免疫检查点抑制剂相关内分泌不良反应的发生及处理：一项单中心真实世界研究

背景免疫治疗相关性内分泌不良反应较为常见,若不及时处理常导致严重后果,但既往文献报道的该不良反应发生率差异较大,且无标准处理流程。目的 探讨免疫检查点抑制剂(ICIs)导致的内分泌不良反应在真实世界中的发生情况及处理流程。方法 回顾性分析2019年1月至2022年3月在郑州市第三人民医院使用ICIs治疗的204例实体瘤患者的临床资料,观察ICIs治疗期间发生的内分泌系统不良反应,并根据不良反应分级标准进行规范管理。结果 204例实体瘤患者中男139例、女65例,中位年龄65.4(8.0,88.4)岁。实体瘤种类以非小细胞肺癌为主(43.1%),治疗药物以信迪利单抗为主(47.1%),治疗模式以免疫联合靶向药物为主(57.4%)。12例患者出现ICIs相关内分泌不良反应,其中9例(4.4%)为甲状腺功能减退(1例Ⅰ级,7例Ⅱ级,1例Ⅲ级),中位发生时间为自第1次免疫药物治疗后7(6,10)周;1例(0.5%)甲状腺功能亢进(Ⅰ级),自免疫治疗后9周发生;1例(0.5%)1型糖尿病(Ⅳ级),自免疫治疗后6周发生;1例(0.5%)肾上腺皮质功能减退(Ⅲ级),自免疫治疗后7周发生。12例ICI...     

Managing spondylitis tuberculosis in a patient with underlying diabetes and hypothyroidism: A case report

BACKGROUNDTuberculosis (TB) remains one of the highest Asia’s health problems. Spondylitis TB in diabetes mellitus (DM) and hypothyroidism patients is a rare case of extrapulmonary tuberculosis. However, there is a lack of therapeutic guidelines to treat spondylitis TB, particularly with type 2 DM (T2DM) and hypothyroidism as comorbidities. Here we present a case of spondylitis TB with T2DM and hypothyroidism in a relatively young patient and its therapeutic procedure.CASE SUMMARYWe report the case of a 35-year-old male patient from Surabaya, Indonesia. Based on anamnesis, physical examination, and magnetic resonance imaging, the patient has been categorized in stage II of spondylitis TB with grade 1 paraplegia. Surprisingly, the patient also had a high HbA1c level, high thyroid stimulating hormone, and low free T₄ (FT₄), which indicated T2DM and hypothyroidism. A granulomatous process was observed in the histopathological section. The antituberculosis drugs isoniazid and rifampicin were given. In addition, insulin, empagliflozin, and linagliptin were given to control hyperglycemia conditions, and also levothyroxine to control hypothyroidism.CONCLUSIONThe outcome was satisfactory. The patient was able to do daily activities without pain and maintained normal glycemic and thyroid levels. For such cases, we recommend the treatment of spondylitis TB by spinal surgery, together with T2DM and hypothyroidism therapies, to improve the patients’ condition. Prompt early and non-invasive diagnoses and therapy are necessary.     

Real-life practice of thyroid hormone use in hypothyroid and euthyroid patients: A detailed view from the THESIS questionnaire survey in France

AimTo describe practices of French physicians regarding thyroid hormone therapy, focusing on available LT4 formulations.Material and methodsMembers of the French Endocrine Society (FES) and affiliated societies (the Endocrine Tumor Group, French College of Teachers of Endocrinology, Diabetes and Metabolic Diseases and the Union of Endocrinology, Diabetology, Metabolic Diseases and Nutrition Specialists) were invited to participate in an online survey.ResultsFive hundred and thirty four of the 2,094 persons contacted (25.5%) completed the survey and were included in the analysis. The vast majority (99.4%) reported that levothyroxine (LT4) is the treatment of choice for hypothyroidism. 7.1% and 14.2% of respondents respectively considered liothyronine (LT3) or a combination of LT4 and LT3 for the treatment of hypothyroidism, mainly when symptoms persisted despite achieving normal TSH concentrations with LT4 therapy. For 44% of respondents, thyroid hormone treatment is never indicated in euthyroid patients, while the remainder would consider treating euthyroid patients with a goiter growing over time (40.2%) and/or euthyroid women with positive anti-TPO antibodies and infertility (31.7%). LT4 tablets were the preferred LT4 formulation. A significant proportion of FES members expected no major clinical differences upon changing to formulations such as soft-gel capsules or liquid solutions, even in specific scenarios such as poor biochemical control or suspicion of malabsorption.ConclusionThe treatment of choice for hypothyroidism in France is LT4. LT3-based therapy is considered by some physicians in case of persistent symptoms of hypothyroidism despite normal TSH level. A significant proportion of respondents (66.0%) would consider treating euthyroid patients, contrary to the present state of knowledge. These outdated practices should be addressed by professional bodies such as the FES.     

