Vol 64, No 6 (2018)

Original Studies
Voice rehabilitation of patients with unilateral laryngeal paresis after thyroid cancer surgery
Choynzonov E.L., Balatskaya L.N., Chizhevskaya S.Y., Cheremisina O.V., Krasavina E.A., Zhuikova L.D.

BACKGROUND: Recurrent laryngeal nerve injury is one of the most frequent complications of surgery for thyroid cancer. This injury may result in vocal cord paresis and respiratory failure. Repeat surgery for recurrent tumors involves increased risk of recurrent nerves paresis.

AIM: to evaluate the efficacy of voice rehabilitation in patients with unilateral laryngeal paresis after surgery for thyroid cancer.

MATERIAL AND METHODS: Between 2008 and 2017, a total of 54 patients with unilateral laryngeal nerve paralysis after surgery for thyroid cancer were treated at the Cancer Research Institute. All patients had histologically verified advanced stage (T3–4N0–2M0–1) of thyroid cancer. Papillary thyroid cancer was diagnosed in 87% cases. Endoscopic or laryngoscopic examination and acoustic voice analysis were the criteria for assessing voice rehabilitation efficacy.

RESULTSPositive outcomes of voice rehabilitation were obtained in 54 patients. The vocal fold mobility was completely restored in 36 (67%) patients. The voice function was recovered due to the compensation provided by the healthy half of the larynx in 11 (21%) patients. In 7 (12%) patients, the vocal sound improved, patients no longer complained of . speech fatigue, but hoarseness persisted. By the time of discharge, the patients were able to go back to work. The effectiveness of voice restoration in patients with unilateral laryngeal paresis was directly dependent on the early start of rehabilitation measures (5–7 days after surgery) subject to interdisciplinary approach. The voice rehabilitation course ranged from 3 to 6 weeks.

CONCLUSIONS: Our technique of voice rehabilitation in patients with unilateral laryngeal paresis after surgery for thyroid cancer shortened the rehabilitation time, reduced disability in oncological patients practicing voice and speech professions and improved the quality of life and social adaptation of these patients.

Problems of Endocrinology. 2018;64(6):356-362
The study of new biomarkers of bone metabolism of sclerostin and cathepsin K in patients with type 2 diabetes mellitus
Nurullina G.M., Akhmadullina G.I.

BACKGROUND: Deterioration of bone tissue in type 2 diabetes mellitus (T2D): lead to the increased bone brittleness and to higher risk of low-energy fractures.

AIM: to study serum levels of sclerostin and cathepsin K in assessing bone metabolism in patients with type 2 diabetes mellitus.

MATERIAL AND METHODS: 102 postmenopausal women aged from 46 to 67 years were examined. All patients were divided into 4 groups: the first group included 39 patients with type 2 diabetes (T2DM) and postmenopausal osteoporosis (PO), the second group — 25 patients with PO without T2DM, the third group included 21 patients with T2DM but without PO, and the fourth group (control) — 17 people. Patinets of all groups were tested for ionized calcium, phosphorus, total alkaline phosphatase (ALP), parathyroid hormone, 25 (OH) vitamin D, bone mineral density in groups I, II, and IV, levels of sclerostin and cathepsin Kin seru, were also obtained.

RESULTS: No statistically significant differences have been observed between groups in sclerostin levels, a positive correlation was found between sclerostin and НbА (r=0.43; p=0.009) in the group of patients with T2DM and PO, a negative correlation was found between sclerostin and ionized calcium (r=–0.45; p=0.037) in the group of patients with PO. Cathepsin C in the first group was lower than in the second group (p=0.046), but taking into account Bonferroni correction this difference was not statistically significant. In the first and third groups, 25 (OH) vitamin D was lower than in the groups without T2D. The ALP negatively correlated with the duration of the postmenopause (r=–0.39 and r=–0.64; р=0.05, respectively).

CONCLUSIONS: Cathepsin С was lower in patients with T2DM2 and PO, which may indirectly indicate a decreased bone resorption. Concentration of sclerostin, which plays a key role in the mechanism of inhibiting osteoblastogenesis, positively correlated with НbА.

Problems of Endocrinology. 2018;64(6):363-370
The effect of hypercaloric diet and Quercetin on the full-transcriptome liver tissue profile of Zucker-LEPRfa rats
Trusov N.V., Apryatin S.A., Gorbachev A.Y., Naumov V.A., Mzhelskaya K.V., Gmoshinski I.V.

