Graves' disease is associated with an altered CXCR3 and CCR5 expression in thyroid-derived compared to peripheral blood lymphocytes

The mechanisms by which T cells accumulate in the thyroid and support the autoimmune process in patients with Graves' disease (GD) are poorly understood. Chemokines and their receptors may be involved in this process. We have analysed the expression of CXCR3 and CCR5 as Th1-specific chemokine receptors, CCR3 as a marker for Th2 cells, CXCR4 (expressed on unprimed, naive T cells) and CCR2 (known to be involved in autoimmunity) on peripheral blood (PBL) and thyroid-derived lymphocytes (TL) using flow cytometry. Chemokine receptor expression on PBL of GD patients (n = 16) did not differ from that of normal controls (n = 10). In GD, CXCR3+ (67.3 +/- 4.0% versus 45.7 +/- 2.1%) and CCR5+ T cells (42.5 +/- 3.4% versus 18.8 +/- 2.1%) showed a significant enrichment in the TL compared to PBL. The positive cells were contributed mainly by the CD4+CD45R0+ subset. TL are mostly primed CD45R0+ T cells, but surprisingly, they had significantly higher levels of CXCR4+ cells among TL (96.2 +/- 1.0%) compared to PBL (66.8 +/- 4.2%). However, CXCR4 has been induced during in vitro isolation of TL. There was no correlation between chemokine receptors and the level of TSH-receptor and thyroid peroxidase autoantibodies. CCR3+ and CCR2+ cells remained unchanged in TL compared to PBL. We could confirm the results using RT PCR and immunohistology. In summary, TL showed a different chemokine receptor pattern compared to PBL from the same patient. This indicates a role for CXCR3 and CCR5 in the recruitment of T cells to the thyroid in GD.     

Absence of the left inferior thyroid artery: clinical implications

Dissection of an adult male cadaver revealed an absence of the left inferior thyroid artery; its usual area of distribution to the thyroid gland was supplied by the right inferior thyroid artery. Absence of the left inferior thyroid artery occurs in 1-6% of cases. The inferior thyroid artery arises commonly from the thyrocervical trunk, passes posterior to the carotid sheath and supplies the inferior pole of the corresponding lobe of the thyroid gland; its branches can course anterior or posterior to or between branches of the recurrent laryngeal nerve. During thyroid surgery it is imperative to identify the relationship of the inferior thyroid artery to the recurrent laryngeal nerve or to establish its absence because injury to the nerve can be a major complication; awareness of significant variations of the surgical anatomy of the thyroid gland is vital for preserving the integrity of important structures.     

Native and sialic acid masked Lewisa antigen reactivity in medullary thyroid carcinoma

Forty-six medullary thyroid carcinomas (MTC) were subjected to a qualitative and quantitative characterization of native and sialic acid masked Lewis^a (Le^a) antigens. Immunohistochemical investigations included monoclonal antibodies (MABs) directed against alpha(2,3)-sialyl-Le^a, i.e. CA19-9 (MAB 19-9), native Le^a (MAB anti Le^a) and alpha(2,3) sialyl type 1 structure, i.e. CA 50 (MAB C50). To detect sialic acid masked Le^a reactivity, MAB anti-Le^a was also applied to native and enzymatically desialylated tissue sections with and without masking of sialic acid residues by sialic acid and sequence specific lectins. Only 7 MTC (15%) displayed a weak expression of CA19-9, while 16 (33%) showed moderate positive staining for native Le^a. Twenty-seven tumours exhibited a strong staining by the N'ase MAB anti Le^a staining sequence. The latter could most effectively be inhibited by the simultaneous masking of alpha(2,3)-and alpha-(2,6)-linked sialic acid residues due to the comptetitive binding of sialic acid and sequence specific lectins: Maackia amurensis agglutinin (specific alpha(2,3)-linked sialic acid) and Sambucus nigra agglutinin (specific alpha(2,6)-linked sialic acid). Thus, in MTC the major portion of sialic acid masked Le^a antigen reactivity is different from that detected by the MAB 19-9. The antigen reactivity is probably due to Le^a structures containing both alpha(2,3) and alpha(2,6)-linked sialic acid residues. A highly significant correlation between the expression of CA50 and that detected by the N'ase MAB anti-Le^a staining sequence indicates that the alpha(2,3)-sialyl type 1 chain represents a common intermediate structure within the pathway of the biosynthesis of sialylated Le^a antigens, excluding the formation of CA19-9 via the formation of the disialyl type 1 structure. This is subsequently fucosylated to the corresponding sialic acid masked Le^a. Preliminary clinicopathological studies indicate that the sialic acid masked Le^a antigens detected by the N'ase MAB anti-Le^a staining sequence are related to biologically aggressive MTC.     

