Ergocalciferol

*仅供医学专业人士阅读参考GC联合放疗后仍活动的TED，替妥尤单抗N01提供治疗新选择。甲状腺眼病（TED），又称甲状腺相关眼病（TAO），是与甲状腺疾病密切相关的器官特异性自身免疫性疾病，位居成人眼眶疾病发病率首位[1]。TED的病理机制涉及胰岛素样生长因子-1受体（IGF-1R）和促甲状腺激素受体（TSHR）在眼眶成纤维细胞表面的协同激活，导致成纤维细胞增殖、脂肪化及透明质酸大量分泌，最终引起眼球突出、复视、软组织炎症乃至视神经压迫[2]。长期以来，糖皮质激素（GC）静脉冲击治疗是中重度活动期TED的一线方案，但其对已形成的眼球突出改善有限，且部分患者存在激素抵抗或不耐受，临床亟需更有效的治疗手段[3]。替妥尤单抗N01作为中国首个获批的IGF-1R靶向抗体药物，通过阻断IGF-1R信号通路，从上游抑制眼眶成纤维细胞的增殖与脂肪化，为TED患者提供了从“以控制炎症为主”到“控制炎症并显著回退突眼”的全新治疗选择[4]。本期，河北医科大学第二医院内分泌科孟凤苓教授分享一例长病程、糖皮质激素联合放疗后仍处于活动期的中重度TED患者的诊疗经过，系统展示替妥尤单抗N01治疗后的多维度显著获益，并由赵占胜教授进行深度点评，以期为临床实践提供参考。病例介绍：一例长病程难治性年轻TED患者的诊疗经过01基本信息患者，男性，26岁。主诉：心悸、多汗伴发作性软瘫2年余，双眼球突出1年9月余，加重伴复视1年7月余。现病史：患者2023年5月因心悸、多汗伴发作性软瘫就诊于我院急诊，查血钾降低、甲状腺功能亢进，确诊为Graves病甲亢并低钾性周期性麻痹，经补钾及抗甲状腺药物治疗后软瘫好转，此后未再发作，规律服用甲巯咪唑并定期复查调整剂量。2023年10月起出现双眼球突出，伴畏光、流泪，因不影响工作未予重视。2023年12月突眼加重，出现眼痛、复视并影响日常工作，就诊我科门诊，诊断甲状腺相关眼病，临床活动度评分（CAS）5分；查TSH 0.014 mIU/L，FT3 6.93 pmol/L，FT4 18.35 pmol/L，TRAb 32.9 IU/L，25-羟维生素D 13.5 nmol/L（缺乏）。予甲巯咪唑5 mg口服，每日一次，补充维生素D，并嘱戒烟，建议择期住院规范行大剂量糖皮质激素冲击治疗。2025年7月因严重突眼和复视影响工作而再次就诊我科，眼病CAS评分4分，EUGOGO分级甲状腺眼病中重度，于2025年7月21日收入院。甲状腺眼病既往治疗史：2024年1月12日患者首次因甲状腺眼病入住我科，CAS评分5分，当日99mTc-DTPA眼眶SPECT/CT显像提示符合活动期甲状腺眼病表现。2024年1月15日至3月10日于我科完成8次甲泼尼龙标准冲击治疗（累积剂量3.5 g），眼红、畏光、流泪有所减轻，但眼球突出及复视改善不明显。经放疗科会诊后，2024年4月25日至5月9日在我院放疗科完成后续甲泼尼龙冲击治疗（每3天一次、每次0.5 g，共3次，结束时累积总量5.0 g）联合球后放疗10次，诉双眼憋胀及复视略好转，但突眼较前变化不大，此后未再针对眼病行特殊治疗。家族史：无甲状腺疾病家族史，无高血压、糖尿病等慢性病家族史。入院体格检查：血压102/73 mmHg，心率75次/分，体温36.2℃，呼吸18次/分，体重80 kg，体质指数（BMI）25.53 kg/m2；甲状腺II度肿大，质地中等，未触及结节，未闻及血管杂音；无胫前黏液性水肿。02眼部专科检查（入院后）患者入院后接受了全面的眼科检查，结果如下（表1）：表1 入院后眼部专科检查图1 患者入院时双眼外观03辅助检查（入院后）▌3.1 实验室检查表2 入院后实验室检查▌3.2 影像学检查（2025-7-23）（1）甲状腺超声：甲状腺体积增大，弥漫性病变，血流较丰富，请结合甲功甲状腺右叶囊性，囊实混合性结节， TI-RADS 3级（2）眼眶99mTc-DTPA SPECT/CT显像：CT示双侧眼球突出（右侧2.6 cm、左侧2.4 cm），双侧眼外肌（直肌）肌腹不同程度增粗，最粗处分别约右侧（cm）：下0.9（1.1），内1.0（0.6），上0.7（0.6），外0.8（1.3）；左侧（cm）：下0.9（1.0），内1.1（0.8），上0.6（0.5），外 0.7（1.1）*。SPECT示双侧下直肌、内直肌、上直肌及视神经显像剂浓聚增强，以内直肌为著，邻近脂肪间隙及眶周软组织显像剂浓聚稍增强，符合甲状腺相关眼病炎性活动期表现。*与2024年1月12日治疗前图像相比，双侧眼外肌肌腹较前增粗（红色标注），提示经一线治疗眼眶炎症并未得到有效控制。图2 治疗前眼眶SPECT/CT显像04入院诊断甲状腺相关眼病（中重度，活动期CAS 4分）；Graves病，甲状腺功能亢进症；甲状腺结节。05替妥尤单抗N01治疗经过及预后鉴于患者为中重度活动期TED，且既往足量GC冲击联合球后放疗后突眼、复视改善不明显，属典型的GC抵抗/难治性患者。完成治疗前评估（听力、血糖、糖化血红蛋白、肝肾功能、感染筛查等）并与患者充分沟通后，决定启用替妥尤单抗N01注射液治疗。治疗方案：采用替妥尤单抗N01注射液静脉输注，首剂负荷剂量10 mg/kg，后续维持剂量20 mg/kg，每3周一次，共完成8次输注。疗效评估：治疗期间及治疗后，患者眼部症状及客观指标呈现持续且显著的改善，具体动态变化如下：表3 替妥尤单抗N01治疗前后关键指标变化图3 替妥尤单抗N01治疗前后双眼外观对比影像学变化：第4次治疗后（2025年10月14日）复查SPECT/CT，双侧眼球突出度均降至约1.9 cm，眶周软组织肿胀及显像剂异常浓聚基本消失，双侧眼外肌增粗伴显像剂浓聚较前明显减轻，报告提示“治疗后明显好转”。第8次治疗后（2026年1月21日）再次复查，双侧眼球稍突出，伴泪腺部分脱垂，较前变化不大；双侧眼外肌增粗伴显像剂浓聚增强，右侧为著，较前明显减轻，双侧视神经稍粗伴显像剂浓聚略强，较前减轻，提示“治疗后明显好转”。图4 治疗前后眼眶SPECT/CT对比（第4次后及第8次后眼外肌增粗及显像剂浓聚较治疗前明显减轻）疗效总结：完成8次替妥尤单抗N01治疗后，患者双眼突眼度（CT测量）分别回退7 mm（右）和5 mm（左），CAS自4分降至0分，眼睑水肿、结膜充血水肿、泪阜肿胀等软组织炎症全部消退，眼压由24.3/28.7 mmHg降至11.5/12.8 mmHg，右眼眼球运动恢复至各方向不受限，左眼向外运动仍受限，复视明显减轻，仅残留左眼内斜所致复视，计划半年后行斜视矫正手术。06不良反应及随访治疗期间患者依从性好，观察到治疗后IGF-1和血尿酸持续升高，谷丙转氨酶一过性升高，结束治疗后一月余恢复正常；左眼视力一过性下降（最低降至0.6），三次治疗后恢复如初。