BACKGROUND: The peptidic hormone leptin (Lep) occupies a central place in the control of energy homeostasis and body weight in mammals. A convenient model for studying the role of impaired Lep reception is the Zucker-LEPRfa rats, which carry a mutation in the homozygote of the LEPR gene. Quercetin (Q; 3.3 ‘, 4’, 5.7-pentahydroxyflavone) is currently being considered as one of the promising biologically active substances, which allows to correct metabolic disorders in obesity and metabolic syndrome.

AIM: to study changes in the expression of genes in liver tissue of rats with impaired receptivity of Lep under the influence of high-fat and high-carbohydrate diet (HFCR) or/and Q supplementation.

MATERIAL AND METHODS: 4 groups of six male Zucker-LEPRfa male rats were used in experiment. Within 61 days the animals of the 1st group (control) received a balanced semi-synthetic diet, the second group received the same diet with the addition of quercetin in a dose of 50 mg/kg of body weight, the third group — the HFCR (30% fat by dry weight and 20% fructose instead of water), the 4th group is the same diet and supplement of quercetin. Full transcriptional profiling of liver tissue was performed on microchips from the Gene Expression Hybridization Kit (Agilent Technologies), a real-time polymerase chain reaction combined with reverse transcription (RT-PCR) was performed for liver transcripts of Crot, FTO, NpY, Prdx1, Prom1, Ugt2b37 and GAPDH genes contained in liver tissue.

RESULTSIt was shown that feeding of Zucker-LEPRfa rats with Q and/or HFCR led to significant changes in the level of transcription of 1604 genes in liver tissue, from which the effect of quercetin proper was manifested for 1396 genes. Changes were more pronounced in the transcriptome of liver tissue caused by HFCR, than caused by the addition of Q against the background of a standard diet. Q influenced the expression of genes responsible for xenobiotic detoxification processes (UGT2b37), redox homeostasis (Prdx1), beta-oxidation of fatty acids (Crot), and central mechanisms affecting hunger and satiety (NpY), and potentiated, or abolished the effects of HFCR against a number of other functionally important genes. Bioinformatic analysis revealed the influence of HFCR and/or Q on 23 metabolic pathways (KEGGS), of which 7 (the metabolism of steroids, arachidonic and linoleic acids, retinoids, drugs and xenobiotics (due to cytochrome P-450), bile secretion) were affected in all experimental groups.

CONCLUSIONS: Changes in the transcriptome of the liver of Zucker-LEPRfa rats, caused by consumption of HFCR and/or Q, were consistent with experimental data on changes in short-term memory, anxiety and mineral metabolism in these animals.

Problems of Endocrinology. 2018;64(6):371-382
Case Reports
Phenotypes of endocrine ophthalmopathy: clinical manifestation and tomographic characteristics
Belovalova I.M., Sviridenko N.Y., Bessmertnaya E.G., Chepurina A.A., Sheremeta M.S., Mikheenkov A.A.

The clinical manifetstations of endocrine orbitopathy (EOP) significantly because autoimmune process may involve various anatomical structures of the eye. Choosing an effective method for EOP treatment requires to determine the selectivity of orbital tissue damage, which is difficult when only clinical criteria are applied. 102 patients with EOP and Graves’ disease were examined. All patients underwent the standard ophthalmological examination and multispiral computed tomography of orbits. The analysis of clinical and tomographic parameters allowed us to distinguish 3 variants of EOP flow: classical, lipogenic, and myogenic. The prevailing symptoms of patients with the lipogenic variant were distinct exophthalmos without a disturbance of the function of extraocular muscles (EOM) and visual disturbances. Oculomotor disorders, diplopia, strabismus, and decreased vision were prevalent in patients with the myogenic variant. Patients with the classical variant suffered from exophthalmos, periorbital edema, and oculomotor disorders. The identification of independent clinical variants of EOP with specific clinical symptoms and different tomographic characteristics testifies different pathogenetic mechanisms of EOP development is to determine personalized approaches to treatment.

Problems of Endocrinology. 2018;64(6):383-389
Chronic thyrotoxic myocarditis complicated by myocardial rupture in a patient with autoimmune thyroiditis
Cherkasova N.A., Zairatyants G.O., Ananitcheva N.A., Kolendo S.E.

