Vol 49, No 4 (2021)

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Bioimpedance phase angle as a marker of sarcopenia in elderly women with multiple comorbidities

Kurmayev D.P., Bulgakova S.V., Zakharova N.O.


Rationale: The progressive decline in skeletal muscle strength and function during aging can lead to disability and premature death. It is of interest to evaluate the potential of bioimpedance phase angle (PhA) as an instrumental marker of sarcopenia in clinical practice.

Aim: To identify an association between the phase angles determined by the bioimpedance analysis of body composition, with functional activity parameters in elderly women with multiple comorbidities.

Materials and methods: The study included 146 elderly women (aged 75 to 84 years, mean age 79.44 ± 2.56 years). Assessments consisted of the Charlson comorbidity index, “Vozrast ne pomekha” (Age is not a hindrance) questionnaire, the Barthel index, the sit-to-stand five-repeat test, the standardized 4-meter walking speed test, and bioimpedance analysis of body composition (ABC-02, Medass, Russia). Muscle strength parameters were assessed by wrist dynamometry with a mechanical wrist dynamometer. The hand dynamometry index was calculated by dividing the hand grip strength by the patient's squared height. According to the EWGSOP2 guidelines for the critical cur-off for hand dynamometry, the patients were divided into two groups: those with the hand grip strength > 16 kg (n = 41) and those with < 16 kg (n = 105).

Results: There were significant correlations of PhA with age (r = -0.369; p =0.017), the results of the screening questionnaire “Vozrast ne pome-kha” (Age is not a hindrance) (r = -0.359; p = 0.023), Barthel index (r = 0.375; p = 0.018), hand dynamometry (r = 0.395; p = 0.014), hand dynamometry index (r = 0.340; p = 0.021), lean body mass (r = 0.414; p = 0.009), musculoskeletal mass (r = 0.819; p < 0.001), proportion of musculoskeletal mass (r = 0.796; p < 0.001), walking speed (r = 0.670; p < 0.001), and the results of the sit-to-stand test (r = -0.541; p < 0.001). Sarcopenia was diagnosed in 61 women (41.8%). There were also significant differences in age, hand dynamometry results, hand dynamometry index, walking speed and results of the sit-to-stand test between the two groups depending on their hand grip strength.

Conclusion: The use of hand dynamometry, physical activity tests, and bioimpedance phase angle can be used in clinical practice to diagnose sarcopenia.

Almanac of Clinical Medicine. 2021;49(4):245-253
pages 245-253 views

The effectiveness of acromegaly treatment according to the Registry of patients with pituitary tumors in the Republic of Tatarstan

Vagapova G.R., Pashaev B.Y., Ashimova R.R., Khafizov A.R., Mokhova I.V.


Background: Acromegaly is a severe progressive neuroendocrine disease caused by chronic elevated concentrations of growth hormone and insulin-like growth factor 1 in individuals with completed physiological growth and leading to early disability and mortality. The Acromegaly Registry with its regular updates makes it possible to merge and systematize all the available information on the diseases, to assess the efficacy of treatment algorithms and to choose an optimal diagnostic and treatment strategy in a given territory.

Aim: To evaluate the efficacy of various treatments for acromegaly based on the analysis of the regional Registry of patients with pituitary tumors in the Republic of Tatarstan.

Materials and methods: The study was based on data from 217 patients with somatotropin producing pituitary adenomas entered in the Registry of patients with pituitary tumors in the Republic of Tatarstan as per January 2021. One hundred and eighty one (181 patients) with sufficient data to assess the remission rates and the disease course were included into the analysis.

Results: Endonasal endoscopic adenomectomy as a first-line treatment has been performed in 93% (169/181) of the patients, with 34% of the cases (57/169) being in the full postoperative remission. The efficacy of surgical treatment depended on the tumor size, invasion grade and aggressiveness. A 1st generation long-acting somatostatin analog (octreotide) has been prescribed to 50% (91/181) of the patients (11 patients as first-line therapy and 80 patients after adenomectomy), with biochemical remission rate of 56% (51/91). Radiological treatment has been completed in 11,6% (21/181) of the patients. The complete remission rate after all treatment modalities (surgical, medical, and radiation therapy) was 60% (108/181).

