Magnesium, aging, and the elderly patient.

Magnesium, beyond any doubt, plays an important role in metabolism. Alterations of magnesium levels have an impact on many organs and systems, especially during aging. We had 156 participants aged 60-93 years (average 74.7 years) in our survey. Of them, 49 were men and 107 were women. Treatment with loop diuretics (Furosemid and Bumetanide) and magnesium levels was correlated, as well as the influence of magnesium levels on life span. Serum magnesium levels were measured in patients receiving diuretics and in the control group. Also, magnesium levels were measured in patients who passed away in the course of their disease and were compared with the control group. Magnesium levels in the diuretic group (100 patients) were 0.93 +/- 0.094 mmol/l, while the average levels in the control group of 56 patients were 0.89 +/- 0.075 mmol/l. In 29 patients who passed away, average magnesium levels were 0.92 +/- 0.078 mmol/l, while in the control group (127 patients), magnesium levels were 0.93 +/- 0.083 mmol/l. The differences were not statistically significant. There were no differences in serum magnesium of the elderly persons investigated regarding age group, gender, or type of diuretics. If methods of determining ionizing magnesium in serum or intracellular magnesium are not available, normal magnesium values in the serum are to be taken with a qualified acceptance.

[Diagnosis of autoimmune thyroid disease].

Autoimmune thyroid disease (AITD) is the most common organ specific autoimmune disorder usually resulting in dysfunction (hyperfunction, hypofunction or both) of the thyroid gland. The syndromes comprising autoimmune thyroid disease are many intimately related illnesses: Graves' disease with goitre, hyperthyroidism and, in many patients, associated ophthalmopathy, Hashimoto's thyroiditis with goitre and euthyroidism or hypothyroidism but also thyroid dysfunction occurring independently of pregnancy and in 5-6% of postpartum women and thyroiditides induced by different drugs and other environmental influences. The immunological mechanisms involved in these diseases are closely related, while the phenotypes probably differ because of the specific type of immunological response that occurs. The syndromes are connected together by their similar thyroid pathology, similar immune mechanisms, co-occurrence in family groups, and transition from one clinical picture to another within the same individual over time. In some patients, other organ specific and nonorgan specific autoimmune syndromes are associated with autoimmune thyroid disease, including pernicious anemia, vitiligo, myasthenia gravis, primary adrenal autoimmune disease, celiac disease, rheumatoid arthritis or lupus. Thyroid peroxydase, TPO, the primary enzyme involved in thyroid hormonogenesis, was initially identified in 1959 as the 'thyroid microsomal antigenn. It is uncertain whether TPO autoantibodies or TPO-specific T cells are the primary cause of thyroid inflammation, which can lead, in some individuals, to thyroid failure and hypothyroidism. TPOAbs are the hallmark of AITB and are present in almost all patients with Hashimoto's thyroiditis, in two-thirds of patients with postpartum thyroiditis and also in 75% of patients with Graves' hyperthyroidism. The antibodies are mainly produced by lymphocytic infiltrate in the thyroid gland and only to a small extent by regional lymph nodes or the bone marrow. Unlike antibodies against thyroglobulin (Tg), TPO antibodies are capable of inducing antibody-dependent cell-mediated cytotoxicity. Antibodies to TSH-R mimic the function of TSH, and cause disease by binding to the TSH-R and stimulating (or inhibiting) thyroid cells. The TSHR, a member of the G protein-coupled receptor family with seven membrane-spanning segments. Patients with autoimmune thyroid disease may have both stimulating and blocking antibodies in their sera, the clinical picture being the result of the relative potency of each species; blocking antibodies seem more common in Graves' patients with ophthalmopathy compared to those without this complication. The major T cell epitopes are heterogeneous and T cell reactivity against certain TSH-R epitopes has been present in high proportion in normal subjects. More diversified response to TSH-R, with heterogeneity of epitope recognition by TSAb, is predictive of likely remission after antithyroid drug treatment for Graves' disease.

[Diagnosis of osteoporosis occurring in autoimmune thyroid gland disease].