未观察到听力损伤、肌肉痉挛等严重不良反应。第8次治疗后随访4月余（截至2026年4月21日复查），患者甲功稳定（TSH 1.62 mIU/L，FT3 5.51 pmol/L，FT4 19.88 pmol/L），TRAb降至3.69 IU/L。目前甲巯咪唑每日2.5 mg（服2天停1天），每周口服维生素D2软胶囊5000单位。内分泌科规律随访甲功及TRAb，眼科随访视力、斜视、复视变化，择期手术干预。专家点评：突破GC抵抗困境，靶向IGF-1R为年轻难治性TED患者带来深度缓解该病例为26岁青年男性，TED病程1年9个月，初诊TRAb 32.9 IU/L，伴吸烟、维生素D严重缺乏及甲亢性低钾性周期性麻痹。一线甲泼尼龙累积5.0 g联合球后放疗后，突眼与复视无明显改善，CAS仍为4分，双眼突眼度CT测量达26/24 mm，核素显像提示眼外肌较治疗前增粗，符合二线治疗启动指征[1]。综合考虑其GC抵抗状态及持续活动性，启用替妥尤单抗N01是合理的治疗选择。替妥尤单抗N01在本病例中展现了多维度的显著疗效。炎症控制方面，CAS由4分降至0分，结膜水肿、泪阜肿胀于第2~3次输注后转阴，第4次SPECT/CT显示眶周软组织肿胀与显像剂浓聚基本消失。突眼回退方面，右眼回退7 mm、左眼回退5 mm，幅度显著超过OPTIC研究中安慰剂组不足0.5 mm的自然波动[5]，亦优于糖皮质激素对突眼改善有限的历史印象[3]。眼压方面，治疗前24.3/28.7 mmHg，疗程结束降至11.5/12.8 mmHg，提示其可能对TED相关高眼压具有针对病因的治疗价值[1]。上述三重获益共同说明，替妥尤单抗N01不仅控制活动期炎症，也能改善部分已形成的眼眶结构改变，机制上与其阻断IGF-1R、抑制成纤维细胞脂肪化及透明质酸合成有关[2,4]。安全性方面，治疗期间IGF-1持续升高，符合IGF-1R阻断后下丘脑-垂体轴负反馈解除的预期药理反应[4]；血尿酸升高、谷丙转氨酶一过性升高及左眼视力一过性下降均在停药或对症处理后恢复，未影响疗程。随着靶向治疗证据的积累，TED的治疗目标已从单纯控制炎症，扩展为兼顾突眼回退、外观恢复与视功能保护的综合管理。本例为年轻、多重危险因素叠加的GC抵抗型TED提供了可借鉴的全程管理范本。病例提供专家简介孟凤苓 教授河北医科大学第二医院内分泌科主任医师、教授，医学硕士，硕士研究生导师曾任河北省康复医学会心身医学分会常委白求恩精神研究会内分泌和糖尿病学分会理事曾获全国医师辩论赛“最佳辩手”及河北医科大学第8届教师授课二等奖主编和参编医学著作7部以第1作者发表学术论文30余篇作为第一助理研究者高质量完成科室十余项国际多中心3期、国内多中心2期、3期GCP临床研究点评专家简介赵占胜 教授河北医科大学第二医院内分泌科主任，医学博士、硕士生导师日本金泽医科大学访问学者中华医学会内分泌学分会青年委员会第九届委员会 委员中国医药教育协会糖尿病专业委员会 副主任委员中国医师协会科学普及分会内分泌学组 副组长中国医师协会介入医师分会超声介入专家工作组甲状腺介入学组 常务委员中华中医药学会络病分会 常务委员北京整合医学学会内分泌眼病专业委员会 常务委员河北省医学会糖尿病学分会 候任主任委员河北省预防医学会内分泌代谢与甲状腺疾病防治专业委员会 主任委员河北省药学会内分泌代谢药物专业委员会 主任委员河北省数理医学学会内分泌代谢与体重管理专业委员会 主任委员河北省医院协会糖尿病足防治专业委员会 主任委员河北省医师协会内分泌代谢科医师分会 副主任委员中国动脉硬化杂志特约审稿专家，河北医药杂志编委参考文献：[1]中华医学会眼科学分会眼整形眼眶病学组，等. 中国甲状腺相关眼病诊断和治疗指南（2022年）[J]. 中华眼科杂志, 2022, 58(9): 646-668.[2] Krieger CC, et al. TSH/IGF1 receptor crosstalk: mechanism and clinical implications[J]. Pharmacol Ther, 2020, 209: 107502.[3] Burch HB, et al. Management of Thyroid Eye Disease: A Consensus Statement by the American Thyroid Association and the European Thyroid Association[J]. Thyroid, 2022, 32(12): 1439-1470.[4] 北京医院国家老年医学中心，中国医药教育协会老年药学专业委员会. 甲状腺眼病的生物制剂治疗专家共识[J]. 临床药物治疗杂志, 2025, 23(3): 1-10.[5] Douglas RS, et al. Teprotumumab for the Treatment of Active Thyroid Eye Disease[J]. N Engl J Med, 2020, 382(4): 341-352.“此文仅用于向医疗卫生专业人士提供科学信息，不代表平台立场”

Not all vitamin D supplements are created equal, and new research suggests that one popular form may have an unexpected downside. Scientists found that taking vitamin D2 can actually lower the body's levels of vitamin D3, the form naturally produced by sunlight and more effective at boosting overall vitamin D. Previous studies also suggest that vitamin D3 may provide stronger immune protection against viruses and bacteria.A common vitamin D supplement may have an unexpected effect inside the body. Research published in 2025 found that taking vitamin D2 can reduce levels of vitamin D3, the form humans naturally make when skin is exposed to sunlight. That distinction matters because vitamin