Vitamin B Deficiency

New development pathway significantly expands addressable patient population for IV Choline ChlorideIV Choline Chloride has the potential to become the first FDA-approved IV formulation of choline for the 40,000 PN patients in the U.S.Approximately 80% of PN patients are choline deficient, which can lead to liver damage and hepatic failure; ASPEN recommends choline replacement for PN patientsCompany expects to start registrational trial to support FDA approval of IV Choline Chloride for PN patients in the first half of 2025 NEW YORK, April 05, 2024 (GLOBE NEWSWIRE) -- Protara Therapeutics, Inc. (Nasdaq: TARA), a clinical-stage company developing transformative therapies for the treatment of cancer and rare diseases, today announced that it has reached alignment with the U.S. Food and Drug Administration (FDA) on a registrational path forward for intravenous (IV) Choline Chloride, an investigational phospholipid substrate replacement. The Company had previously been pursuing an indication in intestinal failure-associated liver disease (IFALD) and following feedback from FDA, will now pursue a broader indication in patients on parenteral nutrition (PN) who are or may become unable to synthesize choline from oral or enteral nutrition sources. The Company plans to advance the development of IV Choline Chloride as a source of choline for adult and adolescent patients on long-term PN. The FDA has granted IV Choline Chloride Orphan Drug Designation for the prevention of choline deficiency in PN patients. “There are currently no IV formulations of choline available or in development for PN patients. The FDA recognizes this as a serious unmet need and has been instrumental in helping us define an efficient regulatory path to provide a much-needed source of IV choline for these patients,” said Jesse Shefferman, Chief Executive Officer of Protara Therapeutics. “We look forward to advancing the clinical development of IV Choline Chloride, which we believe has the potential to become the first FDA approved IV choline therapy for patients dependent on PN. In parallel, we remain keenly focused on advancing our lead product candidate, TARA-002, for patients with non-muscle invasive bladder cancer and lymphatic malformations.” “Approximately 80 percent of PN-dependent patients are choline-deficient and have some degree of liver damage, which may be reversible with effective supplementation,” said Palle Bekker Jeppesen M.D., Ph.D., Clinical Professor and Head of the Department of Intestinal Failure and Liver Diseases, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. “Top professional medical societies in both the U.S. and Europe recognize the impact of long-term choline deficiency on liver health, particularly, the development of liver disease with progressive steatosis, fibrosis, and eventually end-stage liver cirrhosis, and recommend treatment with choline. Access to an IV formulation of choline has the potential to make a meaningful impact for intestinal failure patients for whom oral or enteral choline supplementation is not an option.” Choline is recommended