Vol 57, No 3 (2011)

Epidemiology of primary hyperparathyroidism in Russia (the first results from the database of Federal state institution «Endocrinological Research Centre»)
Dedov I.I., Mokrysheva N.G., Mirnaia S.S., Rostomian L.G., Pigarova E.A., Rozhinskaia L.I.
Abstract
To elucidate specific features of epidemiology of various forms of primary hyperparathyroidism (PHPT) in this country using the information about 561 patients accumulated for 19 years in the database of Federal state institution «Endocrinological Research Centre». The incidence of PHPT in Moscow estimated from the database of Endocrinological Research Centre for 2007 was 6.8 per 1 000 000 adult population and the prevalence as per 2009 was 3.1/100 000. These values are significantly lower than those reported by foreign authors. The men to women ratio among the patients with PHPT was 1:8. The disease largely affects subjects at the age from 50 to 60 years. By the year of 2004, the frequency of the mild form of PHPT did not exceed 20% of the total (based on 2002 Consensus criteria). It increased to 37% during the past 5 years. Conservative treatment of PHPT can be recommended to 14% of the patients presenting with sporadic disease and to 32% of those with MEN syndrome. The frequency of asymptotic PHPT and its normocalcemic forms is estimated at 5% and 9% respectively. The above results are the first data on epidemiology of PHPT in this country; however, they are insufficient to comprehensively evaluate the real significance of the problem. Large-scale epidemiological studies are needed to ensure adequate assessment of the situation.
Problems of Endocrinology. 2011;57(3):3-10
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The differences of clinical picture of macroprolactinomas and their response to medicamental therapy with dopamine agonists between men and women
Astaf'eva L.I., Kadashev B.A., Dedov I.I., Kalinin P.L., Kutin M.A., Tenedieva V.D., Tropinskaia O.F.
Abstract
The data about sex-specific differences of clinical signs and symptoms of macroprolactinomas and their response to medicamental therapy with dopamine agonists between men and women are reported. The present study included 306 patients (the men to women ratio 1.4:1) presenting with macroprolactinomas. Large and giant neoplasms were shown to predominate in men regardless of their age accompanied by clinical symptoms associated with the so-called «mass effect» of the tumour. The occurrence of macroprolactinomas of different size depended on the age of the patients. The majority of the young women had tumours of large and intermediate size and exhibited clinical features of hyperprolactinemic hypogonadism while those aged above 40 years had large and giant tumours accompanied by the symptoms of their «mass effect». The medicamental treatment with cabergolin was equally efficacious in both men and women.
Problems of Endocrinology. 2011;57(3):11-16
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The clinical course of endocrine ophthalmopathy in patients presenting with Graves' disease depending on the effect of radioiodine therapy
Sheremeta M.S., Sviridenko N.I., Belovalova I.M., Garbuzov P.I.
Abstract
The primary objective of the present work was to study the clinical course of endocrine ophthalmopathy (EOP) following radioiodine therapy (RIT) of Graves' disease (GD) and depending on its effect (development of post-radiation hypothyroidism). The secondary objective was to determine risk factors of EOP progression after radioiodine therapy. This prospective study included 38 patients (76 eyes) allocated to two groups. The patients of group 1 (n=19/38 eyes) presented with thyrotoxicosis at each visit and continued to use thyrostatic agents; those in group 2 (n=19/38 eyes) had hypothyroidism at its early stages (3 and 6 months) and were given substitution therapy with levothyroxin. The development of post-radiation hypothyroidism was shown to strongly influence the clinical course of EOP. In the patients of group 1, EOP remained active throughout the entire observation period (12 months) in the absence of appreciable variations of its integral severity index. In group 2, the same index decreased significantly, but active forms of EOP could be detected by the time of onset of hypothyroidism (6 months) (p=0.0000). After 12 months, the level of anti-TSH receptor antibodies in the patients of group 1 was significantly higher than in those of group 2 (10.8±8.3 and 2.9±2.0 respectively, p=0.0003). The regression rate of EOP symptoms following radioiodine therapy (RIT) of Graves' disease was a function of the efficacy of thyroid 131I radioablation. It is concluded that persistence of anti-TSH receptor antibodies was responsible for the deterioration of the clinical picture of endocrine ophthalmopathy after radioiodine therapy.
Problems of Endocrinology. 2011;57(3):17-20
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Specific features of hemodynamics in the patients of different age groups presenting with autoimmune thyroiditis and subclinical hypothyroidism
Nekrasova T.A., Ledentsova O.V., Strongin L.G., Kazakova L.V., Lukushkina A.I.
