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  • Nakajima, Yasuyo  (8)
  • Nishikido, Ayaka  (8)
  • 1
    In: Journal of the Endocrine Society, The Endocrine Society, Vol. 4, No. Supplement_1 ( 2020-05-08)
    Abstract: Recent studies showed that various factors, including age, gender, race, iodine intake, obesity, the thyroid peroxidase antibody (TPO-Ab), and/or smoking, influence the thyroid status. In the present study, we analyzed and investigated the effects of these factors, particularly smoking and the thyroid peroxidase antibody (TPO-Ab) in Japanese euthyroxinemia individuals with serum free T4 level within normal range. A total of 12,289 subjects who underwent health check-ups were analyzed in a cross-sectional and longitudinal study. The mean age of subjects was 50 ± 10 years (age range: 21–88 years). Serum TSH levels and the prevalence of positivity for TPO-Ab increased with age in Japanese euthyroxinemia subjects. Mean and median serum TSH levels increased with age in smokers and non-smokers, but were significantly lower in smokers than in non-smokers among men and women in most age groups; the median 97.5th percentiles of TSH levels were 1.2 mU/liter and 2.9 mU/liter in smokers, and 1.4 mU/liter and 3.9 mU/liter in non-smokers in 31- to 40-year-old men, p & lt;0.01, and 1.4mU/liter and 4.3 mU/liter, and 1.8mU/liter and 6.2 mU/liter in 61- to 70-year-old men, p & lt;0.01. However, smoking had a negligible effect on serum TSH levels in women older than 50 years; 1.3 mU/liter in smokers and 1.6 mU/liter in non-smokers in 31- to 40-year-old women, p & lt;0.01, and 1.5 mU/liter and 1.8 mU/liter in 51- to 60-year-old women, p=0.3. Furthermore, the present study confirmed that serum free T4 levels in men progressively decreased with age, whereas no significant change was observed in women. Smoking did not affect the relationship between age and serum free T4 levels in men or women, except for men in their 20s. Serum TSH levels were significantly higher in subjects with positivity for TPO-Ab than in those with negativity at all ages and in both genders; however, smoking did not affect free T4 levels or the positivity for TPO-Ab. The rate of smokers in men was significantly higher in patients with subclinical hyperthyroidism (25%) than in those with subclinical hypothyroidism (10%, p & lt;0.05). Furthermore, the results of the longitudinal study revealed a significant decrease in serum TSH levels one year after the start of smoking in men (p & lt;0.05). Since smoking appears to lower serum TSH levels in Japanese euthyroxinemia subjects careful consideration of the smoking status is needed when evaluating subclinical thyroid function.
    Type of Medium: Online Resource
    ISSN: 2472-1972
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2020
    detail.hit.zdb_id: 2881023-5
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  • 2
    In: Journal of the Endocrine Society, The Endocrine Society, Vol. 5, No. Supplement_1 ( 2021-05-03), p. A979-A980
    Abstract: Objective: Thyroid hormones have various effects on cardiac and circulatory systems, leading to arrhythmias and heart failure. In Europe and the United States, it has been reported that elevated thyroid hormones within the normal range have been reported to be associated with a risk of atrial fibrillation, however, there was no report on Japanese cases, a country that differs in iodine intake and ethnicity from the West. Therefore, we evaluated the abnormality of thyroid function in a large number of cases of atrial fibrillation (AF) who received catheter ablation (RFCA) in Japan. Methods: We evaluated 2,937 cases of atrial fibrillation (2,084 males, mean age 64.1±10.7 years and 853 females, 69.0±8.5 years) who underwent RFCA at the Gunma Prefectural Cardiovascular Center between 2012 and 2018. As a control we used a total of 15,660 participants for health check-up (9,176 males, mean age 49.7±9.8 years and 6,484 females, 48.9±10.3 years) from 2006 to 2013, and we evaluated thyroid function after adjusting for gender-specific age. Results: The prevalence of overt hyperthyroidism was significantly higher in the RFCA-treated male group (0.43%) than in the control group (0.07%), even after adjusting for age (p & lt;0.01). Similarly, the prevalence of subclinical hyperthyroidism was also significantly higher in the RFCA-treated male group (3.12%) than in the control group (0.94%) after adjusting for age (p & lt;0.01). On the other hand, subclinical hypothyroidism was significantly lower in the RFCA-treated group after adjusting for age (2.97% in the RFCA-treated group and 3.93% in the control group, p & lt;0.01). Females showed the same results as males. Conclusions: In an iodine rich country Japan, not only overt hyperthyroidism but also subclinical hyperthyroidism is an obvious risk factor for severe atrial fibrillation in Japan. Intriguingly, subclinical hypothyroidism might contribute to the prevention of atrial fibrillation, suggesting that slightly higher serum TSH levels might be better for elderlies.