for patients on PN by the American Society for Parenteral and Enteral Nutrition (ASPEN) Recommendations for Changes in Commercially Available Parenteral Multivitamin and Multi–Trace Element Products, as well as by the European Society for Clinical Nutrition and Metabolism (ESPEN) in their Guideline on Home Parenteral Nutrition. The FDA indicated that a single study with an endpoint of restoring choline levels in PN patients could serve as the basis for a regulatory filing for IV Choline Chloride. Based on this feedback, the Company intends to assess the safety and efficacy of IV Choline Chloride in its planned seamless Phase 2b/3 double-blinded, randomized, placebo-controlled THRIVE-3 study in adolescents and adults on long-term PN when oral or enteral nutrition is not possible, insufficient, or contraindicated. The Phase 2b portion of the study, which will seek to establish the pharmacokinetics (PK) profile of IV Choline Chloride, will enroll approximately 24 patients who will receive one of three daily doses of IV Choline Chloride for 24 weeks. During the randomized, double-blind Phase 3 portion of the study, approximately 100 patients will receive either high dose IV Choline Chloride, low dose Choline Chloride, or placebo for 24 weeks. The primary endpoint of this portion of the study will seek to demonstrate IV Choline Chloride as a durable source of choline. Secondary endpoints will assess the impact of choline replacement on liver function. All patients will be eligible to enter an open-label extension. The Company intends to initiate this study in the first half of 2025. In previous studies, treatment with IV Choline Chloride successfully increased plasma choline concentrations in patients on PN and was also shown to improve steatosis, a key marker of liver injury. About IV Choline Chloride IV Choline Chloride is an investigational, intravenous (IV) phospholipid substrate replacement therapy initially in development for patients receiving parenteral nutrition (PN). Choline is a known important substrate for phospholipids that are critical for healthy liver function and also plays an important role in modulating gene expression, cell membrane signaling, brain development and neurotransmission, muscle function, and bone health. PN patients are unable to synthesize choline from enteral nutrition sources, and there are currently no available PN formulations containing choline. Approximately 80 percent of PN-dependent patients are choline-deficient and have some degree of liver damage, which can lead to hepatic failure. There are currently no available PN formulations containing choline. In the U.S. alone, there are approximately 40,000 patients on long-term parenteral nutrition who would benefit from an IV formulation of choline. IV Choline Chloride has the potential to become the first FDA approved IV choline formulation for PN patients. IV Choline Chloride has been granted Orphan Drug Designation by the FDA for the prevention of choline deficiency in PN patients. The Company was issued a U.S. patent claiming a choline composition with a term expiring in 2041. About Protara