Witold Szkróbka

HLA-DRB1 and -DQB1 alleles and gene polymorphisms of selected cytokines in systemic lupus erythematosus

ObjectiveThe objective of this study was to evaluate the genetic profiles of selected cytokines (transforming growth factor beta 1, tumor necrosis factor alpha, interleukin-6, interferon gamma, and interleukin-10) in systemic lupus erythematosus and the contributions of human leukocyte antigen (HLA)-DRB1 and -DQB1 alleles to susceptibility for this disease.Patients and methodsThe study was carried out in 24 SLE patients and 36 healthy controls (from Upper Silesia) using polymerase chain reaction methods. All persons were of Caucasoid origin. Standard association analysis was used to compare the HLA alleles and frequency of cytokine gene polymorphisms between these groups.ResultsOnly the frequency of HLA-DRB1*07 allele was higher in SLE patients than controls (odds ratio 2.92, 95% confidence interval 1.16–7.33), but the difference did not reach statistical significance when Bonferroni’s adjustment procedure was performed. No other significant associations were noted between class II alleles (DR1-DR6, DR8-DR10, DQ1-DQ4) and SLE. The frequency of the interleukin-6 GG and GC genotypes was significantly higher in SLE patients than in controls, and a significantly higher percentage of the G vs C alleles between patients and controls was revealed (odds ratio 2.53, 95% confidence interval 1.37–4.65, chi-squared test 8.16, P<0.05). The most significant association of increased frequency of the G allele with SLE was more commonly noted in HLA-DRB1*07-positive patients (odds ratio 10.29, 95% confidence interval 5.34–19.83, P<0.001). These data indicate that this combination could contribute toward determining the susceptibility to SLE, but its possible significance will require confirmation by further studies.

Different effects of fenofibrate on metabolic and cardiovascular risk factors in mixed dyslipidemic women with normal thyroid function and subclinical hypothyroidism.

AIMS Subclinical hypothyroidism is suggested to increase cardiovascular risk. No previous study compared the effect of any fibrate on plasma levels of lipids and other cardiovascular risk factors in patients with different thyroid function status. METHODS The study included three age-, weight- and lipid-matched groups of women with mixed dyslipidemia in different thyroid function status: patients with untreated subclinical hypothyroidism (group 1, n = 18), women with treated hypothyroidism (group 2, n = 15), and subjects without thyroid disorders (group 3, n = 19). Plasma lipids, glucose homeostasis markers, as well as plasma levels of uric acid, high-sensitivity C-reactive protein (hsCRP), homocysteine, and fibrinogen were determined before and after 12 weeks of fenofibrate therapy. RESULTS Despite similar plasma lipid levels, mixed dyslipidemic patients with untreated hypothyroidism had decreased insulin sensitivity, as well as higher circulating levels of uric acid, hsCRP, homocysteine, and fibrinogen in comparison with the other groups. The effect of fenofibrate on plasma lipids and, with the exception of homocysteine, on circulating levels of all investigated risk factors was stronger in patients from groups 2 and 3 than in patients from group 1. CONCLUSIONS The obtained results indicate that the effect of fenofibrate on plasma lipids and circulating levels of cardiovascular risk factors is partially related to thyroid function. They also suggest that to improve the strength of fibrate action in dyslipidemic patients with subclinical hypothyroidism, they should be administered together with L-thyroxine.

The effect of metformin on prolactin levels in patients with drug-induced hyperprolactinemia

