Vol 44, No 4 (2016)



Gurevich L.E., Korsakova N.A., Voronkova I.A., Ashevskaya  V.E., Titov A.G., Kogoniya L.M., Egorov A.V., Britvin T.A., Vasil'ev I.A.


Background: Prediction of clinical benefits of somatostatin analogues in patients with neuroendocrine tumors (NET) is very important prior to their administration. Data on immunohistochemical assessment of the expression of somatostatin receptors (SSR) of various types, obtained from large samples of NET with various localization, functional activity and degree of malignancy, are scarce; therefore, the study was aimed at assessment of the latter.

Materials and methods: We performed an immunohistochemical study with antibodies to SSR1, 2A, 3 and 5  types on tissue samples obtained during diagnostic and intra-operative biopsies from 399 NETs: 168 from pancreas, 120 from gastrointestinal tract (stomach, 48, from small intestine, 39, 14 of which being from duodenum; appendix, 6, colon and the rectum, 15 and 12, respectively), 84 from lung, 6 from thymus/mediastinum, and 21 from NET metastases of unknown primary localization.

Results: Very high levels expression of receptors SSR2A preferentially binding to somatostatin analogues, which are currently used in clinical practice, were detected in the small intestine NETs (22/25, 88%), appendix (5/6, 83.3%), colon (10/15, 66.7%), thymus (4/6, 66.7%), atypical carcinoids of the lung (10/15, 66.7%), stomach (27/41, 65.8%) and pancreas (105/165, 63.6%). The lowest expression was found in rectal NETs (5/12, 41.7%) and small and large cell neuroendocrine lung carcinomas (20, 11.1%). Among functioning NETs, the highest level of SSR2A was found in gastrinomas (18/19, 94.7%), glucagonomas (15/16, 93.8%), small intestine carcinoids (31/35, 88.6%), and somatostatinomas (2/3, 66.7%). The lowest expression was detected in ACTH secreting tumors with Cushing's syndrome (11/12, 50%), and in insulinomas (34/69, 49.3%). SSR2A expression in functionally inactive pancreatic NETs was significantly higher than in insulinomas (57/82, 34/69 vs 69.5 and 49.3%, respectively). SSR2A expression was associated with the degree of malignancy and is higher in pancreatic NET Grade 2A (Ki67 to 10%), Grade 2B (Ki67 10–19%) and in neuroendocrine carcinomas Grade  3, compared to Grade  1 (16/50 (32%), 37/61 (60.6%), 8/12 (66.7%) and 20/24 (83.3%), respectively). Overexpression of SSR5, which is the second clinically significant receptor, was observed in NETs of the duodenum (7/10, 70%) and appendix (2/5, 60%), and among functionally active NETs in glucagonomas and gastrinomas (12/15, 80%). SSR3 are less common, than SSR2A and 5, and are found most often in the gastric NETs (6/11, 54.5%), insulinomas (16/37, 43.2%), neuroendocrine carcinomas of pancreas Grade  3 (4/9, 44.7%), and typical lung carcinoids (7/16, 41.2%). SSR1 in all tumors are rare, the maximum level of expression was observed in small intestine carcinoids (9/21, 42.9%).

Conclusion: Depending on their localization and grade  of malignancy, neuroendocrine tumors differ in expression of various SSR types. Therefore, determination of the receptor profile of each tumor is necessary before administration of somatostatin analogues.

Almanac of Clinical Medicine. 2016;44(4):378-390
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Kalashnikova M.F., Yazykova D.R., Likhodey N.V., Zilov A.V., Sych Y.P., Maloletkina E.S., Fadeev V.V.


Background: Maintenance of stable glycemic control is an important prerequisite of effective treatment of patients with type 1 diabetes mellitus (DM). The ultra-long-acting basal insulin degludec allows for reduction of glycemic variability and for a substantial reduction in the rates of hypoglycemia with equivalent glycemic control. Evaluation of the impact of this novel insulin on diabetes-dependent quality of life and patient satisfactions with the treatment is necessary for comprehensive assessment of treatment efficacy.