Therapeutics, Inc. Protara is a clinical-stage biotechnology company committed to advancing transformative therapies for people with cancer and rare diseases. Protara’s portfolio includes its lead candidate, TARA-002, an investigational cell-based therapy in development for the treatment of non-muscle invasive bladder cancer (NMIBC) and lymphatic malformations (LMs). The Company is evaluating TARA-002 in an ongoing Phase 2 trial in NMIBC patients with carcinoma in situ (CIS) who are unresponsive or naïve to treatment with Bacillus Calmette-Guérin (BCG), as well as a Phase 2 trial in pediatric patients with LMs. Additionally, Protara is developing IV Choline Chloride, an investigational phospholipid substrate replacement for patients on parenteral nutrition who are otherwise unable to meet their choline needs via oral or enteral routes. For more information, visit www.protaratx.com. Forward-Looking Statements Statements contained in this press release regarding matters that are not historical facts are "forward looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. Protara may, in some cases, use terms such as “predicts,” “believes,” “potential,” “proposed,” “continue,” “designed,” “estimates,” “anticipates,” “expects,” “plans,” “intends,” “may,” “could,” “might,” “will,” “should” or other words or expressions referencing future events, conditions or circumstances that convey uncertainty of future events or outcomes to identify these forward-looking statements. Such forward-looking statements include but are not limited to, statements regarding Protara’s intentions, beliefs, projections, outlook, analyses or current expectations concerning, among other things: Protara’s business strategy, including its development plans for its product candidates and plans regarding the timing or outcome of existing or future clinical trials; statements related to expectations regarding interactions with the FDA; Protara’s financial position; statements regarding the anticipated safety or efficacy of Protara’s product candidates; and Protara’s outlook for the remainder of the year. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Factors that contribute to the uncertain nature of the forward-looking statements include: risks that Protara’s financial guidance may not be as expected, as well as risks and uncertainties associated with: Protara’s development programs, including the initiation and completion of non-clinical studies and clinical trials and the timing of required filings with the FDA and other regulatory agencies; general market conditions; changes in the competitive landscape; changes in Protara’s strategic and commercial plans; Protara’s ability to obtain sufficient financing to fund its strategic plans and commercialization efforts; having to use cash in ways or on timing other than expected; the impact of market volatility on cash reserves; the loss of key members of management; the impact of general U.S. and foreign, economic, industry, market, regulatory, political or public health conditions; and the risks and uncertainties associated with Protara’s business and