Conclusion: The effectiveness of treatment for acromegaly in the Republic of Tatarstan is comparable to that in the all-Russian and international registries. Nevertheless, 40% of the patients with acromegaly in the region do not have their disease biochemically controlled indicating the need to optimize drug treatment.

Almanac of Clinical Medicine. 2021;49(4):254-260
pages 254-260 views

The prevalence rate of hypopituitarism in patients with pituitary macroadenomas with various hormonal activities

Krivosheeva Y.G., Ilovayskaya I.A.


Rationale: According to the recent epidemiological studies, prevalence of pituitary tumors amounts to 1 per 865 to 2688 adults. The prevalence rates of hypopituitarism in pituitary macroadenomas are highly variable and comprise 37% to 85% among newly diagnosed non-functioning pituitary adenomas (NFPA). There is virtually no data on the prevalence of hypopituitarism in the cohort of newly diagnosed macroadenomas secreting prolactin and somatotropic hormone.

Aim: To assess the prevalence of hypopituitarism in patients with pituitary macroadenomas with various hormonal activities and to identify its potential risk factors.

Materials and methods: We analyzed data from 293 patients with pituitary macroadenomas with various hormonal activities: NFPA (n = 121), prolactinomas (n = 59), and somatotropinomas (n = 113). The patients had been examined before any treatment was commenced.

Results: The prevalence rate of hypopituitarism was 59/121 (39.9%) among the patients with NFPA, 18/59 (27.3%) among those with prolactinomas, and 19/113 (14%) among those with somatotropinomas (р < 0.001). The symptoms of chiasmal compression and chiasmal syndrome were significantly more prevalent in the patients with hypopituitarism, than in those without it in all subgroups. The relative risk of hypopituitarism in the patients with chiasmal compression was 2.10 for NFPA (95% confidence interval (CI) 1.50-2.95, р=0.003), 1.667 for prolactinomas (95% CI 1.292.18, р = 0.005), and 1.45 for somatotropinomas (95% CI 1.56-2.48, р = 0.001). The relative risk of hypopituitarism in the patients with chiasmal syndrome was 1.66 for NFPA (95% CI 1.26-2.18, р=0.009), 2.08 for prolactinomas (95% CI 1.602.69, р = 0.001), and 1.97 for somatotropinomas (95% CI 1.56-2.48, р = 0.005). The NFPA subgroup had the highest rate of hypothyroidism (36/59, 61.0%), whereas the prolactinoma subgroup had the highest rate of secondary hypogonadism (34/59, 57.6%); however, hypogonadism is one of the manifestations of persistent pathological hyperprolactinemia typical for prolactinomas. In the somatotropinoma subgroup, secondary hypothyroidism was found in 11/19 (57.9%) of the patients. Conclusion: Identification of hypopituitarism before any treatment depended on the type of hormonal activity of a pituitary tumor and was most frequent in NFPA. The risk factors for hypopituitarism were chiasmal compression, chiasmal syndrome, vertical diameter of the pituitary tumor, and its volume. Secondary adrenal insufficiency, being the most hazardous component of hypopituitarism, manifested most rarely.

Almanac of Clinical Medicine. 2021;49(4):261-267
pages 261-267 views

Risk factors of central diabetes insipidus after transnasal adenomectomy

Mikhaylova D.S., Dzeranova L.K., Rebrova O.Y., Pigarova E.A., Rozhinskaya L.Y., Marova E.I., Azizyan V.N., Ivashchenko O.V., Grigoriev A.Y.


Background: At present, surgical intervention is a major treatment strategy for pituitary adenomas. It is commonly complicated with water and electrolyte imbalance. The prevalence of post-surgical central diabetes insipidus (CDI) may amount to 30%; however, its risk factors have not been established.

Aim: To assess the rates and nosological distribution of CDI after transnasal adenomectomy and to identify its risk factors.

