肿瘤性骨软化症是一种副肿瘤综合征,以低血磷、高尿磷、血钙及甲状旁腺素正常、1,25-二羟维生素D3[1,25-dihydroxyvitamin D3,1,25(OH)2D3]正常或偏低、成纤维细胞生长因子23(fibroblast growth factor 23,FGF-23)升高为主要特征,经过手术治疗可获得根治.其多灶病例非常罕见.现报道多灶性肿瘤骨软化1例并文献复习,探讨该特殊情况下的处理策略.

报道1例ATP敏感性钾通道（ K ATP）基因突变所致青少年起病的成人型糖尿病（MODY）患者的诊疗经过。患者为24岁女性，健康体检偶然发现血糖升高及尿糖（++++）、尿蛋白（+++）。患者对磺脲类药物治疗敏感，临床疑诊MODY。通过全外显子组高通量测序对患者及其父母进行 KCNJ11基因突变位点筛查并使用生物信息学蛋白功能预测软件进行功能预测分析，发现患者及其父亲携带 KCNJ11（NM_000525.3）c.11G>A（p.Arg4His）杂合突变。患者使用小剂量磺脲类药物治疗，随访血糖控制良好。其父亲的高血糖通过饮食控制及规律运动，获得良好控制。结合患者诊疗经过和相关文献报道，提示临床在MODY的临床诊断上应加强与非典型1型糖尿病（T1DM）和2型糖尿病（T2DM）的鉴别，以提高患者生活质量。

目的 分析嗜铬细胞瘤(PCC)合并亚临床库欣综合征(SCS)患者的临床特点,探究SCS对PCC患者的糖脂代谢、肾素-血管紧张素-醛固酮系统(RAAS)的影响.方法 纳入2016年1月至2021年12月解放军总医院第一医学中心内分泌科收治并行肾上腺肿物手术切除,病理确诊为嗜铬细胞瘤的患者128例,收集术前肾上腺功能评估后诊断为合并SCS的患者基本资料、糖脂代谢指标、肾素浓度及醛固酮结果,与单纯PCC患者(0点血清皮质醇＜50 nmol/L)进行组间对比分析.结果 6.25％(8/128)的PCC患者合并SCS,PCC合并SCS患者的总胆固醇水平明显高于单纯PCC组,差异具有统计学意义(P＜0.05),两组间空腹血糖、甘油三酯、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、体质指数、肾素浓度、醛固酮差异均无统计学意义(P＞0.05).结论 SCS加重PCC患者的脂代谢紊乱,可能增加患者的心脑血管疾病风险.

正确分型诊断是原发性醛固酮增多症（PA）治疗决策的基础，也是临床难点。肾上腺静脉取血（AVS）一直是PA分型诊断的金标准。基于液相色谱串联质谱法（LC-MS/MS）的类固醇激素谱检查近年在肾上腺疾病诊治中愈发多见。本文报道1例影像上表现为双侧肾上腺病变的PA行AVS联合类固醇激素谱检查完成诊治，并对病例特点、诊治过程进行总结讨论和文献复习，以期为PA的分型诊断和精准治疗提供更多证据及思路。.

患者女性，20岁，糖尿病伴多囊卵巢综合征病史6年。发病初期使用胰岛素皮下注射治疗效果佳，后停用胰岛素使用口服药治疗。近1年因血糖异常升高再次启用胰岛素皮下注射治疗，但超大剂量胰岛素皮下注射血糖控制不佳；实验室检查示空腹胰岛素轻度升高，未发现拮抗胰岛素激素水平增高的内分泌疾病，基因检测未见异常突变；静脉胰岛素输注可将血糖控制达标。最终诊断为2型糖尿病合并皮下胰岛素抵抗综合征。使用二甲双胍、恩格列净联合肌肉注射胰岛素，患者血糖控制平稳。

