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Impact of dehydroepiandrosterone on thyroid autoimmunity and function in men with autoimmune hypothyroidism
Robert Krysiak · Witold Szkróbka · Bogusław Okopień
Abstract
Background Testosterone administration was found to have a protective effect on thyroid autoimmunity in men with autoimmune (Hashimoto’s) thyroiditis.
Objective The present study was aimed at assessing whether oral dehydroepiandrosterone affects thyroid autoimmunity and hypothalamic-pituitary-thyroid axis activity in men with subclinical hypothyroidism induced by Hashimoto’s thyroiditis.
Setting The study was conducted at the Medical University of Silesia, Katowice, Poland.
Method The study enrolled 32 elderly men with autoimmune hypothyroidism and low dehydroepiandrosterone-sulfate levels. Based on patient preference, the participants either received oral dehydroepiandrosterone (50 mg daily; n=16) or remained untreated (n=16). Apart from measuring antibody titers and hormone levels, we calculated the baseline and post-treatment values of three structure parameters of thyroid homeostasis.
Main outcome measure Serum titers of thyroid peroxidase and thyroglobulin antibodies.
Results At baseline, there were no significant differences in the investigated parameters between both groups of men. All participants completed the study. Oral dehydroepiandrosterone increased dehydroepiandrosterone sulfate and testosterone levels, as well as had a neutral effect on estradiol levels. The increase in dehydroepiandrosterone sulfate correlated with treatment-induced changes in serum testosterone. Moreover, dehydroepiandrosterone reduced titers of thyroid peroxidase and thyroglobulin antibodies decreased serum thyrotropin levels, reduced Jostel’s thyrotropin index as well as increased thyroid’s secretory capacity. Treatment-induced changes in thyroid antibody titers, thyrotropin levels, Jostel’s thyrotropin index, and thyroid’s secretory capacity correlated with the increase in dehydroepiandrosterone-sulfate and testosterone levels.
Conclusion The obtained results show that exogenous dehydroepiandrosterone may exert a beneficial effect on thyroid autoimmunity and hypothalamic-pituitary-thyroid axis activity in men with autoimmune thyroiditis and subclinical hypothyroidism.
Introduction
Autoimmune or Hashimoto’s thyroiditis, the commonest cause of hypothyroidism in developed countries and the most prevalent organ-specific autoimmune disease worldwide is characterized by a strong female preponderance,
suggesting an important role of sex hormones in its development [1, 2]. In line with this hypothesis, men with high values of the estradiol: testosterone ratio were more prone to the development of Hashimoto’s thyroiditis than men with low values of this ratio [3], men with thyroid hypofunction secondary in the majority of cases to autoimmune thyroid disease had low circulating testosterone levels [4], while the age of onset of autoimmune thyroiditis was determined by the (CAG)n repeat polymorphism of the androgen receptor [5]. Recently, we have found that testosterone therapy of men with impaired activity of the hypothalamic-pituitary-testicular axis reduced thyroid antibody titers [6], while the opposite effect was exerted by spironolactone, a drug with multidirectional antiandrogenic properties [7]. The impact of exogenous testosterone and spironolactone on thyroid peroxidase antibodies (TPOAb) and thyroglobulin antibodies (TgAb), considered the biological hallmark of autoimmune thyroiditis [1, 2], correlated with treatment-induced changes in circulating testosterone levels [6, 7]. Unlike testosterone, much less is known about the impact on thyroid autoimmunity of adrenal precursors of androgens. In animal models of autoimmune disorders, dehydroepiandrosterone (DHEA), the main product of the adrenal zona reticularis and the most abundant circulating steroid presents in the human body, suppressed expression of various proinflammatory cytokines and blunted both Th1 and Th2 immunological responses [8]. Women with elevated levels of TPOAb and TgAb were characterized by lower circulating levels of dehydroepiandrosterone sulfate (DHEA-S) than women seronegative for thyroid antibodies [9, 10]. Exogenous DHEA administered to women with autoimmune thyroiditis coexisting with premature ovarian failure reduced titers of TPOAb [10]. No analogous study has been conducted in men.