Osteoporosis or porotic bone is a general, systemic bone disease, which is manifested by fracture as its consequence. The main characteristic of this disease is the loss of bone microarchitecture, bone mass reduction, and its increased fragility. The result, thereof, is susceptibility to fracture. Etiology of osteoporosis is polymorph. Its socio-medical importance is enormous, since there is one osteoporotic fracture every 20 sec. worldwide. Million and six hundred thousand osteoporotic fractures occur annualy throughout the world. Thyroid gland is susceptible to autoimmune reactions that lead to autoimmune diseases, just like many other organs. The autoimmune disorder is a final consequence of a failure, in some instance, within the crucial mechanism of regulation of self tissue tolerance. The main goal is to prove the presence of osteoporosis, its inexpensive and quick diagnostics; to make a distinction among the causes that lead to it. In addition, to indicate the importance of osteoporosis that is caused by normal, metabolic processes which are an inevitable part of ageing. Diagnosis of osteoporosis can be done through laboratory, which is a tiresome, time consuming task. Measurements of BMD could be also performed by using new devices. Osteometers could be constructed on the basis of X-ray photon energy or US. Utilization most contemporary one uses laser beam, and it approximates the distance of additional tissue that also absorbs part of energy changing absorption of the reception unit and thus making the measurement results accurate. In diagnosing BMD by osteometer, one faces with certain difficulties. When axial quantitative CT is used, the value may be falsely lower, because of the loss of energy absorbed by aorta which is often calcified in elderly people. In devices with transversal scanning, of the same nature and technology, a part of the energy is being absorbed by transversal and spinal vertebrals. After the research, one may conclude that the most accurate results can not be achieved. But, this is not considered so important. Values that are to be compared are available anyway. Therapy, if adequate, will show certain improvement which can not be detected even by osteometers. Following the physiatrist treatment, particularly by exercise of muscle strength, the muscle structure will be enhanced and, consequently, a part of pressure will be handled, which would be otherwise taken over by the bone. The movements of the patients will be better in coordinated, which undoubtedly reduces the number of falls and fractures. Results of the research that was conducted at the Clinical Hospital Centre "Dr. Dragisa Misovic" in Belgrade, with over 200 cases, two years, are compatible with literature data. Working with MediTech osteometer DTU ONE that uses ultrasound source in demineralized medium, with indispensable US gel, on constant temperatures, yielded results corresponding to those in patients that were treated by Bisphosphonates, Alphacalcidol and Calcium therapy.

[Autoimmune thyroid disease--clinical symptoms of associated autoimmunity].

Autoimmune diseases are manifested in a broad spectrum. Classic examples of organ-specific autoimmune disease include Addison's disease, insulin-dependent type-1 Diabetes mellitus, Grave's disease (MGB), and Hashimoto thyroiditis (HT). The initial report of this autoimmune thyroid disease (AITD) dates back to Hakira Hashimoto (1912). In HT, as an organ-specific autoimmune disease, massive infiltration of lymphoid cells and parenchyma destruction are a consistent feature. The infiltration appears to be immune-mediated, primarily lymphocytic (T helper, T suppressor cells), NK cells and B cells. The pathological characteristics of AITD include development of the goitre (atrophic form is not so frequent), impaired thyroid gland function (from hyperthyroidism to subclinical and manifested hypothyroidism) and the formation of antithyroidal antibodies against thyroglobulin (AbTg) and the microsomal antigen (Ab TPO). There is a very good correlation between the antibodies against TPO and the histological findings. Morbus Graves Basedow is characterized by autoimmune hyperthyroidism with goitre, and infiltrative orbitopathy. Autoantibodies against the TSH-receptor molecule on the plasma membrane of the thyroid gland follicles cause a nonphysiological activation and an increase of the cellular function. Besides this hyperthyroidal condition, an autoimmune attack against the retrobulbar tissue leading to endocrine orbitopathy, can be noted in about 40% of patients suffering from MGB.

[Autoimmune haemopoietic disturbances simultaneous with autoimmune thyroid diseases].

Out of 362 patients with diagnosis of autoimmune haemopathy treated in eight-year period at the Hematology centre, concomitant autoimmune thyreoideopathy was confirmed in 22 (5.52%). The most frequent was simultaneous manifestation of pernicious anemia and autoimmune thyreoiditis-Phenomenon was less frequently observed in patients with immune thrombocytopenic purpura and Graves disease. In the subgroup of patients with autoimmune hemolytic anemia, there was no evidence of simultaneous autoimmune thyreoideopathy. General opinion is that etiopathogenesis of these immunological disorders does not include unique mechanism of humoral and cellular immune response; more probable, it is the question of normal immune response regulation impairment, based on the paerticular genetic predisposition.