Umbilical cord-derived mesenchymal stem cells (UC-MSCs) have been proved a promising clinical strategy for the treatment of diabetes, and time in range (TIR) has been demonstrated a new metric of glycemic control links to diabetes complications. To further assess the therapeutic effect of UC-MSCs on TIR, a phase II study investigating the efficacy of UC-MSCs in Chinese adults with type 2 diabetes (T2D) assessed by retrospective continuous glucose monitoring (CGM) was conducted. In this randomized and placebo-controlled trial, a total of 73 patients were randomly assigned to receive intravenous infusion of UC-MSCs (n = 37) or placebo (n = 36) 3 times at 4-week intervals and followed up for 48 weeks. The primary endpoint was the changes in TIR and glycosylated hemoglobin (HbA1c). TIR and HbA1c were both significantly improved in UC-MSCs and placebo groups after 48 weeks of therapy compared with baseline. Compared with placebo group, UC-MSCs group exhibited more pronounced changes at 9 and 48 weeks from baseline in TIR (26.54 vs. 15.84 and 21.36 vs. 6.32) and HbA1c (-1.79 vs. -0.96 and -1.36 vs. -0.51). More patients in UC-MSCs group achieved the glycemic control target of TIR ≥ 70% and HbA1c < 7% at 9 and 48 weeks than in placebo group (59.5% vs. 27.8% and 43.2% vs. 11.1%). The C-peptide area under the curve (AUCC-pep) was an independent risk factor associated with efficacy in T2D undergoing UC-MSCs intervention. These results illustrate that UC-MSCs administration via intravenous infusion is an effective approach for ameliorating TIR.

Objective:To investigate the impact of hemoglobin glycation index (HGI) on the diagnosis of diabetes mellitus.Methods:Using the baseline data from the Risk Evaluation of Cancers in Chinese Diabetic Individuals: a longitudinal (REACTION) study, 9 705 participants with complete data, who were selected from Pingguoyuan community of the Shijingshan district in Beijing between January and August 2012, received questionnaires, physical examination and laboratory tests. Laboratory tests consisted of fasting plasma glucose (FPG), glycated hemoglobin A 1c (HbA 1c), 2-hour plasma glucose (2hPG), and lipid profile. A linear regression equation was fitted based on the scatter plots of HbA 1c against FPG. The HGI was then calculated as the difference between the measured HbA 1c value and that predicted by plugging FPG in the above equation (HGI=measured HbA 1c-predicted HbA 1c). Ultimately, 8 480 participants of aged ≥ 40 years and no history of diabetes were included in the final analysis. The participants were categorized into three groups according to tertiles (low, moderate and high) of HGI. We compared the prevalence of diabetes among the three HGI groups with chi-square test, using HbA 1c and oral glucose tolerance test (OGTT) criteria respectively, and examined the diagnostic concordance between the two measures by Cohen′s kappa test. Factors associated with the high HGI phenotype were identified by order multi-classification logistic regression model. Results:Participants were categorized into three groups according to their HGI values: low HGI (HGI<-0.197 3, 2 841 cases) group, moderate HGI (-0.197 3≤HGI<0.135 9, 2 979 cases) group, and high HGI (HGI≥0.135 9, 2 660 cases) group. Among patients with diabetes detected by HbA 1c alone, the high HGI group accounted for 74.8% (677/905), which was much higher than the moderate (15.5%, 140 cases) and the low (9.7%, 88 cases) HGI groups. The agreement between HbA 1c and OGTT for the diagnosis of diabetes was poor (κ=0.488), which was mostly influenced by HGI. The high HGI phenotype was correlated with age, female gender, body mass index, low-density lipoprotein cholesterol, 2 h plasma glucose during an OGTT, and lipid-regulating drug. Conclusion:Using HbA 1c alone for diagnosis could lead to overdiagnosis in high HGI patients and underdiagnosis in low HGI patients.

Objective:To investigate the influence of hemoglobin glycation index (HGI) on the risk of incident chronic kidney disease (CDK) among nondiabetic patients.Methods:Prospective cohort study. At baseline, a total of 7 407 nondiabetic patients without a history of CKD from Pingguoyuan Community of the Shijingshan District in Beijing were included from December 2011 to August 2012, who were then divided into three groups according to the tertiles of their baseline HGI levels. The CKD incidence rate was compared among the different HGI groups at last follow-up. Cox multivariable regression was applied to evaluate whether HGI measures predicted CKD risk. Test for trend across tertiles were examined using ordinal values in separate models.Results:The mean age of the subjects was (56.4±7.5) years, and 4 933 (66.6%) were female. At mean follow-up of 3.23 years, 107 (1.4%) individuals developed CKD. The incidence of CKD was gradually increasing from the low to high HGI groups [1.1% (28/2 473) vs. 1.2% (31/2 564) vs. 2.0% (48/2 370), P=0.016]. In the multivariate Cox regression analysis, after adjustment for potential confounders, the high HGI group had a 68.5% increased risk of CKD compared with the low HGI group ( HR=1.685, 95% CI 1.023 to 2.774). CKD risk increased with increasing HGI tertiles ( P for trend=0.028). Conclusion:High HGI is associated with an increased risk for CKD in the nondiabetic population, indicating that HGI may help identify individuals at high risk for CKD.

