Vol 64, No 2 (2018)

Original Studies
Somatostatin receptor expression in adrenocortical carcinomas
Voronkova I.A., Gurevch L.E., Britvin T.A., Krivosheev A.V., Mel’nichenko G.A.


Background. Adrenocortical carcinoma (ACC) is a rare malignant tumor characterized by an annual incidence of 0.5—2 cases per million population. Surgery is the-first line treatment for ACC. When total tumor resection is not possible due to its proliferation or progression, mitotane (o,p’DDD) is used. In this case, stabilization and partial response (as assessed by RECIST criteria) was observed only in 48.7% of cases, necessitating the search for new therapeutic targets.

Objective — the study was aimed at assessing the somatostatin receptor expression in adrenocortical carcinomas and adrenal cortex tumors with uncertain malignant potential.

Material and methods. Surgical material from adrenocortical tumors of 13 patients (4 males and 9 females aged from 28 to 68 years) was used. In all cases, the diagnosis was verified by morphological and immunohistochemical (IHC) studies: ACC was detected in 10 cases (including 1 case of ACC liver metastasis), oncocytic carcinoma — 1 case, oncocytoma with uncertain malignant potential — 2 cases. Morphological assessment of ACC was carried out according to Weiss criteria (for ACC tumors) and Lin—Weiss—Bisceglia criteria (for oncocytic neoplasms of the adrenal cortex). IHC study was carried out with antibodies to the spectrum of adrenal cortex-specific markers, as well as Ki-67 and somatostatin receptors 2 and 5 (SSTR2 and SSTR5).

Results. The expression of SSTR2 and/or 5 was detected in 8 (61.5%) of 13 cases of ACC. Isolated SSTR2 expression was observed in 4 cases (4/13), while SSTR5 expression was observed in 6 cases (6/10). In 2 cases (2/10), co-expression of both receptor types was observed. SSTR expression was observed both in ACC and ACC liver metastasis, as well as in oncocytic ACC.

Conclusion. SSTR2 and/or 5 expression in ACC tissue expands diagnostic and prognostic capabilities for this pathology.

Problems of Endocrinology. 2018;64(2):72-78
Fertility recovery in patients with non-classical congenital adrenal hyperplasia caused by 21-hydroxylase deficiency
Soboleva E.L., Osinovskaya N.S., Tkachenko N.N., Baranov V.S., Tarasova M.A.


Background. Very little research has been devoted to the studying fertility problem in nonclassical congenital adrenal hyperplasia (NCAH) due to 21-hydroxylase deficiency. It is difficult to draw definitive conclusions regarding the need for glucocorticoid therapy in NCAH women based on limited data. Therefore, evaluating fertility in patients with NCAH and exploring the possibility of correcting its disturbances seemed to us to be a matter of importance.

Aims — to evaluate the reproductive function of patients with NCAH and explore potential treatments for this disorder.

Materials and methods. The study group included 60 patients with NCAH aged between 18 and 33 years old. NCAH was diagnosed based on early-morning serum 17-hydroxyprogesterone (17-OHP) levels above 30 nmol/l or 17-hydroxyprogesterone levels after ACTH stimulation above 26 nmol/l and/or characterized by molecular analysis of the CYP21A2 gene. Ultrasonography of the uterus and ovaries were performed in the cycle’s follicular phase. Total testosterone, dehydroepiandrosterone sulfate (DHEAS), Androstenedione, 17-OHP and Progesterone was measured.

Results. Overall, the patients complained of menstrual cycle disorders (60%), infertility — (28%), hirsutism — (63%). Prior to being diagnosed with NCAH, Thirty-four women sought care because of infertility or recurrent miscarriages. Seventeen women (50%) had miscarriages; later on, five of them developed secondary infertility. Two patients became pregnant without treatment being already diagnosed and progressed to delivery. Once the diagnosis of NCAH was made, 58 women started receiving glucocorticoid therapy, Thirty nine (67%) women became pregnant while on glucocorticoid therapy. Thus glucocorticoid therapy reduced the miscarriage rate from 50 to 10.3%; р<0.001. There was no difference in the miscarriage rate between patients who received or quit glucocorticoid therapy during pregnancy.