financial condition in general, including the risks and uncertainties described more fully under the caption “Risk Factors” and elsewhere in Protara's filings and reports with the United States Securities and Exchange Commission. All forward-looking statements contained in this press release speak only as of the date on which they were made and are based on management's assumptions and estimates as of such date. Protara undertakes no obligation to update any forward-looking statements, whether as a result of the receipt of new information, the occurrence of future events or otherwise, except as required by law. Company Contact:Justine O'MalleyProtara TherapeuticsJustine.OMalley@protaratx.com646-817-2836

Posters to be presented highlighting research investigating pegtibatinase as the first potential disease-modifying treatment for classical homocystinuriaSAN DIEGO, April 04, 2024 (GLOBE NEWSWIRE) -- Travere Therapeutics, Inc., (Nasdaq: TVTX) today announced that the Company will present eight posters in classical homocystinuria (HCU) at Society for Inherited Metabolic Disorders (SIMD) in Charlotte, North Carolina from April 14-17, 2024, and Genetic Metabolic Dieticians International (GMDI) in Charlotte, North Carolina from April 17-20, 2024. At SIMD and GMDI, the Company will present the trial design of the pivotal Phase 3 HARMONY Study of pegtibatinase, a novel investigational enzyme replacement therapy for the treatment of classical HCU. Additionally, the Company will share insights on the development of an innovative tool used for dietary management and monitoring in the Phase 3 HARMONY Study and open-label extension ENSEMBLE Study, and the positive results from cohort 6 in the placebo-controlled Phase 1/2 COMPOSE Study of pegtibatinase in classical HCU. “Classical HCU is an isolating and devastating rare disorder with very limited treatment options, including adherence to highly restrictive diets, leaving patients and their caregivers with immense challenges,” said Jula Inrig, M.D., chief medical officer of Travere Therapeutics. “We look forward to participating at both of these prestigious metabolic medical meetings, and we are excited about our work pioneering the first potential disease-modifying treatment for the thousands of people affected by classical HCU.” SIMD Poster Presentations Latest Results From the COMPOSE Phase 1/2 Trial For the Treatment of Classical Homocystinuria (HCU) Using Pegtibatinase, a Novel Investigational Enzyme Replacement TherapyPoster: 139Abstract Category: Innovative TherapiesSymphony Ballrooms 4-7; April 15, 2024, 8-9 p.m. ET Pegtibatinase, an Investigational Enzyme Replacement Therapy, For The Treatment of Classical Homocystinuria (HCU): Design of the HARMONY Phase 3 Study Poster: 147Abstract Category: Innovative Therapies Symphony Ballrooms 4-7; April 15, 2024, 8-9 p.m. ET Economic Burden of Classical Homocystinuria in the United StatesPoster: 48Abstract Category: Clinical Care/ResearchSymphony Ballrooms 4-7; April 15, 2024, 7-8 p.m. ET Clinical Burden of Classical Homocystinuria in the United States: A Retrospective Claims Analysis Poster: 