目的 比较不同性别亚临床库欣综合征(SCS)患者的临床生化特点、代谢异常情况、激素水平差异及相关影响因素.方法 回顾性分析2010年1月-2020年1月因肾上腺意外瘤(AI)在解放军总医院第一医学中心内分泌科住院诊断的SCS患者118例,其中男38例,女80例,比较不同性别患者的临床特点、生化指标、代谢异常、血促肾上腺皮质激素-皮质醇(ACTH-F)节律、午夜1 mg和经典小剂量地塞米松抑制试验(DST)等检测结果的差异,并行logistic回归分析SCS患者中性别与午夜0:00时皮质醇(F00:00)、1 mg地塞米松抑制实验后晨8:00时皮质醇(1 mg DST-F08:00)及小剂量地塞米松抑制实验后晨8:00时皮质醇(小剂量DST-F08:00)之间的关系.结果 男性SCS患者体重指数[BMI,(28.08±8.30)kg/m2 vs.(25.57±3.76)kg/m2,P=0.026]、三酰甘油水平[(1.68±1.04)mmol/L vs.(1.35±0.69)mmol/L,P=0.045]及糖代谢异常比例(60.5％vs.37.5％,P=0.019)均明显高于女性患者,而年龄、SCS病程、血压水平、高血压患病率、骨代谢指标、骨密度等两组间差异无统计学意义.女性SCS患者F00:00、1 mg DST-F08:00及小剂量DST-F08:00均明显高于男性患者(P<0.05).以年龄、起病年龄、BMI、SCS病程为校正因素行logistic回归分析后,上述指标性别间差异仍有统计学意义(P<0.05).以是否绝经对女性患者进行分层分析,校正年龄、起病年龄、BMI、SCS病程后的logistic回归分析结果显示,是否绝经对女性患者F00:00、1 mg DST-F08:00、小剂量DST-F08:00水平无明显影响.结论 女性SCS患者BMI、三酰甘油及糖代谢异常比例低于男性;但其F00:00、1 mg DST-F08:00、小剂量DST-F08:00水平高于男性,且不受年龄、发病年龄、BMI及病程等因素的影响.

Objective:To analyze and summarize the prevalence and clinical characteristics of endocrine-metabolic abnormalities in a large cohort with POEMS syndrome, and to improve the understanding of endocrine-metabolic abnormalities in this special disease.Methods:The retrospective review was performed in patients with a diagnosis of POEMS syndrome at the First Medical Center of Chinese PLA General Hospital between January 2000 and January 2020. The clinical data about endocrine-metabolic abnormalities were extracted from their medical records.Results:The prevalence of endocrine-metabolic abnormalities was 93.38% (127/136) including gonads, thyroid, adrenal, islets and other endocrine organs involved. Hypogonadism was the most common endocrine-metabolic abnormality (98/136, 72.06%), followed by hypothyroidism (83/136, 61.03%), hypocalcemia (50/136, 36.76%), hyperprolactinemia (47/136, 34.56%), abnormal glucose metabolism (41/136, 30.15%), and adrenal insufficiency (41/136, 30.15%). The prevalence of single endocrinopathy and multiple endocrinopathies were 12.60%(16/127) and 87.40%(111/127) respectively. In patients with multiple endocrinopathies, the percentage of 2, 3, 4, 5 and 6 kinds of endocrine axes involved were 29.92%(38/127), 30.71%(39/127), 17.32%(22/127), 7.09%(9/127), and 2.36%(3/127), respectively. The endocrine-metabolic abnormalities in patients with POEMS syndrome were complex and variable. The median time from symptoms onset to confirmed diagnosis of POEMS was 412 d (198-1 055 d), and the median time for clinically definite was 8 d (4-15 d).Conclusion:The endocrine-metabolic abnormality is variable in POEMS syndrome, which can cause misdiagnosis and incorrect therapy. For patients with confirmed diagnosis of POEMS syndromes, a thorough endocrine evaluation should be performed and hormone supplement should be administrated timely.

