亚临床甲状腺功能减退症的治疗

亚临床甲状腺功能减退症(亚甲减)以基线促甲状腺激素(TSH)水平升高和血清游离甲状腺素水平正常为特征,亚临床或隐匿性甲减常常反映甲状腺激素分泌的缺陷。甲状腺破坏性治疗(甲状腺次全切除术或放射碘治疗)或颈部广泛放射治疗后的亚临床甲减应开始使用左甲状腺素(L-T4)治疗;妊娠和哺乳期的亚甲减也应使用L-T4治疗。其他早期使用甲状腺激素替代治疗的指征包括TSH水平升高以及抗甲状腺过氧化物酶(TPO)抗体阳性,因为这些患者的亚甲减很可能进展为临床甲减。提示存在甲状腺激素相对缺乏的临床体征和症状的所有患者都应该试用L-T4替代治疗,这些患者包括亚临床甲减并发不孕、抑郁症或其他神经心理异常。单纯血清TSH水平升高或高胆固醇血症不是L-T4治疗的适应症,除非患者有甲状腺疾病史以及提示甲状腺激素缺乏的临床症状。     

亚临床甲状腺早衰症与不良妊娠结局

目的由于人类甲状腺也会逐渐衰老,甲减发病率持续上升,因此早期干预,尤其是妊娠期甲状腺衰老的积极治疗,对于预防身体过早衰老有重要的价值。本研究同时探讨经左旋甲状腺素(L-T4)替代治疗的亚临床甲状腺早衰症(甲减)对妊娠结局及胎儿的影响。方法选取2017年1月至2018年12月于北京医院分娩的妊娠期亚临床甲状腺早衰症(甲减)并接受L-T4替代治疗的孕妇共144例,作为观察组。并随机选取同期分娩的甲状腺功能正常的孕妇共150例,作为对照组。比较两组间年龄、孕前体质量指数(BMI)、甲状腺过氧化物酶抗体(TPOAb)、甲状腺球蛋白抗体(TGAb),妊娠期贫血、妊娠期糖尿病、妊娠期高血压疾病、自然流产史、不孕症病史、早产、胎膜早破、产后出血、新生儿低Apgar评分及胎儿生长受限的差异性。结果亚临床甲状腺早衰症组甲状腺自身抗体及不孕症病史阳性率较对照组显著升高,妊娠期贫血发生率较对照组降低。两组间年龄、BMI、其他妊娠合并症发生率及胎儿结局无显著性差异。结论甲状腺自身抗体阳性是妊娠期亚临床甲状腺早衰症的重要发病因素。当以TSH≥4.0mIU/L为诊断标准时,经过L-T4替代治疗的妊娠期亚临床甲状腺早衰症孕妇妊娠合并症风险较甲状腺功能正常孕妇无明显升高,妊娠期无需增加产前检查频次。因此针对妊娠期甲状腺衰老的积极治疗,对于抗衰老有重要意义。     

亚临床甲状腺功能减退症的治疗

亚临床甲状腺功能减退症(亚甲减)以基线促甲状腺激素(TSH)水平升高和血清游离甲状腺素水平正常为特征，亚临床或隐匿性甲减常常反映甲状腺激素分泌的缺陷。甲状腺破坏性治疗(甲状腺次全切除术或放射碘治疗)或颈部广泛放射治疗后的亚临床甲减应开始使用左甲状腺素(L-T4)治疗；妊娠和哺乳期的亚甲减也应使用L-T4治疗。其他早期使用甲状腺激素替代治疗的指征包括TSH水平升高以及抗甲状腺过氧化物酶(TPO)抗体阳性，因为这些患者的亚甲减很可能进展为临床甲减。提示存在甲状腺激素相对缺乏的I临床体征和症状的所有患者都应该试用L-T4替代治疗，这些患者包括亚临床甲减并发不孕、抑郁症或其他神经心理异常。单纯血清TSH水平升高或高胆固醇血症不是L-T4治疗的适应症，除非患者有甲状腺疾病史以及提示甲状腺激素缺乏的临床症状。     

妊娠期甲状腺功能减退症诊治进展

研究表明妊娠期临床甲状腺功能减退症(简称甲减)会增加妊娠不良结局的风险,亚临床甲减也可能有类似影响。其诊断应采用TSH和FT4的妊娠三期及方法特异性参考范围进行。最新研究提示评价妊娠4~6周TSH可采用与非妊娠妇女相同参考范围。妊娠期临床甲减必须治疗。妊娠期亚临床甲减伴TPOAb阳性者应接受L-T4治疗,但不必考虑终止妊娠。     