Aim: To study changes of glycated hemoglobin (HbA1c), rates of hypoglycemia, diabetes-dependent quality of life and treatment satisfaction in patients with type 1 DM, who have been switched to insulin degludec.

Materials and methods: This open 12-week observational comparative study included 25  patients with type  1 DM (median age, 36 [20; 63] years), who were switched to insulin degludec in combination with a  ultra-short insulin analogue. The control group included 21 patients with type 1 DM (median age, 40 [23; 63] years), who continued their treatment with a long-acting insulin analogue glargine. At baseline and at week 12 after switching to insulin degludec, we assessed HbA1c level, mean insulin dose, depression score, diabetes-dependent quality of life and patient satisfaction with the treatment with the use of the Russian versions of the diabetes-specific questionnaires “Audit of Diabetes-Dependent Quality of life” (RuADDQoL), and “Diabetes Treatment Satisfaction Questionnaire” (DTSQ), respectively.

Results: At 3 months, there was a significant reduction of the HbA1c levels in the main and the control groups to 7.57% (Ме 7.5 [7.1; 8.4]; р=0.03) and 8.18% (Ме 7.8% [7.4; 8.7]; р=0.04), respectively. The mean reduction of this parameter under treatment with degludec was slightly higher than under treatment with glargine (0.73 vs 0.57%, respectively), at 3 months the difference being statistically significant (p=0.034). To achieve an equivalent glycemic control, the mean daily dose of insulin degludec was reduced by 26%. Switching to insulin degludec was associated with a significant reduction in non-severe hypoglycemia rates by 45% (р<0.001). In the main group, there was an improvement of the mean total weighted score of Ru-ADDQoL from -2.2 (Ме -1.28 [-2; -0.86]) at baseline to -1.5 (Ме -1.28 [-2; -0.86]) at 12 week, with positive changes in the most domains, demonstrating the improvement of quality of life In the reference group, the mean total weighted Ru-ADDQoL score at 3  months increased 0.4 (Me  0.1 [-0.56; -1] to -1.51 (Me  -1.23 [-2; -1]). In the glargine group there were no significant changes on any of the Ru-ADDQoL domains. There was a  significant improvement in the patients satisfaction with treatment in the degludec group, with an increase of the average DTSQ score by 5 in 3 months of therapy.

Conclusion: Based on the results of this short-term observational study, the following conclusion can be drawn: treatment with insulin degludec in type 1 DM is as effective as treatment with insulin glargine; however, it allows for reduction of the mild hypoglycemia rates by 45%. Therefore, this insulin can be recommended, first of all, to those type 1 DM patients who demonstrate substantial glycemic fluctuations, frequent hypoglycemia, hypoglycemic unawareness or who do not achieve the glycemic goals of treatment. Finally, this would lead to better health-related quality of life and more treatment satisfaction.

Almanac of Clinical Medicine. 2016;44(4):392-405
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Dreval' A.V., Shestakova T.P., Bunak I.V.


Background: New diagnostic criteria for gestational diabetes mellitus (GDM) are being currently implemented into clinical practice. GDM prevalence and pregnancy outcomes in women with GDM diagnosed according to the new criteria have not been studied in Russia.

Aim: To evaluate prevalence of GDM and pregnancy outcomes in women with GDM based on the Russian consensus criteria 2012 ("Gestational diabetes mellitus: diagnosis, treatment and postpartum follow-up") in the population of the Moscow Region.

Materials and methods: The study included 176 pregnant women living in the Moscow Region. We retrospectively analyzed 100  pregnant women (mean age±SD  – 28.3±6 years) who delivered before 2013 with collection of data on blood glucose and gestational age of its measurement, body mass index (BMI) at conception and pregnancy outcomes. The prospective part of the study conducted from January to July  2015 included screening of 820  pregnant women helped to identify 76 cases of GDM (mean age±SD – 30.4±5.5 years); their follow-up included monitoring of glucose levels, gestational term, and pregnancy outcomes.

