多发性内分泌肿瘤1型相关甲状旁腺功能亢进处理的研究进展

目的 总结多发性内分泌肿瘤1型（multiple endocrine tumors type 1,MEN1）相关原发性甲状旁腺功能亢进（primary hyperparathyroidism,PHPT）的处理方式。方法 对近年来国内外关于MEN1相关PHPT处理的相关文献进行归纳和总结。结果 MEN1相关PHPT的症状明显时,手术是其有效治疗手段,除常规的甲状旁腺全切除加部分自体移植术、甲状旁腺次全切除术外,切除范围较小的小于甲状旁腺次全切除、单腺体切除术也被证实有效。结论 结合MEN1相关PHPT患者的临床表现与甲状旁腺受累情况,个体化地选择适宜的手术时机、手术术式能够帮助MEN1相关PHPT患者获得理想的甲状旁腺功能状态,最大程度上保证MEN1相关PHPT患者的生活质量。     

多发性内分泌肿瘤诊治体会

多发性内分泌肿瘤 (ＭＥＮ)临床少见 ,易漏诊、误诊。我们报告 4例 ,并对其型别、诊治特点进行分析。1.病例资料 :例 1,女 ,31岁 ,阵发性头痛、心慌 5年。血压 110～ 2 6 0 /80～ 140ｍｍＨｇ。甲状腺右侧叶直径 2ｃｍ质硬肿物 ,按压右肾区血压升至 2 10 /12 0ｍｍＨｇ并典型症状发作。组织胺激发及苄胺唑啉抑制试验均阳性。腹膜后充气造影见右肾上腺区肿物。行右肾上腺肿瘤切除 ,病理示嗜铬细胞瘤 ,术后血压正常。1年后行甲状腺肿瘤切除 ,病理示 :甲状腺髓样癌 (ＭＴＣ)。又 3个月后行右侧甲状腺全切及同侧颈淋巴结清扫术 ,术后无复发 ,7年…     

多发性内分泌肿瘤Ⅰ型相关的胰腺内分泌肿瘤

多发性内分泌肿瘤Ⅰ型（MEN-1）由MEN-1抑癌基因突变所致,胰腺内分泌肿瘤是其主要病变之一,具有病理类型多样、发病早、多发等特点。基因测序是重要诊断方法,对基因突变携带者应定期筛查胰腺内分泌肿瘤。手术是控制激素过度分泌症状和预防转移的主要手段。     

多发性内分泌肿瘤2型的诊断和外科处理

目的 探讨多发性内分泌肿瘤2型（multiple endocrine neoplasia,MEN2）的诊断和外科处理方法.方法 回顾性研究1997年6月至2006年6月我院诊断和治疗的MEN2患者28例的临床资料.结果 MEN2a型25例,其中23例分属7个家系,均有RET基因11外显子634编码子突变;MEN2b型3例,无家族史,为RET基因16外显子918编码子突变.MEN2a型中22例有甲状腺肿物伴降钙素升高,其中17例经病理证实为甲状腺髓样癌;12例合并嗜铬细胞瘤,其中5例为多发性,2例恶性;5例合并甲状旁腺功能亢进症,3例无临床症状及生化改变.3例MEN2b型均为甲状腺髓样癌合并黏膜神经瘤病和马凡样体形,其中1例伴双侧肾上腺嗜铬细胞瘤.MEN2a型中12例接受双侧甲状腺全切除＋双侧颈淋巴清扫,5例行甲状腺肿物切除;甲状旁腺病变在甲状腺手术时一并处理;9例接受11次肾上腺肿瘤摘除术,3例为双侧肾上腺手术.3例MEN2b型均行双侧甲状腺全切除＋双侧颈淋巴清扫.结论 MEN2型以甲状腺髓样癌为主要病变,基因筛查可帮助早期诊断.根治性甲状腺切除能预防和治疗甲状腺髓样癌.     

