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Bogusław Okopień - One of the best experts on this subject based on the ideXlab platform.
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The impact of oral hormonal contraception on metformin action on Hypothalamic-Pituitary-Thyroid Axis activity in women with diabetes and prediabetes: A pilot study.
Journal of Clinical Pharmacy and Therapeutics, 2020Co-Authors: Robert Krysiak, Karolina Kowalcze, Monika Wolnowska, Bogusław OkopieńAbstract:WHAT IS KNOWN AND OBJECTIVE: The impact of metformin on thyrotropin levels is sex-dependent. No previous study has assessed whether sex steroids determine metformin action on thyrotrope and thyroid cell functioning. The aim of the present study was to compare the effect of this agent on Hypothalamic-Pituitary-Thyroid Axis activity and thyroid function tests between women receiving oral contraceptive pills and women not using any contraception. METHODS: The study population included 52 women with subclinical hypothyroidism and prediabetes or diabetes, 20 of whom had been using oral contraceptive pills for at least 12 months before the beginning of the study. Over the entire study period (4 months), all participants received oral metformin (1.7-3 g daily). Circulating levels of glucose, insulin, thyrotropin, free thyroid hormones, oestradiol, gonadotropins and prolactin were measured, while the structure parameters of thyroid homeostasis and the degree of insulin sensitivity were calculated at the beginning and at the end of the study. RESULTS AND DISCUSSION: The study groups differed in oestradiol, gonadotropins and prolactin levels and in structure parameter inference approach (SPINA)-GT. In both groups, metformin reduced glucose levels, homeostasis model assessment 1 of insulin resistance index (HOMA1-IR), thyrotropin levels and Jostel's thyrotropin index, as well as increased SPINA-GT. In women receiving oral contraceptive pills, the drug slightly decreased serum prolactin levels. The impact on metformin on HOMA1-IR, thyrotropin, prolactin, Jostel's thyrotropin index and SPINA-GT was more pronounced if women received oral contraception, as well as more pronounced in patients treated with higher doses of this agent. Treatment-induced changes in thyrotropin and Jostel's thyrotropin index correlated with their baseline values, baseline levels of oestradiol and gonadotropins, as well as with the degree of a reduction in HOMA1-IR. WHAT IS NEW AND CONCLUSION: This study is the first one to have shown that oral oestrogens potentiate the effect of metformin on Hypothalamic-Pituitary-Thyroid Axis activity.
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The Impact of Testosterone on Metformin Action on Hypothalamic-Pituitary-Thyroid Axis Activity in Men: A Pilot Study.
The Journal of Clinical Pharmacology, 2019Co-Authors: Robert Krysiak, Witold Szkróbka, Bogusław OkopieńAbstract:The effect of metformin on thyrotrope function seems to be sex dependent. The aim of this study was to determine the role of endogenous testosterone in the impact of metformin on Hypothalamic-Pituitary-Thyroid Axis activity. The study population consisted of 2 groups of men with nonautoimmune hypothyroidism matched for age, weight, insulin sensitivity, and thyrotropin levels. The first group (n = 11) included subjects with low serum testosterone levels, while the second (n = 12) men with testosterone levels within the reference range. Because of concomitant type 2 diabetes, all men were treated with metformin (2550-3000 mg daily). Circulating levels of glucose, prolactin, testosterone, gonadotropins, thyrotropin, and free thyroid hormones were measured, while the structure parameters of thyroid homeostasis and the degree of insulin sensitivity were calculated at baseline and 16 weeks later. In both study groups, metformin decreased plasma glucose levels and improved insulin sensitivity. However, only in men with low testosterone levels, the drug decreased thyrotropin levels, reduced Jostel's thyrotropin index, and increased SPINA-GT. Metformin-induced changes in thyrotropin and Jostel's index correlated with their baseline values, baseline levels of testosterone, and with the effect of treatment on insulin sensitivity. In men with neither low or normal testosterone levels, metformin affected free thyroid hormones, prolactin, testosterone, gonadotropins, and SPINA-GD. The obtained results suggest that the impact of metformin on thyrotrope function depends on the androgen status of a patient.