64Abstract Category: Clinical Care/ResearchSymphony Ballrooms 4-7; April 15, 2024, 7-8 p.m. ET Association Between Homocysteine and Clinical Outcomes in Patients with Classical Homocystinuria: A Systematic Literature ReviewPoster: 68Abstract Category: Clinical Care/ResearchSymphony Ballrooms 4-7; April 15, 2024, 7-8 p.m. ET GMDI Poster Presentations Latest Results from the COMPOSE Phase 1/2 Trial of Pegtibatinase, a Novel Investigational Enzyme Replacement Therapy for Classical Homocystinuria (HCU) Poster: 10April 18, 2024, 4:30-5:15 p.m. ET Novel Tool for Dietary Management and Monitoring in Clinical Trials of Pegtibatinase, an Investigational Enzyme Replacement Therapy for Classical Homocystinuria Poster: 16April 18, 2024, 4:30-5:15 p.m. ET Novel Dietary Management Strategies for Classical Homocystinuria (HCU) in HARMONY/ENSEMBLE Phase 3 Studies of Pegtibatinase, an Investigational Enzyme Replacement Therapy Poster: 33April 18, 2024, 5:15-6 p.m. ET About Classical Homocystinuria Classical homocystinuria (HCU) is a rare genetic metabolic disorder caused by a deficiency in the enzyme cystathionine beta synthase (CBS). CBS is a pivotal enzyme that is essential for the management of methionine and cysteine in the body. Classical HCU leads to toxic levels of homocysteine that can result in life-threatening thrombotic events such as stroke, pulmonary embolism and deep vein thrombosis, ophthalmologic and skeletal complications, as well as developmental delay. Current treatment options are limited to protein-restricted diet and use of vitamin B6 and betaine. About Pegtibatinase Pegtibatinase is an investigational PEGylated, recombinant enzyme replacement therapy designed to address the underlying cause of classical homocystinuria (HCU). In preclinical studies, pegtibatinase has demonstrated an ability to reduce total homocysteine levels and improve clinical parameters. Pegtibatinase is currently advancing in the ongoing Phase 1/2 COMPOSE Study to assess its safety, tolerability, pharmacokinetics, pharmacodynamics and clinical effects in patients with classical HCU. In May 2023, the Company announced that data from four patients treated with the highest dose of pegtibatinase showed a clinically meaningful 67.1% mean relative reduction in total homocysteine from baseline and was generally well-tolerated after 12 weeks of treatment. To date, the pegtibatinase program has been granted Breakthrough Therapy designation, Rare Pediatric Disease and Fast Track designations by the FDA, as well as Orphan Drug designation in the U.S. and Europe. About Travere Therapeutics At Travere Therapeutics, we are in rare for life. We are a biopharmaceutical company that comes together every day to help patients, families and caregivers of all backgrounds as they navigate life with a rare disease. On this path, we know the need for treatment options is urgent – that is why our global team works with the rare disease community to identify, develop and deliver life-changing therapies. In pursuit of this mission, we continuously seek to understand the diverse perspectives of rare patients and to courageously