多发性内分泌肿瘤-1型相关胰腺内分泌肿瘤的诊断与治疗

目的 总结多发性内分泌肿瘤-1型(MEN-1)相关胰腺内分泌肿瘤(PET)的诊治经验.方法 2004年1月至2007年12月上海交通大学医学院附属瑞金医院外科共收治MEN-1相关PET患者10例,其中男性2例,女性8例.来院时均未诊断为MEN-1,首次出现PET相关症状年龄为11～49岁,平均(32±11)岁.通过对患者进行定性、定位检查和基因测序明确诊断.并对患者进行药物治疗、手术干预和随访观察.结果 10例患者中诊断胰岛素瘤9例,其中多发性胰岛素瘤2例,单发胰岛素瘤合并多发无功能性胰岛细胞瘤及十二指肠恶性胃泌素瘤肝转移1例;胰高血糖素瘤1例.10例患者中,有家族史5例,检出MEN1基因突变9例.所有患者中,7例患者经过9次手术治疗,发现胰岛素瘤12个、无功能胰岛细胞瘤4个、十二指肠胃泌素瘤1个;2例患者接受饮食和药物治疗;1例患者放弃治疗.随访1个月～11年,除1例患者放弃治疗死亡外,其余9例患者病情稳定,血糖均在正常范围之内.结论 加强对PET及MEN-1的认识,及时诊断MEN-1相关的PET,进行合理积极的手术治疗,能够改善患者生活质量,并有望延长患者的生存期.     

多发性内分泌肿瘤1型的诊断和外科处理

目的探讨多发性内分泌肿瘤1型（multiple endocrine neoplasia type 1，MEN1）的诊断和外科处理。方法回顾性分析1974年至2005年我院诊断和治疗的MEN1患者的临床资料。结果本组MEN1患者17例，其中11例分属4个家系。1997年后的14例均发现MEN1基因突变。17例患者中甲状旁腺受累11例，并发胰岛素瘤6例，垂体腺瘤8例，肾上腺受累6例，胸腺类癌2例，皮肤纤维瘤样增生合并皮下脂肪瘤2例。2例4种腺体受累，3例3种腺体受累，7例2种腺体受累，4例1种腺体受累，1例12岁携带者尚未检出临床症状及生化改变。6例以肾结石、6例以胰腺内分泌功能障碍为首发症状，2例无明显自觉症状。17例患者中4例行甲状旁腺次全切除，1例行甲状旁腺腺瘤摘除，4例行胰岛素瘤切除手术，2例胸腺类癌行胸腺肿瘤摘除术。结论MEN1临床表现多样，即使同一家系病例亦可有不同表型。基因检查有助明确诊断。手术主要针对甲状旁腺增生、胰岛素瘤和胸腺类癌，在治疗肿瘤同时可改善患者的生存质量。     

多发性内分泌肿瘤1例报告

病人男性 ,3 1岁。 1996年因阵发性高血压 ,伴有剧烈头痛、头晕 ,皮肤、面色苍白等症状 ,在外院诊断为双侧肾上腺嗜铬细胞瘤。于 1996及 1997年在该院分别作左、右侧肾上腺嗜铬细胞瘤切除。术后均经病理检查确诊。 2 0 0 3年 4月体检发现左侧肾上腺嗜铭细胞瘤复发 ,并有双侧甲状腺结节性肿。 2 0 0 3年 4月行腹腔镜左侧肾上腺全切除术。术后证实为左侧肾上腺嗜铬细胞瘤复发。同年 5月到我院就医 ,入院后经检查拟诊为多发性内分泌肿瘤Ⅱ型 ,行双侧甲状腺全切除术 +颈淋巴结切除。术后病理检查为双侧甲状腺髓样癌并颈淋巴结转移、左侧甲状旁腺…     