血清胰岛素样生长因子1及胰岛素抵抗与2型糖尿病合并甲状腺功能减退症的相关性研究

背景流行病学研究显示糖尿病患者甲状腺功能异常患病率显著高于普通人群,且女性高于男性患者,合并甲状腺功能减退症发生率高于甲状腺功能亢进症,甲状腺功能异常影响降糖治疗的效果,甲状腺功能减退症的诊治在糖尿病中有重要临床价值。血清胰岛素样生长因子1(IGF-1)是重要的甲状腺激素调节因子。目的分析2型糖尿病(T2DM)合并甲状腺功能减退症患者的IGF-1及胰岛素抵抗的差异。方法选取2017年8月-2018年5月华北理工大学附属医院内分泌科住院的T2DM患者100例,将T2DM合并甲状腺功能减退症患者50例作为观察组,单纯T2DM患者50例作为对照组。测定并比较两组空腹血糖(FPG)、餐后2h血糖(2hPG)、空腹胰岛素(FINS)、餐后2h胰岛素(2hINS)、空腹C肽、餐后2hC肽、IGF-1、三碘甲状腺原氨酸(T3)、甲状腺素(T4)、促甲状腺激素(TSH)、游离三碘甲状腺原氨酸(FT3)、游离甲状腺素(FT4)、甲状腺过氧化物酶抗体(TPOAb)、甲状腺球蛋白抗体(TgAb)、糖化血红蛋白(HbA1c)、三酰甘油(TG)、总胆固醇(TC)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)以及胰岛素抵抗指数(HOMA-IR)。结果观察组女性、糖尿病病程、体质指数(BMI)、TSH、TgAb、HbA1c、TG、TC、HDL、HOMA-IR均高于对照组,IGF-1、FT3、FT4、LDL均低于对照组(P<0.05)。IGF-1与年龄、糖尿病病程、BMI、TgAb、HDL呈负相关,与FPG、2hPG、FINS、HOMA-IR呈正相关(P<0.05)。非条件二分类Logistic回归分析结果显示,IGF-1〔OR=0.970,95%C(I0.954,0.988)〕、HOMA-IR〔OR=1.342,95%C(I1.051,1.715)〕是T2DM合并甲状腺功能减退症的影响因素(P<0.05)。结论T2DM合并甲状腺功能减退症患者血清IGF-1水平降低、胰岛素抵抗加重,定期检测T2DM患者血清IGF-1并评估胰岛素抵抗程度对T2DM合并甲状腺功能减退症诊断及治疗尤为重要。     

Primary hypothyroidism with exuberant dermatological manifestations

Thyroid hormone has effects on the skin. Patients with hypothyroidism have changes such as dry, scaly and rough skin. Increase carotene in the dermis becomes a yellowish tone to the skin of the patient with hypothyroidism. There is an increase in capillary cycle (anagen phase) and nail growth and a reduction in eccrine gland secretion. It is a case of primary hypothyroidism with nail manifestations associated with dermatologic disorders and successful treatment with levothyroxine. Receptors for thyroid hormone have already been found in keratinocytes, fibroblasts, hair follicles and sebaceous glands. Genes responsive to thyroid hormones and elements of the hypothalamic–pituitary–thyroid axis were identified on the skin. This report highlights the importance of cutaneous manifestations as markers of thyroid disease.     

Acute hypothyroidism has no effect on pulmonary vascular resistance

Summary The effect of acute hypothyroidism on the pulmonary circulation was studied in 9 nonobese athyreotic patients by right heart catheterization at rest and during exercise. The patients were studied while they were hypothyroid 2 weeks after ceasing triiodothyronine treatment and while they were euthyroid on replacement therapy. At rest, pulmonary blood flow [4.0±0.6 l/min vs 5.8±1.0 l/min,p<0.01] and systolic pulmonary artery pressure [18±3 mmHg vs 23±2 mmHg,p<0.01] were lower when the patients were hypothyroid than when they were euthyroid. The mean and diastolic pressures in the pulmonary artery and the pulmonary capillary pressures were not different among the groups. Likewise, thyroid hormone levels had no significant effect on pulmonary vascular resistance [100±25 dyn-s-cm^–5 vs 90±23 dyn-s-cm^–5]. With supine exercise, pulmonary blood flow [10.1±1.6 l/min vs. 13.2±2.0 l/min,p<0.01], mean pulmonary artery pressure [25±6 mmHg vs 30±6 mmHg,p<0.02], and systolic pulmonary artery pressure [36±6 mmHg vs 44±8 mmHg,p<0.01] were lower when the patients were hypothyroid. The diastolic pulmonary artery pressure and the pulmonary capillary pressure were similar in both thyroid states. Again, thyroid deficiency had no effect on pulmonary vascular resistance [81±23 dyn-s-cm^–5 vs 76±24 dyn-s-cm^–5]. The lower systolic pressures in the pulmonary artery seen in hypothyroidism are probably due to the decreased systolic volume load of the pulmonary circulation. The data do not suggest that thyroid hormones play a role in the regulation of pulmonary vascular resistance.Abbreviations PVR pulmonary vascular resistance - PAP_M mean pulmonary artery pressure - PCP_M mean pulmonary capillary pressure - PBF pulmonary blood flow     