Results: In the retrospective part of the study, 19  women (19%) were identified with their fasting glucose levels≥5.1  mmol/L (5.39±0.29  mmol/L) at 14.4±9.3  weeks of gestation, that corresponds to diagnosis of GDM with 2012 criteria. The comparison of pregnant women with and without fasting hyperglycemia showed no difference in age and pre-pregnancy BMI values. Women with fasting hyperglycemia had high total rates of adverse pregnancy outcomes than those without (52.6%  vs 24.6%, respectively, p<0.017), as well as higher rates of fetal asphyxia during delivery and clavicle fractures (15.8%  vs 3.7%, p=0.04 and 10.5% vs 0%, p=0.03). In the prospective part of the study, 820  pregnant women were screened for GDM, and it was found in 76 (9.2%) of them. Among those, in 50 (65.8%) the diagnosis of GDM was based on fasting glucose in venous plasma (5.5±0.3 mmol/L) at 11.3±6.1 weeks of gestation. Pregnant patients with fasting hyperglycemia in the retrospective and prospective parts of the study did not differ in their age, pre-pregnancy BMI, fasting glucose levels and terms of assessment; however, in the prospective study, the rate of fasting hyperglycemia was lower than in the retrospective (6% vs 19%). The second phase of the screening performed at 20 to 30 weeks of gestation helped to identify 26  women (34.2%) with GDM: in 15 of them (19.7%) the diagnosis was based on repeatedly high fasting glucose (5.5±0.3 mmol/L) and in 11 (14.5%), on the results of the oral glucose tolerance test. To all pregnant women with GDM, diet and blood glucose self-monitoring were recommended. Pregnancy outcomes were assessed in 64 GDM patients, with their comparison in compliant patients (n=30) vs non-compliant (n=34). Patients with poor compliance had higher rates of preterm delivery (11.4% vs 0%, р=0.05), macrosomia (32.3%  vs 6.6%, р=0.01) and other adverse outcomes (76.5% vs 50%, р=0.03) than those with good compliance.

Conclusion: The prevalence of GDM in a district of the Moscow Region in the prospective study was 9.2%. The retrospective analysis showed an overestimated rate of fasting hyperglycemia (19%). In the majority of GDM patients, the diagnosis was based on an increased fasting glucose level in venous plasma (85.5%). Treatment of GDM patients helps to reduce adverse pregnancy outcomes.

Almanac of Clinical Medicine. 2016;44(4):406-413
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Sorokina E.Y., Pogozheva A.V., Peskova E.V., Makurina O.N., Baturin A.K.


Background: Type 2 diabetes mellitus (T2DM) represents from 90 to 95% of all diabetes and usually occurs in obese individuals above 40 years of age, is highly prevalent, associated with high morbidity and mortality from complications involving, first of all, the cardiovascular system. The risk of T2DM is determined by combined effects of genetic and environmental factors. Genes associated with T2DM have been identified, including the gene of ATPdependent potassium channel (KCNJ11); the prevalence of its polymorphisms may have some regional characteristics.

Aim: To study an association between rs5219 KCNJ11  gene polymorphisms and the risk of T2DM in the population of the Moscow Region.

Materials and methods: The study involved 1050  subjects, including 311  men and 739 women, 139 of whom (17 men and 122 women) had T2DM. Genotyping of rs5219 KCNJ11 gene polymorphisms was performed with the use of allele-specific amplification, the real-time detection and TaqMan-probes complementary to the DNA polymorphism sites.

Results: The analysis of rs5219 KCNJ11 polymorphism frequencies showed that 14.2% of patients had TT genotype, 44.8 – CT genotype, and 41.1% – normal (wild) CC genotype. The prevalence of the mutant T allele was 36.6%, that of the C allele – 63.4%. The frequency of the mutant T allele in patients with obesity (body mass index≥30  kg/m²) was not significantly different from that in patients without obesity (body mass index<30 kg/m²) (38.8% and 35.7%, respectively, odds ratio (OR) 1.14, 95%  confidence interval (CI) 0.907–1.439, p=0.26). At the same time, energy expenditure at rest per kg of lean body mass was significantly lower in men who have rs5219 KCNJ11 gene polymorphism, both in homoand heterozygotes. The frequency of the T allele and TT genotype in diabetic patients was higher than in the control group. An association between TT genotype and the risk of T2DM was found (OR  2.35, CI 1.018–5.43, p=0.04).

