Clinical endocrinology
Cellular and humoral immunity values and nonspecific defense factors were compared in 152 diabetics: 62 with type I, 80 with type II, and 10 with secondary condition. Control group consisted of 144 normal subjects matched for age and sex. Immunity parameters were changed in all diabetics. Characteristic immunological features of type I diabetes are autoantibodies to pancreatic islets, decreased activity of suppressor cells (signs of autoaggression), and manifest sensitization of lymphocytes to insulin. Type II diabetes is characterized by latent sensitization of lymphocytes to insulin detected during inhibition of functional activity of prostaglandin-producing cells. In secondary diabetes the counts of T-lymphocytes and NBT test are normal, but a high activity of suppressor cells and probably toxic effect of ethanol in some patients result in a low proliferative activity of lymphocytes in response to mitogen; there is no lymphocyte sensitization to insulin, latent or manifest.
Adrenaline, noradrenaline, and DOPA were measured in the urine and lacrimal fluid and hydrocortisone in the serum and lacrimal fluid of 108 patients with different stages of diabetic angioretinopathy (39 men and 69 women) aged 41— 65 years (mean age 52 ± 2.1 years) with diabetes of different severity. The stage of functional changes in the microcircula- tory bed of the bulbar conjunctiva (MCBBC) is associated with the predominant increase of noradrenaline level in the tears, a lesser increase of adrenaline, and a moderate increase of hydrocortisone in the serum; these changes are compensatory and are aimed at optimizing the blood supply to, and transcapillary metabolism in the retina under conditions of metabolic disorders caused by diabetes mellitus. The stage of organic changes of MCBBC is characterized by depressed activity of the mediator compound of the sympathoadrenal system in the presence of increased concentrations of adrenaline and hydrocortisone.
Seventy-two patients with insulin-dependent diabetes mellitus were treated at Endocrinology Research Center. The mean age of patients was 28.5 years, duration of diabetes 12-31 years. The majority of patients presented with decompensated diabetes and drastic 24-h fluctuations of glycemia. Mean level of glycated hemoglobin in these patients was 10.6 ± 4.9%.
Transconjunctival cryocoagulation was carried out in 48 patients (64 eyes) with coarse proliferative changes in the fundus oculi, growth of new vessels into the vitreous, and frequent repeated hemorrhages into the vitreous. Posterior pole scleroplasty and transscleral cryocoagulation were carried out in 24 patients (46 eyes) with coarse exudative proliferative changes in the fundus oculi and partial traction detachment of the retina.
Vision improved the next day after transconjunctival cryocoagulation in 18 patients out of 48. Objectively, vitreous opacity decreased. In 29 (60.4%) patients vitreous opacities notably resolved after 1.5-2 months; in 21 (43.7%) of these patients regressive development of proliferative tissue and devastation of new vessels were observed. Visual acuity improved from 0.01-0.05 to 0.1-0.3 and stabilized at this level for 2-24 months.
No complications were observed during the early postoperative period after transscleral cryocoagulation and posterior pole scleroplasty. Vision improved 3 months after surgery in 17 (70.8%) patients, pathological process did not progress in 4 (16.6%)), deterioration was observed in 3 (12.5%)), neovascularization in the posterior pole progressed in 2, and secondary rubeous glaucoma developed in 1 patient.
Insertion/deletion (I/D) polymorphism of angiotensin I-converting enzyme gene (ACE) as a potential marker of genetic susceptibility to myocardial infarction (MI) was studied in 76 patients with non-insulin-dependent diabetes (NIDDM) surviving after MI, 115 NIDDM patients without history of MI, and 165 subjects without diabetes from the general Moscow population. Case-control association study failed to reveal significant differences in distribution of ACE gene alleles and genotypes between patients with and without MI. However, we observed a tendency of I allele frequency to decrease and of D allele frequency to increase in infarction. Moreover, patients with MI had almost the same pattern of I and D allele and DD genotype distribution as normal subjects from general population (34.9, 65.1, and 46.1% vs. 35.8, 64.2, and 48.5%, respectively). On the other hand, diabetics without infarction had a slightly higher prevalence of I allele and I allele-containing genotypes (ID and II) than patients with documented MI (40.4, 46.1, and 17.4% vs. 34.9, 38.2, and 15.7%, respectively) and lower DD genotype frequency (36.5 vs. 46.1%), respectively). Therefore, we suppose that in Moscow a higher incidence of D allele in comparison with I allele and of its genotypes ID and II may be regarded as a genetic protective factor, whereas D allele and DD genotype as a factor of genetic susceptibility to MI in NIDDM patients.