妊娠期甲状腺功能减退症的研究进展

妊娠期间由于血清甲状腺素结合球蛋白、人绒毛膜促性腺激素水平增加以及肾脏对碘的清除率增加等,致使妊娠期甲状腺激素的产生、循环、代谢和调节会随妊娠的不同阶段而改变.这为妊娠期间甲状腺疾病的诊断和治疗带来困难.因此,建立妊娠特异性血清甲状腺激素的正常参考范围非常必要,这将降低妊娠期甲状腺疾病的漏诊率和误诊率.妊娠期母体甲状腺功能不足包括临床甲状腺功能减退症(甲减)、亚临床甲减和低甲状腺素血症,可以对后代的神经智力发育造成损伤.妊娠期甲减妇女应该接受左甲状腺素(L-T4)替代治疗,治疗目标为血清促甲状腺激素(TSH)水平在妊娠早期不超过2.5 mIU/L;妊娠中期和妊娠晚期不超过3.0 mIU/L或者不超过妊娠期特异性血清TSH的正常参考范围.     

倡导妊娠期甲状腺疾病筛查,保护后代智力发育

临床前瞻性观察和动物实验研究均表明妊娠早期亚临床甲状腺功能减退症能够导致后代智力受损,及时诊断和有效的治疗有可能预防这些危害.所以,我们建议在妊娠早期(最好在妊娠8周前)对妇女、特别是对有甲状腺疾病危险因素的妇女积极筛查甲状腺功能,对妊娠期亚临床甲减妇女进行左旋甲状腺素(L-T4)干预治疗,启动时机应当在12周前,干预期间需要密切监测甲状腺功能,及时调整L-T4剂量,尽早达标,以保证正常的胎儿脑发育和后代智力发育.     

老年甲状腺功能减退症的管理

老年人的下丘脑-垂体-甲状腺轴功能下降.老年甲状腺功能减退症(甲减)患病率高,在诊断和治疗方面存在诸多的争议,是目前的研究热点.老年甲减的临床表现不典型,往往合并多种疾病.亚临床甲状腺功能减退对老年人心血管、认知、生活质量和寿命的影响和左旋甲状腺素片(L-T4)替代治疗获益不确定.年龄特异性促甲状腺激素(TSH)参考值...     

左旋甲状腺素治疗妊娠期亚临床甲减妇女对后代神经智力发育影响的前瞻性研究

目的 通过前瞻性观察妊娠期亚临床甲状腺功能减退(甲减)妇女左旋甲状腺素(L-T4)治疗后甲状腺功能指标的动态变化和后代神经智力的发育情况,探讨L-T4对妊娠期亚临床甲减妇女后代神经智力发育的影响.方法17例亚临床甲减孕妇未接受治疗(SCH组),23例亚临床甲减孕妇接受L-T4治疗(SCH+LT4组),24例正常孕妇(C组)作为对照组.3组孕妇分别在妊娠12周(G12)、16周(G16)、20周(G20)、24周(G24)、28周(G28)、32周(G32)和(或)36周(G36)接受随访检查,检测血清TSH、TT4、FT4、TT3、FT3、甲状腺过氧化物酶抗体(TPOAb)和甲状腺球蛋白抗体(TgAb).应用Bayley量表对所有孕妇的后代在14～30月龄检测智力和运动评分.结果SCH组、SCH+LT4组和C组孕妇后代的智力发育指数(MDI)分别为115.12分、118.56分和117.63分;运动发育指数(PDI)分别为115.47分、120.65分和117.50分.与其他两组比较,SCH+LT4组MDI和PDI评分均较高,SCH组MDI和PDI评分均较低,但3组间比较没有统计学差异.SCH组孕妇的血清TSH在妊娠过程中始终保持在2.0 mIU/L以上,各时点都明显高于C组(均P＜0.05);血清TT4和FT4水平除G28和G32外其他时点均略低于同时点C组水平.SCH+LT4组孕妇基础血清TSH水平明显高于其他两组(均P＜0.01),血清TT4和FT4水平则低于其他两组;在接受L-T4治疗后血清TSH水平明显下降,自G12至孕末期始终与C组水平相当,且低于同时点SCH组孕妇的水平;血清TT4和FT4水平则明显升高至与对照组相当的水平.结论L-T4的及时治疗能够维持妊娠早期亚临床甲减患者妊娠全程血清TSH在正常水平,这很可能会避免后代智力和运动能力发育水平的下降.     