Abstract
This study was designed to elucidate the relationship between the age of the patients presenting with autoimmune thyroiditis and subclinical hypothyroidism and the changes in their cardiovascular system. The following characteristics were estimated: the structure of the left ventricle, its overall and segmental diastolic function (by tissue Doppler echocadiography), and rigidity of the arterial walls (from the Young's modulus of elasticity, by ultrasonography). The patients were 95 women at the age of 20 to 50 years of whom 47 presented with autoimmune thyroiditis and subclinical hypothyroidism and 48 with euthyroidism (controls). They were divided into 3 age groups to be compared in the «subclinical hypothyroidism vs control» mode. Group 1 comprised 12 ad 13 women respectively aged 20-30 years, Group 2 contained 12 and 10 patients (31-40 years), group 3 included 23 and 25 patients (41-50 years). Young women with subclinical hypothyroidism were characterized by high values of Young's modulus and a large number of dysfunctional left ventricular segments (p<0.05). In the patients of the intermediate age, subclinical hypothyroidism also tended to have high values of Young's modulus in the absence of diastolic dysfunction. The oldest patients showed no signs of left ventricular dysfunction or arterial wall rigidity compared with controls (p<0.05). The results of the study indicate that the patient's age influences manifestations of changes in the cardiovascular system characteristic of subclinical hypothyroidism. In young women, this condition is associated with more pronounced disturbances of both overall and segmental diastolic functions and arterial elasticity than in control subjects. The women of older age groups show less apparent cardiovascular and metabolic abnormalities while the role of subclinical hypothyroidism as a cardiovascular risk factor is relatively insignificant.
Problems of Endocrinology. 2011;57(3):21-24
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Clinical, hormonal, and molecular-genetic characteristics of two cases of abnormal sex formation (ASF) in 46XY subjects caused by type 3 17-beta hydroxysteroid dehydrogenase deficiency
Kolodkina A.A., Kalinchenko N.I., Nizhnik A.N., Nokel' M.A., Tiul'pakov A.N.
Abstract
Type 3 17-beta hydroxysteroid dehydrogenase (17HSD3) deficiency is a rare form of abnormal sex formation (ASF) in 46XY subjects in which the conversion of androstendione to testosterone is blocked; this defect results in compromised masculinization of the external genitalia during the intrauterine development. A distinctive feature of this form of sex development is masculinization at puberty due to the extragonadal conversion of androstendione to testosterone. Two clinical cases are reported: both girls were born with the female-type of external genitalia and 46XY karyotype, but progressive virilization in the pubertal period gave reason to suspect diagnosis of 17HSD3 deficiency. In both cases, this diagnosis was confirmed in molecular genetic studies (the following mutations were identified in the HSD17B3 gene: c.728-734delGATAACCp.1244fsX254/c.277+4A>T and c.277+4A>T). These two cases are the first reports of 17HSD3 deficiency in the Russian literature.
Problems of Endocrinology. 2011;57(3):25-30
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Androgen deficiency in women and possibilities for its hormonal diagnostics
Goncharov N.P., Katsiia G.V., Melikhova O.A., Smetnik V.P.
Abstract
The authors describe the distribution patterns of free testosterone concentrations in the saliva of women who previously underwent ovariectomy, in postmenopausal women, in those presenting with clinical signs of hyperandrogenism, and in healthy women in the follicular phase of the menstrual cycle. The level of salivary free testosterone in postmenopausal women and after ovariectomy was lower than in younger premenopausal patients. Women with clinical signs of hyperandrogenism showed higher free testosterone levels than the age-matched young healthy subjects. The salivary free testosterone levels in 60-75% of the ovariectomzed, postmenopausal, and hyperandogenic women remained within their normal range in young healthy women. It is concluded that high analytical sensitivity of the chemiluminescent method for the measurement of free testosterone in the saliva makes possible its application to the screening for androgen status of the women at risk of testosterone deficiency.
Problems of Endocrinology. 2011;57(3):31-36
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Victosa: the experience with clinical application in patients with type 2 diabetes mellitus
Voĭchik É.A.