Effects of thyroid status on clonidine-induced hypo-activity responses in the developing rat

Summary Clonidine-induced hypoactivity was studied in rats made neonatally hypo- and hyperthyroid (PTU or T₄ administered between 1–27 days postnatally) as an indication of central presynaptic ₂-adrenoceptor function. Paradoxically, at 28 days postnatally both treatments caused an increase in clonidine-hypoactivity compared with untreated control animals, which was not due to sex differences amongst littermates in the various groups. It is proposed that whereas the hyperthyroid neonate data perhaps reflect an enhancement of presynaptic ₂ function similar to that seen in the adult rat brain, the result obtained for the hypothyroid neonates could perhaps be due to a retardation of the ontogeny of central noradrenergic neurones.     

皮肤涂抹雌三醇对裸鼠甲状腺功能和肿瘤影响的效果观察

目的研究经皮涂抹外源性雌三醇(E₃)对裸鼠甲状腺功能及甲状腺移植瘤的影响。方法使用123只4周龄裸鼠,按体质量采用随机数字表法分为9组:①对照组、②低E₃组、③高E₃组、④乳头状甲状腺癌组(PTC组)、⑤乳头状甲状腺癌+高E₃组(PTC+高E₃组)、⑥滤泡状甲状腺癌组(FTC组)、⑦滤泡状甲状腺癌+高E₃组(FTC+高E₃组)、⑧未分化型甲状腺癌组(ATC组)和⑨未分化型甲状腺癌+高E₃组(ATC+高E₃组),均正常饮食饮水。除对照组、PTC组、FTC组和ATC组外,其余5组每日给予皮肤涂抹雌三醇乳膏,低E₃浓度为市售化妆品人均每日使用量中雌三醇含量的25倍、高剂量为100倍。40天后,收集各组裸鼠的24h尿样;尿碘采用砷铈催化分光光度法测定,尿E₃、血清E₃、血清甲状腺激素[游离三碘甲状腺原氨酸(FT3)、游离甲状腺素(FT4)、促甲状腺素(TSH)]和甲状腺抗体[甲状腺球蛋白抗体(TgAb)、甲状腺过氧化物酶抗体(TpoAb)],采用酶联免疫吸附实验[ELISA]测定。在接种肿瘤后的第4日起,每3 d测量肿瘤大小。结果①各组裸鼠血清E₃和尿E₃水平比较差异有统计学意义;其中FTC+高E₃组和ATC+高E₃组的血清E(310.22、14.18 pmol/L)和尿E(36.40、8.18 pmol/L)水平均分别显著低于FTC组和ATC组的血清E(326.52、22.80 pmol/L)和尿E(38.91、11.49 pmol/L)水平;而PTC+高E₃组仅血清E₃水平(12.17 pmol/L)显著低于PTC组(23.05 pmol/L);高E₃组的尿E₃水平显著低于低E₃组(6.92、8.94 pmol/L);低E₃组的尿E₃水平显著高于对照组(8.94、7.17 pmol/L),PTC组、FTC组和ATC组的血清E₃水平显著高于对照组和高E₃组(23.05、26.52、22.80比13.23、14.46 pmol/L)。②各组血清FT3水平比较差异没有统计学意义。各组血清FT4和TSH水平与对照组比较,差异均有统计学意义,其中各实验组的FT4水平均显著低于对照组,TSH水平均显著高于对照组,但PTC组与PTC组+高E₃组、FTC组与FTC+高E₃组、ATC组与ATC+高E₃组分别进行两两比较,FT4和TSH水平并差异无统计学意义。③各组裸鼠血清TgAb和TpoAb水平比较差异均有统计学意义。其中低E₃组、高E₃组、PTC+高E₃组、FTC组、ATC组和ATC+高E₃组的TgAb水平均显著高于对照组;各实验组的TpoAb水平均显著高于对照组。④各组裸鼠尿碘水平比较差异没有统计学意义。⑤各组裸鼠肿瘤体积大小比较差异均有统计学意义,PTC+高E₃组与PTC组比较,在接种肿瘤后的第7 d、16 d、25 d、28 d和37 d,肿瘤体积发生显著性差异(71.54、226.05、730.26、893.34、1242.12比49.87、325.50、551.28、664.38、967.78 mm³);FTC+高E₃组与FTC组比较,在接种肿瘤后的第25 d、28 d、37 d和40 d,肿瘤体积发生显著性差异(392.60、475.70、794.68、943.51比214.82、238.32、422.19、490.00 mm³);ATC+高E₃组与ATC组比较,在接种肿瘤后的第37 d和40 d,肿瘤体积发生显著性差异(217.53、432.10比577.19、1146.66 mm³)。结论外源性雌三醇能够诱导裸鼠发生甲状腺功能减退和抗体水平增高,同时对乳头状甲状腺癌和滤泡状甲状腺癌的生长有着促进作用,对未分化甲状腺癌的生长有抑制作用。     