forge new paths to make a difference in their lives and provide hope – today and tomorrow. For more information, visit travere.com Forward Looking Statements This press release contains “forward-looking statements” as that term is defined in the Private Securities Litigation Reform Act of 1995. Without limiting the foregoing, these statements are often identified by the words “anticipate,” “believe,” “expect,” “intend,” “may,” “might,” “objective,” “plan,” “will” or similar expressions. In addition, expressions of our strategies, intentions or plans are also forward-looking statements. Such forward-looking statements include, but are not limited to, statements regarding pegtibatinase as the first potential disease-modifying treatment for classical homocystinuria, references to the HARMONY study and the other studies described herein, including statements regarding expectations related thereto, and statements regarding the development of an innovative tool used for dietary management and monitoring. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statement can be guaranteed. Among the factors that could cause actual results to differ materially from those indicated in the forward-looking statements are risks related to the timing and outcome of the HARMONY study and the other studies described herein; risks and uncertainties associated with the regulatory review and approval process, risks associated with enrollment of clinical trials for rare diseases, and risks that ongoing or planned clinical trials may not succeed or may be delayed for safety, regulatory or other reasons. The Company faces risks related to its business and finances in general; risks related to the commercial launch of a new product; risks associated with market acceptance of FILSPARI and other current and future products, including efficacy, safety, price, reimbursement and benefit over competing therapies; and the risk that the Company’s clinical candidates will not be found to be safe or effective and that current or anticipated future clinical trials will not proceed as planned. Specifically, the Company faces risks related to the timing and potential outcome of the FDA’s potential acceptance for filing and review of the sNDA submission for full approval of FILSPARI in IgAN, and the timing and potential outcome of the European Commission’s decision regarding conditional marketing authorization of sparsentan for IgAN. There is no guarantee that the FDA will accept the sNDA submission for filing, that the European Commission will grant conditional marketing authorization of sparsentan for IgAN, or that regulators will grant full approval of sparsentan for IgAN or FSGS. The Company also faces the risk that it will be unable to raise additional funding that may be required to complete development of any or all of its product candidates, including as a result of macroeconomic conditions; risks relating to the Company's dependence on contractors for clinical drug supply and commercial manufacturing; uncertainties relating to patent protection and exclusivity periods and intellectual property rights