Serum free thyroid hormones are decreased by betamethasone treatment in Graves' disease

38 patients with Graves' disease were treated at random with the glucocorticosteroid betamethasone or with placebo. The daily oral dose was 6.0 mg for the first 5 days, 4.5 mg for the following week, and then 3.0 mg. The serum free triiodothyronine (FT3) concentration decreased within 5 days, while the free thyroxine (FT4) level was reduced first after 3 weeks of betamethasone treatment. The suppressed serum thyrotropin concentration did not change. In the placebo group no significant constant alterations were found in any of the variables studied. The results corroborate that betamethasone decreases FT3 and to a less degree also FT4, which earlier has been indicated by indirect methods, although the mechanisms behind the changes remain to be clarified. Since FT3 is more readily available for the metabolic effects in tissues the rapid striking fall in its concentration is an argument for glucocorticoid treatment in selected patients with severe hyperthyroidism of Graves' disease.     

Serum lipid levels in patients with Alzheimer's disease

The role of lipids in the aetiology and progress of Alzheimer's disease (AD) is still unclear High lipid levels could be one of the risk factors for AD, but no association or even protective effects of high cholesterol levels in the development of the AD were also found. The aim of the study was to determine serum levels of total cholesterol, high-density-lipoprotein cholesterol (HDL-C), low-density-lipoprotein cholesterol (LDL-C) and triglycerides (TG) in female patients with AD and in healthy elderly controls. The 50 patients met the diagnostic criteria of probable AD according to the NINDS-ADRDA and DSM-IV criteria. Cognitive impairment was evaluated using the Mini Mental State Examination (MMSE). Patients were subdivided into two groups of 19 patients in the middle (MMSE 10-19) and 31 patients in the late (MMSE 0-9) phase ofAD. Psychotic and non-psychotic features, evaluated by means of Neuropsychiatric Inventory, were presented in 13 and 37patients with AD, respectively. Control group consisted of 58 subjects without cognitive impairment (MMSE >27) and with lipid levels within normal range. Serum lipid levels were determined by the enzymatic colour tests and by the enzymatic clearance assay. Significantly lower lipid levels were found in patients with AD, than in controls. Patients in the late phase of AD had significantly lower entire lipid profile than controls and significantly lower cholesterol and LDL-C levels than patients in the middle stage ofAD. There was no difference in lipid levels between patients with and without psychotic features. The significant positive correlations were found between MMSE scores and cholesterol, LDL-C levels and age in all AD patients. The results support the presumption that lipid profile might be connected with the aetiology and progress of AD and showed the association between low serum cholesterol and LDL-C levels and cognitive decline in patients with AD. Further studies are needed to confirm the relationship between lipid levels and cognition, and to validate the lipid profile as a biological marker for the progress of AD.     

Lysosomal dysfunction in muscle with special reference to glycogen storage disease type II

The importance of proper lysosomal activity in cell and tissue homeostasis is underlined by "experiments of nature", i.e. genetic defects in one of the at least 40 lysosomal enzymes/proteins present in the human cell. The complete lack of 1-4 alpha-glucosidase (glycogen storage disease type II (GSD II) or Pompe disease) is life-threatening. Patients suffering from GSD II commonly die before the age of 2 years because of cardiorespiratory insufficiency. Striated muscle cells appear to be particularly vulnerable in GSD II. The high cytoplasmic glycogen content in muscle cells most likely gives rise to a high rate of glycogen engulfment by the lysosomes. The polysaccharides become subsequently trapped in these organelles when 1-4 alpha-glucosidase activity is absent. During the course of the disease, muscle wasting occurs. It is hypothesised that the gradual loss of muscle mass is caused by a combination of disuse atrophy and lipofuscine-mediated apoptosis of myocytes. Moreover, we hypothesise that in the remaining skeletal muscle cells, longitudinal transmission of force is hampered by swollen lysosomes, clustering of non-contractile material and focal regions with degraded contractile proteins, which results in muscle weakness.     