Conclusion: In the population of the Moscow Region, gene polymorphism rs5219 KCNJ11 contributes to the risk of developing T2DM which is most obvious and statistically significant in homozygotes.

Almanac of Clinical Medicine. 2016;44(4):414-421
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Starostina E.G., Shavrikova E.P.


Background: А  specific questionnaire is necessary to perform quantitative assessment of compliance to medical nutrition therapy in patients with type 2 diabetes mellitus (DM).

Aim: Тo develop a questionnaire to assess how type 2 diabetic patients adhere with the principles of medical nutrition therapy and to identify factors associated with good dietary compliance.

Materials and methods: We proposed a questionnaire "Dietary adherence test" (DAT) and validated it in 300 inand out-patients with type 2 DM. DAT was validated against the diabetes-related behavior score, diabetes-related knowledge score, and HbA1c level; the internal consistency coefficient (Cronbach's alfa) was also calculated.

Results: Cronbach's alfa for primary raw and standardized data were 0.7444 and 0.7413, respectively, thus meeting the required range of 0.7–0.8. The score on DAT item 1 (the title item) and total score (the sum of scores of item 2 to 10) correlated with the diabetes-related behavior score (r=0.21, р=0.0006 and r=0.34, р<0.0001, respectively). Patients with poor dietary compliance (average DAT score≤2) had a significantly lower score on the subscale "Nutrition" of the diabetes knowledge test, than those with good dietary compliance (average DAT score≥2) (44.9±15.6 vs 60.2±16.2, р<0.0001). Patients who perceived their diet as the most burdensome element of life with diabetes, had lower total DAT score (24.1±4.6) than those who did not see their diet as a problem (25.9±5.1, р=0.001). There was a  significant difference in average DAT score between patients on insulin therapy and patients on oral treatment (2.8±0.6 vs 2.9±0.6, respectively, р=0.019). Patients with poor and good dietary adherence, according to DAT, differed in their duration of diabetes, social status and diabetes-related behavior score. There was a  weak correlation between the DAT score and duration of diabetes (r=0.16, р=0.009), and weak inverse correlation between the DAT score and total serum cholesterol levels (r=-0.16, р=0.01).

Conclusion: The diagnostic characteristics of the proposed questionnaire meet the criteria of face, content and external validity and internal consistency, or reliability. This self-report questionnaire allows to assess the type 2 DM patient's awareness and adherence to medical nutritional therapy, at no additional time expenses of the doctor. No associations between dietary adherence and main parameters of treatment efficacy in type 2 DM were found.

Almanac of Clinical Medicine. 2016;44(4):422-429
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Komerdus I.V., Dreval' A.V., Chekanova A.V., Akulkina L.A.


Background: Cushing's disease (CD) is a  severe multimorbid disorder that affects primarily young people in their productive age. In most cases, the diagnosis is delayed and patients with complications of hypercorticism are seen by doctors of various specialties.

Aim: To identify the most frequent clinical signs and symptoms of CD at the time of diagnosis, to assess an association between clinical manifestations of hypercorticism and main clinical and laboratory parameters.

Materials and methods: We examined 44 CD patients registered in the database of CD patients of the Moscow Regional Research and Clinical Institute (MONIKI).

Results: The mean age of patients was 37.9±10.5 years, with most of them (68.2%) being in the age range of 30 to 50 years. The median of disease duration was 35.5 [22; 75] months. Facial plethora, which is the most characteristic sign of hypercorticism, was seen in 97.7% of patients. Striae, thought to be most often associated with hypercorticism, were found only in 38.6% of patients. The most frequent complaints (> 80%) were weight gain, fatigue, headache, and menstrual dysfunction. Some of the symptoms showed a positive correlation with cortisol levels.