Ⅰ型多发性内分泌肿瘤综合征相关胰岛素瘤诊治分析

目的 探讨Ⅰ型多发性内分泌肿瘤综合征（MEN-1）相关胰岛素瘤的诊断与外科治疗策略。方法 回顾性分析北京协和医院自1995年1月至2010年1月诊治有完整病历资料的合并MEN-1的胰岛素瘤21例临床资料。结果 共收集到21例,男6例,女15例。6例有胰腺内分泌肿瘤或MEN-1家族史。9例为多发性,2例为恶性胰岛素瘤。其他腺体中甲状旁腺受累最为常见,其次为垂体、肾上腺。19例接受手术治疗,根据高激素水平对机体影响严重程度采用一期手术、分期手术等多种治疗方案。胰腺手术中肿瘤摘除术应用最为常见,共切除病灶58个,65.5%病灶直径<1cm。5例病人发生B级胰瘘,保守治疗后痊愈。结论 MEN-1相关胰岛素瘤有其特殊临床特点,对于高危人群应提高警惕,术中应全面探查胰腺,配合术中超声、血糖监测等方法,保证切除全部病灶,对于其他受累腺体可一期或后续处理,需与相关科室加强协作及建立必要的转诊制度。     

Findings and long-term results of parathyroid surgery in multiple endocrine neoplasia type 1

Forty-two patients with primary hyperparathyroidism (HPT) of multiple endocrine neoplasia type 1 (MEN-1) were evaluated a mean of 8.9 years after subtotal parathyroid resection (SPX, n=34) or total parathyroidectomy with autotransplantation to the forearm (TPX, n=23). TPX as the primary operation revealed asymmetric and mainly nodular enlargement of the parathyroid glands with the presence of at least one normal-size gland in half of the individuals. TPX and SPX were accompanied by resolution of the hypercalcemia in 78% and 38% of the patients. Persistent and recurrent HPT occurred in 22% and 61% of the patients, while hypoparathyroidism requiring oral supplements occurred in 30% and 12% of the patients, respectively. Intact serum parathyroid hormone (PTH) in the arm of parathyroid autograft was high in the normocalcemic patients, somewhat lower in the patients with recurrent HPT, and normal to very low in the hypoparathyroid patients. Ratios of intact PTH between the grafted and non-grafted arms varied from 1 to 56.3, with average of 28.1 in the normocalcemic individuals, 8.2 in the patients with recurrent HPT, and 3.3 in those requiring supplements to maintain normocalcemia. These findings substantiate an 80% to 92% reversal of hypercalcemia during long-term follow-up of MEN-1 patients undergoing total parathyroidectomy or subtotal resection of 3–4 parathyroid glands as primary operative procedures and demonstrate the usefulness of intact serum PTH for functional evaluation of parathyroid autografts.

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Resumen Se valoraron 42 pacientes con hiperparatiroidismo primario (HPT) de neoplasia endocrina múltiple tipo 1 (NEM 1) a los 8.9 años, en promedio, después de resección paratiroidea subtotal (PTS, n=34) o de paratiroidectomia total con autotrasplante al antebrazo (PTX, n=23). La PTX como operación primaria reveló crecimiento asimétrico, y principalmente nodular, de las glándulas paratiroideas con la presencia de por lo menos una glándula de tamanño normal en ta mitad de los casos. La PTX y la PTS se acompañaron de hipercalcemia que revirtió espontáneamente en 78% y 38% de los casos, respectivamente, de una incidencia combinada proporcional de HPT persistente o recurrente de 22% y 61%, respectivamente, en tanto que se produjo hipoparatiroidismo dependients de terapia de sustitución en 30% y 12%, respectivamente. El nivel sérico de parathormona (PTH) intacta en el antebrazo con el autoinjerto apareció elevado en los pacientes normocalcémicos, algo más bajo en los pacientes con recurrencia y en los pacientes normales, y normal a muy bajo en los pacientes hipoparatiroideos. La relación de la PTH intacta entre los pacientes trasplantados y los no trasplantados varió entre 1 y 56.3, con promedios de 28.1 en los individuos normocalcémicos, 8.2 en los individuos con HPT recurrente y 3.3 en los que fue necesaria la sustitución para mantener normocalcemia. Estos hallazgos demuestran la reversión de la hipercalcemia en 80–92% de los casos en el curso del seguimiento a largo plazo de pacientes con NEM 1 sometidos a paratiroidectomía total o a resección subtotal de 3–4 glándulas como procedimientos operatorios primarios, y demuestra la utilidad de determinar el nivel sérico de PTH intacta en la evaluación funcional de los autoinjertos paratiroideos.