Dynamic changes in soluble interleukin-2 receptor levels during treatment of Graves' disease. Correlation with disease activity

The activation of T lymphocyte is accompanied by the release of soluble interleukin-2 receptors (sIL-2R) which can be assessed in biological fluids. A prospective study of the dynamic changes in sIL-2R levels was performed in the serum of 10 patients undergoing a medical treatment for Graves' disease. All patients received carbimazole during the study and, when necessary, L-thyroxine to compensate hypothyroidism. sIL-2R levels were measured before (M0) and after the 1st (M1), 3rd (M3) and 6th month (M6) of treatment. The levels of sIL-2R were high at M0 and M1, and decreased significantly between M1 and M3 (p = 0.03). At M0, the levels of sIL-2R were highly correlated with triiodothyronine (T3) levels (p = 0.0003), early [131I] uptake (p = 0.007) and, to a lesser degree, with anti-thyrotropin receptor antibody levels (p = 0.02). At M6, no correlation was found anymore. We conclude that sIL-2R levels are increased in patients with untreated Graves' disease. They are highly correlated with the markers of Graves' disease activity and decrease during medical treatment.     

Decreased nerve growth factor levels in hyperthyroid Graves' ophthalmopathy highlighting the role of neuroprotective factor in autoimmune thyroid diseases

Nerve growth factor (NGF), which is a neurotrophic factor, is involved in autoimmune and inflammatory processes. Serum NGF levels were investigated in 131 patients with autoimmune (95 with Graves' disease, of whom 57 had ophthalmopathy, 19 with Hashimoto's thyroiditis) and nonimmune thyroid diseases (17 with toxic nodular goitre), and 20 controls. NGF levels were measured via enzyme-linked immunosorbent assay. Twenty-nine positive cases for NGF were detected: 21 cases in Graves' disease, 7 cases in Hashimoto's thyroiditis, no case in toxic nodular goitre and one case in controls. NGF levels were higher in patients with Graves' disease and particularly with Hashimoto's thyroiditis compared with controls (1786.47+/-34.79 pg/ml and 1996.27+/-77.71pg/ml vs 1579.16+/-57.45pg/ml, P<0.049 and P<0.0001, respectively). Increased NGF levels associated with Graves' hyperthyroidism and correlated with FT(3) (P<0.01). Patients with the presence of antibodies against TSH receptor showed higher NGF levels than those with no antibodies (1938.61+/-56.44pg/ml vs 1712.12+/-54.22pg/ml, P<0.009). Decreased NGF levels were demonstrated in hyperthyroid Graves' ophthalmopathy compared with those without eye symptoms (1746.65+/-51.98pg/ml vs 1910.47+/-55.62pg/ml, P<0.036). NGF may be involved in the pathomechanism of autoimmune thyroid diseases. Decreased NGF levels in hyperthyroid Graves' ophthalmopathy highlight the importance of NGF in the neuroprotection of orbital tissues.     

Serum long acting thyroid stimulator protector in pregnancy complicated by Graves' disease.

Activities of serum long acting thyroid stimulator protector were measured in a series of nine pregnancies in eight mothers who had Graves'' disease, one of whom had been successfully treated by surgery. In all but two instances the activities tended to decline as pregnancy progressed. After delivery activities rose in three out of five patients in whom these had disappeared in pregnancy and, as this occurred, the patients relapsed. In the two patients whose activities did not decline thyrotoxicosis persisted throughout pregnancy and after delivery. None of the nine babies in this study suffered from neonatal thyrotoxicosis because maternal activities of the thyroid stimulator protector, though high enough to induce Graves'' disease in adults, were not above the threshold for the induction of thyroid overactivity in neonates.     