Results
At baseline, both groups were comparable with respect to age, body mass index, smoking and drinking habits, hormone levels, antibody titers, all calculated parameters of thyroid homeostasis, and the estimated glomerular filtration rate (Table 1). Because DHEA treatment was well tolerated, all participants completed the study and were included in the statistical analyses. In untreated patients, serum antibody titers, hormone levels, and all structure parameters of thyroid homeostasis remained at similar levels throughout the study. Expectedly, oral DHEA increased circulating levels of DHEA-S and testosterone. Moreover, DHEA reduced titers of thyroid peroxidase and thyroglobulin antibodies, decreased serum thyrotropin levels, reduced Jostel’s thyrotropin index as well as increased SPINA-GT. The drug has a neutral effect on circulating levels of free thyroxine, free triiodothyronine, and estradiol, as well as on SPINA-GD and the estimated glomerular filtration rate (Table 2). Both study groups differed in post-treatment values of DHEA-S, testosterone, thyroid antibody titers, thyrotropin levels, Jostel’s thyrotropin index, and SPINA-GT (Table 2).
Discussion
The present study enrolled elderly men with mild autoimmune thyroid hypofunction. A relatively narrow age range helped to obtain two relatively homogenous groups of patients. The prevalence of autoimmune thyroiditis in men is growing worldwide [14]. Hypothyroidism occurs more often in elderly patients [15], and these patients are often treated with levothyroxine. However, levothyroxine interacts with or its absorption is affected by many drugs commonly used by the geriatric population, including anticoagulants, antidiabetics, antidepressants, sympathomimetics, cardiac glycosides, ß-blockers, anti-arrhythmic, anti-convulsants, some statins, antacids, proton pump inhibitors, calcium salts, cimetidine and oral iron [16]. Moreover, the risk of levothyroxine intolerance increases with age [17]. Therefore, levothyroxine does not seem to be an ideal drug for elderly patients with mild thyroid hypofunction. Theoretically, DHEA may be an interesting alternative because in men over the age of 40, secretion of adrenal androgens progressively declines, often reaching very low or negligible levels in the elderly [18].
Conclusion
Six-month treatment of elderly men with autoimmune thyroiditis with oral DHEA led to a decrease in serum titers of TPOAb and TgAb, as well as partially normalized hypothalamic-pituitary-thyroid axis activity. The beneficial effect of exogenous DHEA correlated with baseline titers of thyroid antibodies and with treatment-induced increases in DHEA-S and testosterone. The obtained results indicate that DHEA alleviates thyroid autoimmunity and improves thyroid function in the studied population of men. Owing to study limitations, our findings need to verify in larger clinical trials.
Robert Krysiak · Witold Szkróbka · Bogusław Okopień
Abstract
Background Testosterone administration was found to have a protective effect on thyroid autoimmunity in men with autoimmune (Hashimoto’s) thyroiditis.
Objective The present study was aimed at assessing whether oral dehydroepiandrosterone affects thyroid autoimmunity and hypothalamic-pituitary-thyroid axis activity in men with subclinical hypothyroidism induced by Hashimoto’s thyroiditis.
Setting The study was conducted at the Medical University of Silesia, Katowice, Poland.
Method The study enrolled 32 elderly men with autoimmune hypothyroidism and low dehydroepiandrosterone-sulfate levels. Based on patient preference, the participants either received oral dehydroepiandrosterone (50 mg daily; n=16) or remained untreated (n=16). Apart from measuring antibody titers and hormone levels, we calculated the baseline and post-treatment values of three structure parameters of thyroid homeostasis.
Main outcome measure Serum titers of thyroid peroxidase and thyroglobulin antibodies.
Results At baseline, there were no significant differences in the investigated parameters between both groups of men. All participants completed the study. Oral dehydroepiandrosterone increased dehydroepiandrosterone sulfate and testosterone levels, as well as had a neutral effect on estradiol levels. The increase in dehydroepiandrosterone sulfate correlated with treatment-induced changes in serum testosterone. Moreover, dehydroepiandrosterone reduced titers of thyroid peroxidase and thyroglobulin antibodies decreased serum thyrotropin levels, reduced Jostel’s thyrotropin index as well as increased thyroid’s secretory capacity. Treatment-induced changes in thyroid antibody titers, thyrotropin levels, Jostel’s thyrotropin index, and thyroid’s secretory capacity correlated with the increase in dehydroepiandrosterone-sulfate and testosterone levels.
Conclusion The obtained results show that exogenous dehydroepiandrosterone may exert a beneficial effect on thyroid autoimmunity and hypothalamic-pituitary-thyroid axis activity in men with autoimmune thyroiditis and subclinical hypothyroidism.