Abstract
Type 2 diabetes mellitus that comes from insulin resistance and deficit of insulin secretion has recently been described as associated with reduced incretin effect. The efficiency of traditional hypoglycemic therapy (metformin, secretagogues, glitazones, insulin) gradually decreases due to progressive loss of functioning beta-cell mass. The achievement of target blood glucose levels for the prevention of complications and cardiovascular pathology as a rule leads to such adverse events as increased body weight and hypoglycemia. The search for an «ideal» drug included the study and the use of incretin effect in DM2 patients. Liralglutide, the first analog of human glucagon-like peptide (GPP-1), is an innovative preparation with the desired properties the action of which is not confined to traditional hypoglycemic effects and improvement of glycemic control (as many as 65% of the patients have the targeted HbA1c level <7% at a minimal risk of hypoglycemia). It also prevents a rise in body weight, decreases arterial pressure and trigyceride levels, improves beta-cell function. This paper reports the first experience with clinical application of liraglutide (marketed in this country under commercial name Victosa since November 2010) for the treatment of patients with type 2 diabetes mellitus. Our data confirm results of the randomized placebo-controlled clinical study LEAD 1-6.
Problems of Endocrinology. 2011;57(3):37-41
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Synthesis of new exenatide analogs and investigation of their influence on glycemia and renal function in rats
Bogolepova A.E., Kutina A.V., Marina A.S., Nikol'skaia S.K., Shakhmatova E.I., Titov M.I., Natochin I.V.
Abstract
New analogs of exenatide with amino acid substitutions at 14, 35, and 39 have been synthesized. They were shown to be more stable than original exenatide in aqueous solutions. In vivo testing on rat models of glucose loading showed that exenatide and its novel analogs possess hypoglycemic activity and stimulate renal excretion of sodium and magnesium ions and osmotically free water but have virtually no effect on the elimination of potassium ions. Experiments with isolated skin and urinary bladder preparations from male frogs showed that exenatide and its analogs promote biosynthesis of physiologically active compounds modulating renal functions.
Problems of Endocrinology. 2011;57(3):42-47
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How can we avoid the danger of hypoglycemia, one of the most serious complications of therapy of type 2 diabetes mellitus? The role of DPP-4 inhibitors
Pavlova M.G., Zilov A.V.
Abstract
Optimal or near-optimal compensation of diabetes mellitus is almost inevitably fraught with the risk of hypoglycemia. In patients with type 2 diabetes (DM2), especially in those of old-age groups, the development of hypoglycemia increases the risk of CV death, cardiac rhythm disturbances, dementia, and depressive states. Whether absolutely all diabetic patients should be treated so as to ensure blood glucose levels close the physiological values thus far remains a matter of controversy. The results of large-scale clinical studies carried out in the recent years suggest the necessity to revise the existing algorithms for the treatment of patients with DM2. Highly efficacious agents for the purpose should be chosen with reference to both their glucose-normalizing activity and "the safety profile" (i.e. reduced risk of hypoglycemia). A panel of experts for the Russian Association of Endocrinologists (RAE) developed and published «Consensus Algorithm on the initiation and intensification of therapy of type 2 diabetes mellitus». Its main provisions emphasize the necessity of treating diabetics on an individual basis and establish target levels of glycemia for each patient. Special attention should be given to the patients belonging to high risk groups, i.e. those with manifest macrovascular pathology, unable to recognize hypoglycemia, and having serious concomitant diseases. The following first line preparations are recommended to enhance the safety of DM2 therapy: metformin, dipeptidyl peptidase-4 (DPP-4) inhibitors and agonists of glucagon-like peptide-1 (GLP-1) receptors. The results of both national and international clinical studies of vildaglyptin give reason to recommend this DPP-4 inhibitor for a wider application to the treatment of patients with type 2 diabetes mellitus.
Problems of Endocrinology. 2011;57(3):48-52
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Basal insulin therapy in patients with type 2 diabetes mellitus: aspects of early initiation, advantages, constraints, and prospects
Vikulova O.K.
Abstract
Intensive control of glycemia starting from the onset of type 2 diabetes mellitus (DM2) is of primary importance for the long-term prognosis of the disease and the reduction of risk of cardiovascular complications. The strategy of early intensive therapy of DM2 thus far remains a matter of fierce dispute among diabetologists. The problem of choice of an optimal regime for the start of insulin therapy does not have an unambiguous solution either. Hypoglycemia is the main factor that traditionally hampers wide application of insulin therapy in patients with type 2 diabetes mellitus. The choice in favour of basal therapy with insulin analogs has the advantage of reaching the target parameters of carbohydrate metabolism at a significantly lower risk of hypoglycemia compared with other strategies of insulin therapy.
Problems of Endocrinology. 2011;57(3):53-59
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