Glucose compensation, serum lipids and thyroid hormones (rT3 and rT3/T3 ratio in non-insulin-dependent (type 2) diabetics: 2

In 45 type 2 diabetics it was unable to be found a relation between the plasma lipids and the fasting blood glucose (G), HbA1c, reverse T3 (rT3), rT3/T3 ratio, and relative body weight (R.B.W.). The conclusion was reached that the alteration of the lipoprotein metabolism and the thyroid hormones in type 2 diabetics could be primitive and independent from the availability of the insulin.     

rT3 production in normal man, assessed from variations in serum rT3 during short-term rT3 infusion.

The metabolic clearance rate (MCR) of 3,3'5'-triiodothyronine (reverse T3, rT3) was estimated in normal human subjects by a modified noncompartmental method using the integrated increase in serum rT3 following intravenous infusion of 0.10 nmol/min rT3 for 4 hr. The MCR-rT3 was calculated to be 102.8 +/- 17.01/day and the daily rT3 disposal to be 33.0 +/- 9.5 nmol (mean +/- SD, n = 6). The MCR-rT3 compares well to that of previous studies employing tracer kinetic methods. The disposal rate of rT3 estimated in the present study is considerably lower than found in some previous studies. The discrepancy is due to differences in the measured levels of serum rT3 in normal subjects.     

An elevation of BUN/creatinine ratio in patients with hyperthyroidism

Blood urea nitrogen (BUN/creatinine ratio was abnormally high (24.8 +/- 0.6) in untreated hyperthyroid patients due to both increase in BUN and decrease in creatinine concentration. BUN, creatinine and BUN/creatinine ratio were all completely normalized after restoration of euthyroid status. On the other hand, BUN/creatinine ratio was slightly suppressed in hypothyroidism before treatment and it was reversed by thyroxine treatment (12.6 +/- 4.0 and 16.3 +/- 3.3, before and after treatment, respectively). An age-related increase in BUN/creatinine ratio, which was primarily due to an age-related increase in BUN, was also found in hyperthyroid subjects (21.9 +/- 2.8 vs 27.7 +/- 9.0; first vs fifth decade) and in normal controls (13.7 +/- 2.8 vs 16.0 +/- 2.9; first vs fifth decade). To elucidate reasons for abnormal increase in BUN/creatinine ratio in hyperthyroidism, measurement of cardiac output and kinetic analysis on urea nitrogen (UN) and creatinine were performed. The results indicated a marked increase in cardiac output. Serum creatine concentration was clearly increased in hyperthyroid patients. Thus, serum creatinine concentration was suppressed due to a decrease in creatinine synthesis and an increase in renal creatinine excretion. BUN was high, primarily due to an increase in UN production secondary to excessive protein catabolism together with insufficient excretion of UN.     

Reduced serum acylated ghrelin levels in patients with hyperthyroidism

BACKGROUND AND OBJECTIVE: Recent studies have revealed that circulating ghrelin levels seem to play a role in energy homeostasis. The effect of hyperthyroidism on ghrelin levels is not fully known. METHODS: Serum levels of ghrelin and its relationship with insulin resistance were evaluated in 48 patients with hyperthyroidism and 43 euthyroid healthy controls. Thyroid hormones, insulin, glucose, ghrelin levels and lipid parameters were measured in all subjects. Insulin sensitivity was determined using the homeostasis model assessment. RESULTS: Serum ghrelin levels were significantly decreased in hyperthyroid patients than in controls (32.5 +/- 23.3 vs. 54.1 +/- 35.5 pg/ml, p < 0.001). Circulating ghrelin levels significantly correlated with age (r = -0.26, p = 0.01), fasting glucose (r = -0.21, p = 0.01), free triiodothyronine (r = -0.18, p = 0.04), free thyroxine (r = -0.23, p = 0.02) and thyroid stimulating hormone (r = 0.21, p = 0.04), but not with blood pressure, body mass index, lipid parameters, insulin and homeostasis model assessment (p > 0.05). Multiple regression analysis revealed glucose level to be the most important predictor of circulating ghrelin level. CONCLUSION: These results indicate that hyperthyroidism has effect on serum ghrelin levels. Further studies are needed for the exact mechanism.     