老年亚临床甲状腺功能减退症的诊治特点

亚临床甲状腺功能减退症(甲减)是老年人群常见的疾病.诊断标准为血清促甲状腺激素(TSH)水平升高伴游离甲状腺素(FT4)水平正常.TSH正常值上限随年龄增长而升高,但临床上尚缺乏根据年龄调整的TSH正常值范围.老年亚临床甲减与老龄化症状极为相似,易于被忽视.持续性亚临床甲减可对老年人心血管、认知、肌肉骨骼等方面带来负面影响,而TSH小于10 mIU/L的轻度亚临床甲减可能与75岁以上老人长寿相关.老年亚临床甲减的治疗应该强调个体化,TSH大于10 mIU/L或存在其他危险因素时,应给予左旋甲状腺素(L-T4)治疗.初始剂量推荐25～75μg/d,每4～6周根据TSH水平和临床表现调整剂量,至维持剂量后每6～12个月监测甲状腺功能.     

亚临床甲状腺功能减退症与妊娠

妊娠期亚临床甲状腺功能减退症(甲减)的患病率较高,美国流行病调查显示约占妊娠妇女的2%~5%。多项研究证实妊娠妇女患亚临床甲减可影响其后代的智力发育,并可能产生各种产科并发症。妊娠期亚临床甲减影响后代智力发育的确切机制尚不清楚。专家多主张对血清促甲状腺激素升高的孕妇或计划怀孕的妇女,应及时给予左旋甲状腺素治疗。但是对于妊娠期妇女是否应常规进行亚临床甲减的筛查仍存在争议,另外左旋甲状腺素替代治疗的效果还需大量循证医学资料来证实。     

The immunoneuroendocrine role of melatonin

Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.     

Response of rat pineal melatonin to calcium, magnesium, and lithium is circadian stage dependent

Abstract: Herein we documented the response of pineal melatonin production to electrolytes known to be effective on pineal function in view of a possible circadian stage dependence. We studied the release of melatonin by perifused rat pineal glands at 2 different circadian stages corresponding to the middle of the light and dark periods, i.e., respectively, 7 and 19 HALO (Hours After Light Onset, L:D = 12:12). The initial efflux rates were, as expected, much higher in the perifusates of glands removed from rats sacrificed during the dark phase than of those removed during the light phase. After 3 hr of perifusion, melatonin release reached similar levels which were found constant up to the 8th hr of perifusion, whatever the circadian stage. Perifusion of the glands with physiological concentrations for the rat of calcium (5.2 mmol/1) and magnesium (1.34 mmol/1) resulted in a stimulatory effect on the pineal glands removed from rats sacrificed in the middle of the dark period (19 HALO), whereas no effects were observed on the pineal glands removed from rats sacrificed during the light (7 HALO). Lithium (0.28 and 0.55 mmol/1) was ineffective on melatonin release in pineal glands removed 7 and 19 HALO. Our results show differences in the initial efflux rates of melatonin and in the response of perifused pineal glands to calcium and magnesium according to the circadian stage.     

Changes in connexin43, the gap junction protein of astrocytes, during development of the rat pineal gland

Abstract: The abundance of gap junctions between rat pineal astrocytes formed by connexin43 (Cx43) was studied during development. Levels and distribution of Cx43 were measured by immunoblotting and indirect immunofluorescence, respectively. The amount of Cx43 in cells located within the gland was low until about the 7th postnatal day and increased to adult values between the 14th and 21st days postpartum. Although astrocytes, recognized by their vimentin immunoreactivity, were scarce before birth, they were abundant by the 7th postnatal day suggesting that the low levels of Cx43 found at this age corresponded to a low expression of this protein. Localization of the immunoreactivity to Cx43 and vimentin showed a close correlation, indicating that mature or immature pineal astrocytes form gap junctions made of Cx43. Since Cx43 levels attained their adult values at about the time the innervation and the functional state of the gland reached maturity (2–3 weeks after birth), it is proposed that astrocyte gap junctions are involved in the function of the adult rat pineal gland.     

Conservative management of perforated duodenal diverticulum： A case report and review of the literature

Duodenal diverticula are a relatively common condition. They are asymptomatic, unless they become complicated, with perforation being the rarest but most severe complication. Surgical treatment is the most frequently performed approach. We report the case of a patient with a perforated duodenal diverticulum, which was diagnosed early and treated conservatively with antibiotics and percutaneous drainage of secondary retroperitoneal abscesses. We suggest this method could be an acceptable option for the management of similar cases, provided that the patient is in good general condition and without septic signs.     