肺结节患者的临床特征在判断良恶性中的意义

目的探究肺结节特点与其病理结果的相关性,分析患者临床特征（临床因素、检验结果、胸部CT影像特征）对判断肺结节良恶性的临床意义。 方法回顾性分析147例肺结节患者,根据病理活检结果分为良性组39例,恶性组108例。比较两组患者的一般情况（性别、年龄、吸烟史、恶性肿瘤家族史）、肺癌4项[癌胚抗原（CEA）、鳞状上皮细胞抗原（SCCAg）、神经元特异性烯醇化酶（NSE）、细胞角蛋白19片段（Cyfra21-1）]以及高分辨率CT征象,评估差异有统计学意义的因素在鉴别良恶性肺结节中的效能。 结果两组患者在性别、吸烟史、4个肺癌指标（CEA、SCCAg、NSE、Cyfra21-1）、结节大小、结节边缘、毛刺征的比较,差异均无统计学意义（均P＞0.05）,在年龄、恶性肿瘤家族史、结节形态、分叶征、空泡征、胸膜牵拉征、血管集束征的比较,差异均有统计学意义（均P＜0.05）。在高分辨率CT征象中,分叶征对判断肺结节良恶性的效能最高,敏感度达79.6%。Logistic线性回归分析显示磨玻璃结节、分叶征、空泡征都是恶性的危险因素（均P＜0.05）。 结论患者的年龄、恶性肿瘤家族史、结节形态（磨玻璃结节）、分叶征、空泡征、胸膜牵拉征、血管集束征对鉴别肺结节良恶性有一定的参考意义。     

131I的电离辐射对甲状腺功能早期影响的研究

目的探讨131I的电离辐射与甲状腺组织功能早期改变的关系,如血清TNF、IL-1β、IL-6、IL-8等细胞因子水平变化以及甲状腺组织本身的病理改变等.方法选用兔作动物实验(15只),分别在0、6、24、48、72h及1周时抽血做IL-1β、IL-8测定,并每次随机处死1～2只兔以做病理切片观察,1周时同时做甲功测定(TT3、TT4、FT3、FT4)并与0h比较.17例病情中及重度甲亢患者用治疗剂量的131I治疗(每人次用量146.2～469.9MBq,平均267.5MBq),治疗前和治疗后4～7天抽血做TNF、IL-1β、IL-6和IL-8测定.结果①使用131I6h后即可见兔血清IL-1β增高(P<0.05),IL-8于48h达高峰(P<0.01),两种细胞因子于1周时皆降低到0h水平(P>0.05).1周内兔血清甲状腺激素水平无明显变化(P>0.05).②甲亢患者131I治疗前后血清细胞因子的变化与兔有所不同,TNF无明显变化(P>0.05),IL-6和IL-8升高(P<0.05),而IL-1β反而降低,且差异显著(P<0.05).③摄取131I后兔甲状腺组织在不同时间内呈现不同的病理改变.结论①甲状腺组织摄取一定剂量的131I在不同时间内呈现不同的病理改变,但短期内甲状腺激素水平无明显变化.②某些细胞因子IL-1β、IL-6、IL-8等似可用作观察甲状腺组织对131I辐射效应反应的指标,但其临床价值有待于进一步探讨.     