Conclusions. Glucocorticoid therapy is a highly efficacious method of fertility restoration in NCAH patients. Use of glucocorticoids during pregnancy planning significantly reduced the miscarriage rate. No difference in pregnancy outcome between the patients who received glucocorticoid therapy during pregnancy as opposed to those who did not indicates the advisability of treatment discontinuation once pregnancy is determined.

Problems of Endocrinology. 2018;64(2):79-84
Monitoring of insulin pump therapy in children, adolescents, and young adults with type 1 diabetes mellitus in the Russian Federation
Laptev D.N., Pereverzeva S.V., Emelyanov A.O., Peterkova V.A.


Background. Insulin pump therapy in increasingly frequently used in the Russian Federation in recent years, which requires an evaluation of the treatment in order to improve its efficacy and safety.

Objective — the study was aimed at complex monitoring (long-term efficacy and safety, state of medical care, factors associated with metabolic control, and factors hindering its use) of the continuous subcutaneous insulin infusion (CSII) in children, adolescents, and young adults with type 1 diabetes mellitus (DM1) from various regions of the Russian Federation.

Material and methods. Data of 395 DM1 children and adolescents from 60 regions of the Russian Federation were collected from the pediatric CSII register of the Endocrinology Research Center. The following data were analyzed in different age groups (0 to 7 years, 8 to 11 years, 12 to 17 years, and 18 to 25 years): glycemic control, the incidence of acute complications, discontinuation of CSII, characteristic features of blood glucose monitoring, and supplies coverage.

Results. Initiation of CSII is accompanied by decrease in HbA1c level with the lowest values within the period from 6 to 24 months (–0.7±1.5% compared to the baseline level). However, 6 years after CSII initiation, HbA1c values do not differ significantly from the baseline values. The target HbA1c level (less than 7.5%) is observed in 43.6% of children aged 0 to 7 years, 32.7% of children aged 8 to 11 years, 24.2% of adolescents aged 12 to 17 years, and 28% of young adults aged 18 to 25 years. Regular self-monitoring of glycemia, 4 and more times per day, was performed by 83% of patients, while the frequency of continuous glucose monitoring (CGM) was low, 12.7% in the whole population. The incidence of acute complications in children and adolescents under 18 years did not differ significantly and the lowest incidence was observed in the age group 18 to 25 years. The effectiveness of CSII depended on the frequency of self-monitoring, CGM use, and supplies coverage. CSII discontinuation rate was 4.6 cases per 100 patient-years. The main reasons for discontinuation of CSII included the inconvenience of its use and the cost of supplies.

Conclusions. Many children and the majority of adolescents with DM1, who use CSII, did not reach target HbA1c level despite the adequate self-monitoring. Many patients do not use CGM and refuse CSII. This necessitates the efforts to improve the efficacy and overcome barriers to the use of CGM and CSII.

Problems of Endocrinology. 2018;64(2):85-92
The psychological component of comprehensive lifestyle modification program in overweight (obese) patients with type 2 diabetes mellitus
Andreeva S.I., Rudina L.M., Savelyeva L.V., Gurkina M.V., Surkova E.V., Galstyan G.R., Shestakova M.V.


Background. Despite the emergence of new modern classes of antihyperglycemic medications, lifestyle modification of patient with type 2 diabetes mellitus (T2DM) is a necessary component of the therapeutic approach in this disease. Clinically significant weight reduction and its maintenance is extremely important, but elusive goal for most patients with T2DM in the real clinical practice. The use of specially developed programs with involvement of the different profiles specialists (endocrinologists, dieticians, psychologists, instructors or сlinical exercise physiologists) can greatly contribute to this task.