of third parties; risks associated with regulatory interactions; and risks and uncertainties relating to competitive products, including current and potential future generic competition with certain of the Company's products, and technological changes that may limit demand for the Company's products. The Company also faces additional risks associated with global and macroeconomic conditions, including health epidemics and pandemics, including risks related to potential disruptions to clinical trials, commercialization activity, supply chain, and manufacturing operations. You are cautioned not to place undue reliance on these forward-looking statements as there are important factors that could cause actual results to differ materially from those in forward-looking statements, many of which are beyond our control. The Company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise. Investors are referred to the full discussion of risks and uncertainties, including under the heading “Risk Factors”, as included in the Company’s most recent Form 10-K, Form 10-Q and other filings with the Securities and Exchange Commission. Contact Info Media:888-969-7879 mediarelations@travere.comInvestors:888-969-7879 IR@travere.com

甲状腺疾病全球流行病学情况与人口碘摄入情况密切相关。根据《中国老年人甲状腺疾病诊疗专家共识（2021）》，中国甲状腺疾病总体患病率为50.96%。在碘充足地区，甲状腺功能亢进症（甲亢）和亚临床甲亢各影响约5%的人口，以毒性弥漫性甲状腺肿（Grave's病）多见；在碘缺乏地区，甲亢患病率较高，甲亢和亚临床甲亢的患病率可高达10%~15%，毒性结节性甲状腺肿比Grave’s病更多见，若采取有效措施纠正碘缺乏，则甲亢发病率呈现出短期内增加，而后逐渐降低至与碘充足地区类似的水平。近日，《柳叶刀》（The Lancet）发表一项研讨会内容，阐述了甲状腺疾病的病因、临床表现、并发症、诊断、治疗策略和未来研究重点方向，以期为临床预防和治疗甲状腺疾病提供参考。截图来源：The Lancet常见3大甲状腺疾病甲状腺毒症指各种原因导致的循环中甲状腺激素过量，引起以神经、循环、消化等系统兴奋性增高和代谢亢进为主要表现的一系列临床综合征，根据是否有甲亢，可分为甲亢性甲状腺毒症和非甲亢性甲状腺毒症。甲亢是甲状腺毒症的病因之一，是甲状腺自主持续性合成和分泌甲状腺激素增多而引起的甲状腺毒症，以Grave’s病最为常见，约占甲亢所有类型的80%。尽管甲状腺毒症和甲亢的术语经常互换使用，不同病因引起的甲状腺毒症患者临床表现相似，但治疗方案和预后不同，在临床上需要仔细鉴别甲状腺毒症的病因。临床实践中，Grave’s病、毒性结节性甲状腺肿和甲状腺炎是尤为常见的疾病类型，相比之下，其他原因（如卵巢甲状腺肿）引起的甲状腺毒症较为罕见。哪些表现可能是甲状腺疾病？由于甲亢病因并不完全明确，不同患者之间的症状表现差异较大。年龄可能是影响因素之一，通常老年人很少出现甲亢相关症状，尽管如此，对于以不明原因体重减轻、房颤或房扑、心悸、情绪改变和其他非特异性表现的主诉的老年人，仍然应提高疑似甲亢的临床判断。Grave’s病患者最常见的症状为甲状腺眼病，也称为“Grave’s眼病”或“眼眶病”，患病率约为25%~40%，而甲状腺皮肤病（胫前粘液水肿）、甲状腺肢端病（杵状指）和其他自身免疫性疾病，如脾肿大、胸腺肿大、脱发、白癜风、恶性贫血和荨麻疹等则较少见。甲亢患者病情严重时可能出现甲亢危象，可伴有一个或多个器官失代偿，发病率约为0.2%，60岁以上人群甲亢危象死亡率高达10%~17%。甲亢危象患者多表现为发热、精神状态改变、胃肠功能紊乱、心动过速伴心律失常和心衰，通常同时伴有急症，如感染、手术或分娩，几乎很少有患者在患病初期就出现甲亢危象。甲状腺疾病的临床指标有何变化？甲状腺毒症的特征为：游离甲状腺素（FT4）和总三碘甲状腺原氨酸（TT3）或游离三碘甲状腺原氨酸（FT3）浓度升高，血清促甲状腺激素（TSH）水平降低，通常低于0.01 mU/L。部分患者可能患有T3甲状腺毒症（FT4浓度在正常范围，但T3浓度增高），多见于病情较轻或早期患者。亚临床甲亢患者甲状腺激素水平在正常范围，但TSH水平异常。对于疑似Grave’s病的患者，特别是患者无典型Grave’s眼病或其他临床症状时，促甲状腺激素受体抗体（TRAb）是关键诊断指标。对于甲状腺毒症病因不明的患者，甲状腺造影和放射性同位素有助于明确病因，通常Grave’s病患者放射性同位素摄碘率升高或升高至正常，而甲状腺炎患者的放射性同位素摄碘率通常非常低或不存在。对于毒性甲状腺结节性甲状腺肿患者，甲状腺造影可以显示甲亢和甲减区域，即“热结节”和“冷结节”。甲状腺超声适用于确定在体格检查或扫描发现的甲状腺结节。甲状腺疾病的三大治疗策略β-受体阻滞剂可缓解甲亢症状。非选择性β-受体阻滞剂——普萘洛尔可长期使用，更长效的β1-受体阻滞剂，如阿替洛尔和美托洛尔也同样有效。甲状腺毒症伴甲亢首选治疗方式取决于潜在的病理生理机制，常用的治疗策略有：抗甲状腺药物、放射性碘治疗和甲状腺切除术。这三种治疗策略对Grave’s病同样有效，但抗甲状腺治疗药物更可能是患者首选治疗方式。对于毒性腺瘤或多结节性甲状腺肿的患者，放射性碘治疗和手术是首选方案。抗甲状腺药物硫氨酰胺类抗甲状腺药物包括：丙基硫氧嘧啶（PTU）、卡比马唑及其代谢产物甲巯咪唑。根据美国和欧洲指南的建议：对于新诊断为Grave’s甲亢的患者，可选用卡比马唑和甲巯咪唑治疗12~18个月，直到TSH水平恢复正常且TRAb为阴性，方可停药。若治疗期间患者TRAb水平持续升高或停药后复发，则可考虑选择卡比马唑和甲巯咪唑继续治疗12个月或更长时间，亦或是选择放射性碘治疗、甲状腺切除术等方式。