The levels of glycated fibrinogen (GF) and glycated hemoglobin Hb A1c are measured in 80 diabetics aged 16-66 years with disease duration of 2 weeks to 35 years during compensated stage (HbA1c < 7.5%) and in 49 normal subjects. During compensation of both diabetes types, GF level in the blood of patients with microalbuminuria (initial nephropathy) is higher than in patients with normoalbuminuria. The content of Hb A1c does not depend on proteinuria. GF content is in good correlation with glycemia (r = +0.6), p < 0.05), content of Hb A1c (r = +0.9, p < 0.05), platelet aggregation (r = +0.9, p < 0.05), and fibrinolytic activity (r = —0.4, p < 0.05), but not with fibrinogen content. Hb Alc correlates with glycemia (r = +0.5) and platelet aggregation (r = +0.4, p < 0.05) but not with fibrinolytic activity. A stable increase of GF content over 0.06 mmole FA/10 mg in patients with both types of diabetes signals a high risk of microalbuminuria and progress of diabetic nephropathy.
Ten men and 11 women with diabetes mellitus are examined in order to develop a comprehensive program for psychosocial rehabilitation within the framework of positive psychotherapy model for diabetics. Pronounced social and emotional dysadaptation is detected; the value of social and emotional actual capacities is low. The most acceptable methods for escaping or managing the conflicts for the examinees were "escape into work" and "escape into communication ". Main family concepts of the patients are analyzed. A program for psychotherapist's work with patients and their families in an inpatient and outpatient setting is proposed. A positive approach becomes a priority because of the need in full-value adaptation of patients.
A retrospective analysis of case histories of 426 patients with primary chronic adrenal insufficiency (1-AI), followed up at Endocrinology Research Center, Russian Academy of Medical Sciences, and/or Endocrinology Clinic of I. M. Setchenov Moscow Medical Academy in 1954-1977, was carried out in order to assess the etiological and clinical structure of this disease. The idiopathic form of Addison 's disease prevailed over its tuberculous form (70 and 30%), respectively); dynamic assessment of morbidity over the above period showed a progressive predominance of the idiopathic form. 1-AI is more than 2 times more incident in women, and the incidence of the disease in women vs. men is ever growing. There are at least 2.5 times more women than men among patients with idiopathic Addison's disease, while for the tuberculous form the ratio is 1:1. The mean age of 1-AI manifestation is 34.3 ± 0.46 years. The peak of clinical manifestation of idiopathic Addison's disease occurs between 20 and 40 years (at the age of 32.8 years on average), while for the tuberculous form this age is 30-50 years (37.4), which indicates a later manifestation of this form (p < 0.01). In 28%) cases idiopathic Addison's disease coursed in the presence of autoimmune polyglandular syndromes (APS): type 1 in 3%o and type II in 25% cases. Dynamic assessment of the ratio of the incidence of 1-AI alone to that in the presence of APS showed that from the thirties to the fifties, idiopathic Addison's disease was a component of APS in 13 % cases and by the eighties and nineties this values increased to 34%), which permits a conclusion about pathomorphism of 1-AI, consisting in gradual transfer of this disease into APS. Many patients with 1-AI develop concomitant autoimmune diseases; analysis of family history of such patients reveals autoimmune diseases in close relatives in many cases, while the majority of patients with the tuberculous form of Addison 5 disease have a family history of tuberculosis.
Adenomectomy was carried out in 41 patients with Icenko-Cushing’s disease. Before surgery, computer-aided tomography showed pituitary adenomas in all the patients. The patients were divided into 2 groups. Group 1 consisted of 31 patients in whom the disease was diagnosed for the first time and group 2 of 10 patients previously treated by other methods (proton ther- ару and unilateral adrenalectomy) without effect. Pituitary adenomas were removed in all patients. Histological study showed hormone-active pituitary adenomas in all cases. The levels of hydrocortisone and ACTH in the plasma and daily urine were increased in both groups before the operation. Ten-twenty days after surgery, the levels of hydrocortisone and ACTH in group 1 were significantly lower than in group 2. We consider that the lower are the levels of these hormones early after surgery, the lower is the probability of a relapse. Postoperative hypocorticalism (10-20 days postoperation) is a good prognostic sign indicating radical removal of pituitary adenoma. Adenomectomy is indicated for patients with Icenko-Cushing’s disease as primary method of treatment.