    Type of Medium: Online Resource
    ISSN: 2472-1972
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2021
    detail.hit.zdb_id: 2881023-5
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  • 3
    In: Journal of the Endocrine Society, The Endocrine Society, Vol. 5, No. Supplement_1 ( 2021-05-03), p. A851-A851
    Abstract: Objectives: The hypothalamic-pituitary-thyroid (HPT) axis plays a significant role in the regulation of energy expenditure. Previous reports demonstrated that thyroid hormones are critically involved in metabolic process, and hypothyroidism was induced by fasting. The mechanism by which TRH neurons sense alterations in peripheral energy stores is supposed to be regulated by leptin, an adipose tissue-derived hormone. Leptin was initially considered as a hormone to prevent obesity, it was later showed that the major role of leptin is to signal the switch from the fed to the starved state at the hypothalamic level. Recently, we generated TRH-deficient mice (TRH-/-). The mice exhibit tertiary/central hypothyroidism with characteristic elevation of serum TSH level and diminished TSH biological activity. In this study, we used TRH-/- to investigate the physiological role of TRH in fasting energy expenditure, including the mechanism regulated by leptin. Methods: Twelve-week-old male F2 hybrid ICR mice were used in this study. (1) Wild-type mice (WT) and TRH-/- were fasted up to 50 hrs. Blood samples were collected from tail veins at various points. Anterior pituitary samples were obtained from euthanized mice before and after 16 hrs fasting. (2) Serum free T4 (FT4) and TSH levels assessed. (3) The expression level of TSHβ mRNA in anterior pituitary were detected using qPCR assays. (4) We repeated these experiments using mice with leptin administration; leptin (0.5μg/g•BW) was administrated every 6 hours starting at after 2 hours fasting. Results: In WT, the level of FT4 was decreased chronologically during fasting to approximately 50% at 50 hrs after fasting. Serum TSH decreased to 70% and the expression level of TSHβ mRNA in anterior pituitary also decreased to 30% compared to before fasting. Administration of leptin recovered the level of FT4 to basal level. However, the level of serum TSH and TSHβ mRNA in pituitary were not recovered to basal levels. By contrast, in TRH-/-, the level of FT4 were also decreased after fasting indicating that the decrease of FT4 by fasting was independent of TRH. However, the level of FT4 was not recovered by leptin suggesting that the recovery of FT4 by leptin was TRH dependent. Serum TSH level decreased to 75% after fasting, and no recovery to basal level with leptin administration was observed in TRH-/- same as WT. In TRH-/-, the pituitary TSHβ mRNA expression level was about 50% of WT before fasting. It did not correlate with the serum TSH level. In addition, no increase in TSHβ mRNA expression level by leptin administration was observed in TRH-/-. These findings suggested that the TSHβ mRNA expression level in the pituitary is completely TRH-dependent in TRH-/-. Conclusion: Fasting-induced hypothyroxinemia was independent of TRH. Leptin regulates H-P-T axis via TRH during fasting-induced energy expenditure. Leptin may modulate the biological activity of TSHβ.