D2 and vitamin D3 are often treated as interchangeable sources of the same nutrient. Both can increase overall vitamin D status, but a growing body of evidence indicates that D3 is generally more effective at raising and maintaining the main form of vitamin D measured in the blood. Current guidance from the U.S. National Institutes of Health reflects that evidence, noting that D3 tends to raise vitamin D levels more and keep them elevated for longer than D2. Vitamin D is essential for helping the body absorb calcium and maintain healthy bones. It also plays roles in muscle, nerve, and immune function. In the UK, people are advised to consider taking 10 micrograms (µg) of vitamin D each day during the darker months, when sunlight is generally too weak for the skin to make enough of the vitamin. Vitamin D2 and D3 Are Not Quite the Same Vitamin D supplements generally contain one of two forms. Vitamin D2, also called ergocalciferol, is commonly produced from fungi or yeast exposed to ultraviolet light. Vitamin D3, or cholecalciferol, is the same form produced in human skin after exposure to ultraviolet B radiation from sunlight. Traditionally, vitamin D3 in supplements has often come from lanolin obtained from sheep's wool. However, animal-free D3 made from sources such as lichen is also available, an important consideration for people following vegan or plant-based diets. Once vitamin D enters the body, it goes through several processing steps. The liver converts it into 25-hydroxyvitamin D, the form doctors commonly measure in blood tests to estimate a person's vitamin D status. Vitamin D2 produces 25-hydroxyvitamin D2, while vitamin D3 produces 25-hydroxyvitamin D3. It is this D3-derived form that researchers found could fall after people took vitamin D2. Vitamin D2 Was Linked to a Drop in Vitamin D3 The 2025 study, published in Nutrition Reviews by researchers from the University of Surrey, John Innes Centre and Quadram Institute Bioscience, brought together evidence from randomized controlled trials to examine this effect more closely. Researchers reviewed 20 studies, with 11 providing data suitable for the main meta-analysis. Compared with people who did not receive vitamin D2, those taking D2 had significantly lower concentrations of 25-hydroxyvitamin D3. Depending on how the results were analyzed, the average reduction was roughly 9 to 18 nanomoles per liter. Importantly, that does not mean vitamin D2 simply removes vitamin D from the body or that taking it is necessarily harmful. Vitamin D2 itself raises 25-hydroxyvitamin D2 and can contribute to total vitamin D status. Instead, the surprising finding is that increasing one form appears to coincide with a reduction in the other. Emily Brown, PhD Research Fellow and Lead Researcher of the study from the University of Surrey's