were examined: 62 patients with newly diagnosed acromegaly (de novo), 25 patients were receiving somatostatin analogues treatment (SSA) and 23 patients underwent transsphenoidal sugery (TSS). The prevalence of carbohydrate metabolism disturbances (CMDs) in groups de novo, the SSA and the TSS was 53.3, 88.0 and 43.4%, respectively. Levels of fasting plasma insulin (FPI), index of insulin resistance (HOMA-IR index) did not differ in groups SSA and TSS and were more than 1.5 times lower than in the de novo group (p<0.05). Аrea under insulin curve in the first 30 minutes (AUC ins.30) of oral glucose tolerance test in the SSA group was 5.3 times lower than in the TSS, and 6.7 times lower than in the de novo group (p<0.05). Among the 23 de novo patients controlled acromegaly in 6 months was at 46% in group SSA and 50% of patients TSS. In the SSA group there were found increase of fasting plasma glucose levels (FPG), HbA1c (p=0.05), in the TSS group - decrease of FPG (p<0.05). There were the tendency to decrease of HOMA-IR (p=0.06), decrease of FPI and AUCins. (p<0.05) in SSA and TSS groups. Extent of decrease in AUCins.30 on SSA therapy exceeded the extent of decrease in UC ins.30-120 (in 11.0 and 2.3 times, respectively, p<0.05), but after TSS - these changes were comparable (2.4 and 3.2 times, respectively, p<0.05). Despite comparable reduction in insulin resistance on SSA therapy and after TSS decrease of the first phase of insulin secretion on SSA therapy leads to the development of CMD.

Early carbohydrate metabolism disorders (ECMDs) and diabetes mellitus (DM) are frequently associated with acromegaly. We aimed to assess the prevalence of ECMDs in patients with acromegaly and to compare the results with those in adults without acromegaly using two population-based epidemiologic surveys. We evaluated 97 patients with acromegaly in several phases of their disease (mean age, 56 years and estimated duration of acromegaly, 12.5 years). An oral glucose tolerance test was done in those not yet diagnosed with DM to reveal asymptomatic DM or ECMDs (impaired glucose tolerance+impaired fasting glucose). Comparisons were made between patients with acromegaly and participants from the general adult population (n=435) and an adult population with multiple type 2 diabetes risk factors (n=314), matched for gender, age and BMI. DM was diagnosed in 51 patients with acromegaly (52.5%) and 14.3% of the general population (P<0.001). The prevalence of ECMDs was also higher in patients with acromegaly than in the general population and in the high-risk group; only 22% of patients with acromegaly were normoglycaemic. The prevalence of newly diagnosed ECMDs or DM was 1.3-1.5 times higher in patients with acromegaly compared with the high-risk group. Patients with acromegaly having ECMDs or DM were older, more obese and had longer disease duration and higher IGF1 levels (Z-score). Logistic regression showed that the severity of glucose derangement was predicted by age, BMI and IGF1 levels. In patients with acromegaly, the prevalence of DM and ECMDs considerably exceeds that of the general population and of a high-risk group, and development of DM depends on age, BMI and IGF1 levels.

A detailed study of the dynamics of leptin in the various types of disturbances in carbohydrate metabolism could reveal its role in the pathogenesis of Type 2 Diabetes Mellitus (T2DM).The aim of this study was to investigate the Fasting Leptin Level (FLL) and effect of acute hyperinsulinemia during the Intravenous Glucose Tolerance Test (IVGTT) on the leptin levels in women with Insulin Resistance Syndrome (IRS).Materials and Methods: In total, 59 obese women (54.0 [48.5-60.0] yrs; BMI -33.2 [29.0-37.2] kg/m(2)) with IRS (12 -obesity (NGT), 18 - ITG and 30 - T2DM) were observed. The IVGTT test was done only in women with impaired glucose tolerance (IGT) and T2DM. The leptin level was investigated during fasting conditions and again 120 min post glucose loading. Then the Hepatic glucose production Index (H-index) was calculated using the IVGTT data.Results: The FLL in women with normal glucose tolerance (NGT) was almost two times greater than in women with IGT and T2DM. A negative relationship was found to exist between FLL and HbA1c in T2DM (r=0.3, p<0.05). A positive correlation (r=0.3, p<0.05) was also recorded between FLL and the H-index in compensated T2DM women (HbA1c<7%), a negative correlation (r=0.3, p<0.05) was recorded between FLL and the H-index in decompensated T2DM women (HbA1c>8%). The leptin level significantly decreased at 120 min of IVGTT in both the IGT and T2DM groups (p<0.05).Conclusion: The FLL depended upon the degree of glucose metabolism impairment; postprandial leptin response to the glucose load was lower in the IGT group than in the T2DM subjects.