The hypothalamic-pituitary-adrenal system was studied in 25 participants in the aftermath of the Chernobyl accident (liquidators) using a test with insulin and determining the secretion of growth hormone (STH) and cortisol during the test. In all liquidators, insulin administration caused a significant decrease in blood sugar. Baseline cortisol and STH levels were within normal limits. During the test, the examined individuals did not show a significant increase in the level of cortisol. 94% of the liquidators received a release of STH in response to hypoglycemia, but this reaction was significantly less pronounced than in individuals in the control group. Preliminary data indicate the presence of insufficient secretion of GH and the absence of a significant increase in cortisol levels. Thus, the liquidators have violations of the hypothalamic-pituitary system, indicating a decrease in the adaptive capacity of the body.
For practitioners
The treatment of acute metabolic decompensation in diabetes mellitus (DM), especially its extreme manifestations - diabetic com - still presents significant difficulties for many endocrinologists, resuscitators and other doctors, although in practice they often have to deal with this. In the scope of this lecture, we are not able to dwell in detail on the pathogenesis, biochemical and clinical features of acute diabetic decompensation of metabolism, therefore, it will mainly examine the most important principles of its treatment and the most frequently encountered diagnostic and tactical errors.
Congenital dysfunction of the adrenal cortex (VCD) is a group of diseases with an autosomal recessive type of inheritance, which are based on a defect in one of the enzymes or transport proteins involved in the biosynthesis of cortisol in the adrenal cortex. Common in the pathogenesis of these diseases is a decrease in cortisol synthesis, leading to the overproduction of adrenocorticotropic hormone (ACTH) and, as a result, the development of adrenal cortical hyperplasia and the accumulation of metabolites preceding the defective stage of steroidogenesis.
Experimental endocrinology
Experiments on intact and diabetic rats demonstrated that 10-day injections of [Arg8]-vasopressin (intracerebroventricu- lar (icv) daily dose 24 fM, intraperitoneal (ip) 240 pM) leads to increase in insulin content in pancreatic beta-cells in nor- moglycaemic rats by 6.6 ± 0.2% in comparison with the controls and in hyperglycaemic diabetic rats by 25.6 ± 0.6% after icv injection and by 15.9 ± 0.8% after ip injection. Injection of vasopressin to diabetic animals decreased the level of glycaemia by 37% but did not affect the destruction of Langerhans’ islets. The insulin-stimulating effect of chronic icv vasopressin can be explained by modulation of the functional activity of the hypothalamic centers of feeding behavior and with the vagus nerve dorsal motor nucleus, while ip injection of the peptide directly stimulates the production of insulin in beta-cells.
Relationship between increased level of sex hormones during systemic injection of hormones and the training capacity and trace memory and behavior is studied in rats of both sexes. Active and passive avoidance and open field tests were carried out. Increase in testosterone or estradiol levels did not affect passive training. Increase of testosterone level in male rats disturbed active training and did not change the behavior. Increase of estradiol level in female rats accelerated active training and stimulated behavioral activity of animals.
Reviews
In recent years, increasing attention of specialists has been attracted by the problems of the relationship between cardiovascular pathology and the state of the endocrine system of the body, in particular the functioning of the gonads. Clinical observations indicate that cardiovascular diseases, including MI, can quite often form on a certain “unfavorable” endocrine basis, and their development is largely determined by gender [5, 68, 72]. hormonal function of the ovaries is significantly lower than in men of the same age, with the onset of menopause, this difference between the sexes disappears [3, 68]. The unequal orientation of the action of estrogen hormones on the cardiovascular system of women and supper, while in the former under conditions of estrogen deficiency their substitution is protective, in men, the use of female sex hormones increases the risk of cardiovascular disease [3, 5, 8, 68]. In vitro and in vivo significant coronary dilator reactions and modulating the effect with respect to the paradoxical coronary spastic effects of atherosclerotically altered blood vessels of the heart was observed with the administration of 17p-estradiol only to postmenopausal women, but not to men [22, 51].
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