Changes in serum autoantibodies to thyroid peroxidase during antithyroid drug therapy for Graves' disease

Thyroid microsomal antigen is considered to be identical with thyroid peroxidase (TPO). Although there have been many reports concerning changes in microsomal autoantibody during the course of antithyroid drug therapy for Graves' disease, little is known about this matter in relation to TPO autoantibody (TPOab). Therefore, in this paper, we studied serial changes in the latter autoantibody. Initial levels of serum TPOab (% immunoprecipitation) in 13 patients with hyperthyroid Graves' disease ranged from -11.3% to +84.5% (mean +/- SD, 38.9 +/- 31.8%). Of three patients with persistently increased serum TPOab throughout drug therapy, all had recurrence of hyperthyroidism after the drug was discontinued. Of seven patients whose TPOab levels were initially high but subsequently decreased, four had remission of the disease after drug therapy. Inhibition by TPOab of the TPO activity was also demonstrated by both guaiacol and iodide assays, and changes in this inhibitory activity during therapy varied among individuals. This inhibition was not correlated with disease remission. The decrease in serum TPOab observed in some antithyroid drug-treated patients may reflect a decline in disease activity or may be a direct effect of the drug.     

Studies on the association of NIDDM in Japanese patients with hyperthyroid Graves' disease.

We attempted to analyze the association of hyperthyroid Graves' disease with non-insulin-dependent diabetes mellitus (NIDDM). Forty-nine patients (23 males and 26 females; 7.6%) of a total of 647 patients with hyperthyroid Graves' disease had NIDDM, several years before or after Graves' disease was diagnosed. Only 1 patient had insulin-dependent diabetes mellitus. Compared with the general Japanese population (n = 9,133), the incidence of NIDDM (n = 348; 3.9%) in patients with Graves' disease was higher in all age groups. Only 4 patients (8.2%) of the 49 hyperthyroid patients with NIDDM had a history of being overweight (body mass index > 25). In contrast, 276 (79.9%) of the 348 diabetic patients were currently or previously overweight. Moreover, the incidence of a family history of diabetes (13 of the 49 hyperthyroid Graves' patients with NIDDM; 26.5%) was also lower in the patients with NIDDM in the general Japanese population (50% incidence). The male:female ration in patients with Graves' disease and NIDDM was 1:1.1; much different from that in the total Graves' disease population (1:4.1). Analysis of the HLA loci A, B, C, DR and DQ (35 determinations) in 35 hyperthyroid patients with NIDDM and in 386 subjects from the general population revealed a highly significant difference between them in the incidence of HLA-Cw4, -DR2, -DQw1, -DQw3 and -DQw4. This study suggests that there was an association of Graves' disease with NIDDM. A significant association of HLA-DR and -DQ loci was observed in hyperthyroid Graves' patients with NIDDM.     

Correlation between thyroid stimulating immunoglobulins and thyrotropin binding inhibitory immunoglobulins levels in patients with Graves' disease

INTRODUCTION: The II generation method using human recombination thyrotropin receptors for measurement of thyrotropin binding inhibitory immunoglobulins (TBII) is characterized by increased sensitivity and specificity in comparison with I generation method. AIM OF STUDY was to determine, whether TBII levels measured with II generation assay reflect thyroid stimulation and whether measurement of thyroid stimulating antibodies (TSI) could be replaced by TBII determinations. Specific aim was to evaluate, whether correlation between TSI and TBII levels is stable during antithyroid therapy. MATERIAL AND METHODS: 41 patients with the newly diagnosed Graves' disease were included in the study. TSI (cAMP levels in CHO cell line) and TBII (II generation assay) levels were determined before treatment and after 1, 3, 6, 9 and 12 months of thiamazol therapy. Moreover, thyroid blocking antibodies were determined after 12 months of treatment. RESULTS: 32 patients (82.05%) had positive basic TSI level and 35 patients (89.74%) had positive basic TBII level. After 12 months of therapy negative level of TSI was observed in 67.57% of patients and negative level of TBII was founded in 45.85% of patients. Correlation between TSI and TBII levels was positive during treatment course except time after 9 months of therapy. CONCLUSIONS: TBII level is adequate parameter to assess thyroid stimulation intensity. Positive correlation between TSI and TBII levels is present during almost whole treatment course. TBII seems to be reliable parameter in disease activity monitoring and response to therapy.     