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Effect of Metformin on Hypothalamic‐Pituitary‐Thyroid Axis Activity in Elderly Antipsychotic‐Treated Women With Type 2 Diabetes and Subclinical Hypothyroidism: A Preliminary Study
The Journal of Clinical Pharmacology, 2017Co-Authors: Robert Krysiak, Witold Szkróbka, Bogusław OkopieńAbstract:Metformin was found to reduce elevated serum thyrotropin levels, and this effect was partially determined by endogenous dopaminergic tone. The aim of this study was to compare the effect of metformin treatment on Hypothalamic-Pituitary-Thyroid Axis activity in elderly women with subclinical hypothyroidism treated with antipsychotic agents and not receiving this drug. The study population consisted of 34 elderly women with subclinical hypothyroidism, 16 of whom received antipsychotic drugs. Because of coexistent type 2 diabetes, these women were treated with metformin (2.55-3 g daily). Glucose homeostasis markers as well as serum levels of thyrotropin, free thyroid hormones and prolactin were measured at the beginning of the study and 6 months later. Thirty women completed the study. With the exception of prolactin, baseline serum levels of the assessed hormones were comparable in both study groups. Although metformin reduced serum thyrotropin levels in both groups, this effect was more pronounced in the antipsychotic-treated than in the antipsychotic-naive patients. The effect on serum prolactin was observed only in antipsychotic-treated patients. The impact on serum thyrotropin levels correlated with improvement in insulin sensitivity and with a reduction in prolactin levels. Free thyroxine and free triiodothyronine remained at a similar level throughout the study. The obtained results indicate that metformin reduces serum thyrotropin levels in elderly women, and this effect is particularly pronounced in women with diminished dopaminergic transmission.
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Sex-dependent effect of metformin on Hypothalamic-Pituitary-Thyroid Axis activity in patients with subclinical hypothyroidism
Pharmacological Reports, 2016Co-Authors: Robert Krysiak, Witold Szkróbka, Bogusław OkopieńAbstract:Abstract 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 (1.7–3.0 g 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.
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The Effect of Metformin on Hypothalamic-Pituitary-Thyroid Axis Activity in Women with Interferon-Induced Hypothyroidism: A Pilot Study.
Experimental and Clinical Endocrinology & Diabetes, 2016Co-Authors: Robert Krysiak, Witold Szkróbka, Bogusław OkopieńAbstract:Background: One of the most frequent adverse effects of interferon-α therapy is thyroiditis. Metformin was found to improve insulin sensitivity in hepatitis C patients, as well as to reduce elevated thyrotropin levels in patients with hypothyroidism. The aim of this study was to investigate the effect of metformin on Hypothalamic-Pituitary-Thyroid Axis activity in patients with interferon-induced thyroiditis. Methods: The study included 2 matched groups of women with type 2 diabetes and untreated subclinical hypothyroidism: patients with interferon-induced thyroiditis (n=8) and patients with Hashimoto’s thyroiditis (n=12). Fasting plasma glucose, 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 and insulin-like growth factor-1 (IGF-1) were assessed at baseline and after 4 months of metformin treatment. Results: Apart from reducing plasma glucose, HOMA1-IR and glycated hemoglobin, metformin decreased serum levels of thyrotropin. Circulating levels of thyroid hormones, prolactin and IGF-1 remained at a similar level throughout the study. The effect of metformin on serum thyrotropin was stronger in patients with interferon-induced thyroiditis than in patients with Hashimoto’s thyroiditis, as well as correlated with its impact on insulin sensitivity. Conclusions: Our results indicate that metformin may be an effective agent in patients with interferon-induced hypothyroidism.
Fredric E. Wondisford - One of the best experts on this subject based on the ideXlab platform.
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Disorders of the Hypothalamic–Pituitary–Thyroid Axis
Handbook of Neuroendocrinology, 2012Co-Authors: Aniket Sidhaye, Fredric E. WondisfordAbstract:Publisher Summary This chapter reviews disorders that are not primarily related to thyroid gland pathology. Thyroid hormone synthesis and secretion is stimulated by the action of thyrotropin (TSH), which is secreted into the general circulation from the anterior pituitary thyrotrope cells. Thyrotropin (TSH) is a member of the glycoprotein hormone family, which includes luteinizing hormone (LH), follicle-stimulating hormone (FSH) and human chorionic gonadotropin (hCG). Hyperthyroxinemia in the setting of a nonsuppressed TSH level is secondary to two different clinical disorders that include resistance to thyroid hormone (RTH) and TSH-secreting pituitary adenoma (TSHoma). The cause of RTH is a germline defect, and as such there is no cure for this condition. As many patients are clinically euthyroid, those compensated patients without symptoms do not require any treatment. TSH-secreting pituitary adenoma is a rare tumor of the anterior pituitary. Nearly three-quarters of all TSHomas secrete only TSH. Patients with hypopituitarism have decreased quality of life, despite replacement hormonal therapy.