Low serum reverse T3 levels in patients with primary hyperparathyroidism

Although patients with primary hyperparathyroidism (1 degree HPT) were euthyroid, we measured serum thyroid hormone levels in 16 patients with 1 degree HPT together with 17 patients with hypercalcemia due to malignant diseases (HCM). In patients with 1 degree HPT, serum levels of T3, T4 and T3U were within normal range, but serum rT3 (reverse T3) levels (205 +/- 37 pg/ml, mean +/- SD) were significantly decreased as compared with those in normal controls (276 +/- 44 pg/ml, P less than 0.01). A significant inverse correlation was observed between the serum levels of rT3 and parathyroid hormone (PTH) (r = 0.54, P less than 0.05). After parathyroidectomy, serum rT3 levels were significantly elevated (240 +/- 56 pg/ml) compared to preoperative levels (P less than 0.01). Low levels of serum rT3 seemed to be attributed to the high levels of serum PTH. On the other hand, serum levels of T3 and T4 were low and serum rT3 levels were high in patients with HCM. Low serum rT3 allows for the differentiation of patients with 1 degree HPT from those with HCM.     

Acetylation phenotype and serum levels of T3 and T4 in patients with hypertension treated with propranolol

The acetylation phenotype has been investigated in 76 patients with untreated hyperthyroidism. In 65 of these patients including 23 with fast and 42 with slow acetylation phenotype, the blood serum concentrations of thyroxine and triiodothyronine were determined before and after propranolol therapy involving propranolol administration of a dose of 160 mg per day for 6 days. The occurrence of the fast acetylation phenotype among the patients with hyperthyroidism was similar to that found in the healthy population. Propranolol therapy caused a significant decrease in the blood serum concentration of triiodothyronine only in the patients with the slow acetylation phenotype.     

Serum TSH, T4, T3, FT4, FT3, rT3, and TBG in youngsters with non-ketotic insulin-dependent diabetes mellitus

Several parameters of thyroid function were studied in 112 non-ketoacidotic youngsters with insulin-dependent diabetes mellitus (IDDM). Levels of thyroxine (T4), reverse triiodothyronine (rT3), thyroxine-binding globulin (TBG) and T3 were lower than in controls, whereas FT4, and FT3 were normal. T4 levels in IDDM patients were positively related to T3, rT3 and TBG, and inversely related to haemoglobin A1 (HbA1). However, only 4 patients showed biochemical hypothyroidism (T4 less than 5 micrograms/100 ml), whereas their FT4, FT3 and thyroid-stimulating hormone (TSH) levels were normal. Concurrent variations of T3 and rT3 levels were found in IDDM patients; thus, their T3/rT3 ratios were stable or higher than in controls, indicating that peripheral deiodination of T4 is preferentially oriented to production of rT3 only during ketoacidosis. Although changes in thyroid function may reflect the degree of metabolic control of diabetes in a large population, the clinical usefulness of serum thyroid hormone measurements in an individual case still appears to be limited.     

T mu and T gamma-lymphocyte counts and their ratio in patients with brucellosis

The levels of circulating T mu- and T gamma-lymphocytes in brucellosis patients have been studied in relation to the clinical form of the disease, the severity of the process and the allergic transformation of the body. A decrease in the content of lymphocytes, affecting mainly T mu-cells and less commonly T gamma-cells, as well as a change in their ratio has been revealed. The level of this decrease depended on the clinical form of brucellosis, the severity of the course of acute and subacute brucellosis, the phase of chronic brucellosis and the allergic transformation of the body. The disproportion of immunoregulating cells in brucellosis, revealed in this study, is supposed to be of pathogenetic importance.     