Introduction
Autoimmune or Hashimoto’s thyroiditis, the commonest cause of hypothyroidism in developed countries and the most prevalent organ-specific autoimmune disease worldwide is characterized by a strong female preponderance,
suggesting an important role of sex hormones in its development [1, 2]. In line with this hypothesis, men with high values of the estradiol: testosterone ratio were more prone to the development of Hashimoto’s thyroiditis than men with low values of this ratio [3], men with thyroid hypofunction secondary in the majority of cases to autoimmune thyroid disease had low circulating testosterone levels [4], while the age of onset of autoimmune thyroiditis was determined by the (CAG)n repeat polymorphism of the androgen receptor [5]. Recently, we have found that testosterone therapy of men with impaired activity of the hypothalamic-pituitary-testicular axis reduced thyroid antibody titers [6], while the opposite effect was exerted by spironolactone, a drug with multidirectional antiandrogenic properties [7]. The impact of exogenous testosterone and spironolactone on thyroid peroxidase antibodies (TPOAb) and thyroglobulin antibodies (TgAb), considered the biological hallmark of autoimmune thyroiditis [1, 2], correlated with treatment-induced changes in circulating testosterone levels [6, 7]. Unlike testosterone, much less is known about the impact on thyroid autoimmunity of adrenal precursors of androgens. In animal models of autoimmune disorders, dehydroepiandrosterone (DHEA), the main product of the adrenal zona reticularis and the most abundant circulating steroid presents in the human body, suppressed expression of various proinflammatory cytokines and blunted both Th1 and Th2 immunological responses [8]. Women with elevated levels of TPOAb and TgAb were characterized by lower circulating levels of dehydroepiandrosterone sulfate (DHEA-S) than women seronegative for thyroid antibodies [9, 10]. Exogenous DHEA administered to women with autoimmune thyroiditis coexisting with premature ovarian failure reduced titers of TPOAb [10]. No analogous study has been conducted in men.
Results
At baseline, both groups were comparable with respect to age, body mass index, smoking and drinking habits, hormone levels, antibody titers, all calculated parameters of thyroid homeostasis, and the estimated glomerular filtration rate (Table 1). Because DHEA treatment was well tolerated, all participants completed the study and were included in the statistical analyses. In untreated patients, serum antibody titers, hormone levels, and all structure parameters of thyroid homeostasis remained at similar levels throughout the study. Expectedly, oral DHEA increased circulating levels of DHEA-S and testosterone. Moreover, DHEA reduced titers of thyroid peroxidase and thyroglobulin antibodies, decreased serum thyrotropin levels, reduced Jostel’s thyrotropin index as well as increased SPINA-GT. The drug has a neutral effect on circulating levels of free thyroxine, free triiodothyronine, and estradiol, as well as on SPINA-GD and the estimated glomerular filtration rate (Table 2). Both study groups differed in post-treatment values of DHEA-S, testosterone, thyroid antibody titers, thyrotropin levels, Jostel’s thyrotropin index, and SPINA-GT (Table 2).
Discussion
The present study enrolled elderly men with mild autoimmune thyroid hypofunction. A relatively narrow age range helped to obtain two relatively homogenous groups of patients. The prevalence of autoimmune thyroiditis in men is growing worldwide [14]. Hypothyroidism occurs more often in elderly patients [15], and these patients are often treated with levothyroxine. However, levothyroxine interacts with or its absorption is affected by many drugs commonly used by the geriatric population, including anticoagulants, antidiabetics, antidepressants, sympathomimetics, cardiac glycosides, ß-blockers, anti-arrhythmic, anti-convulsants, some statins, antacids, proton pump inhibitors, calcium salts, cimetidine and oral iron [16]. Moreover, the risk of levothyroxine intolerance increases with age [17]. Therefore, levothyroxine does not seem to be an ideal drug for elderly patients with mild thyroid hypofunction. Theoretically, DHEA may be an interesting alternative because in men over the age of 40, secretion of adrenal androgens progressively declines, often reaching very low or negligible levels in the elderly [18].
Conclusion
Six-month treatment of elderly men with autoimmune thyroiditis with oral DHEA led to a decrease in serum titers of TPOAb and TgAb, as well as partially normalized hypothalamic-pituitary-thyroid axis activity. The beneficial effect of exogenous DHEA correlated with baseline titers of thyroid antibodies and with treatment-induced increases in DHEA-S and testosterone. The obtained results indicate that DHEA alleviates thyroid autoimmunity and improves thyroid function in the studied population of men. Owing to study limitations, our findings need to verify in larger clinical trials.
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