A case of thyrotoxic myocarditis in a 60-year-old female patient is oresented. With the diagnosis of «Unstable angina» she was admitted to the intensive care unit for patients with myocardial infarction at the Yudin city clinical hospital in Moscow. Earlier, the patient had been treated with tyrosol for thyrotoxicosis, but she independently abolished the drug. She ecperienced pain in the chest for the first time in her life. Emergency, coronaroangiography was performed. No hemodynamically significant damage to the blood vessels of the heart was detected. Later, according to the outpatient blood test for thyroid hormones, a diagnosis was established — «severe thyrotoxicosis». The next day after hospitalization, treatment with tyrosol was started at a dose of 30 mg per day. Sinus tachycardia persisted. A reliable increase in cardiospecific enzymes was detected. The pain in the chest did not recur. Echocardiography did not reveal impairment of local or global myocardial contractility.

On the fifth day of hospital treatment the patient suddenly died of cardiac and respiratory arrest.

The autopsy study revealed autoimmune thyroiditis, thyrotoxic serous-lymphocytic myocarditis, which was complicated by a rupture of the myocardium, and pericardial gemotamponade.

The difficulties of differential diagnosis of myocarditis and acute coronary syndrome and the features of treatment tactics in elderly patients with thyrotoxicosis are discussed.

Problems of Endocrinology. 2018;64(6):390-396
Secondary acquired nasolacrimal duct obstruction after radioiodine therapy
Yartsev V.D., Atkova E.L.

Secondary acquired nasolacrimal duct obstruction after radioiodine therapy is a comparatively rare complication but it requires treatment at an early stage. The symptoms of secondary acquired nasolacrimal duct obstruction are tearing, eye redness, discharge at ocular surface, a mass growing at lacrimal sac site. The considered complication occurs after radioiodine therapy in dose of 150 mCi, the rate of occurrence is dose-dependent. There are no clinical guidelines for preventing this complication but there are reports of nasolacrimal duct preventive intubation and those about developing new drug agents that block an action of the protein that uptakes iodine in the nasolacrimal duct mucosa. For diagnosing, special diagnostic procedures and an ophthalmologist consultation are required. For the correction of this complication, conservative treatment (with low efficacy) and special surgical treatment are used, including nasolacrimal duct recanalization with different techniques and anastomosis between nasolacrimal duct and nasal cavity formation. In cases of early patient encounter, it is possible to use more functional and less invasive surgical techniques, in cases of late encounter, more invasive surgical techniques are used.

Problems of Endocrinology. 2018;64(6):397-401
Clinical guidelines
Russian national consensus. Diagnostics and treatment of hypopituitarism in children and adolescences
Nagaeva E.V., Shiryaeva T.Y., Peterkova V.A., Bezlepkina O.B., Tiulpakov A.N., Strebkova N.A., Kiiaev A.V., Petryaykina E.E., Bashnina E.B., Мalievsky O.A., Тaranushenko Т.Е., Коstrova I.B., Shapkina L.A., Dedov I.I.

The materials of the National Consensus reflect the modern domestic and international experience on this issue.

Before conducting a specialized endocrinological examination of a short child, all other causes of short stature should be excluded: severe somatic diseases in a state of decompensation that can affect growth velocity, congenital systemic skeletal diseases, syndromic short stature (all girls with growth retardation require a mandatory study of karyotype, depending on the presence or absence of phenotypic signs of Turner syndrome), endocrine diseases in decompensation.

A specialized examination of the state of GH-IGF-I axis is carried out when the proportionally folded child has pronounced short stature: if the child’s height is < –2.0 SDS, if the difference between the child’s height SDS and child’s midparental height SDS exceeds 1.5 SDS and/or a low growth velocity.

The consensus reflects clear criteria for the diagnosis of GH-deficiency, central hypothyroidism, central hypocorticosolism, central hypogonadism, diabetes insipidus, hypoprolactinemia, and also the criteria for their compensation.

The dose of somatropin with GH-deficiency in children and adolescents is 0.025–0.033 mg/kg/day. With total somatotropic insufficiency, especially in young children, it is advisable to start therapy with somatropin from lower doses: 25–50% of the substitution, gradually increasing it within 3–6 months to optimal. In children with a growth deficit when entering puberty, the dose may be increased to 0.045–0.05 mg/kg/day.