Thyroid hormones,Sertoli cell proliferation and differentiation in progenies from carbamazepine-treated rat dams during pregnancy and lactation

Carbamazepine (CBZ) is used in the control of seizure and affective disorders, causing hypothyroidism. Thyroid hormones regulate the Sertoli cell proliferation and differentiation. Clinical aspects must be considered since epileptic fertile women need to continuously use CBZ during pregnancy and lactation. This study aimed to evaluate the effects of CBZ on testis development of rat offspring from dams treated during pregnancy/lactation. Rat dams received CBZ (20 mg kg⁻¹ day⁻¹) or vehicle by intra-peritoneal route during gestation and lactation. Progenies were euthanised at 4, 14, 41, 63 and 93-days post-partum (dpp) for the evaluation of T3, T4 and TSH plasma total levels. Testicular cross sections were submitted to anti-Ki67, anti-PCNA, anti-p27^kip1 and anti-transferrin immunolabelling for the evaluation of Sertoli cells. There was a significant reduction in p27^kip1-positive Sertoli cell numerical densities and an increase in TSH level at 14 dpp. CBZ exposure affected the volume density of transferrin-positive immunolabelling at 63 dpp. These results suggest that CBZ may cause a dysregulation of the controller system of thyroid hormones homeostasis leading to an increase in the proliferation rate at the neonatal phase and a differentiation delay of the Sertoli cell, culminating in an altered function at late puberty. The occurrence of hypothyroidism cannot be completely discarded.     

Investigation and management of the neck lump

A neck lump is a common presenting sign in both the paediatric and adult population and may represent a broad range of benign or malignant diagnoses. The appropriate initial assessment, investigation and management is key to delivering appropriate treatments and to avoid missing potentially serious diagnoses. There is a range of imaging modalities available to the treating clinician and huge variability in the appropriate surgical or non-surgical management of disease. In this article we discuss the approach to the assessment of patients with a neck lump, including the history and examinations which should take place. We discuss the imaging modalities which are most appropriate for each condition and the range of management options available. Both common and rarer diagnoses are discussed through the course of the review.     

Is patient age associated with risk of malignancy in a ≥4 cm cytologically benign thyroid nodule?

BackgroundCurrent data regarding the risk of malignancy in a large thyroid nodule with benign fine-needle aspiration biopsy(FNAB) is conflicting. We investigated the impact of patient age on the risk of malignancy in nodules≥4 cm with benign cytology.MethodsWe performed a single-institution retrospective review of patients who underwent surgery from 07/2008–08/2019 for a cytologically benign thyroid nodule ≥4 cm. The relationship between malignant histopathology and patient and ultrasound features was assessed with multivariable logistic regression.ResultsOf 474 nodules identified, 25(5.3%) were malignant on final pathology. In patients <55 years old, 21/273(7.7%) nodules were malignant, compared to 4/201(2.0%) in patients ≥55. Patient age ≥55 was independently associated with significantly lower risk of malignancy(OR:0.2,95%CI:0.1–0.7,p = 0.011). Increasing nodule size >4 cm and high-risk ultrasound features were not associated with risk of malignancy(OR:1.0,95%CI:0.7–1.4,p = 0.980, and OR:9.6,95%CI:0.9–107.8,p = 0.066, respectively).ConclusionsPatients <55 years old are 3.7-fold more likely to have a falsely benign FNA biopsy in a nodule≥4 cm.