Presence of immunoreactive growth hormone and prolactin in the ovine pineal gland

Abstract: The use of antisera raised against bovine growth hormone (GH) and ovine prolactin (PRL) enabled the detection of related immunoreactive (ir) sequences of proteins in ovine pineal tissue. The isolation of PRL-like ir-material was accomplished using a 0.25 M ammonium sulphate (pH 5.5) extraction followed by ethanol precipitation, whereas the resulting 2.0 M ammonium sulphate (pH 7.0) precipitate contained a GH-like immunoreactivity. Gel chromatography of the GH-like immunoreactivity (Sephadex G-100) indicated the presence of several GH-like fragments ranging in the M_r range of 7,000 to 55,000. Analyses of the PRL-like ir-material found in pineal tissue on HPLC using a TSK 545-DEAE column led to the resolution into a single peak of immunoreactivity. A single peak of activity was also observed following chromatofocusing and hydrophobic interaction chromatography of the ir-peak from the TSK 545-DEAE column. The PRL-like ir-material inhibited the binding of [¹²⁵I]ovine PRL-S14 to anti-ovine PRL antibodies without showing an affinity for binding to anti-rat PRL or anti-bovine GH antibodies. Scatchard analysis of the binding of pineal PRL-like ir-material and pituitary ovine PRL-S14 to liver membranes from day-20 pregnant rats revealed similar affinity constants (K_a of 4.7 ± 0.2 × 10⁹ M^-1). In addition, the replication of Nb 2 Node rat lymphoma cells was stimulated by pineal PRL-like ir-material, an effect known to be specific for lactogenic hormones. The pineal PRL-like immunoreactivity appeared on sodium dodecyl sulfate polyacrylamide gels as a single major band of M_r 24,000. The functional status of PRL-and GH-like ir-material in the ovine pineal remains to be determined, but evidence is presented that the overall protein synthesis rate of the rat pineal responded to circulating concentrations of PRL.     

Microbiology of human immunodeficiency virus anorectal disease

PURPOSE: Individuals who are seropositive for the human immunodeficiency virus are at high risk for opportunistic infection and anorectal disorders. Little prospective information is available regarding anorectal pathogens in these patients. METHODS: One hundred sixty-three HIV-seropositive patients presented to the colorectal clinic between 1989 and 1992. Forty-seven (29 percent) patients were thought to have an infectious process and were prospectively studied using a standardized multiculture protocol. RESULTS: Mean age was 33 (range, 19–59) years. All were male; high-risk behavior accounted for 87 percent of HIV transmissions. Presenting complaints included anorectal pain (79 percent), pus per anum (28 percent), and blood per anum (26 percent). Examination revealed perianal tenderness (60 percent), condyloma (38 percent), perianal ulcers (38 percent), and anal fissures (34 percent). Sixty-six sets of cultures were performed; 28 patients had one set, 15 had two sets, and 4 had three sets. Thirty-two of these 47 patients (68 percent) had positive cultures including herpes (50 percent), cytomegalovirus (25 percent),Neisseria gonorrhoeae (16 percent), chlamydia (16 percent), acidfast bacilli (2 percent), and others (9 percent). Six of 32 patients with positive cultures had more than one organism cultured. Sixteen (50 percent) patients with positive cultures were treated medically, 8 (25 percent) were treated surgically and 8 (25 percent) were treated with both modalities. Sixty-one procedures were performed on 17 patients for condylomata. Eighteen patients had 20 procedures for abscesses, 50 percent of whom had positive cultures for other than common bowel flora; all improved. Fourteen patients underwent 33 procedures for perianal fistulas.Mycobacterium fortuitum was cultured from one patient who required 13 procedures for abscesses and fistulas. Forty-five (96 percent) patients were followed for an average of 12.5 months ±2.9 SEM (range, 1–94 months). Symptoms were improved or resolved in 22 of 32 (69 percent) patients with positive cultures and in 11 of 13 (84 percent) with negative cultures. CONCLUSIONS: Specific pathogens may often be identified in human immunodeficiency virus-seropositive patients with anorectal disorders if aggressively sought. Although patients without specific pathogens identified may be expected to improve with planned empiric treatment, positive identification allows more directed therapy.