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minireview thyrotropin releasing hormone and the thyroid hormone feedback mechanism
Endocrinology, 2009Co-Authors: Maria Izabel Chiamolera, Fredric E. WondisfordAbstract:Thyroid hormone (TH) plays a critical role in development, growth, and cellular metabolism. TH production is controlled by a complex mechanism of positive and negative regulation. Hypothalamic TSH-releasing hormone (TRH) stimulates TSH secretion from the anterior pituitary. TSH then initiates TH synthesis and release from the thyroid gland. The synthesis of TRH and TSH subunit genes is inhibited at the transcriptional level by TH, which also inhibits posttranslational modification and release of TSH. Although opposing TRH and TH inputs regulate the Hypothalamic-Pituitary-Thyroid Axis, TH negative feedback at the pituitary was thought to be the primary regulator of serum TSH levels. However, study of transgenic animals showed an unexpected, dominant role for TRH in regulating the Hypothalamic-Pituitary-Thyroid Axis and an unanticipated involvement of the thyroid hormone receptor ligand-dependent activation function (AF-2) domain in TH negative regulation. These results are summarized in the review.
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Dominant Role of Thyrotropin-releasing Hormone in the Hypothalamic-Pituitary-Thyroid Axis
Journal of Biological Chemistry, 2005Co-Authors: Amisra A. Nikrodhanond, Tania M. Ortiga-carvalho, Nobuyuki Shibusawa, Koshi Hashimoto, Xiao Hui Liao, Samuel Refetoff, Masanobu Yamada, Masatomo Mori, Fredric E. WondisfordAbstract:Abstract Hypothalamic thyrotropin-releasing hormone (TRH) stimulates thyroid-stimulating hormone (TSH) secretion from the anterior pituitary. TSH then initiates thyroid hormone (TH) synthesis and release from the thyroid gland. Although opposing TRH and TH inputs regulate the Hypothalamic-Pituitary-Thyroid Axis, TH negative feedback is thought to be the primary regulator. This hypothesis, however, has yet to be proven in vivo. To elucidate the relative importance of TRH and TH in regulating the Hypothalamic-Pituitary-Thyroid Axis, we have generated mice that lack either TRH, the β isoforms of TH receptors (TRβ KO), or both (double KO). TRβ knock-out (KO) mice have significantly higher TH and TSH levels compared with wild-type mice, in contrast to double KO mice, which have reduced TH and TSH levels. Unexpectedly, hypothyroid double KO mice also failed to mount a significant rise in serum TSH levels, and pituitary TSH immunostaining was markedly reduced compared with all other hypothyroid mouse genotypes. This impaired TSH response, however, was not due to a reduced number of pituitary thyrotrophs because thyrotroph cell number, as assessed by counting TSH immunopositive cells, was restored after chronic TRH treatment. Thus, TRH is absolutely required for both TSH and TH synthesis but is not necessary for thyrotroph cell development.
Robert Krysiak - One of the best experts on this subject based on the ideXlab platform.
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The impact of oral hormonal contraception on metformin action on Hypothalamic-Pituitary-Thyroid Axis activity in women with diabetes and prediabetes: A pilot study.
Journal of Clinical Pharmacy and Therapeutics, 2020Co-Authors: Robert Krysiak, Karolina Kowalcze, Monika Wolnowska, Bogusław OkopieńAbstract:WHAT IS KNOWN AND OBJECTIVE: The impact of metformin on thyrotropin levels is sex-dependent. No previous study has assessed whether sex steroids determine metformin action on thyrotrope and thyroid cell functioning. The aim of the present study was to compare the effect of this agent on Hypothalamic-Pituitary-Thyroid Axis activity and thyroid function tests between women receiving oral contraceptive pills and women not using any contraception. METHODS: The study population included 52 women with subclinical hypothyroidism and prediabetes or diabetes, 20 of whom had been using oral contraceptive pills for at least 12 months before the beginning of the study. Over the entire study period (4 months), all participants received oral metformin (1.7-3 g daily). Circulating levels of glucose, insulin, thyrotropin, free thyroid hormones, oestradiol, gonadotropins and prolactin were measured, while the structure parameters of thyroid homeostasis and the degree of insulin sensitivity were calculated at the beginning and at the end of the study. RESULTS AND DISCUSSION: The study groups differed in oestradiol, gonadotropins and prolactin levels and in structure parameter inference approach (SPINA)-GT. In both groups, metformin reduced glucose levels, homeostasis model assessment 1 of insulin resistance index (HOMA1-IR), thyrotropin levels and Jostel's thyrotropin index, as well as increased SPINA-GT. In women receiving oral contraceptive pills, the drug slightly decreased serum prolactin levels. The impact on metformin on HOMA1-IR, thyrotropin, prolactin, Jostel's thyrotropin index and SPINA-GT was more pronounced if women received oral contraception, as well as more pronounced in patients treated with higher doses of this agent. Treatment-induced changes in thyrotropin and Jostel's thyrotropin index correlated with their baseline values, baseline levels of oestradiol and gonadotropins, as well as with the degree of a reduction in HOMA1-IR. WHAT IS NEW AND CONCLUSION: This study is the first one to have shown that oral oestrogens potentiate the effect of metformin on Hypothalamic-Pituitary-Thyroid Axis activity.