With the development of side effects, the dose of somatropin can be reduced (by 30–50%), or temporarily canceled (depending on the severity of the clinical picture) until the complete disappearance of undesirable symptoms. With swelling of the optic nerve, treatment is temporarily stopped until the picture of the fundus of the eye fully normalizes. If therapy has been temporarily discontinued, treatment is resumed in smaller doses (50% of the initial) with a gradual (within 1–3 months) return to the optimum.

GH treatment at pediatric doses not continue beyond attainment of a growth velocity below 2–2.5 cm/year, closure of the epiphyseal growth zones, or earlier, when: the achievement of genetically predicted height, but not more than 170 cm in girls, 180 cm in boys, the patient’s desire and his parents / legal representatives satisfied with the achieved result of the final height.

Re-evaluation of the somatotropic axis is carried out after reaching the adult height, after 1–3 months GH therapy will be discontinued. Patients with isolated GH-deficiency or patients with 1 (besides GH) pituitary hormone deficiencies in the presence of a normal IGF-1 level (against the background of somatropin withdrawal) and not having molecular genetic confirmation of the diagnosis need re- evaluation. Patients with two or more (besides GH) pituitary hormone deficiencies, acquired hypothalamic-pituitary lesions due to operations on the pituitary and irradiation of the hypothalamic-pituitary area (if the IGF-1 level is low against somatropin withdrawal), specific pituitary/ hypothalamic structural defect on MRI, gene defects of the GH-IGF-I system do not need re- evaluation.

If GH deficiency is confirmed, treatment with somatropin is resumed at metabolic doses of 0.01—0.003 mg/kg/day under the control of the IGF-I level in the blood (measurement 1 time in 6 months), the indicator should not exceed the upper limit of the reference value for the corresponding age and floor.

Problems of Endocrinology. 2018;64(6):402-411
In honor of the 85th anniversary of Vladimir Vasilyevich Potemkin

We are celebrating the 85 anniversary and 61 years of research, pedagogical and medical activities of one of the nation’s leading endocrinologists, the promoter of academic endocrinology, the founder and the first head of the department of endocrinology of the Pirogov Russian National Research Medical University (RNIMU)

Honored Doctor of the Russian Federation, Professor Vladimir Vasilyevich Potemkin.

V.V. Potemkin was the first in our country who began to teach endocrinology at the department of internal diseases of the pediatric faculty of the 2nd Moscow State Medical Institute (now Pirogov Russian National Research Medical University (RNIM). In 1972, after his transfer to the Department of General Medicine, V.V. Potemkin established a course of endocrinology at the chair of internal medicine. Soon, endocrinology became an independent course and on its basis a separate chair was set up.

Heading first the course and then the chair for 40 years, V.V. Potemkin proved himself a talented teacher, scientist, and excellent clinicist.

V.V. Potemkin is the author of 7 textbooks on various aspects of endocrinology, including the nation’s first fundamental manual Endocrinology, published, in addition to Russian, also in French, Spanish and twice in English.

In his research work, V.V. Potemkin focuses on the problems of pathogenesis, clinical aspects, and treatment of diabetes and obesity. Research results obtained by V.V. Potemkin in studying the development of oxidative stress and impaired insulin-binding blood activity in patients with newly diagnosed T2D with normal body weight and suffering from obesity made it possible to find two different pathogenetic mechanisms underlying their hyperglycemia.

V.V. Potemkin studied the role of cytokines in the development of diabetic foot syndrome, which led to the conclusion that the criteria for the effectiveness of treatment of patients with type 2 diabetes complicated by diabetic foot syndrome, along with normoglycemia are also decreased activity of lipid peroxidation, stabilization of antioxidant defence, normalization of the level of TNF-alpha proinflammatory cytokine.

In troduction of V.V. Potemkin’s findings into clinical practice helps to improve the results of treatment of patients with diabetic foot syndrome, prevent gangrene, and reduce their direct and indirect financial costs.

Professor V.V. Potemkin celebrates his anniversary at the heirght of his creative powers. We wish our dear colleague good health, inexhaustible energy, and new creative successes for many years!

Problems of Endocrinology. 2018;64(6):412-414

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