Objective:To summarize the clinical characteristics and management of functional pancreatic neuroendocrine neoplasms(PanNENs) in a large Chinese cohort.Methods:Retrospective review was performed in patients with a definite diagnosis of functional PanNENs administrated in the First Clinical Center of Chinese PLA Hospital between January 2000 and July 2020. The clinical data, related hormone examinations, imaging examinations and pathological findings were extracted from their medical records and analyzed.Results:A total of 286 patients (male 103, female 183) aged (45.55±15.23) years were diagnosed to have definite functional PanNENs, with a duration of 24(12, 60)months. The most frequent functional PanNENs was insulinoma (266/286), followed by glucagonoma (10/286), somatostatinoma (3/286), adrenocorticotropic hormone (ACTH) producing-tumor (3/286), gastrinomas (2/286) and vasoactive intestinal polypeptide (VIP) tumor (2/286). Nine patients were diagnosed to have multiple endocrine neoplasia type 1 (MEN1) in which all the associated functional PanNENs were insulinomas. Two hundred and eighty patients with tumor localized in pancreas or with limited metastasis underwent surgery. The symptoms associated with hormonal over-secretion relieved significantly after surgery. Five patients with unresectable or recurrent metastases after surgery underwent systemic chemotherapy or other targeted therapies. With these various therapies, the symptoms also partially relieved. According to findings in pathological and immunochemical examination, all the functional PanNENs were categorized to neuroendocrine tumors (NET) G1(41.95%), NET G2(54.90%), NET G3(3.15%), and neuroendocrine carcinoma(NEC) (0%).Conclusion:Multidisciplinary collaboration is essential for precise diagnosis and tumor localization, as well as successful surgery or other targeted therapies, to improve the prognosis of patients suffered from these disorders.

目的 对分泌雄激素的卵巢性索间质瘤(sex cord stromal tumor,SCST)患者的诊治资料进行分析,总结其临床特征.方法 回顾性分析近年来解放军总医院第一医学中心收治的10例经病理证实为分泌雄激素的SCST患者的临床资料.结果 1)一般资料:10例女性患者,年龄13～69岁,病程1～6年.2)首诊情况及临床表现:5例首诊于内分泌科,5例首诊于妇科;7例青春期及育龄期女性因月经稀发或继发闭经首诊,3例绝经后女性因男性化表现首诊.临床表现:10例女性患者中,8例多毛,3例痤疮,5例嗓音改变,5例阴蒂肥大,2例脱发.3)睾酮水平:术前睾酮3.90～44.07 nmol/L,术后第2天复查睾酮0～6.51 nmol/L,较前明显下降.4)影像学表现:10例患者,其中8例通过妇科超声发现卵巢占位,2例无影像学证据,最终经手术探查确诊.5)病理:10例均为单侧卵巢肿物,直径为0.7～8.0 cm.病理结果 均支持卵巢性索间质瘤,其中2例为Leydig细胞瘤,3例为黄体瘤,2例为非特异性类固醇细胞瘤,2例为支持-间质细胞瘤,1例为粒层细胞瘤.结论 对于存在显著高雄激素血症的女性患者,需注意卵巢性索间质瘤可能,手术切除肿瘤可消除高雄激素临床表现.