    Type of Medium: Online Resource
    ISSN: 2472-1972
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2021
    detail.hit.zdb_id: 2881023-5
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  • 4
    In: Biochemical and Biophysical Research Communications, Elsevier BV, Vol. 562 ( 2021-07), p. 139-145
    Type of Medium: Online Resource
    ISSN: 0006-291X
    RVK:
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
    detail.hit.zdb_id: 1461396-7
    SSG: 12
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  • 5
    In: Endocrine Journal, Japan Endocrine Society, Vol. 65, No. 8 ( 2018), p. 805-813
    Type of Medium: Online Resource
    ISSN: 0918-8959 , 1348-4540
    Language: English
    Publisher: Japan Endocrine Society
    Publication Date: 2018
    detail.hit.zdb_id: 2133773-1
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  • 6
    In: Journal of the Endocrine Society, The Endocrine Society, Vol. 5, No. Supplement_1 ( 2021-05-03), p. A851-A852
    Abstract: Introduction: Retinal cone photoreceptor cells contain short (S) and medium (M) wavelength opsins, which are light-sensitive substances involved in color vision and visual acuity by sensing lights of different wavelengths. Thyroid hormones promote M-opsin expression and suppress S-opsin expression during the differentiation of cone photoreceptors. It was previously reported that M-opsin expression was delayed and S-opsin expression increased in TSH receptor-deficient mice and methimazole-induced hypothyroid mice. In addition, no M-opsin expression and increased S-opsin expression were observed in thyroid hormone receptor (TR) β2-deficient mice (Ng L et al, Nature Genetics. 2001; 27(1): 94-98.). This suggested that impaired thyroid function affects opsin development. We therefore examined retinal development in TRH-deficient mice, which are a model of central hypothyroidism established in our laboratory. Methods: We performed HE staining of the retina at postnatal 30 days and electroretinography at postnatal 10 weeks using TRH-/- and wild-type (WT) mice. We also examined expression levels of S/M opsin mRNA in WT, TRH-/- and TRH-/- pups born from TRH-/- dams at postnatal 12,17 and 30 days, and TRβΔ337T knock-in mice (TRβmut/mut) at postnatal 30 days. Furthermore, we performed immunohistochemistry to examine S/M opsin protein expression in these mice. Results: The retinal structures by HE staining and retinal functions by electroretinography in TRH-/- mice were unchanged compared with those in WT mice. Although M-opsin expression was not detected and S-opsin expression was higher in TRβmut/mut mice than in WT mice, the mRNA and protein expression levels of S/M-opsin did not significantly differ between TRH-/- pups born from TRH+/- dams and WT pups at all postnatal days. TRH-/- pups born from TRH-/- dams exposed to maternal hypothyroidism had similar serum total T4 levels to TRH-/- pups born from TRH+/- with normal maternal thyroid function. In contrast, the mRNA expression level of M-opsin was significantly lower (1.00±0.06 vs 0.64±0.05: mean ± SE, p & lt;0.01) and the protein expression level was lower in TRH-/- pups born from TRH-/- dams than in WT pups at postnatal 12 days. However, these differences disappeared after postnatal 17 days, and there was no difference in M-opsin expression in TRH-/- pups born from TRH-/- dams compared with WT pups. Conclusions: Although no delay in opsin development was observed in TRH-/- pups born from TRH+/- dams, TRH-/- pups born from central hypothyroid dams exhibited delayed opsin development, suggesting that maternal hypothyroidism affects the development of retinal opsin in the neonatal period.
    Type of Medium: Online Resource
    ISSN: 2472-1972
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2021
    detail.hit.zdb_id: 2881023-5
    Location Call Number Limitation Availability
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  • 7
    In: Journal of the Endocrine Society, The Endocrine Society, Vol. 3, No. 12 ( 2019-12-01), p. 2385-2396
    Abstract: We previously identified factors affecting thyroid status, including sex, age, and smoking. Objective In the current study, we increased the number of subjects examined and investigated the effects of these factors, particularly smoking and the thyroid peroxidase antibody (TPO-Ab), in Japanese patients with euthyroxinemia and serum free T4 levels within the normal range. Participants A total of 12,289 subjects who underwent health checkups were analyzed in a cross-sectional and longitudinal study. Results The mean age of subjects was 50 ± 10 years (age range: 21 to 88 years). Serum TSH levels and the prevalence of positivity for TPO-Ab increased with age in Japanese subjects with euthyroxinemia. Mean serum TSH levels were significantly lower in the smoking group than in the nonsmoking group except for women older than 50 years. Serum TSH levels were significantly higher in subjects with positivity for TPO-Ab than in those with negativity at all ages and in both sexes; however, smoking did not affect free T4 levels or positivity for TPO-Ab. Among men, the rate of smokers was significantly higher in patients with subclinical hyperthyroidism (25%) than in those with subclinical hypothyroidism (10%; P 〈 0.05). Furthermore, the results of the longitudinal study revealed a significant decrease in serum TSH levels 1 year after the start of smoking in men (P 〈 0.05). Conclusion Because smoking appeared to lower serum TSH levels in Japanese subjects with euthyroxinemia, their smoking status warrants careful consideration when evaluating subclinical thyroid function.
    Type of Medium: Online Resource
    ISSN: 2472-1972
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2019
    detail.hit.zdb_id: 2881023-5
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  • 8
    In: Molecular and Cellular Endocrinology, Elsevier BV, Vol. 501 ( 2020-02), p. 110657-
    Type of Medium: Online Resource
    ISSN: 0303-7207
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2020
    detail.hit.zdb_id: 1500651-7
    SSG: 12
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