BACKGROUND In bromocriptine-treated hyperprolactinemic patients with impaired glucose tolerance, metformin was found to reduce plasma levels of prolactin. No previous study has investigated its impact on plasma prolactin in patients with drug-induced hyperprolactinemia. METHODS The study included 20 women with antipsychotic-induced hyperprolactinemia and 12 normoprolactinemic women, who, because of coexisting glucose metabolism abnormalities, were treated for 6months with metformin. Hyperprolactinemic patients with prediabetes received moderate doses of metformin (1.7g daily), while hyperprolactinemic and normoprolactinemic patients with type 2 diabetes were treated with high-dose metformin (2.55-3g daily). Fasting plasma glucose levels, the homeostatic model assessment 1 of insulin resistance ratio (HOMA1-IR), glycated hemoglobin, as well as plasma levels of prolactin, thyrotropin, adrenocorticotropic hormone and insulin-like growth factor-1 were assessed at baseline and after 6months of treatment. RESULTS Despite reducing plasma glucose, HOMA1-IR, and glycated hemoglobin in all treatment groups, metformin decreased prolactin levels only if given at high doses to patients with elevated prolactin levels. No changes in thyrotropin, adrenocorticotropic hormone, and insulin-like growth factor-1 were observed in any treatment groups. CONCLUSIONS The obtained results suggest that the effect of metformin on plasma prolactin depends on its dose and is observed only in patients with elevated levels of this hormone.

The effect of metformin on the hypothalamic-pituitary-thyroid axis in patients with type 2 diabetes and subclinical hyperthyroidism.

In hypothyroid patients, metformin was found to reduce serum levels of TSH. No previous study investigated metformin action on hypothalamic-pituitary-thyroid axis in patients with hyperthyroidism. The aim of our study was to assess the effect of metformin treatment on thyroid function tests in patients with untreated subclinical hyperthyroidism. We studied 15 patients with low but detectable TSH levels (0.1-0.4 mIU/L) (group 1), 12 patients with suppressed TSH levels (less than 0.1 mIU/L) (group 2) and 15 euthyroid patients with a history of hyperthyroidism, who because of coexisting 2 diabetes were treated with metformin (2.55-3 g daily). Glucose homeostasis markers, as well as serum levels of TSH and total and free thyroxine and triiodothyronine levels were assessed at baseline and after 3 and 6 months of therapy. As expected, metformin reduced plasma glucose, insulin resistance and glycated hemoglobin. However, with the exception of an insignificant decrease in TSH levels after 3-month therapy in group 2, metformin therapy did not affect thyroid function tests. Our results indicate that metformin has a negligible effect on hypothalamic-pituitary-thyroid axis activity in type 2 diabetic patients with subclinical hyperthyroidism.

Kikuchi-Fujimoto disease: a case report

Kikuchi-Fujimoto disease is a rare benign cervical lymphadenopathy, which often affects young adult women. Its etiology and pathogenesis are unknown. We present the case of Kikuchi-Fujimoto disease in the Polish population and analyse the difficulties in differentiating this disease from the systemic lupus erythematosus.

Sex-dependent effect of metformin on hypothalamic-pituitary-thyroid axis activity in patients with subclinical hypothyroidism

BACKGROUND Metformin was found to reduce elevated serum thyrotropin levels. No previous study has compared the effect of this drug on serum levels of thyrotropin and thyroid hormones between men and women. METHODS The study included 23 women and 12 men with subclinical hypothyroidism, who because of coexisting diabetes or impaired fasting glucose were treated with metformin (1.7-3.0g daily). Fasting plasma glucose levels, the homeostatic model assessment 1 of insulin resistance ratio (HOMA1-IR), glycated hemoglobin, serum levels of thyrotropin, free and total thyroid hormones and prolactin, as well as thyroid peroxidase and thyroglobulin antibodies were assessed at baseline and after 4 months of metformin treatment. RESULTS Baseline serum levels of thyrotropin, free thyroxine and free triiodothyronine, as well as a percentage of patients with positive thyroid peroxidase and thyroglobulin antibodies were comparable in both sexes. Metformin treatment reduced plasma glucose and insulin resistance, irrespective of the gender. However, only in women, metformin decreased serum thyrotropin levels. Neither in men nor in women, metformin affected serum levels of thyroid hormone and prolactin, as well as in the subgroups of patients with thyroiditis thyroid antibody titers. CONCLUSIONS The obtained results suggest that sex may determine the effect of metformin on hypothalamic-pituitary-thyroid axis activity.