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The Impact of Testosterone on Metformin Action on Hypothalamic-Pituitary-Thyroid Axis Activity in Men: A Pilot Study.
The Journal of Clinical Pharmacology, 2019Co-Authors: Robert Krysiak, Witold Szkróbka, Bogusław OkopieńAbstract:The effect of metformin on thyrotrope function seems to be sex dependent. The aim of this study was to determine the role of endogenous testosterone in the impact of metformin on Hypothalamic-Pituitary-Thyroid Axis activity. The study population consisted of 2 groups of men with nonautoimmune hypothyroidism matched for age, weight, insulin sensitivity, and thyrotropin levels. The first group (n = 11) included subjects with low serum testosterone levels, while the second (n = 12) men with testosterone levels within the reference range. Because of concomitant type 2 diabetes, all men were treated with metformin (2550-3000 mg daily). Circulating levels of glucose, prolactin, testosterone, gonadotropins, thyrotropin, and free thyroid hormones were measured, while the structure parameters of thyroid homeostasis and the degree of insulin sensitivity were calculated at baseline and 16 weeks later. In both study groups, metformin decreased plasma glucose levels and improved insulin sensitivity. However, only in men with low testosterone levels, the drug decreased thyrotropin levels, reduced Jostel's thyrotropin index, and increased SPINA-GT. Metformin-induced changes in thyrotropin and Jostel's index correlated with their baseline values, baseline levels of testosterone, and with the effect of treatment on insulin sensitivity. In men with neither low or normal testosterone levels, metformin affected free thyroid hormones, prolactin, testosterone, gonadotropins, and SPINA-GD. The obtained results suggest that the impact of metformin on thyrotrope function depends on the androgen status of a patient.
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Effect of Metformin on Hypothalamic‐Pituitary‐Thyroid Axis Activity in Elderly Antipsychotic‐Treated Women With Type 2 Diabetes and Subclinical Hypothyroidism: A Preliminary Study
The Journal of Clinical Pharmacology, 2017Co-Authors: Robert Krysiak, Witold Szkróbka, Bogusław OkopieńAbstract:Metformin was found to reduce elevated serum thyrotropin levels, and this effect was partially determined by endogenous dopaminergic tone. The aim of this study was to compare the effect of metformin treatment on Hypothalamic-Pituitary-Thyroid Axis activity in elderly women with subclinical hypothyroidism treated with antipsychotic agents and not receiving this drug. The study population consisted of 34 elderly women with subclinical hypothyroidism, 16 of whom received antipsychotic drugs. Because of coexistent type 2 diabetes, these women were treated with metformin (2.55-3 g daily). Glucose homeostasis markers as well as serum levels of thyrotropin, free thyroid hormones and prolactin were measured at the beginning of the study and 6 months later. Thirty women completed the study. With the exception of prolactin, baseline serum levels of the assessed hormones were comparable in both study groups. Although metformin reduced serum thyrotropin levels in both groups, this effect was more pronounced in the antipsychotic-treated than in the antipsychotic-naive patients. The effect on serum prolactin was observed only in antipsychotic-treated patients. The impact on serum thyrotropin levels correlated with improvement in insulin sensitivity and with a reduction in prolactin levels. Free thyroxine and free triiodothyronine remained at a similar level throughout the study. The obtained results indicate that metformin reduces serum thyrotropin levels in elderly women, and this effect is particularly pronounced in women with diminished dopaminergic transmission.