Background Functional pancreatic neuroendocrine neoplasms (PanNENs) are very rare disorders but have complex spectrum, including insulinoma, gastrinoma, glucagonoma, somatostatinoma, and VIPoma. Patients with PanNENs usually present with characteristic symptoms caused by corresponding hormone hypersecretion. It has always been challenging in dealing with such rare but complicated disorders. In this report, we analyzed the clinical characteristics of functional PanNENs in a large cohort of Chinese patients and summarized our clinical experience in diagnosis and treatment. Methods The retrospective analysis was performed in patients with a definite diagnosis of functional PanNENs hospitalized in Chinese PLA General Hospital between 2000 and 2020. The clinical characteristics, surgical information, and pathological findings were extracted from their medical records and were analyzed. Results Totally, 286 patients (gender: male 103 and female 183; age: 45.55 ± 15.23 years old) were diagnosed with definite functional PanNENs. The most frequent functional PanNENs were insulinoma (266/286) followed by glucagonoma (10/286), somatostatinoma (3/286), adrenocorticotropic hormone- (ACTH-) producing tumor (3/286), gastrinoma (2/286), and VIPoma (2/286). Nine patients were diagnosed with multiple endocrine neoplasia type 1 (MEN1) in which all the associated functional PanNENs were insulinomas. The duration from symptoms' onset to confirmed diagnosis was 3.67 ± 4.28 years. Two hundred and eighty patients with tumor localized in pancreatic or with limited metastasis underwent surgery. The symptoms associated with hormonal oversecretion were improved significantly after surgery. Five patients with unresectable metastases or tumor recurrence after surgery were administrated with systemic chemotherapy or other targeted therapies. With these various therapies, the symptoms were also partially relieved. According to findings in pathological and immunochemical examination, all the functional PanNENs were categorized into NEN-G1 (41.95%), NEN-G2 (54.90%), NEN-G3 (3.15%), and NEC-G3 (0%). Conclusion Patients with suspected functional PanNENs should have a systematic endocrine examination at diagnosis. Multidisciplinary collaborations are essential for precise diagnosis and tumor localization. A successful surgery or other targeted therapies can improve the prognosis of patients with such rare but complex disorders.

目的 探讨非经典型21-羟化酶缺乏症(21-hydroxylase deficiency,21-OHD)的临床特点及诊治经验,提高该病的诊疗水平.方法 回顾性分析我中心近年收治的16例非经典21-OHD患者的临床资料并结合文献进行总结.结果 16例患者中,男性6例,女性10例,就诊年龄15～70岁.10例女性表现为月经稀发(5/10)、多毛/痤疮(7/10)、原发不孕(5/10);6例男性表现为皮肤色素沉着(2/6)、性早熟(4/6)、不育(1/6)、无症状(1/6).促肾上腺皮质激素(adrenocorticotropic hormone,ACTH)水平(20.91±8.01)pmol/L;17-羟孕酮(17-hydoxy progesterone,17-OHP)水平:女性(16.49±12.17)ng/ml,男性(16.25±5.31)ng/ml;中剂量地塞米松抑制试验17-OHP抑制率>50％(15/15);ACTH兴奋试验60 min 17-OHP>15 ng/ml(4/4).肾上腺CT表现为肾上腺双侧增生(7/16)、双侧结节(5/16)、单侧腺瘤(2/16)及未见异常(2/16).15例应用糖皮质激素替代治疗.随访中9例女性患者坚持治疗,月经均恢复正常.结论 对于女性高雄激素血症及男性儿童期性早熟和成年后不育患者,应行非21-OHD的筛查和甄别,糖皮质激素补充替代治疗能够改善预后.

目的 通过纵向研究探讨基线期的颈围(neck circumference,NC)能否预测未来高尿酸血症(hyperuricemia,HUA)的发生风险,为HUA的预防及早期治疗提供便捷的参考指标.方法 本研究纳入2015年参加"中国糖尿病患者肿瘤发生风险的流行病学研究"的北京市部分社区居民共4383人(1445名男性和2938名女性,基线期均未患高尿酸血症)作为研究对象.以该研究人群2015年资料作为基线数据,随访3年,采集新发高尿酸血症的情况.采用Cox回归模型分析基线颈围与3年随访期间HUA发病风险的关系.结果 在3年随访期间,男性受试者HUA的累积发病率高于女性(15.4％vs 13.1％,P=0.033).根据基线期NC四分位数由低到高将不同性别分别分为Q1～Q4组,在男性及女性人群中,Q2～Q4组在随访期间HUA的患病率明显高于Q1组(男性HUA患病率:Q1组10.5％vsQ2组15.5％,Q3组19.1％,Q4组18.0％;女性HUA患病率:Q1组7.7％vsQ2组12.6％,Q3组14.8％,Q4组19.6％;P均<0.05).女性受试者在调整混杂因素后,较高的基线NC与3年随访期间发生HUA的风险呈正相关(P趋势<0.001).与Q1组相比,基线NC的Q3组和Q4组中HUA风险显著增加(HR,Q3组1.43,Q4组1.76;P<0.05).男性受试者在调整混杂因素后,基线NC与3年随访期间发生HUA风险之间无显著相关性.结论 女性基线期NC较高者未来3年患HUA的风险显著增加,而男性基线NC无法预测未来3年患HUA的风险.