Materials and methods: This retrospective study included 96 patients aged 20 to 65 years (median [Q1; Q3] 43 [34.5; 53.5]), who had transnasal adenomectomy in 2010-2011 due to Cushing's disease, acromegaly, prolactinoma, non-functioning pituitary adenoma. All patients underwent clinical examination and laboratory work-up before and after surgery. Their post-surgical course was assessed for 5 to 7 years. Depending on identified manifestations, the patients were categorized into the permanent CDI (n = 15) and transient CDI (n = 34); 47 patients had no CDI.

Results: Cushing's disease (odds ratio (OR) 6.1, 95% confidence interval (CI) 2.3-16.1), secondary adrenal insufficiency (OR 6.8, 95% CI 2.618.3) and adrenocorticotropic hormone levels of < 15.8 pg/mL (OR 5.0, 95% CI 1.9-13.5), microadenoma (OR 4.5, 95% CI 1.7-11.5) promote transient postoperative CDI, whereas macroadenoma decrease this risk (OR 0.2, 95% CI 0.1-0.5). The transient CDI was also more common in patients with secondary hypothyroidism, cortisol level of<200 nmol/L, adenoma's volume at magnetic resonance imaging of < 0.83 cm3 at trend level and more rare in patients with acromegaly and loss of tropic hormones before surgery at trend level as well. No significant risk factors were identified for permanent CDI, but it could be more often associated with secondary hypothyroidism, absence of any adenoma at magnetic resonance imaging and pituitary injury during the surgery and less frequent in patients with macroadenomas at trend level.

Conclusion: The proportion of permanent postoperative CDI was 16% (95% CI 9-24), and that of the transient form 35% (95% CI 25-45). Cushing's disease, microadenoma, development of secondary adrenal insufficiency and adrenocorticotropic hormone levels of < 15.8 pg/mL after surgery increase the probability of transient CDI, whereas macroadenoma does decrease this risk. No significant risk factors were identified for permanent CDI.

Almanac of Clinical Medicine. 2021;49(4):268-276
pages 268-276 views

Study of urine steroid profiles by gas chromatography-mass spectrometry in patients with adrenocortical cancer in the course of treatment

Velikanova L.I., Vorokhobina N.V., Shafigullina Z.R., Bokhian V.Y., Stilidi I.S., Kalugina V.V., Malevanaya E.V., Strelnikova E.G., Kushlinskii N.E.


Background: Adrenocortical carcinoma (ACC) is a rare and aggressive disease. There are only few studies evaluating the diagnostic value of gas chromatography-mass spectrometry (GC-MS) for detection of ACC recurrence after surgery. It is necessary to conduct an in-depth study to search for the most informative markers of the disease relapse.

Aim: To study urine steroid metabolism by GC-MS during treatment to identify early signs of metastatic disease and relapse.

Materials and methods: Thirty nine (39) ACC patients were examined before and after surgery, in the early postoperative period (< 1 year) and late postoperative period (at 2 to 5 years). Ten (10) patients were disease-free at less than 1 year after surgery. Twenty nine (29) patients had metastases in lungs and other organs: 14, within 1 year after surgery, and 15, at 2 to 5 years. The control group included 25 patients with nonfunctioning adrenocortical adenomas (NAA) without malignant characteristics at histological examination. Urine steroid profiles were assessed with a gas chromatograph-mass spectrometer Shimadzu GCMS-QP2020.