The effect of metformin on the hypothalamic-pituitary-thyroid axis in patients with type 2 diabetes and amiodarone-induced hypothyroidism.

BACKGROUND Chronic metformin treatment was found to reduce elevated thyrotropin levels. Amiodarone treatment is associated with a range of effects in thyroid function from mild derangements to overt thyroid dysfunction. No previous study has investigated the effect of metformin on hypothalamic-pituitary-thyroid axis activity in patients with amiodarone-induced hypothyroidism. METHODS The study included three age-, sex- and weight-matched groups of amiodarone-treated patients with type 2 diabetes: patients with treated overt hypothyroidism (group I, n=15), patients with untreated subclinical hypothyroidism (group II, n=15), and subjects without thyroid disorders (group III, n=18). The lipid profile, fasting plasma glucose levels, the homeostatic model assessment 1 of insulin resistance ratio (HOMA1-IR), glycated hemoglobin, the estimated glomerular filtration rate, as well as serum levels of thyrotropin, thyroid hormones, prolactin, insulin and insulin-like growth factor-1 (IGF-1) were assessed at baseline and after 6 months of metformin treatment (2.55-3g daily). RESULTS In all groups of patients, metformin reduced plasma glucose and triglycerides, serum insulin, glycated hemoglobin as well as HOMA1-IR. The estimated glomerular filtration rate, thyroid hormones, prolactin and IGF-1 remained at a similar level throughout the study. In patients with untreated amiodarone-induced hypothyroidism, but not in the other groups of patients, metformin reduced serum levels of thyrotropin and this effect correlated weakly with its action on insulin sensitivity. CONCLUSIONS The obtained results indicate that the effect of metformin on hypothalamic-pituitary-thyroid axis activity is partially related to thyroid function. Metformin treatment may bring clinical benefits to patients with amiodarone-induced hypothyroidism and poor tolerance of exogenous L-thyroxine.

The effect of l-thyroxine treatment on sexual function and depressive symptoms in men with autoimmune hypothyroidism

BACKGROUND Thyroid autoimmunity and mild hypothyroidism in women seem to be associated with sexual dysfunction and depressive symptoms. Data concerning similar associations in men are limited. The aim of this study was to investigate sexual functioning and depressive symptoms in men with autoimmune hypothyroidism. METHODS The study population consisted of three groups: men with autoimmune overt hypothyroidism (group A), men with autoimmune subclinical hypothyroidism (group B) and healthy euthyroid males without thyroid autoimmunity (group C). Apart from measuring serum levels of thyrotropin and free thyroid hormones and thyroid antibody titers, all included patients completed a questionnaires evaluating male sexual function (International Index of Erectile Function-15: IIEF-15) and assessing the presence and severity of depressive symptoms (Beck Depression Inventory-Second Edition - BDI-II) before and after 6 months of levothyroxine treatment. RESULTS Men with overt hypothyroidism obtained lower scores in all five domains of IIEF-15, while men with subclinical hypothyroidism only in erectile function. The total BDI-II score was higher in groups A than in groups B and C, as well as higher in group B than in group C. L-thyroxine improved erectile function and normalized intercourse satisfaction, orgasmic function, sexual desire and overall satisfaction in group A, as well as normalized erectile function in group B. In group A, L-thyroxine reduced, while in group B tended to reduce total BDI-II. CONCLUSIONS The obtained results suggest that autoimmune hypothyroidism in men is characterized by sexual and mood disturbances and that hypothyroid patients with sexual dysfunction and depressive symptoms benefit from L-thyroxine treatment.BACKGROUND Thyroid autoimmunity and mild hypothyroidism in women seem to be associated with sexual dysfunction and depressive symptoms. Data concerning similar associations in men are limited. The aim of this study was to investigate sexual functioning and depressive symptoms in men with autoimmune hypothyroidism. METHODS The study population consisted of three groups: men with autoimmune overt hypothyroidism (group A), men with autoimmune subclinical hypothyroidism (group B) and healthy euthyroid males without thyroid autoimmunity (group C). Apart from measuring serum levels of thyrotropin and free thyroid hormones and thyroid antibody titers, all included patients completed a questionnaires evaluating male sexual function (International Index of Erectile Function-15: IIEF-15) and assessing the presence and severity of depressive symptoms (Beck Depression Inventory-Second Edition - BDI-II) before and after 6 months of levothyroxine treatment. RESULTS Men with overt hypothyroidism obtained lower scores in all five domains of IIEF-15, while men with subclinical hypothyroidism only in erectile function. The total BDI-II score was higher in groups A than in groups B and C, as well as higher in group B than in group C. L-thyroxine improved erectile function and normalized intercourse satisfaction, orgasmic function, sexual desire and overall satisfaction in group A, as well as normalized erectile function in group B. In group A, L-thyroxine reduced, while in group B tended to reduce total BDI-II. CONCLUSIONS The obtained results suggest that autoimmune hypothyroidism in men is characterized by sexual and mood disturbances and that hypothyroid patients with sexual dysfunction and depressive symptoms benefit from L-thyroxine treatment.