Aims — to study individual psychological characteristics in overweight (obese) patients with T2DM and to evaluate the dynamic of these characteristics, anthropometric, clinical and metabolic parameters during the comprehensive lifestyle modification program.

Material and methods. The lifestyle modification program was developed. The main structural components of this program were dietary intervention, dosed individualized exercise intervention, specific model of team psychotherapeutic work (health coaching), comprehensive group education and dynamic medical support of patients with the adaptation of drug therapy. Psychological characteristics of patients, clinical and metabolic parameters and the level of physical activity were assessed before inclusion, at 3 and 12 months of follow-up.

Results. The study was completed by 55 people of 60 (5 people dropped out of the study because of various reasons). There were not undesirable phenomena, directly related to participation in the program. At the end of the study we noted the positive dynamics of psychological characteristics in patients: 15% of men and 22% of women became less inclined to self-blame and hyper-responsibility; the locus of control in a relationship to own capabilities of health management changed from external to internal in 30% of women and 41% of men. 65% of participants achieved clinically significant weight loss (most patients reduced MT by 10% or more) and retained this result during 1 year. Improvement of clinical and metabolic parameters was also noted.

Conclusions. The multidisciplinary lifestyle modification program in overweight (obese) patients with T2DM, the most important part of which was team psychotherapeutic work, showed high effectiveness of both the reduction of MT and the improvement of clinical and metabolic parameters in the long-term period.

Problems of Endocrinology. 2018;64(2):93-104
Case Reports
Late-diagnosed salt-wasting congenital adrenal hyperplasia in adult patient
Rozhinskaya L.Y., Kalinchenko N.Y., Belaya Z.E., Zenkova T.S., Lutsenko A.S., Bittirova A.A.


We describe a unique case of diagnosing salt-wasting congenital adrenal hyperplasia (CAH) caused by 21-hydroxylase deficiency in a 32-year-old male patient. Before establishing the diagnosis, the main patient complaint was infertility. In childhood, the patient suffered from developmental delay, often illness, overconsumption of salt, and often vomiting; he stopped growing at the age of 12 years. In the adolescent period, his physical condition improved. Later, the patient got married, but was infertile. Plasma steroid profiling by gas chromatography-mass spectrometry (GC-MS) revealed markedly increased levels of 17-hydroxyprogesterone and 21-deoxycortisol and a decreased cortisol level, which enabled the diagnosis of CAH and 21-hydroxylase deficiency. The diagnosis was confirmed by a molecular genetic study that detected a CYP21 gene mutation — l2 splice in the homo(hemi)zygotic state, which was characteristic of the salt-wasting form of CAH. Also, the patient had secondary adrenal cortical adenoma caused by prolonged ACTH hyperstimulation and secondary hypogonadism associated with excessive production of adrenal androgens, which led to elevated levels of estrogens inhibiting production of LH and FSH. Treatment of the patient with glucocorticoids and mineralocorticoids and then with androgens improved his clinical condition and hormonal parameters.

Problems of Endocrinology. 2018;64(2):105-110
A familial case of insulin-dependent diabetes mellitus with a mutation in the PTF1A gene
Svetlova G.N., Kuraeva T.L., Sechko E.A., Peterkova V.A.


Diabetes mellitus (DM) is a genetically heterogeneous disease, and some cases of type 1 diabetes mellitus (T1DM) are caused by a mutation of one gene. The child has suffered from brittle diabetes since the age of 1 year and received insulin. The HbA1c level is 9.9—11.4%. The patient was examined at the age of 14 years; the disease duration is 13 years. The daily dose of insulin is 1.15—1.35 U/kg. DM complications include initial manifestations of distal diabetic polyneuropathy as well as cheiropathy. The mother (39 years) and grandmother (74 years) have T1DM with multiple complications. A genetic study revealed that all three family members had a heterozygous substitution p.P274 in the PTF1A gene with an unknown pathological significance.