Electrophoretic and enzymatic analysis of glycosaminoglycans in the blood serum of patients with hyperthyroidism

An effect of hyperthyroidism on the composition and levels of glycosaminoglycans in the blood serum was studied. Glycosaminoglycans isolated from 1-ml blood samples were assayed with the following techniques: carbazole, electrophoretic and enzymatic. Separation and assay of particular GAG were made with bidirectional electrophoresis. Isomers of the remaining chondroitin sulphates were assayed enzymatically. Electrophoretograms of GAG in blood serum of healthy women have shown two fractions: low sulphate chondroitin sulphate and chondroitin-4-sulphate. The same fractions of GAG were found in blood serum of the female patients with hyperthyroidism. Mean concentration of GAG in the blood serum of hyperthyroid patients increased by 51%: low sulphate chondroitin sulphate and chondroitin-4-sulphate concentrations increased by 22% and 190% respectively. Chondroitin sulphates in the blood serum of both groups were degraded to unsaturated disaccharides not containing sulphur and unsaturated 4-sulphate disaccharides. Concentrations of unsaturated 4-sulphate and unsaturated sulphur-free disaccharides increased by 71% and 17% in hyperthyroidism. Observed changes in the blood serum GAG concentrations reflect changes in the connective tissue metabolism in hyperthyroidism.     

Decreased serum brain-derived neurotrophic factor in Chinese patients with Type 2 diabetes mellitus

Brain-derived neurotrophic factor （BDNF） is a member of neurotrophin family associated with the proliferation, differentiation, activity-dependent plasticity, and survival of neurons in the central nervous system [1]. BDNF influences glucose metabolism and insulin sensitivity. For example, BDNF decreases serum glucose, insulin, and HbAlc levels in diabetic rats, suggesting that the BDNF may improve insulin sensitivity. In addition, animal models showed that BDNF levels in the central nervous system are highly related to peripheral serum BDNF levels [2]. It was found that BDNF may ameliorate glucose metabolism and prevent pan- creatic exhaustion in obese diabetic mice [3].     

Hypothalamic-pituitary-testicular axis in patients with hyperthyroidism

To test whether chronic thyroid hormone excess influences the hypothalamic-pituitary-testicular axis, 8 hyperthyroid men were given two identical intravenous GnRH tests. The first test was performed before any treatment had been instituted, the second 6-13 months later, when medical treatment had made the patients euthyroid. Although basal serum luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone (T) levels were of similar magnitudes before and after the medical treatment, LH and FSH responsiveness to gonadotropin-releasing hormone (GnRH), as reflected by the hormone incremental areas (U/l X min), were significantly larger in the thyrotoxic state compared with the euthyroid state (LH incremental areas: 3,999 +/- 665 vs. 2,640 +/- 430, p less than 0.02; FSH incremental areas: 825 +/- 193 vs. 542 +/- 98, p less than 0.05). Furthermore, serum T increased significantly in response to GnRH when the patients were hyperthyroid (T incremental area: 162 +/- 51, p less than 0.02), but failed to do so when they were euthyroid (T incremental area: 92 +/- 53, NS). These results imply that chronic thyroid hormone excess makes the pituitary gonadotrophs 'hypersensitive' to exogenous GnRH. This may in turn explain why human Leydig cells respond more powerful to exogenous GnRH in thyrotoxic patients than in euthyroid subjects.     

Thyroid cancer in patients with hyperthyroidism

Thyroid cancer can be associated with thyrotoxicosis caused by Graves' disease, toxic multinodular goiter, or autonomously functioning thyroid adenoma. The objective of this study was to summarize current evidence regarding the association of thyroid cancer and hyperthyroidism, particularly with respect to the type of hyperthyroidism found in some patients, and whether this affects the outcome of the patient. A PubMed search was performed up to August 2011. Articles were identified using combinations of the following keywords/phrases: thyroid cancer, papillary thyroid cancer, follicular thyroid cancer, medullary thyroid cancer, anaplastic thyroid cancer, hyperthyroidism, Graves' disease, auto-nomous adenoma, toxic thyroid nodule, and toxic multinodular goiter. Original research papers, case reports, and review articles were included. We concluded that the incidence, as well as the prognosis of thyroid cancer associated with hyperthyroidism is a matter of debate. It seems that Graves' disease is associated with larger, multifocal, and potentially more aggressive thyroid cancer than single hot nodules or multinodular toxic goiter. Patients with Graves' and thyroid nodules are at higher risk to develop thyroid cancer compared to patients with diffuse goiter. Every suspicious nodule associated with hyperthyroidism should be evaluated carefully.     

