Maternal photoperiodic programming enlightens the internal regulation of thyroid‐hormone deiodinases in tanycytes

Seasonal rhythms in physiology are widespread among mammals living in temperate zones. These rhythms rely on the external photoperiodic signal being entrained to the seasons, although they persist under constant conditions, revealing their endogenous origin. Internal long‐term timing (circannual cycles) can be revealed in the laboratory as photoperiodic history‐dependent responses, comprising the ability to respond differently to similar photoperiodic cues based on prior photoperiodic experience. In juveniles, history‐dependence relies on the photoperiod transmitted by the mother to the fetus in utero, a phenomenon known as “maternal photoperiodic programming” (MPP). The response to photoperiod in mammals involves the nocturnal pineal hormone melatonin, which regulates a neuroendocrine network including thyrotrophin in the pars tuberalis and deiodinases in tanycytes, resulting in changes in thyroid hormone in the mediobasal hypothalamus. This review addresses MPP and discusses the latest findings on its impact on the thyrotrophin/deiodinase network. Finally, commonalities between MPP and other instances of endogenous seasonal timing are considered, and a unifying scheme is suggested in which timing arises from a long‐term communication between the pars tuberalis and the hypothalamus and resultant spontaneous changes in local thyroid hormone status, independently of the pineal melatonin signal.     

Lower proportion of CD19+IL-10+ and CD19+CD24+CD27+ but not CD1d+CD5+CD19+CD24+CD27+ IL-10+ B cells in children with autoimmune thyroid diseases

Abstract

Introduction: As it is generally known, regulatory B cells (Bregs) control inflammation and autoimmunity. The significance of Bregs in the population of children with autoimmune thyroid diseases (AITD) still offers plenty of potential to explore. The aim of this study was to estimate the expression of Bregs (phenotype CD19⁺CD24⁺CD27⁺IL-10⁺, CD19⁺IL-10⁺, CD1d⁺CD5⁺CD19⁺IL-10⁺ and CD1d⁺CD5⁺CD19⁺CD24⁺CD27⁺) in a paediatric cohort with AITD and in health controls.

Materials and methods: A total of 100 blood samples were obtained from 53 paediatric patients with Graves’ disease (GD) (N?=?12 newly diagnosed, mean age 12.5?±?3.5 and N?=?17 during methimazole therapy, mean age 12.7?±?4.4), Hashimoto’s thyroiditis (HT) (N?=?10 newly diagnosed, mean age 13.3?±?2.9 and N?=?10 during L-thyroxine therapy, mean age 13.7?±?3.4) and compared with healthy controls (C) (N?=?15, mean age 13.1?±?3.1). The expressions of the immune cell populations were analysed by four-color flow cytometry using a FASC Canto II cytometer (BD Biosciences).

Results: There was a decreasing tendency in the number of lymphocytes B producing IL-10 (B10) cells among all B lymphocytes and more widely, also among all lymphocytes, in each study group, as compared to C. We reported a reduction in IL-10 production in Bregs with the expression of CD19⁺CD24⁺CD27⁺IL-10 and CD1d⁺CD5⁺CD19⁺IL-10⁺ in both untreated and treated AITD.

Conclusions: Our data demonstrate that the reduction in the number of Bregs with CD19⁺CD24⁺CD27⁺IL-10⁺ and CD19⁺IL-10⁺ expression could be responsible for breaking immune tolerance and for AITD development in children.     

促甲状腺激素抑制疗法对分化型甲状腺癌患者骨代谢、CD44V6、sIL-2R水平的影响

目的 研究促甲状腺激素（TSH）抑制疗法对分化型甲状腺癌（DTC）患者骨代谢、白细胞分化抗原44变异型6（CD44V6）及可溶性白细胞介素-2受体（sIL-2R）水平的影响。方法 选取2019年3月—2022年1月内蒙古医科大学附属医院收治的100例DTC患者,按照随机数字表法分为对照组和TSH组,每组50例。对照组术后给予甲状腺素替代疗法,TSH组术后给予TSH抑制疗法。比较两组治疗前后甲状腺功能［TSH、游离三碘甲状腺原氨酸（FT₃）、游离甲状腺激素（FT₄）］、骨代谢［总I型胶原氨基酸延长肽（PINP）、β-胶原特殊序列（β-Crosslaps）］、免疫功能［T淋巴细胞亚群（CD3⁺、CD4⁺、CD8⁺）］、血清CD44V6、sIL-2R水平的变化情况,并评价两组用药的安全性。结果 治疗后3个月,TSH组血清TSH水平较对照组低（P <0.05）,而血清FT₃、FT₄水平较对照组高（P <0.05）;两组治疗前后血清PINP、β-Crosslaps水平比较,差异无统计学意义（P >0.05）;治疗后3个月,TSH组CD3⁺、CD4⁺水平较对照组高（P <0.05）,而CD8⁺水平较对照组低（P <0.05）;治疗后3个月,TSH组CD44V6、sIL-2R水平较对照组低（P <0.05）;两组不良反应发生率比较,差异无统计学意义（P >0.05）。结论 TSH抑制疗法可有效改善DTC患者甲状腺功能,增强免疫功能,降低血清CD44V6、sIL-2R水平,对骨代谢影响较小,且用药安全性良好。     