At present, it can not be asserted that the identified mutation is the etiologic factor of diabetes in the described case. We can not exclude T1DM in this child because specific antibodies have not been tested. However, the mutation is detected in all three members of the same family with diabetes, which does not exclude the discovery of a new form of MODY, not described earlier.

Problems of Endocrinology. 2018;64(2):111-115
Problems of the differential diagnosis of MODY3 in obesity
Sechko E.A., Andrianova E.A., Ivanova O.N., Kuraeva T.L.


MODY3 is one of the most common subtypes of MODY. Obesity in MODY3 patients modifies the disease course and complicates diagnostics at the clinical stage.

A proband was diagnosed with type 2 diabetes mellitus (T2DM) at the age of 12 years; metformin therapy was used. A family history of DM involves three generations: the mother, aunt, and maternal grandfather have suffered from insulin-dependent DM since the age of 23, 22, and 40 years, respectively. The patient was examined at the age of 14 years. Obesity was present (SDS BMI 2.3). The insulin and C-peptide levels were 4.4 μU/mL and 1.5 ng/mL, respectively. The HbA1c level was 7.3%. Under glucose load, glycemia reached diabetic values; hyperinsulinemia and insulin resistance were not detected. Specific pancreatic antibodies were absent. Metformin was discontinued, and a sulfonylurea (SU) drug was prescribed, which had a positive effect. The heterozygous mutation p.P291fs was identified in the HNF1A gene. Therefore, MODY3 was verified.

The presence of concomitant obesity in the patient significantly complicates the differential diagnosis, and only a careful comprehensive analysis of clinical and laboratory parameters and a family history makes it possible to suspect the diagnosis of MODY3 (requiring subsequent molecular genetic verification) and prescribe pathogenetic therapy.

Problems of Endocrinology. 2018;64(2):116-120
Bone and joint structural impairments in acromegaly
Tsoriev T.T., Belaya Z.E.


Elevated serum levels of growth hormone (GH) and insulin-like growth factor 1 (IGF-1) in patients with acromegaly result in intensified bone turnover, as evidenced by increased levels of bone remodeling markers and higher risk of low-traumatic vertebral fractures. However, it was repeatedly observed that bone mineral density (BMD) is normal or even increased in patients with acromegaly (including the active stage of the disease). Increased secretion of GH/IGF-1 causes structural changes in the vertebrae and peripheral joints (osteophyte formation and cartilage hypertrophy), resulting in pain and various deformities of the articular system. These changes are known under the common name «acromegalic arthropathy». It is quite specific complication of the disease. Skeletal complications of acromegaly can persist even after radical treatment, i.e., their course and progression, presumably, do not necessarily depend on the remission level of the underlying disease. This review summarizes the current understanding of the pathophysiology, clinical presentation, diagnosis, and treatment of osteo-articular complications of acromegaly.

Problems of Endocrinology. 2018;64(2):121-129
The role of indirect calorimetry in assessing of resting metabolic rate in obese children
Okorokov P.L.


Basal metabolism accounts for more than half of daily energy expenditure and characterizes energy expenditure necessary to maintain the vital body functions at rest. The lean body mass makes the greatest contribution to the formation of basal metabolism. The «gold standard» for assessing basal metabolism is indirect respiratory calorimetry. This technique also evaluates, apart from basal metabolism, the rate of macronutrient oxidation, which is an important component of a personalized diet. In clinical practice, formulas for calculating basal metabolism are widely used, but their accuracy in children should be verified. Indirect calorimetry is characterized by a high variability of the measured parameters, which is related to the experimental peculiarities. This review briefly describes the main techniques for assessing basal metabolism and the methodology of indirect respiratory calorimetry in adults and its use in the child population. Also, we provide the literature data on the accuracy of assessing basal metabolism in obese children based on the most commonly used calculation formulas. Investigation of the energy metabolism features is necessary to elucidate the mechanisms of obesity pathogenesis and develop new techniques for its prevention and treatment.

Problems of Endocrinology. 2018;64(2):130-136

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