Thyroid cancer in patients with hyperthyroidism

OBJECTIVE: The coexistence of hyperthyroidism and thyroid cancer is considered a rare event. With the aim of assessing the clinical relevance of this association, we have retrospectively analyzed the incidence of thyroid cancer in 425 hyperthyroid patients seen and treated by surgery in our institutions. METHODS: Among these hyperthyroid patients, we observed 241 (56.7%) cases of multinodular toxic goiter, 120 (28.3%) of uninodular toxic goiter and 64 (15%) cases of Graves' disease. RESULTS: Thyroid cancer was diagnosed in 7 (1.65%) hyperthyroid patients. Histological examination revealed the presence of papillary carcinoma in 5 cases and follicular carcinoma in 2 cases. Neoplasia was detected in 4 patients with nodular toxic goiter and in 3 with uninodular toxic goiter. None of the patients with Graves' disease had thyroid cancer. During the follow-up of 74 months (range 4-154), there were no deaths or any recurrences. CONCLUSION: Although the occurrence of thyroid cancer in hyperthyroid patients is a rare event, the presence of a 'cold' nodule in a hyperfunctioning thyroid should be carefully evaluated to exclude the presence of concurrent malignancy.     

Decreased serum interleukin 27 in Brazilian systemic lupus erythematosus patients

The immunological role of interleukin 27 has been reported in various inflammatory diseases, but its importance in systemic lupus erythematosus pathogenesis is not completely established. The aim of this study was to evaluate serum levels of IL-27 in SLE patients and its correlation with clinical manifestations and disease activity. IL-27 levels were assessed in 70 SLE patients and 30 healthy controls by ELISA. Clinical and laboratory parameters were recorded. Statistic analyzes were performed by Graph Prism 3.02 software. The IL-27 serum levels were significantly decreased in SLE patients compared with controls (mean 899.92 and 1,531.22 pg/ml, P = 0.0005). There was a correlation between IL-27 levels and C3 levels (P = 0.004). Nevertheless, there was no association of serum IL-27 levels with disease activity evaluated by SLEDAI score (P = 0.9605). No significant difference was found regarding IL-27 levels between SLE patients with and without nephritis, haematuria, proteinuria and positive anti-dsDNA. Correlation analysis between serum IL-27 levels and SLEDAI, SLICC, proteinuria levels, C4 and CH50 levels also showed no association. These data demonstrated decreased serum levels of IL-27 in SLE patients but further studies are needed to clarify the precise role of this cytokine and its potential use as therapeutic target.     

Behaviour of serum T3, rT3, TT4, FT4 and TSH levels after exercise on a bicycle ergometer in healthy euthyroid male young subjects

In order to know thyroid function during physical activity, just studied by several authors without univocal findings, we have submitted 10 young subjects, non athletes, aged 22-25 years (mean age 23, 6 +/- 1, 43) to a biologically maximal exercise on a bicycle ergometer. We have also examined the change of TSH serum levels during exercise. Our data show an evident increase of T4 (18, 60% at 10'), p less than 0.025, an increment of FT4 (28, 49 soon after the strain), and no relevant change of T3 and rT3 serum levels. Moreover TSH values show a reduction at 30' (-26, 15%) in comparison with the basal level. Our findings confirm the known increment of T4 and FT4 serum level after physical activity. It can be due, more than an hemoconcentration supported by others, to a real rise of thyroid incretion as in our opinion TSH levels reduction suggests. Concluding we think that the increase of T4 and decrease of TSH could be due to a direct influence of the physical activity on the system interested in their production.