Aim of this study was to investigate efficiency and safety of OctreotidLong FS in patients with acromegaly. Materials and methods. 41 patients with acromegaly (8 – de novo and 33 patients after different somato statin analogs treatment) was treated OctreotidLong FS one injection in 28 days. Growth hormone (GH), Insulin like Growth Factor 1 (IFG1), fasting glucose (FG) and HbA1c were assess after 3, 6 and 12 month of therapy. Results. We found out the decreasing of GH and IGF1 from 12,8 (8,0–82,7) mU/ml to 3,8 (1,6–13,8) mU/ml ( p 0,05) and %IGF1 increasing (% IGF1) from 231 (150–286)% to 9,5 (−26–111)% ( p 0,05) in 8 de novo acromegalic patients. We also revealed that IGF1 didn’t change and GH decreased after 3 month (33 patients), 6 month (22 patients) and 12 month (8 patients) of OctreotidLong FS treatment. We didn’t observed negative effect of OctreotidLong FS treatment to carbohydrate metabolism in patients with acromegaly. Conclusion. The therapy of OctreotidLong FS leads to induce successful control of GH and IGFI in 50% de novo patients and didn’t change the number of patients with control of acromegaly after another somato statin analogs treatment. Carbohydrate metabolism also didn’t change after OctreotidLong FS treatment.

Aim. To characterize leptin secretion in fasting state and upon intravenous glucose administration in patients with type 2 diabetes mel- litus (T2DM), prediabetes and obesity. Materials and methods. 59 female patients took part in this study: 12 had no signs of glycemic disorder, 18 were diagnosed with prediabetes and 30 ? with newly diagnosed T2DM. Median age was 54 [48.6?60] years, median BMI ? 33.2 [29.0?37.2] kg/m2. All participants were tested for fasting leptin, fasting insulin and blood glucose levels. Prediabetic and diabetic subjects also received a bolus intravenous injection of 40% glucose solution (0.75 g/kg of body mass) with subsequent additional measurement of insulin levels at 2, 70 and 120 min upon injection, and leptin levels ? at 120 min. Results. Median fasting leptin in obese and patients with weight excess was 42.0 [22?60] ng/mL, which is about 2 times higher than normal reference maximum (27.6 ng/mL). Subjects with prediabetes and T2DM showed significantly lower median fasting leptin levels of 29.1 ng/mL [13.5?45.7] and 21.3 [14.3?42.2], respectively (p

Aim of the study was to investigate the features of glucose metabolism in patients with acromegaly depending on treatment. Materials and methods: 63 patients with acromegaly: 29 patients with newly diagnosed acromegaly, 25 patients receiving somatostatin analogs (SSA) therapy and 9 patients underwent surgical treatment. Patients with earlier revealed diabetes mellitus (DM) were not included. The characterization of glucose metabolism was carried out by means of an assessment of fasting insulin plasma levels (FIP) and indexes of an insulinresistance (IR) HOMA-R and an insulinsensivity (IS) MATSUDA. Results: In patients receiving SSA therapy the carbohydrate metabolism disorders (CMD) were revealed in 92%, among newly diagnosed acromegalic patients – in 62% and in patients after surgical treatment in 33% of cases. In newly diagnosed acromegalic patients index MATSUDA was 3,5 times lower than in patients receiving SSA therapy, and 4 times lower than in patients after surgical treatment ((р=0,001). НОМА-R in newly diagnosed acromegalic patients was 3,7 times higher than in other groups, p=0,003 and the level of FIP was 4,3 times higher than in patients receiving SSA therapy and 2,9 times higher than in patients after surgical treatment (р=0,001). The index MATSUDA in newly diagnosed acromegalic patients with early CMD was 2,9 times lower, р=0,006, НОМА-R – 2,5 times higher, р=0,025 and FIP 2,4 times higher, р=0,039 than in patients with early CMDs without acromegaly. Conclusions: In patients with newly diagnosed acromegaly in the absence of CMDs increase in IR is compensated by hyperinsulinemia. In patients, receiving SSA therapy the IR decreases, however suppression of secretion of insulin leads to increase in percentage of DM in this group. After surgical treatment IR decreases against higher level of fasting plasma insulin that leads to normalization of carbohydrate metabolism. Keywords: Acromegaly, secondary diabetes mellitus, insulinresistance, MATSUDA, HOMA-R.