Nutrition, Exercise, Chronobiology & Sleep Discipline, said: "Vitamin D supplements are important, especially between October and March, when our bodies cannot make vitamin D from sunlight in the UK. However, we discovered that vitamin D2 supplements can actually decrease levels of vitamin D3 in the body, which is a previously unknown effect of taking these supplements. This study suggests that subject to personal considerations, vitamin D3 supplements may be more beneficial for most individuals over vitamin D2." Why Would Vitamin D2 Lower Vitamin D3? Scientists do not yet have a definitive explanation. One possibility involves the body's mechanisms for regulating vitamin D. When concentrations of vitamin D metabolites rise, the body may accelerate the breakdown and removal of these compounds to keep levels under control. Researchers have proposed that increasing vitamin D2 could therefore increase the disposal of existing 25-hydroxyvitamin D3. Earlier experiments have also suggested that the relationship may work in both directions, with D3 supplementation sometimes reducing D2-derived metabolites. Exactly how important this balancing effect is for health remains unresolved. Professor Cathie Martin, Group Leader at the John Innes Centre, said: "This meta-analysis highlights the importance of ensuring plant-based vitamin D3 is accessible in the UK." That goal has become increasingly practical because plant-based and animal-free sources of vitamin D3 are now available, including D3 derived from lichen. D3 May Affect the Immune System Differently The findings also fit with earlier work suggesting that D2 and D3 may not have identical effects beyond their ability to raise vitamin D levels. A study published in Frontiers in Immunology and led by Professor Colin Smith from the University of Surrey examined how supplementation affected gene activity in the blood. The researchers found substantial differences between the responses to D2 and D3, including changes involving the immune system. In particular, vitamin D3 appeared to stimulate activity associated with type I interferon signaling, while vitamin D2 did not. Type I interferons are signaling proteins that help alert cells when an infection is developing and form an important part of the body's early defenses against viruses and other pathogens. Professor Colin Smith said: "We have shown that vitamin D3, but not vitamin D2, appears to stimulate the type I interferon signaling system in the body -- a key part of the immune system that provides a first line of defense against bacteria and viruses. Thus, a healthy vitamin D3 status may help prevent viruses and bacteria from gaining a foothold in the body." The immune findings are intriguing, but they should not be interpreted as proof that taking D3 will prevent a particular infection. Changes in gene activity