Conclusion: Clinical manifestations of CD are mostly non-specific. Only facial plethora was highly prevalent of all typical symptoms of hypercorticism. At least one of the "specific" symptoms was found in all patients.

Almanac of Clinical Medicine. 2016;44(4):430-438
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Lyubimova N.V., Kushlinskii N.E.


This review summarizes current data on neuroendocrine tumors (NET), which, unlike other neoplasms, are able to produce biologically active substances (hormones, vasoactive peptides, amines). It is exactly their main characteristic that allows to unify this heterogeneous group and that may determine their clinical course. We present integrated recommendations for biochemical diagnosis and confirmation of over-secretion syndromes based on a  panel assessment of NET biochemical markers. Data from the literature are reviewed on evaluation of clinical significance of generic and specific NET markers, as well as the results of the studies performed by the authors themselves. Three hundred and thirty patients were examined with NETs of various localization (pancreas, stomach, small intestine and large intestine, lungs) and with metastatic NET disease with unknown primary location, who were treated in the N.N. Blokhin Russian Cancer Research Center. The control group included 115 healthy individuals. Before and during the treatment, plasma and serum chromogranin A (CgA) and serotonin levels, as well as 5-hydroxyindoleacetic acid (5-HIAA) in a  24-hour urine sample were measured with standardized immunoenzyme plate-based assays (“Chromogranin A ELISA kit”, Dako A/S; “Serotonin ELISA and 5-HIAA ELISA”, IBL International GMBH). We evaluated clinical importance of CgA as a generic NET marker, as well as that of serotonin and its metabolite 5-HIAA as specific markers of the carcinoid syndrome. CgA was shown to be the most efficient biochemical marker for diagnosis, assessment of prevalence and monitoring of NETs. CgA has a  high diagnostic sensitivity (63.4 to 88.9%) in various NETs. An association between CgA secretion and prevalence and biological activity of the tumor was confirmed. CgA measurement is particularly important in functionally inactive tumors, where serotonin and 5-HIAA have lower sensitivity, being specific markers of the carcinoid syndrome.
Almanac of Clinical Medicine. 2016;44(4):439-450
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Ilovayskaya I.A., Dreval' A.V., Krivosheeva Y.G., Astaf'eva L.I., Stashuk G.A.


Background: Pituitary adenoma is not as infrequent as thought previously. The prevalence of macroadenomas in general population is up to 0.16–0.2%. Magnetic resonance imaging (MRI) is a method of choice in diagnosis of pituitary adenomas. Until now, specifics of imaging of pituitary adenomas with various hormonal activities have not been discussed.

Aim: To analyze comparatively the size, volumes and growth direction in pituitary macroadenomas with various hormonal activities.

Materials and methods: We analyzed MRI images of 305 patients with hypophyseal adenomas of more than 10 mm diameter, among them with non-functioning adenomas (n=109), prolactinomas (n=58), and somatotropinomas (n=138).

Results: Depending on their hormonal activity, hypophyseal adenomas had different volumes (р<0.001): non-functioning hypophyseal adenomas had the volume of 6620 [2637; 14492] mm3 , prolactinomas – 5365 [1495; 10316] mm3 , somatotropinomas – 3052 [1696; 5727] mm3 . In the majority of patients from all groups, extrasellar growth at several directions was observed. Onedirectional growth was seen in 29% of non-functioning hypophyseal adenomas, 41% of prolactinomas and 37% of somatotropinomas (р>0.05). Non-functioning hypophyseal adenomas and prolactinomas demonstrated mostly suprasellar growth (in 83.5 and 79.3% of cases, respectively), whereas somatotropinomas were growing mostly in infrasellar direction (66.1%).

Conclusion: These characteristic features of hypophyseal macroadenomas with various hormonal activities could be used for differential diagnosis, which may help to optimize patient assessment during the diagnostic work-up.