[Subclinical and manifested hypothyroidism as a consequence of thyroid autoimmune disease].

Chronic thyroiditis (Hashimoto's disease) is a slowly developing persistent inflamation of the thyroid gland, which frequently leads to hypothyroidism. Some of the up-to-date knowledge about hypothyroidism, both subclinical and manifested, caused by autoimmune disease, was presented. Autoimmune thyroid gland disease can occur at any age, but predominantly affects women after periods of high emotional and physical stress or accidents, as well as during periods of hormonal changes. It can also develop in families, and having an autoimmune disease slightly increases the risk of developing another. This paper showed an increasing incidence of subclinical hypothyroidism (4.17%) in elderly, and, at the same time, the incidence of primary hypothyroidism accounting for 1%. It is very usefull to estimate the stimulated thyrotropin (TSH) response, as well as the value of fast, short time thyroid gland reserves, analyzed by T3 and T4 serum level at 60th minute after TRH stimulation. Treatment of choice for HT (hypothyroidism of any cause) is thyroid hormone replacement. Drug of choice is orally administered levothyroxine sodium, usually for life-time. The standard dose is 1.6-1.8 mcg/kg body weight per day, but is in most cases patient dependent. Elderly patients usually require smaller replacement dose of levothyroxine, sometimes less than 1 mcg/kg body weight per day with coronary dilatator at the same time.

[Dilated cardiomyopathy associated with autoimmune disease of thyroid gland].

Congestive heart failure is the main cause of cardiovascular morbidity and mortality with more than one million hospitalizations per year. Dilated cardiomyopathy is one of the main causes of congestive heart failure characterized by diminished function of the left, right or both ventricles and ejection fraction less than 40%. Numerous studies reported that the diseases of thyroid gland among the patients with dilated cardiomiopathy were very frequent: with prevalence from 18% to 49%. The impaired thyroid gland function was found as primary cause of cardiomyopathy in 1% of patients. At the same time, among patients with terminal dilated cardiomyopathy, euthyroid sick syndrome was very frequent with low values of T3. According to our results, 29.4% of patients with dilated cardiomyopathy also had autoimmunity disorder of thyroid gland with present antithyroglobin and antimicrosomal antibodies. These patients had lower ejection fraction and worse prognosis. In American College of Cardiology/American Heart Association guidelines for the evaluation and treatment of the congestive heart failure, evaluation of thyroid gland function was recommended; but the evaluation of antitireoglobulin antibodies and free T3 and free T4 was also essential, as was calculation of their ratio. This is the way to discover the autoimmunity disorder of thyroid gland and/ or "euthyroid sick syndrome". In patients with dilated cardiomyopathy and low-T3 syndrome, short-term administration of thyroid hormones resulted in improvement of ejection fraction, diminishing of symptoms and better survival.

[Molecular basis of glucocorticoid action].

Glucocorticoid hormones are involved in regulation of cell processes and coordinate physiological response to diverse signals. These hormones, through interaction with specific intracellular receptors, coordinate components of physiological repertoires by activating the expression of gene networks. Thus hormone-receptor complexes may function as key constituent in regulation of specific cell functions as well as in provoking differentiation in already determined cells. Analysis of steroid receptors are important for understanding of molecular details of transcriptional control as well as providing the insight as to how an individual transcriptional factor such as glucocorticoid receptor, contributes to cell identity and function. The purpose of this review is to establish the general molecular mechanism of glucocorticoid action and mechanism associated hormone-receptor complexes with the control of differential patterns (i.e. "positive" and "negative") of gene expression. One of the examples of two signal pathways regulating opposite gene expression are NF-kB and GR-mediated signal pathways. These pathways have important and opposite roles in the immune function. NF-kB is transcription factor which induces the expression of many genes that participate in immune and inflamatory response, while GR is transcription factor that serves as antiinflammatory agent and immune suppressor. Their interactions within the cell, although not yet completely understood, appear to be an important, possibly even the primary mechanism of immune homeostasis. It has not been established that glucocorticoid sensitivity can be caused by mechanisms other than changes of GR number and properties, although recent studies have indicated that receptor isoforms and transcriptional factors may modulate glucocorticoid responsiveness by interacting with receptor protein or directly at the site of DNA binding. The aim of this review is also to describe the role of glucocorticoid receptors in mechanism of glucocorticoid action on cell functions, including immune responses, as well as to present emerging issues on clinical aspects of molecular mechanisms of glucocorticoid action.