Results: As assessed by GC-MS, 16 major ACC biomarkers were found before surgery, including etiocholanolone, dehydroepiandrosterone (DHEA) and its metabolites, pregnanediol, pregnanetriol, 5-ene-pregnenes, and tetrahydro-11-deoxycortisol (THS). Their urine excretion was increased compared to that in the patients with NAA (р < 0.002). A non-classic 5-ene-pregnene, 3β,16,20-pregnenetriol (3β,16,20-dP3), was identified, with its urine excretion of > 500 mcg/day that was typical for ACC patients. After surgery, decreased urinary excretion of THS (р < 0.0001) and 3β,16,20-dP3 (р < 0.0001), increased 3α,16,20-dP3/3β,16,20-dP3 ratio (р = 0.003), compared to those before surgery, were indicative of the absence of any metastases. No difference of urine THS excretion and 3α,16,20-dP3/3e,16,20-dP3 ratio from the corresponding values before surgery (p > 0.05) is a sign of metastatic diseases in the ACC patients at less than 1 year after the surgery, of the disease relapse at 2 to 5 years, and of the disease relapse after chemotherapy. In addition, in the ACC patients with metastatic disease within 1 year after surgery, increased progestogen urine excretion was found. Urine excretion of DHEA and its metabolites in the patients with the disease relapse after chemotherapy was not different from those in the ACC patients before surgery (p > 0.05).

Conclusion: Determination of urine excretion of THS, DHEA and its metabolites, etiocholanolone, 5-ene-pregnenes, 3β,16,20-dP3, and 3α,16,20-dP3/3β,16,20-dP3 ratio by GC-MS is of utmost importance in the monitoring of treatment for ACC and early diagnosis of the disease progression.

Almanac of Clinical Medicine. 2021;49(4):277-284
pages 277-284 views


Postprandial hypoglycemia after upper gastrointestinal tract surgery: prevalence and pathophysiology (part 1)

Yukina M.Y., Chernova M.O., Troshina E.A., Evdoshenko V.V., Platonova N.M.


Nowadays obesity is a major health problem worldwide. Surgery is the most promising treatment for morbid obesity. There are two types of bariatric procedures, one to reduce the food intake volume and the other to limit the absorption of nutrients. Despite the indisputable advantages of bariatric surgery for weight loss, it is necessary to remember the potential risk of severe complications, such as hypoglycemic syndrome at 2 to 3 hours after ingestion of rapidly absorbable carbohydrates manifested by adrenergic and neuroglycopenic symptoms. According to the literature, the prevalence of post-bariatric postprandial hyperinsulinemic hypoglycemia (PHH) varies from 10% to 75%. PHH in post-bariatric patients should be differentiated from the syndrome of non-insulinoma pancreatogenic hypoglycemia and from insulinoma; however, these diseases are described also in patients after bariatric surgery.

The mechanisms of PHH as an outcome of shunting bariatric procedures are currently not fully clear. According to the recent studies, incretin hypersecretion in response to the accelerated flow of carbohydrates into the small intestine plays a leading role in the inappropriate excess production of insulin by the pancreas. In addition, there are hypotheses on a slower normalization of insulin production during more rapid bodyweight decrease and regression of insulin resistance, the role of alpha-cell dysfunction, disturbed negative feedback between insulin and ghrelin, compensatory hyperplasia and hypertrophy of the remaining enterocytes (including L-cells), changes in gut microflora, bile acids level and composition. A number of other mechanisms have also been proposed that require further studies.

Almanac of Clinical Medicine. 2021;49(4):285-296
pages 285-296 views


Radiotheranostics of neuroendocrine neoplasms: quo vadis

Rumyantsev P.O.


Neuroendocrine neoplasms are grouped based on their neuroendocrine origin and represented by a heterogeneous tumor cluster with various malignancy potentials and types of biological behavior. These tumors can localize anywhere, but most commonly within the gastrointestinal tract. The ability of tumor cells to express specific receptors and particulars of their metabolism make it possible to successfully use molecular visualization (single-photon emission computed tomography / positron emission tomography) and radiotargeted therapy for diagnosis and treatment of patients with neuroendocrine tumors. In clinical practice, somatostatin receptor (receptors type 2) radiotheranostics has been used most widely. Improvement of diagnostic and therapeutic characteristics of new radioligands, discovery of new receptor and metabolic targets, widening of the medical isotope spectrum and development of new theranostic pairs open wide horizons for radiotheranostics as an integral field in modern biomedicine. The paper summarizes the worldwide experience, highlights the state-of-the-art and future development of radiotheranostics of neuroendocrine tumors.

Almanac of Clinical Medicine. 2021;49(4):297-303
pages 297-303 views

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