Primary blood TSH/back up TSH measurements: an improved approach for neonatal thyroid screening

Objective: Neonatal hypothyroidism is one of the most common endocrine disorders related to mental impairment and growth retardation in newborns. In many countries, the neonatal thyroid screening programs are performed for rapid diagnosis and treatment of hypothyroidism. The major aim of this investigation was to improve the thyroid screening program using primary blood TSH/back up TSH measurements as some patients are missed due to technical and human errors. Methods: A total of 9,118neonates were evaluated on the protocol. On top of that, the quality control procedures were applied to improve the sampling technique and the laboratory results. Results: Three missed neonates by current programs using the cutoff point more than 20 mU/l for blood TSH were found by our approach. Conclusion: Results showed that the programs based on the primary blood TSH/back up TSH measurements improve the thyroid screening results. J. Clin. Lab. Anal. 25:61–63, 2011. © 2011 Wiley‐Liss, Inc.     

Thyroid hormone concentrations and inhibition of thyroid stimulating hormone secretion in euthyroid subjects with autonomous thyroid nodules

Abstract. Sixty-four euthyroid patients with autonomous thyroid nodules and normal thyroxine (T₄) concentrations and tri-iodothyronine resin uptake have been studied. The serum tri-iodothyronine (T₃) concentration of the patients was 2.24 (±0.67) ng/ml, significantly higher than in a group of fifty-seven euthyroid control subjects (1.58 ± 0.30 ng/ml). When no extranodular tissue was visible on the basal thyroid scan, the T₃ was 2.31 (±0.63) ng/ml, significantly higher than in patients with some extranodular uptake on the basal scan (1.91 ± 0.42 ng/ml). There was no significant difference in the serum T₄ concentrations of the patients (7.37 ± 2.10 μg/100 ml) compared to the control group (6.88 ± 1.89 μg/100 ml). The T₄ concentrations were not correlated with total or partial inhibition of the extranodular tissue. The thyroid hormone concentrations were not directly correlated to the size of the nodule assessed by scan imaging. The thyroid stimulating hormone (TSH) concentration of the patients (1.52 ± 0.38 μU/ml) was significantly lower than in normals (2.49 ± 0.96 μU/ml). No significant difference was found in the TSH concentrations of patients with partial or total inhibition of extranodular tissue irrespective of the T₃ concentration. A thyrotrophin releasing hormone stimulation test in twelve patients did not increase the serum TSH, irrespectively of the T₃ concentration.
These data show the high frequency of elevated serum T₃ concentrations despite normal serum T₄ concentration in euthyroid patients with autonomous thyroid nodules. They confirm that inhibition of TSH secretion can occur when thyroid hormone concentrations are in the normal range.     

Comparison of Therapeutic Efficacy and Clinical Parameters Between Recombinant Human Thyroid Stimulating Hormone and Thyroid Hormone Withdrawal in High-Dose Radioiodine Treatment with Differentiated Thyroid Cancer

Purpose

High-dose radioiodine treatment (HD-RIT) after injection of recombinant human thyroid stimulating hormone (rh-TSH) has become widely used. This study compared the therapeutic efficacy of HD-RIT and clinical parameters between rh-TSH supplement and thyroid hormone withdrawal (THW) after total thyroidectomy in patients with differentiated thyroid cancer.

Methods

We retrospectively reviewed 266 patients (47 male and 219 female; age, 49.0 ± 10.9 years) with differentiated thyroid cancer detected from September 2011 to September 2012. Patients comprised THW (217, 81.6 %) and rh-TSH (49, 18.4 %). Inclusion criteria were: first HD-RIT; any TN stage; absence of distant metastasis. To evaluate the complete ablation of the remnant thyroid tissue or metastasis, we reviewed stimulated serum thyroglobulin (sTg), I-123 whole-body scan (RxWBS) on T4 off-state, and thyroid ultrasonography (US) or [F-18]-fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT) 6–8 months after HD-RIT. We defined a complete ablation state when all three of the follow-up conditions were satisfied; <2.0 ng/ml of the sTg, I-123 RxWBS (−), and thyroid US or F-18 FDG PET/CT (−). If one of the three was positive, ablation was considered incomplete. We also compared various clinical biomarkers (body weight, body mass index, liver and kidney function) between THW and rh-TSH groups.

Results

The rates of complete ablation were 73.7 % (160/217) for the THW group and 73.5 % (36/49) for the rh-TSH group. There was no significant difference between the two groups (p = 0.970). The follow-up aspartate transaminase (p = 0.001) and alanine transaminase (p = 0.001) were significantly higher in the THW group. The renal function parameters of blood urea nitrogen (p = 0.001) and creatinine (p = 0.005) tended to increase in the THW group. The change of body weight was + Δ0.96 (±1.9) kg for the THW group and was decreased by -Δ1.39 (±1.5) kg for the rh-TSH group. The change of body mass index was 0.4 (±0.7) kg/m² in the THW group and was decreased by −0.6 (±0.6) kg/m² in the rh-TSH group.

Conclusions

Consistent with previous studies, the rates of complete ablation between the THW and rh-TSH groups were not significantly different. The clinical parameters, as we mentioned above, were elevated for THW group but were irrelevant for the rh-TSH group. The findings favor HD-RIT after rh-TSH, especially for patients with chronic liver and kidney disease.