Almanac of Clinical Medicine. 2016;44(4):451-456
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Fedotova A.V., Chernysheva E.N., Panova T.N., Akhtyamova K.V.


Background: The metabolic syndrome is seen as a  cluster of high cardiovascular risk factors. New hormone-like substances, such as adipokines leptin and apelin, produced by fat tissue, are important for the pathophysiology of the metabolic syndrome.

Aim: To evaluate levels of plasma apelin and serum leptin in patients with metabolic syndrome.

Materials and methods: We examined 122 male patients with metabolic syndrome and 30 healthy males aged from 25 to 60 years. All patients were assessed accordingly to confirm the diagnosis of the metabolic syndrome, with additional measurements of serum leptin and plasma apelin.

Results: Serum leptin levels were 10-fold higher and plasma apelin levels 3-fold higher in patients with metabolic syndrome (n=122), compared to the controls (n=30): 25.43 vs. 3.99 ng/mL (p<0.05) and 1.13 vs. 0.66 ng/mL (p<0.05), respectively. Serum leptin levels correlated with all parameters of the excess body weight, such as body mass (r=0.79, р<0.05), body mass index (r=0.93, р<0.05), waist circumference (r=0.61, р<0.05), hip circumference (r=0.57, р<0.05), and waist-to-hip ratio (WHR; r=0.4, р<0.05). Plasma apelin levels correlated with the waist circumference (r=0.27, р<0.05) and WHR (r=0.29, р<0.05). There was a significant increase of serum leptin dependent on the bodyweight category: 19.8 ng/mL in patients with obesity Grade I  (n=49) and 28.7  ng/mL in those with obesity Grade II (n=46) (р<0.05). There was a  non-significant trend towards an increase in plasma apelin depending on bodyweight. As far as abdominal obesity is concerned, in patients with WHR<1 (n=35), plasma apelin level was 0.36  ng/mL, whereas in those with WHR of ≥1 (n=87), it was 3-fold higher (1.09 ng/mL, р<0.05); the increase in serum leptin levels was non-significant. There was no association between plasma apelin and serum leptin in patients with metabolic syndrome (r=0.1, р>0.05).

Conclusion: The adipokine levels in men with metabolic syndrome are higher than in normal men. Serum leptin level is a  sensitive parameter indicating accumulation of the fat tissue, irrespective of its localization. Plasma apelin is less sensitive, but it does reflect fat accumulation of the central (abdominal) type.

Almanac of Clinical Medicine. 2016;44(4):457-461
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Tsoriev T.T., Belaya Z.E., Mel'nichenko G.A.


Two-dimensional dual-energy X-ray absorptiometry (DXA, osteodensitometry) is currently considered as the gold standard for diagnosis of osteoporosis. However, despite good operational characteristics, this type of investigation cannot help to assess bone microarchitecture and the degree of its derangement in osteoporosis. Therefore, trabecular bone score (TBS) has been developed as a  non-invasive method of indirect description of bone microarchitecture based on data derived from a  standard DXA of the lumbar spine. Not being a direct mapping of the physical measurements of trabecular microarchitecture, TBS nevertheless shows a positive correlation with quantitative values obtained from micro-computed tomography and high resolution peripheral quantitative computed tomography, i.e. with the bone volume fraction, junction density, trabecular numbers and their disintegration. There is also an association between the ability of the bone tissue to resist stress in experimental studies ex vivo and TBS measurement. Due to TBS, there is a possibility to detect bone microarchitecture impairment even in individuals with normal bone mineral density (BMD), i.e. higher TBS values correlate with improved bone microstructure, whereas a  reduced TBS shows its deterioration. Limitation of TBS use are primarily related to the DXA image quality: image faults caused either by technical reasons or by too low or too high body mass index can lead to an overestimation/underestimation of the index. Assessment of the lumbar TBS has been repeatedly performed in cross-sectional and prospective studies in representative patient samples (mainly postmenopausal women) and significant numbers of healthy subjects, and proved to be a predictor (independent of BMD) of fracture risk. An evaluation of the possibility to use TBS for early diagnosis of secondary osteoporosis (related to various endocrine disorders)  would be of great interest, as BMD, as known from clinical practice, is not always a  reliable measurement of the bone endurance, especially in diabetes, steroid osteoporosis and acromegaly.  The use of TBS along with BMD as a  marker of efficacy of current treatment for secondary osteoporosis is also possible, but it is not yet evidence-based; therefore, research has to be continued.
Almanac of Clinical Medicine. 2016;44(4):462-476
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Hypoparathyroidism: etiology, clinical manifestation, current diagnostics and treatment