含丙硫异烟胺和对氨基水杨酸方案治疗耐多药结核病患者致甲状腺功能减退症的临床分析

目的 分析含丙硫异烟胺(protionamide,Pto)和(或)对氨基水杨酸(para-aminosalicylic acid,PAS)方案治疗耐多药结核病(multidrug resistant tuberculosis,MDR-TB)致甲状腺功能减退症(简称“甲减症”)的发生情况及治疗效果。方法 收集2017年10月1日至2019年6月30日成都市公共卫生临床医疗中心结核科入院及门诊就诊的MDR-TB患者,符合纳入排除标准且使用含Pto 和(或)PAS抗结核方案治疗者336例。依据抗结核药物使用情况分为两组,其中仅含Pto治疗方案的患者91例(简称“Pto组”),含Pto和PAS治疗方案的患者245例(简称“Pto+PAS组”)。所有患者均在抗结核药物治疗前及第1、3、6、9、12、18、24个月分别进行甲状腺功能检查,分析甲状腺功能减退症的发生率、出现时机,以及采用优甲乐治疗的时机、治疗率及治疗剂量、疗效情况。结果 336例MDR-TB患者中,药物性甲减症的发生率为28.87%(97/336),其中4例出现黏液性水肿、2例出现乏力伴脱发经检查甲状腺功能后确诊,其余91例患者均无明显自觉症状,均在复诊检测甲状腺功能时发现。 Pto+PAS组甲减症的发生率[32.24%(79/245)]明显高于Pto组[19.78%(18/91)](χ²=5.020,P=0.025),男性甲减症的发生率[24.07%(52/216)]明显低于女性[37.50%(45/120)](χ²=6.772,P=0.009)。发生药物性甲减症的比率随治疗时间的延长而下降,用药后1.5个月内、3个月内、3~6个月内、6个月后的占比分别为40.20%(39/97)、24.74%(24/97)、17.53%(17/97)、17.53%(17/97);Pto+PAS组在1.5个月内甲减症的发生率 [46.83%(37/79)]明显高于Pto组[11.11%(2/18)](Fisher确切概率法,P=0.018)。78例甲减症患者需要采用优甲乐治疗,Pto+PAS组需要采用优甲乐治疗的比率 [84.81%(67/79)]明显高于Pto组[61.11%(11/18)](χ²=5.227,P=0.022)。优甲乐最终使用剂量分别为49例(62.82%)≤50μg/d、20例(25.64%)51~75μg/d、9例(11.54%)>75μg/d;其中4例Pto+PAS组患者使用优甲乐剂量超过125μg/d后甲减症仍控制不佳而停用Pto及PAS,其余74例患者均达到治疗效果。结论 MDR-TB患者采用含Pto联合PAS方案较单含Pto方案治疗更易出现甲减症,抗结核药物治疗前3个月甲减症发生率高,需密切监测甲状腺功能。采用优甲乐治疗的药物性甲减症患者,如果在不同剂量治疗后效果较好而不必停用Pto及PAS。     

Does assessment of carbonic anhydrase activity support the diagnosis of various thyroid disorders

ObjectiveTo evaluate the activity of carbonic anhydrase (CA) in various thyroid disorder patients and their results were compared with euthyroid acting as a control.MethodsTwo hundred and sixty-three participants were enrolled for the present study with ages ranging from 6 months to 74 years. Among them, hypothyroid, hyperthyroid and euthyroid subjects were chosen. Twelve hours' fasting blood samples were collected from all the patients reported to Medicine Out Patients Department and assessment of CA activity was done in all the three category patients. The data from the patients and controls were compared by using the student's t-test. The values were expressed as mean±standard deviation. Microsoft Excel for Windows 2003 was used for statistical analysis. P<0.05 were considered to indicate statistical significance.ResultsThe serum levels of CA activities were observed to be higher in hyperthyroid patients compared to hypothyroid ones and the CA activity in euthyroid subjects were comparatively higher than hypothyroid subjects. It was also observed that the serum CA activity was significantly correlated with both T4 (r=0.997, P<0.001) and FT4 (r=0.590, P=0.039) values.ConclusionThough our study contains a very small sample size, as a pilot study we have demonstrated that the serum levels of CA activity is associated with the serum thyroxine levels.