A Neutral Effect of Metformin Treatment on Macroprolactin Content in Women with Macroprolactinemia

Background: Metformin decreases serum levels of monomeric prolactin. No previous study has investigated the effect of metformin on macroprolactin content in patients with macroprolactinemia. Methods: We studied three age-, sex- and weight-matched groups of patients: 15 women with monomeric prolactin, 12 women with macroprolactin, as well as 15 women with normal prolactin levels. Because of coexisting 2 diabetes or prediabetes all patients were treated with metformin (1.7-3 g daily). Plasma lipids, glucose homeostasis markers, as well as serum levels of prolactin and macroprolactin were assessed at baseline and after 4 months of metformin treatment. Results: As expected, metformin reduced plasma glucose and triglycerides, as well as improved insulin sensitivity in all treatment groups. Moreover, the drug reduced post-polyethylene glycol prolactin levels and tended to reduce pre-polyethylene glycol prolactin levels in women with monomeric prolactin but not in women with macroprolactinemia and women with normal prolactin levels. Conclusion: The obtained results indicate that metformin has a negligible effect on macroprolactin levels.

The Effect of Vitamin D on Thyroid Autoimmunity in Levothyroxine-Treated Women with Hashimoto’s Thyroiditis and Normal Vitamin D Status

Background: Low vitamin D status is associated with autoimmune thyroid disease. Oral vitamin D supplementation was found to reduce titers of thyroid antibodies in levothyroxine-treated women with postpartum thyroiditis and low vitamin D status. Methods: The study included 34 women with Hashimotos thyroiditis and normal vitamin D status (serum 25-hydroxyvitamin D levels above 30 ng/mL) who had been treated for at least 6 months with levothyroxine. On the basis of patient preference, women were divided into 2 groups, receiving (n=18) or not receiving (n=16) oral vitamin D preparations (2000 IU daily). Serum levels of thyrotropin, free thyroxine, free triiodothyronine and 25-hydroxyvitamin D, as well as titers of thyroid peroxidase and thyroglobulin antibodies were measured at the beginning of the study and 6 months later. Results: There were no significant differences in baseline values between both study groups. 25-hydroxyvitamin D levels inversely correlated with titers of thyroid antibodies. No changes in hypothalamic-pituitary-thyroid axis activity and thyroid antibody titers were observed in vitamin-naïve patients. Vitamin D increased serum levels of 25-hydroxyvitamin D, as well as reduced titers of thyroid antibodies. This effect was more pronounced for thyroid peroxidase than for thyroglobulin antibodies and correlated with their baseline titers. Conclusions: Vitamin D preparations may reduce thyroid autoimmunity in levothyroxine-treated women with Hashimotos thyroiditis and normal vitamin D status.