Mokrysheva N.G., Eremkina A.K., Kovaleva E.V.


Parathyroid hormone (PTH) is the main regulator of calcium and phosphorus metabolism. PTH deficiency or tissue resistance to its effects results in hypoparathyroidism characterized by low serum calcium and elevated serum phosphate levels. The most common is post-operative hypoparathyroidism caused by an inadvertent damage or removal of the parathyroid glands, deterioration of blood supply to the neck region, most often during thyroid surgery. The second common form of the disease is the autoimmune one related with immune destruction of parathyroid cells. Less frequent causes of hypoparathyroidism include a variety of genetic syndromes, mitochondrial genome defects, and hypomagnesemia. The main signs and symptoms of hypoparathyroidism are related to hypocalcaemia and hyperphosphatemia land result in increased neuromuscular irritability and general autonomic reactivity, with finger and toe tingling, muscle cramps, tonic seizures, laryngo- and bronchospasm, and neurosis. These symptoms are closely associated with serum calcium levels; their severity depends on the degree of hypocalcaemia. Laboratory parameters confirming the diagnosis of hypoparathyroidism are hypocalcaemia, hyperphosphatemia, and reduced serum PTH. Treatment of hypoparathyroidism involves management of hypocalcaemic crisis and maintenance therapy. Acute hypocalcaemia, a  potentially life-threatening condition, is treated as an emergency with intravenous calcium combined with oral calcium and active vitamin D. Standard chronic treatment for hypoparathyroidism is based on oral calcium and active metabolites of vitamin  D / vitamin  D analogs and is aimed at the balance between optimal low-normal serum calcium concentrations and normocalciuria. Worsening hypercalciuria is often underestimated by specialists, although it can cause severe renal problems, such as nephrocalcinosis and neprolithiasis. Hypoparathyroidism is one of the few endocrine deficiencies for which replacement treatment with recombinant PTH is not widely used. Replacement therapy with recombinant human PTH is a  promising area, especially in severe clinical cases, refractory to conventional treatment.

Almanac of Clinical Medicine. 2016;44(4):477-492
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Misnikova I.V.


In the recent years, an association between sleep apnea and a  number of endocrine diseases has been established. The secretion of many hormones after falling asleep is considerably changed, compared to the period of wakefulness. In patients with endocrine disorders, abnormal hormonal secretion and its pathological consequences may contribute to sleep apnea. Sleep fragmentation and intermittent hypoxia arising in sleep apnea result in a decrease in insulin sensitivity, which contributes to the development of type 2 diabetes mellitus. The prevalence of sleep apnea increases in acromegaly, which may affect the risk of cardio-pulmonary complications. There is an association between sleep apnea and testosterone treatment in men, as well as in postmenopausal women. Sleep apnea in hypothyroidism is most frequently related to the development of hypothyroidism per se and can therefore be reversed with thyroid hormone replacement therapy. Timely detection and treatment of sleep apnea in patients with endocrine disorders can improve their survival prognosis and quality of life.
Almanac of Clinical Medicine. 2016;44(4):493-500
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Dolzhenko A., Richter T., Sagalovsky S.


