Modern reports about molecular mechanisms of the effects of thyroid hormones and the pathogenesis of autoimmune thyroid diseases are reviewed. The significance of fundamental studies in thyroidology for deciphering the pathogenesis of the most prevalent endocrine and other than endocrine diseases is emphasized.
Clinical endocrinology
Time course of psychological status of diabetics during automonitoring training is analyzed. Seventeen patients with insulin-dependent diabetes mellitus aged 15-43 years with disease standing of 1-17 years were followed up, who were never trained automonitoring before. Two control groups were not trained, which helped assess the results from different viewpoints. The levels of depression, anxiety, energy, positive sensations, total well-being, satisfaction with treatment, subjective perception of hypoglycemic reactions, and subjective perception of hyperglycaemia were assessed using special questionnaires. Compensation of diabetes was improved both in the main and control groups. Psychological status of diabetics improved after training: levels of depression and anxiety decreased, levels of energy, psychological well-being, and general psychological status increased (p<0.05). In the controls all the above parameters were unchanged over the period of hospitalization. The incidence of subjective perception of hyperglycaemia decreased in trained patients (p<0.05) but not in the controls. The data indicate that the program of diabetic training can be recommended as a method for improving the efficacy of treatment as regards both metabolism compensation and improvement of the psychological status of patients.
Craniography, computer-aided tomography (CAT), and magnetic imaging (MI) are carried out in 236 patients with suspected pituitary adenoma. Causes of hypo- and hyperdiagnosis are analyzed. Algorithm of using radiodiagnostic methods is developed. Pituitary adenomas are recognized by assessing the size of the pituitary and sella turcica, detailed study of pituitary structure and status of the sella turcica walls and the adjacent tissues. Radiodiagnosis in combination with clinical laboratory findings permit the differentiation of pituitary adenomas from other pathological processes in this gland (hyperplasia, atrophy, inflammation, and dystrophy) and from changes in the neighboring tissues (calcification of different origin, increase of intracranial pressure, etc.). For minimizing the diagnostic errors, craniography is to precede CAT or MI. CAT or MI should be carried out in the “amplification ” mode, and in difficult diagnostic cases should be repeated over time. For an experienced specialist, MI by its informative value is the method of choice for the diagnosis of pituitary diseases (adenomas, cysts, etc.).
For assessing the efficacy of intraoperative laser autofluorescent spectroscopy (IOLAS), 46 patients with thyroid diseases of different etiology are examined. The patients ’ aged varied from 30 to 65 years. The following morphological types of diseases were observed: benign nodular formations in 42 patients, thyroid cancer in 4, papillary TINO MO in 2, and follicular cancer TINO MO in 2 cases. Out of benign formations, 36 were multinodular colloid goiter and 6 follicle-cell adenomas. As a result of using IOLAS, thyroid cancer was diagnosed during surgery in 8 (17.4%) out of 36 patients with multinodular colloid goiter; this diagnosis necessitated more extensive intervention than was planned: subtotal resection had to be extended to thyroidectomy. In all the cases IOLAS data were confirmed by urgent and later planned histological analyses. Due to this method, no reoperations were needed, which previously had to be performed because of the data of planned histological analysis, and therefore, the probable complications of reoperations were prevented. Our data indicate that IOLAS more accurately identifies the type and morphology of thyroid involvement and helps choose adequate volume of intervention. The first experience with laser fluorescent study as optic biopsy holds good promise as regards improvement of intraoperative rapid diagnosis of thyroid diseases.
Sixty-seven children (55 girls and 12 boys) aged 5-16 years were examined. Autoimmune thyroiditis (AT) was diagnosed in 28 and diffuse nontoxic goiter (DNG) in 39. The diseases were diagnosed on the basis of case history, results of examination and palpation of the thyroid, ultrasonic findings, presence of antibodies to thyroglobulin (in AT) or their absence (in DNG), and the microsomal fraction detected by enzyme immunoassay using Boehringer Mannheim kits. AT diagnosis was confirmed cytomorphologically in all patients. Intrathyroid stable iodine (ISI) was measured by a Russian noninvasive x-ray fluorescent analyzer. ISI concentration was notably decreased in children with autoimmune thyroiditis confirmed by cytomorphological methods: below the threshold level of the method in 46%) cases and 120±10 mcg/g in 54%). This confirms a high informative value of the proposed method in this disease. Measurements of ISI in children with enlarged thyroid helps differentiate the hypertrophic form of AT from DNG: ISI concentration under 200 mcg/g is characteristic of AT, while in DNG the concentration of ISI in Moscow children is 500±40 mcg/g (M±m).