抗甲状腺药物也有缺点，主要是单疗程治疗后复发率较高（约50%），特别是停药后的前6个月。不过，一项针对128例复发性Grave’s病的纵向研究显示，超过75%的患者在接受了抗甲状腺药物第二疗程治疗后，可达到长期缓解。此外，有证据表明，长期（5~10年）甚至终身使用低剂量的卡比马唑和甲巯咪唑是安全有效的。抗甲状腺药物的初始剂量取决于甲亢严重程度和甲状腺大小。初步控制住病情大约需要1~3个月，而后可将抗甲状腺药物剂量控制在维持正常甲状腺功能所需最低剂量。若病情难以被控制，可以考虑采用阻断和替代治疗方案，即用大剂量抗甲状腺药物完全阻断甲状腺功能，并使用左旋甲状腺素，以避免发生甲减。治疗4~6周后应开始检测甲状腺功能，避免过度治疗引起甲减，特别是Grave’s病，因为患者可能出现严重的甲状腺眼病。若患者达到生化甲状腺功能正常，随访间隔可延长至2~4个月。安全性方面，约有5%的患者可能出现轻微不适反应，包括瘙痒和胃肠道不适。抗甲状腺药物严重副作用比较罕见，仅有不到0.5%的患者可能出现粒细胞缺乏症，通常在治疗3个月发生，表现为发热、咽喉痛或二者兼有，若出现相关症状，且经临床医生证实为粒细胞缺乏症，则需永久停用抗甲状腺药物。放射性碘治疗放射性碘治疗是毒性腺瘤和毒性多结节性甲状腺肿的一线治疗方式，特别是患有合并症的老年患者，因为他们手术的风险很高。放射性碘治疗后第一周，T4和T3的浓度可能会短暂升高，不过Grave’s病中50%~85%的患者最终会进入甲减。此外，大约有10%的甲亢患者在采用放射性碘治疗后，仍无法缓解甲亢症状。放射性碘治疗可以作为一种明确的治疗选择，但并不能达到“立竿见影”的治疗效果，部分多结节甲状腺肿的体积可缩小60%，当然这也要看初始治疗时甲状腺的大小情况。一般来说，在开始放射性碘治疗前需要使用卡比马唑、甲巯咪唑或β受体阻滞剂，以控制甲亢并降低治疗后症状加重的风险，特别是老年患者和重度甲亢患者，通常在治疗前3~7天停药，然后在治疗后3~7天重新开始用药，一直到甲状腺功能正常。安全性方面，放射性碘治疗可能引起颈部压痛、已有甲状腺眼病病情进展或恶化，特别是吸烟人群。因此，放射性碘治疗禁用于伴有重度眼眶病变的Grave’s病患者，若是轻度眼眶病变或临床医生判定存在新发眼眶病变风险的患者（如吸烟、重度甲亢患者等），在接受放射性碘治疗之前，建议使用糖皮质激素进行预防。此外，放射性碘治疗的禁忌证还包括：怀孕（或计划未来6个月怀孕）、母乳喂养和无法遵守辐射安全预防措施人群。最后，尽管有部分研究认为，放射性碘治疗固定剂量和灵活剂量方案对癌症发病率和死亡率影响不存在差异，但也有证据表明，放射性碘治疗与实体瘤的死亡率之间存在剂量依赖性正相关，不过，相关研究结果仍存争议。甲状腺切除术甲状腺切除术可被视为毒性结节性甲状腺肿的一线治疗方案，以及Grave’s病的确定性治疗方案，特别是当其他治疗方案无效、患者无法耐受或存在治疗禁忌证、（疑似）恶性结节、大的甲状腺肿或并发原发性甲旁亢，或是甲状腺切除术为患者首选治疗方式时。对于Grave’s病，甲状腺全切术比甲状腺次全切除术效果更好，并发症情况类似，因此全切是首选。术前患者需要使用抗甲状腺药物，以使甲状腺功能正常；根据临床实践指南的推荐，术中可使用卢戈碘或碘化钾做预处理，以减少患者术中出血；术后患者还需使用左旋甲状腺素治疗。对于毒性结节性甲状腺肿，根据甲状腺结节的数量和分布情况，部分甲状腺切除术或甲状腺全切术都可能是合适的，且术后出现并发症几率较低（1%~2%），特别是主刀医生具有丰富的手术操作经验时（年手术次数＞25~50次）。术后可能出现的并发症包括：术后出血、甲状旁腺功能减退引起的低钙血症（通常为暂时性）和喉返神经损伤，发生概率均在1%左右。此外，还有些特殊类型的甲状腺疾病，如亚临床甲亢、妊娠甲亢等，本文不一一阐述。甲状腺疾病治疗的未来展望在过去的80年里，Grave’s病的治疗选择几乎没有发生过变化。尽管在治疗操作和安全性方面已取得了长足的进步，但现有的治疗方式仍较为有限，特别是停用抗甲状腺药物后，患者疾病复发率较高；以及放射性碘治疗或手术治疗后出现的甲状腺功能减退的问题。过去的10年里，关于Grave’s病的潜在治疗方法的不同作用机制已得到部分验证，不过这些临床研究规模较小，多为开放标签的1期和2期试验，仍有待更多的大型随机对照研究来佐证这些有希望的初步研究结果。达到并维持甲状腺功能正常，或是诱导和治疗甲状腺功能减退似乎有望改变甲亢死亡率高的问题。特别是使用放射性碘诱导甲减，随后采用T4替代疗法，或可降低心血管疾病和总死亡风险。但临床实践中，使用抗甲状腺药物让甲状腺功能维持正常，也不一定能降低死亡风险，这可能是因为患者在接受药物治疗时，甲状腺功能并不总是正常，且在停止药物治疗后还可能复发。目前，长期低剂量抗甲状腺药物治疗对心血管和总死亡的影响尚不明确，但或许是控制甲亢和避免复发的可行性策略，可能优于短期或重复治疗，且似乎对Grave’s病和结节性甲状腺肿同样有效。考虑到即将推出的新型免疫调节和其他靶向药，长期低剂量抗甲状腺药物或将成为治疗Grave’s病的有力选择之一，让我们共同期待这些治疗方式在未来的应用情况。对于部分自主良性甲状腺结节的患者，射频消融术或可作为替代治疗方案。此外，很多患者关心膳食补充剂（如维生素D、硒和Ω-3脂肪酸）是否可预防或治疗Grave’s病，从现有证据来看，虽然有部分研究探索了几种膳食补充剂的作用，但不同研究之间的数据存在相互矛盾的问题。最后，老年群体更容易罹患亚临床甲亢，而非甲亢。考虑纳入观察性研究的荟萃分析结果显示，亚临床甲亢患者更容易发生髋部和其他部位骨折、骨质疏松、心血管事件和死亡风险增加等问题，现有临床指南建议：对于血清TSH浓度低于0.1 mU/L的亚临床甲亢患者，无论是否有症状，都建议采取相关治疗措施（特别是老年患者）。不过，需要指出的是，尽管业内对于轻度亚临床甲亢的治疗尚未形成共识，但短期内开展相关临床对照试验以进一步了解和解决这一问题的可能性也较低。参考资料[1] Chaker L, Cooper DS, Walsh JP, Peeters RP. Hyperthyroidism. Lancet. 2024 Feb 24;403(10428):768-780. doi: 10.1016/S0140-6736(23)02016-0. Epub 2024 Jan 23. PMID: 38278171.[2]中华医学会老年医学分会老年内分泌代谢疾病学组,中华医学会内分泌学分会甲状腺学组.中国老年人甲状腺疾病诊疗专家共识(2021)[J].中华内分泌代谢杂志, 2021, 37(5):20.DOI:10.3760/cma.j.cn311282-20210502-00273.撰文 | 阿拉斯加宝编辑 | 阿拉斯加宝● 必须要重视了!!同一医院先后两名医学生自杀，一个月内三起！这些规培实习生为何如此绝望？如何避免悲剧再次发生？要警惕“维特效应”● Science重磅：长出头发和皮肤修复，都离不开这种常见的维生素！● “神药”减肥的机制明确了！连发两篇Nature，二甲双胍抑制食欲，竟与运动殊途同归？版权说明：梅斯医学（MedSci）是国内领先的医学科研与学术服务平台，致力于医疗质量的改进，为临床实践提供智慧、精准的决策支持，让医生与患者受益。欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。点击下方「阅读原文」 立刻下载梅斯医学APP！