Vascular calcification or ectopic mineralization in blood vessels is an active, cell-regulated process, increasingly recognized as a general cardiovascular risk factor. Ectopic artery mineralization is frequently accompanied by decreased bone mineral density or disturbed bone turnover and development of the osteoporosis. The latest data support the correlation of osteoporosis and atherosclerosis, indicating the parallel progression of two tissue destruction processes with increased fatal and nonfatal coronary events, as well as a  higher fracture risk. Patients with osteoporosis, have a  higher risk of cardiovascular diseases than subjects with normal bone. Many proteins responsible for bone formation and resorption have been identified in the arterial wall. Vascular calcification includes mostly osteogenic and, to a  lesser extent chondrogenic differentiation of osteoblasts and osteoclast-like cells. It has been shown that many of the regulators of bone formation and resorption some bone structural proteins, such as osteoprotegerin (OPG), receptor activator of nuclear factor-κB ligand (RANKL) are also expressed in the atherosclerotic plaque. When RANKL binds to RANK, osteoclasts are activated and bone resorption occurs and processes of vascular calcification become also activated. OPG, protein homologue to receptor activator of nuclear factor-κB (RANK), can bind to RANKL, blocking the binding of RANKL to RANK, that results in inhibition of differentiation of preosteoclasts to mature osteoclasts, lower osteoclast capacity for resorption of bone mineral matrix, and development vascular calcification. The latest data supports that cathepsin K, a cysteine protease, can efficiently degrade type  I  and II collagen, both of which are major matrix components of the bone and atherosclerotic plaque. These findings further underscore the potential of cathepsin K as a target for novel molecules to treat osteoporosis and atherosclerosis. Thus, the discovery of the cytokine RANKL-RANK-OPG system and significant role of the cathepsin K in the process of bone remodeling, vascular calcification and atherosclerosis has made progress in understanding the mechanisms of disease development and possibly to develop new dual therapies. New therapies for osteoporosis and atherosclerosis that may potentially improve or augment existing treatments include the recently approved anti-receptor activator of NF-κB-ligand monoclonal antibody fms (denosumab) and the cathepsin  K  inhibitor odanacatib, presently in the late stage of clinical development.
Almanac of Clinical Medicine. 2016;44(4):513-534
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Troshina E.A., Mazurina N.V., Logvinova O.V.


This article provides our own clinical observation of the patient with multiple endocrine neoplasia type 2B (MEN2B) associated with a  germinal mutation in the RET proto-oncogene. Although there are highly informative laboratory methods available, in clinical practice MEN2B syndrome is often diagnosed lately, which results in decrease in patients’ life expectancy and quality.
Almanac of Clinical Medicine. 2016;44(4):535-539
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Kotova I.V., Voronkova I.A., Kazantseva I.A.


We present a clinical case of parathyroid cancer in a patient with relapsing secondary hyperparathyroidism at 4 years after subtotal parathyroidectomy. Its unique character is related to the combination of relapsing secondary hyperparathyroidism, parathyromatosis, ectopic of an adenomatous hyperplastic parathyroid gland into the thyroid gland, and parathyroid cancer. Several most complicated aspects of parathyroid surgery are disclosed, such as the choice of strategy for surgical intervention in secondary hyperparathyroidism, complexity of morphological and cytological diagnostics of this disorder.
Almanac of Clinical Medicine. 2016;44(4):540-543
pages 540-543 views



Yukina M.Y., Troshina E.A., Bel'tsevich D.G., Platonova N.M.


Hypertension is a  very common disease with high morbidity and reduction in quality of life. Endocrine disorders are the most common cause of secondary hypertension affecting ~3% of the population. Primary aldosteronism can be the cause of endocrine hypertension more often than other endocrine disorders. Other less common causes of endocrine hypertension include Cushing syndrome, pheochromocytoma, thyroid disorders, and hyperparathyroidism. Endocrine hypertension is potentially curable if the underlying cause is identified and treated accordingly. Younger age at manifestation of resistance to multiple antihypertensive drugs, together with other clinical signs of an endocrine disorder, should raise the suspicion and prompt the appropriate evaluation.
Almanac of Clinical Medicine. 2016;44(4):501-512
pages 501-512 views

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