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Sex-dependent effect of metformin on Hypothalamic-Pituitary-Thyroid Axis activity in patients with subclinical hypothyroidism
Pharmacological Reports, 2016Co-Authors: Robert Krysiak, Witold Szkróbka, Bogusław OkopieńAbstract:Abstract 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 (1.7–3.0 g 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.
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The Effect of Metformin on Hypothalamic-Pituitary-Thyroid Axis Activity in Women with Interferon-Induced Hypothyroidism: A Pilot Study.
Experimental and Clinical Endocrinology & Diabetes, 2016Co-Authors: Robert Krysiak, Witold Szkróbka, Bogusław OkopieńAbstract:Background: One of the most frequent adverse effects of interferon-α therapy is thyroiditis. Metformin was found to improve insulin sensitivity in hepatitis C patients, as well as to reduce elevated thyrotropin levels in patients with hypothyroidism. The aim of this study was to investigate the effect of metformin on Hypothalamic-Pituitary-Thyroid Axis activity in patients with interferon-induced thyroiditis. Methods: The study included 2 matched groups of women with type 2 diabetes and untreated subclinical hypothyroidism: patients with interferon-induced thyroiditis (n=8) and patients with Hashimoto’s thyroiditis (n=12). Fasting plasma glucose, 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 and insulin-like growth factor-1 (IGF-1) were assessed at baseline and after 4 months of metformin treatment. Results: Apart from reducing plasma glucose, HOMA1-IR and glycated hemoglobin, metformin decreased serum levels of thyrotropin. Circulating levels of thyroid hormones, prolactin and IGF-1 remained at a similar level throughout the study. The effect of metformin on serum thyrotropin was stronger in patients with interferon-induced thyroiditis than in patients with Hashimoto’s thyroiditis, as well as correlated with its impact on insulin sensitivity. Conclusions: Our results indicate that metformin may be an effective agent in patients with interferon-induced hypothyroidism.
Witold Szkróbka - One of the best experts on this subject based on the ideXlab platform.
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The Impact of Testosterone on Metformin Action on Hypothalamic-Pituitary-Thyroid Axis Activity in Men: A Pilot Study.
The Journal of Clinical Pharmacology, 2019Co-Authors: Robert Krysiak, Witold Szkróbka, Bogusław OkopieńAbstract:The effect of metformin on thyrotrope function seems to be sex dependent. The aim of this study was to determine the role of endogenous testosterone in the impact of metformin on Hypothalamic-Pituitary-Thyroid Axis activity. The study population consisted of 2 groups of men with nonautoimmune hypothyroidism matched for age, weight, insulin sensitivity, and thyrotropin levels. The first group (n = 11) included subjects with low serum testosterone levels, while the second (n = 12) men with testosterone levels within the reference range. Because of concomitant type 2 diabetes, all men were treated with metformin (2550-3000 mg daily). Circulating levels of glucose, prolactin, testosterone, gonadotropins, thyrotropin, and free thyroid hormones were measured, while the structure parameters of thyroid homeostasis and the degree of insulin sensitivity were calculated at baseline and 16 weeks later. In both study groups, metformin decreased plasma glucose levels and improved insulin sensitivity. However, only in men with low testosterone levels, the drug decreased thyrotropin levels, reduced Jostel's thyrotropin index, and increased SPINA-GT. Metformin-induced changes in thyrotropin and Jostel's index correlated with their baseline values, baseline levels of testosterone, and with the effect of treatment on insulin sensitivity. In men with neither low or normal testosterone levels, metformin affected free thyroid hormones, prolactin, testosterone, gonadotropins, and SPINA-GD. The obtained results suggest that the impact of metformin on thyrotrope function depends on the androgen status of a patient.