and immune signaling do not necessarily translate directly into fewer illnesses, and larger clinical studies are needed to establish what the differences mean for everyday health. Newer Evidence Adds an Important Caveat Research published since the 2025 analysis makes the picture more nuanced. A separate 2026 systematic review and meta-analysis examined 26 randomized trials involving vitamin D2. It found that D2 supplementation significantly reduced parathyroid hormone levels and produced a small increase in blood calcium, demonstrating that D2 continues to have meaningful biological effects even though it may reduce circulating D3. That finding is important because the reduction in D3 should not be confused with evidence that D2 is ineffective. Current NIH information continues to state that both D2 and D3 can increase overall blood levels of vitamin D. The difference is that the accumulated evidence favors D3 for producing a larger increase and maintaining that increase for longer. This is also consistent with previous meta-analyses comparing the two forms directly. One analysis of 24 studies found D3 was more effective than D2 at improving overall vitamin D status, while another focused on frequent dosing reached a similar conclusion. Scientists Still Need to Know What the Difference Means The central unanswered question is not whether D2 can reduce circulating D3. The randomized trial evidence strongly suggests that it can. What remains uncertain is whether that reduction produces meaningful differences in health outcomes. Researchers say additional studies are needed to determine how D2 and D3 are metabolized, whether their effects on immune function meaningfully differ, and whether D3 should become the preferred form for routine supplementation when there is no individual reason to use D2. Professor Martin Warren, Chief Scientific Officer at the Quadram Institute, said: "Vitamin D deficiency represents a significant public health concern, especially during the winter months with significant deficiency across the UK population. This collaborative research effort aligns well with the Quadram Institute's mission to deliver healthier lives through food innovation to enhance the nutrient density of the food we eat. Tackling this with the most effective form of vitamin D supplementation or fortification is of the utmost importance to the health of the nation." For now, the evidence increasingly suggests that the label on a vitamin D supplement matters. D2 and D3 can both contribute to vitamin D status, but they are not necessarily metabolically interchangeable, and D3 appears to have an advantage when the goal is raising and sustaining vitamin D levels. What scientists still need to establish is whether those biochemical differences translate into important differences in long-term health.