High prevalence of diffuse euthyroid goiter and inefficiency of conservative treatment aimed at normalization of thyroid volume necessitate search for optimal methods of treatment.
Results of thyroxin and potassium iodide (antistrumin) therapy of 110 children with diffuse toxic goiter, living in a region with medium-grave iodine deficiency, are analyzed. The diagnosis was verified by clinical data, ultrasonic examinations, and hormone measurements.
Changes in the volume of the thyroid under the effect of thyroxin and antistrumin therapy could be variously directed: the involved thyroid might enlarge, shrink, or not change at all. Therapeutic effects of thyroxin and antistrumin on the degree of thyroid decrease and incidence of positive results after 6-month therapy were virtually the same.
Thyroxin in a daily dose of 2.0-2.5 \xg/kg promoted a decrease and normalization of the thyroid size. Efficacy of thyroxin significantly increased if it was used longer than for 6 months.
Potassium iodide (antistrumin) in a weekly dose of 2000 pg (equivalent to daily 200 pg iodine) led to decrease of goiter size and normalization of the thyroid volume. The best results were observed after a no more than 6-month course of treatment. A longer course brought about a tendency to a higher incidence of untoward effects (enlargement of the thyroid).
A cohort of children exposed in utero after the Chernobyl accident is formed (n=422). Individual absorbed dose (AD) for the fetal thyroid was estimated from direct measurements of dose power for the maternal thyroid and was 0.01-4.5 Gy. The mean AD for the thyroid of pregnant women was 24.09+1.17 sGy, that of prenatally exposed children 44.74+2.58 sGy. Thyroid status of 195 exposed children and 220 controls is examined. Thyroid hormones were radioimmunoassayed and measured by enzyme immunoassay using standard diagnostic kits. Serum triiodothyronine concentrations were significantly increased in prenatally exposed children of both sexes (p<0.05 for boys and p<0.01 for girls). Serum thyroxin and thyroxin-binding globulin (TBG) levels were decreased in exposed boys in comparison with the control (p<0.05). In exposed girls thyroxin levels were virtually normal, but there was a tendency to an increase of thyroglobulin (t=1.6) and to a decrease of TBG (t= 1.7) in comparison with the control. The mean TBG concentration in the serum was below the norm in both groups. The results can be indicative of thyroid dysfunction in remote periods after prenatal exposure to radioactive iodine.
A total of 1419 children aged 5-14 years living in 4 agricultural regions of the Central Russia (in Southern Belgorod and Central Western Voronezh regions) were examined in August 1997 within the framework of Program of the UN International Childhood Foundation, WHO, and its International Committee for Iodine Deficiency Diseases Control “Thyroid: Standardized Analysis of Iodine Supply in Europe”. Standard sampling in each region consisted of 10 subgroups for each year of life, 35-36 subjects per subgroup, with equal number of boys and girls. Iodine was measured in the morning urine by the cerium arsenite method. The parents were interviewed about nutrition using universal questionnaires. Slight iodine deficiency was detected in the region, the median of ioduria varying from 69 to 86 mcg/liter. Renal iodine excretion below the threshold normal value (<100 mcg/liter) was detected in 63% children. In girls the trace element excretion was significantly (10%) higher than in boys. A three-phase age-specific pattern of intensity of iodine loss with urine was detected, characterized by minimal values at the age of 6-11 years and two peaks with significantly higher ioduria at 5 and 12-14 years. Consumption of sea fish influenced iodine supply parameters only if it was regular and sufficiently frequent, at least 6 times a month. However, only less than 5% examined families ate sea fish regularly, and still less (only 2%) families used iodinated salt. Dairy products do not affect iodine status of children. The results prompt the necessity of introducing a state program of iodine prophylaxis in Southern European Russia.