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Résumé Quarante-deux patients ayant une hyperparathyroïdie primaire (HPT) dans le cadre d'une néoplasie endocrine multiple de type 1 (NEM 1) ont été explorés en moyenne 8.9 ans après une parathyroïdectomie subtotale (SPX, n=34) ou une parathyroïdectomie totale avec une autotransplantation à l'avant-bras (TPX, n=23). Lorsqu'était pratiquée une TPX comme intervention première, l'histologie révelait une asymétrie et principalement une hypertrophie nodulaire des glandes parathyroïdes avec la présence d'au moins une glande parathyroïde normale dans 50% des cas. Les hypercalcémies ont été normalisées par les résections de type TPX et SPX dans respectivement 78% et 38% des cas. L'hypercalcémie persistante ou récidivée a été constatée dans 22 et 61% des cas, alors qu'une hypocalcémie nécessitant un traitement substitutif a été notée dans respectivement, 30 et 12% des cas. Le taux d'hormone parathyroïde (PTH) intacte dans le greffon de l'avant-bras était élevée chez les individus normocalcémiques, un peu moins chez les patients ayant une récidive, et très bas chez les patients ayant une hypoparathyroïdie postopératoire. Le rapport de PTH intacte chez les patients greffés/patients non greffés variait entre 1 et 56.3, avec une moyenne de 28 1 chez les patients normocalcémiques, de 8.2 chez les patients ayant une récidive, et de 3.3 chez les patients ayant recours à un traitement substitutif pour maintentir leur calcémie normale. Globalement on constate que 80–92% des hypercalcémies se sont normalisées à long terme chez les patients ayant une NEM 1 qui ont eu une parathyroïdectomie totale ou subtotale de 3–4 glandes parathyroïdes comme intervention première, et que ces résultats démontrent l'utilité du dosage de la PTH intacte pour évaluer la valeur fonctionelle des autotransplants parathyroïdes.

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Presented at the International Association of Endocrine Surgeons in Stockholm, Sweden, August, 1991.     

Primary hyperparathyroidism in patients with multiple endocrine neoplasia syndromes. Surgical experience

Forty-five patients with biochemically documented primary hyperparathyroidism as part of multiple endocrine neoplasia syndrome types 1 or 2 were surgically treated from 1960 through 1980. Hyperplasia occurred in 69% of the patients, single adenoma in 27%, and double adenomas in 4%. All but two patients with hyperplasia underwent subtotal parathyroidectomy. In this group, the cure rate was 93% and the incidence of permanent postoperative hypoparathyroidism 23%. In the adenoma group, treatment included excision of the adenoma and biopsy of at least one other gland. The cure rate was 76%, with no postoperative hypoparathyroidism. Analysis of patients with persistent hyperparathyroidism suggested that failure to recognize multiple gland disease was the principal cause of postoperative hypercalcemia. In view of the high incidence of hypocalcemia after subtotal parathyroidectomy, approximately 500 mg of tissue should be cryopreserved to allow transplantation should hypocalcemia ensue postoperatively.     

Management of pheochromocytomas in patients with multiple endocrine neoplasia type 2 syndromes.