The thyroid function of Graves' disease patients is aggravated by depressive personality during antithyroid drug treatment

Background

Sleep disturbance is a major health issue in Japan. This before-after study aimed to evaluate the immediate effects of forest walking in a community-based population with sleep complaints.

Methods

Participants were 71 healthy volunteers (43 men and 28 women). Two-hour forest-walking sessions were conducted on 8 different weekend days from September through December 2005. Sleep conditions were compared between the nights before and after walking in a forest by self-administered questionnaire and actigraphy data.

Results

Two hours of forest walking improved sleep characteristics; impacting actual sleep time, immobile minutes, self-rated depth of sleep, and sleep quality. Mean actual sleep time estimated by actigraphy on the night after forest walking was 419.8 ± 128.7 (S.D.) minutes whereas that the night before was 365.9 ± 89.4 minutes (n = 42). Forest walking in the afternoon improved actual sleep time and immobile minutes compared with forest walking in the forenoon. Mean actual sleep times did not increase after forenoon walks (n = 26) (the night before and after forenoon walks, 380.0 ± 99.6 and 385.6 ± 101.7 minutes, respectively), whereas afternoon walks (n = 16) increased mean actual sleep times from 342.9 ± 66.2 to 475.4 ± 150.5 minutes. The trend of mean immobile minutes was similar to the abovementioned trend of mean actual sleep times.

Conclusions

Forest walking improved nocturnal sleep conditions for individuals with sleep complaints, possibly as a result of exercise and emotional improvement. Furthermore, extension of sleep duration was greater after an afternoon walk compared to a forenoon walk. Further study of a forest-walking program in a randomized controlled trial is warranted to clarify its effect on people with insomnia.     

Vitamin D and disease prevention with special reference to cardiovascular disease

Circulating 25-hydroxyvitamin D [25(OH)D] is the hallmark for determining vitamin D status. Serum parathyroid hormone [PTH] increases progressively when 25(OH)D falls below 75 nmol/l. Concentrations of 25(OH)D below 50 nmol/l or even below 25 nmol/l are frequently observed in various population groups throughout the world. This paper highlights the relationship of vitamin D insufficiency with cardiovascular disease and non-insulin dependent diabetes mellitus, two diseases that account for up to 50% of all deaths in western countries. There is evidence from patients with end-stage renal disease that high PTH concentrations are causally related to cardiovascular morbidity and mortality. Activated vitamin D is able to increase survival in this patient group significantly. Moreover, already slightly enhanced PTH concentrations are associated with ventricular hypertrophy and coronary heart disease in the general population. Experimental studies have demonstrated that a lack of vitamin D action leads to hypertension in mice. Some intervention trials have also shown that vitamin D can reduce blood pressure in hypertensive patients. In young and elderly adults, serum 25(OH)D is inversely correlated with blood glucose concentrations and insulin resistance. Sun-deprived lifestyle, resulting in low cutaneous vitamin D synthesis, is the major factor for an insufficient vitamin D status. Unfortunately, vitamin D content of most foods is negligible. Moreover, fortified foods and over-the-counter supplements usually contain inadequate amounts of vitamin D to increase serum 25(OH)D to 75 nmol/l. As a consequence, legislation has to be changed to allow higher amounts of vitamin D in fortified foods and supplements.     

Hypertension in pregnancy with special reference to its treatment]

Definition and classification of the arterial hypertension in pregnancy are discussed. An emphasis is on the problems of differential diagnosis between pre-eclampsia and other forms of hypertension. Use of hypotensive drugs in pregnant patients with particular reference to emergencies is also discussed. The treatment of pregnant women with hypertension is still a problem which require close co-operation of both an obstetrician and internist. Follow-up after labour is GP duty to find out if the patient remains hypertensive. If so, etiology of the disease should be again searched.