Relationships between secretion of pituitary gonadotropic hormones, adrenal glucocorticoid and androgenic function, and ovarian steroid production were studied in 14 patients with the polycystic ovaries syndrome (POS) under conditions of suppressed endogenous gonadotropic secretion, which was induced by tonic administration of busereline, a GnRH agonist. The bRH/iRH ratio is not changed in POS patients under conditions of suppressed gonadotropic secretion. Inhibition of gonadotropic secretion leads to decrease of estrogen secretion in the ovaries and does not affect the adrenal glucocorticoid function. Activation of adrenal androgen production by the delta-5 pathway was observed in 57% patients under conditions of gonadotroph inhibition. Three months after busereline was discontinued, adrenal steroidogenesis normalized. The results permit a conclusion that prolonged inhibition of gonadotropic secretion with GnRH agonist does not change the bLH/iLH ratio but can lead to activation of adrenal androgen production in part of patients with POS.
Pseudohypoparathyroidism (PGPT) - Albright's hereditary osteodystrophy is a sex-related disease rarely seen in medical practice. Inherited by the dominant type. It is caused by insensitivity of the kidneys and bones to parathyroid hormone (PG), which is secreted in normal or slightly elevated amounts [6, 10]. GH may not have a specific effect on cells due to pathology of GH receptors, impaired expression of information RNA synthesis by an unchanged hormone-receptor complex, the presence of pathological components of adenylate cyclase, pathological AMP-dependent protein kinase, or a defect in the synthesis of kinase substrates in the presence of circulating GH antagonists [5, 10 ].
Experimental endocrinology
Experiments on cell cultures demonstrated that isolated cells of clinically inert pituitary tumors release several hormones in small amounts into the medium: luteinizing and follicle-stimulating hormones, alpha-subunit of glycoprotein hormones, prolactin, and growth hormone. Multihormonal secretion of these cells indicates their poor morphofunctional differentiation. In contrast to normal pituitary cells, cells of clinically inert pituitary tumors respond nonspeciflcally to hypothalamic thyrotropin releasing hormone: by increased secretion of prolactin, gonadotropins, glycoprotein hormone alpha-subunit, and growth hormone. This capacity of tumor cells detected in vitro agrees with the probability of increased levels of gonadotropins and glycoprotein hormone alpha-subunit in the serum of patients with clinically inert pituitary tumors during pharmacodynamic thyrotropin releasing hormone test.
The pleiotropic effect of insulin is based on signal transfer from insulin receptor to a series of intracellular effector systems, one of which is glycosyl phosphatidyl inositol (GPI) specific phospholipase C (PLC), hydrolyzing membranous inositol-containing glycophospholipids to produce diacylglycerol, a phospholipase C activator, and inositolphosphoglycane (IPG), a probable secondary messenger in transfer of insulin metabolic signal. For disclosing the mechanisms of GPI-PLC conjugation with insulin receptors and growth factors, we analyzed GPI hydrolysis in Rati cells and found that insulin and epidermal growth factors (EGF) activate GPI hydrolysis to IPG by 20 and 40%o, respectively (p<0.001), while specific phosphatidylinositol- 3’-kinase (PIj kinase) inhibitor vortmannin cancels this insulin and EGF effect. These data permit us to hypothesize the participation of PIj kinase in signal transfer from insulin and EGF receptor GPI-PLC.
Reviews
Autoimmune polyglandular syndromes (APS) are the primary defeat of the autoimmune process of 2 peripheral endocrine glands and more, leading, as a rule, to their insufficiency, often combined with various organ-specific non-endocrine autoimmune diseases.
The intensive development of biology and its branches, their active interaction with chemistry, physics, and also with the technical sciences in the second half of the 20th century led to a significant enrichment of the field of medicine called laboratory. Both in the diagnosis of most diseases and in monitoring their course, laboratory studies have firmly taken the place of a very extensive source of valuable information about the patient’s body condition. They play a role in preventive examinations and during follow-up, and in monitoring the condition in critical situations. The research results help the doctor to verify their diagnostic assumptions or turn to a new hypothesis. Despite the fact that not every case of the disease can be finally recognized on the basis of laboratory data, the vast majority of hospitalized patients and a significant proportion of outpatients undergo one or another laboratory study. For 1 patient in Russian hospitals in 1996, an average of 32.7 analyzes were made, and for 1 visit to the clinic - 0.88 analyzes.
The monograph under review is devoted to one of the most important sections of clinical diabetology. As you know, damage to the lower extremities in patients with diabetes mellitus (DM) is quite common and has an adverse effect on the fate of patients, causing their early disability, and in some cases premature death.
ISSN 2308-1430 (Online)