OBJECTIVE: The authors sought to determine the optimal surgical management of pheochromocytomas that develop in patients with multiple endocrine neoplasia (MEN) type 2 syndromes. SUMMARY BACKGROUND DATA: The performance of empirical bilateral adrenalectomy in patients with MEN 2A or MEN 2B, whether or not they have bilateral pheochromocytomas, is controversial. METHODS: The results of unilateral or bilateral adrenalectomy were studied in 58 patients (49 with MEN 2A and 9 with MEN 2B). Recurrence of disease was evaluated by measuring 24-hour urinary excretion rates of catecholamines and metabolites and by computed tomography (CT) scanning. RESULTS: The mean postoperative follow-up was 9.40 years. There was no operative mortality and malignant or extra-adrenal pheochromocytomas were not present. Twenty-three patients with a unilateral pheochromocytoma and a macroscopically normal contralateral gland underwent unilateral adrenalectomy. A pheochromocytoma developed in the remaining gland a mean of 11.87 years after the primary adrenalectomy in 12 (52%) patients. Conversely, 11 (48%) patients did not develop pheochromocytoma during a mean interval of 5.18 years. In the interval after unilateral adrenalectomy, no patient experienced hypertensive crises or other complications related to an undiagnosed pheochromocytoma. Ten (23%) of 43 patients having both adrenal glands removed (either at a single operation or sequentially) experienced at least one episode of acute adrenal insufficiency or Addisonian crisis, including one patient who died during a bout of influenza. CONCLUSIONS: Based on these data, the treatment of choice for patients with MEN 2A or MEN 2B and a unilateral pheochromocytoma is resection of only the involved gland. Substantial morbidity and significant mortality are associated with the Addisonian state after bilateral adrenalectomy.     

Parathyroid surgical failures with sufficient decline of intraoperative parathyroid hormone levels: unobserved multiple endocrine neoplasia as an explanation

HYPOTHESIS: A sufficient decline in levels of parathyroid hormone measured intraoperatively (ioPTH) precludes early and late surgical failures. DESIGN: A case series of consecutive patients undergoing parathyroidectomy with ioPTH measurement. SETTING: A university hospital. PATIENTS AND INTERVENTION: Two hundred sixty-nine consecutive patients with sporadic primary hyperparathyroidism who underwent first-time parathyroid surgery with ioPTH measurement were followed up for as long as 10 years after surgery. Data on all patients have been collected in a prospective database. MAIN OUTCOME MEASURES: Surgical failures up to 10 years after parathyroid surgery. RESULTS: With an average follow-up of 3.6 years (range, 6-120 months), the overall cure rate was 96%. The ioPTH level correctly predicted long-term outcome in 248 (92%) of 269 patients. Six patients had a false-positive ioPTH finding. Five of these patients were found to have germline mutations in the gene for multiple endocrine neoplasia. The remaining patient has not undergone genetic testing. The mutations have rarely (n = 1) or never (n = 4) been described before, to our knowledge. CONCLUSIONS: Intraoperative measurement of PTH level has a high overall accuracy with a mean follow-up of 3.6 years. However, among the late surgical failures with false-positive ioPTH findings, overlooked mutations in the multiple endocrine neoplasia gene should be suspected, and therefore genetic analyses in these patients are of great importance.     

Nuclear DNA analysis of hyperplastic parathyroid glands in multiple endocrine neoplasia type I.

Twenty-four hyperplastic parathyroid glands from 11 patients with multiple endocrine neoplasia type I (MEN-I), and 36 hyperplastic parathyroid glands in 15 patients with sporadic primary hyperparathyroidism, ie, not associated with MEN, were analyzed for DNA by flow cytometry. Sixteen of 24 hyperplastic parathyroid glands from patients with MEN-I were DNA diploid, and eight were DNA aneuploid. Thirty-three of 36 hyperplastic parathyroid glands from patients without MEN were DNA diploid, and only three were DNA aneuploid. The mean percentage of 4c level (a measure of the G2M phase of the cell cycle) of DNA diploid hyperplastic parathyroid glands taken from patients with MEN-I was 8.1% +/- 4.5%, which is significantly higher than the 3.5% +/- 3.4% for those taken from patients without MEN. Our results show that there is a difference in nuclear DNA content between hyperplastic parathyroid glands in patients with MEN-I and those in patients without MEN.