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Effect of Metformin on Hypothalamic‐Pituitary‐Thyroid Axis Activity in Elderly Antipsychotic‐Treated Women With Type 2 Diabetes and Subclinical Hypothyroidism: A Preliminary Study
The Journal of Clinical Pharmacology, 2017Co-Authors: Robert Krysiak, Witold Szkróbka, Bogusław OkopieńAbstract:Metformin was found to reduce elevated serum thyrotropin levels, and this effect was partially determined by endogenous dopaminergic tone. The aim of this study was to compare the effect of metformin treatment on Hypothalamic-Pituitary-Thyroid Axis activity in elderly women with subclinical hypothyroidism treated with antipsychotic agents and not receiving this drug. The study population consisted of 34 elderly women with subclinical hypothyroidism, 16 of whom received antipsychotic drugs. Because of coexistent type 2 diabetes, these women were treated with metformin (2.55-3 g daily). Glucose homeostasis markers as well as serum levels of thyrotropin, free thyroid hormones and prolactin were measured at the beginning of the study and 6 months later. Thirty women completed the study. With the exception of prolactin, baseline serum levels of the assessed hormones were comparable in both study groups. Although metformin reduced serum thyrotropin levels in both groups, this effect was more pronounced in the antipsychotic-treated than in the antipsychotic-naive patients. The effect on serum prolactin was observed only in antipsychotic-treated patients. The impact on serum thyrotropin levels correlated with improvement in insulin sensitivity and with a reduction in prolactin levels. Free thyroxine and free triiodothyronine remained at a similar level throughout the study. The obtained results indicate that metformin reduces serum thyrotropin levels in elderly women, and this effect is particularly pronounced in women with diminished dopaminergic transmission.
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Sex-dependent effect of metformin on Hypothalamic-Pituitary-Thyroid Axis activity in patients with subclinical hypothyroidism
Pharmacological Reports, 2016Co-Authors: Robert Krysiak, Witold Szkróbka, Bogusław OkopieńAbstract:Abstract 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 (1.7–3.0 g 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.
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The Effect of Metformin on Hypothalamic-Pituitary-Thyroid Axis Activity in Women with Interferon-Induced Hypothyroidism: A Pilot Study.
Experimental and Clinical Endocrinology & Diabetes, 2016Co-Authors: Robert Krysiak, Witold Szkróbka, Bogusław OkopieńAbstract:Background: One of the most frequent adverse effects of interferon-α therapy is thyroiditis. Metformin was found to improve insulin sensitivity in hepatitis C patients, as well as to reduce elevated thyrotropin levels in patients with hypothyroidism. The aim of this study was to investigate the effect of metformin on Hypothalamic-Pituitary-Thyroid Axis activity in patients with interferon-induced thyroiditis. Methods: The study included 2 matched groups of women with type 2 diabetes and untreated subclinical hypothyroidism: patients with interferon-induced thyroiditis (n=8) and patients with Hashimoto’s thyroiditis (n=12). Fasting plasma glucose, 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 and insulin-like growth factor-1 (IGF-1) were assessed at baseline and after 4 months of metformin treatment. Results: Apart from reducing plasma glucose, HOMA1-IR and glycated hemoglobin, metformin decreased serum levels of thyrotropin. Circulating levels of thyroid hormones, prolactin and IGF-1 remained at a similar level throughout the study. The effect of metformin on serum thyrotropin was stronger in patients with interferon-induced thyroiditis than in patients with Hashimoto’s thyroiditis, as well as correlated with its impact on insulin sensitivity. Conclusions: Our results indicate that metformin may be an effective agent in patients with interferon-induced hypothyroidism.
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The effect of metformin on the Hypothalamic-Pituitary-Thyroid Axis in patients with type 2 diabetes and amiodarone-induced hypothyroidism.
Pharmacological Reports, 2015Co-Authors: Robert Krysiak, Małgorzata Gilowska, Witold Szkróbka, Bogusław OkopieńAbstract: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.
Maria Izabel Chiamolera - One of the best experts on this subject based on the ideXlab platform.
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minireview thyrotropin releasing hormone and the thyroid hormone feedback mechanism
Endocrinology, 2009Co-Authors: Maria Izabel Chiamolera, Fredric E. WondisfordAbstract:Thyroid hormone (TH) plays a critical role in development, growth, and cellular metabolism. TH production is controlled by a complex mechanism of positive and negative regulation. Hypothalamic TSH-releasing hormone (TRH) stimulates TSH secretion from the anterior pituitary. TSH then initiates TH synthesis and release from the thyroid gland. The synthesis of TRH and TSH subunit genes is inhibited at the transcriptional level by TH, which also inhibits posttranslational modification and release of TSH. Although opposing TRH and TH inputs regulate the Hypothalamic-Pituitary-Thyroid Axis, TH negative feedback at the pituitary was thought to be the primary regulator of serum TSH levels. However, study of transgenic animals showed an unexpected, dominant role for TRH in regulating the Hypothalamic-Pituitary-Thyroid Axis and an unanticipated involvement of the thyroid hormone receptor ligand-dependent activation function (AF-2) domain in TH negative regulation. These results are summarized in the review.