中枢性甲亢2例及文献复习

目的: 探讨中枢性甲状腺功能亢进症的诊断和治疗。 方法: 回顾在我院住院的2例中枢性甲亢患者的诊治经过并结合文献进行分析。 结果: 两例患者均有甲状腺肿大和甲亢症状,血甲状腺激素(fT4,fT3)和促甲状腺激素(TSH)都轻度升高。其中1例甲亢症状经2年口服抗甲状腺药物和2次放射性131I治疗症状亦无缓解,垂体MRI示垂体侵袭性大腺瘤,且伴生长激素分泌过多依据,经蝶行垂体瘤切除术,瘤体组织免疫组化TSH和 GH染色阳性,术后血FT3, FT4 和TSH较术前明显下降,诊断垂体TSH腺瘤。另外1例垂体MRI未见异常,血TSH可被地塞米松和溴隐亭抑制,甲状腺激素受体β亚单位基因(THRB)检测未发现突变。诊断为选择性垂体甲状腺激素抵抗综合征(PRTH), 选择非特异性对症治疗。结论: 对有甲亢临床表现、血fT4和fT3升高而 TSH不降低(明显有别于Graves 病等原发性甲亢)的甲亢患者,应考虑中枢性甲状腺功能亢进症,其病因可能为垂体TSH腺瘤或PRTH。进一步进行垂体MRI,TSH抑制或兴奋试验,TSHα亚单位检测,THRB基因突变检测,等检查有助于垂体TSH腺瘤和PRTH的诊断以及两者的鉴别诊断,以利选择正确的治疗方案。     

中枢性甲状腺功能亢进症的新认识

中枢性甲状腺功能亢进症（甲亢）包括垂体促甲状腺激素（TSH）瘤和垂体选择性甲状腺激素抵抗综合征（PRTH）两类,以血清甲状腺激素升高伴TSH正常或升高为基本特征,患者均有典型的甲亢表现,TSH瘤的发病机制尚不明了,主要与pit-1基因异常有关,患者血中TSH－α亚单位明显增高,治疗以手术为首选。PRTH主要源于甲状腺激素受体β基因突变,多数患者TSH对促甲状腺激素放激素（TRH）刺激有反应,本病以内科保守治疗为主,目前尚无理想的治疗方案。     

垂体促性腺激素瘤的临床分析

目的探讨垂体促性腺激素瘤的临床特点。方法对72例免疫组织化学诊断为垂体促性腺激素瘤患者进行回顾性分析。结果发病以40～60岁男性多见。临床表现以肿瘤压迫症状为主,性腺功能异常的表现不多见。免疫组织化学均为促性腺激素卵泡刺激素（FSH）和（或）黄体生成素（LH）阳性,以FSH阳性多见,伴催乳素（PRL）和促甲状腺激素（TSH）阳性各1例,但均无相应的临床表现。病理诊断多数为促性腺激素腺瘤。治疗以手术为主,首选经蝶骨手术。结论免疫组织化学是目前诊断促性腺激素瘤的最可靠的方法,以FSH阳性为主。免疫组化特征与临床表现的关联不大。治疗以经蝶骨手术为主。     

以低血糖昏迷就诊的多发性内分泌腺瘤1型四例并文献复习

目的 探讨以低血糖昏迷就诊的多发性内分泌腺瘤1型(MENI型)的临床特点及诊治经验.方法 对因复低血糖昏迷住院、经内分泌激素和影像检查及手术确诊为MEN1型的4例患者临床资料进行分析.结果 (1)4例患者均具备Whipple三联征,影像榆查显示胰腺内占位性病变,手术病理证实为胰岛素瘤,其中2例为多发性.(2)1例合并垂体瘤、甲状旁腺瘤(术后复发)和肾上腺皮质腺瘤,1例合并垂体瘤、甲状旁腺瘤(2个)和肾卜腺结节增生,1例合并垂体瘤和甲状旁腺瘤,另1例合并垂体瘤及可疑甲状旁腺瘤.结论 (1)对于胰岛素瘤患者,应仔细检查是否存在MENl型.(2)对于MEN1型患者,手术时应关注甲状旁腺瘤(或增生)和胰岛素瘤是否为多发及异位等情况.术后应定期随访以监测病变的复发和新病变发生.     

以低钾性周期性麻痹和雄激素异常升高为主要表现的垂体促甲状腺激素细胞腺瘤一例

垂体促甲状腺激素（TSH）细胞腺瘤是临床罕见的垂体腺瘤类型。本文报道1例合并周期性麻痹及雄激素异常升高的患者,以反复四肢麻痛、活动障碍起病,进而发现血钾低、睾酮水平显著升高,甲状腺激素明显升高而TSH水平未被抑制,垂体磁共振成像（MRI）提示垂体腺瘤,诊断为垂体TSH细胞腺瘤。完善术前准备后行手术治疗,术后甲状腺功能恢...     

多内分泌腺瘤病的研究现状

多内分泌腺瘤病分为1型(MEN1)和2型(MEN2),其中MEN2又可分为MEN2A和MEN2B。MEN1主要临床表现为甲状旁腺腺瘤、胃肠胰肿瘤(以胃泌素瘤和胰岛素瘤常见)和垂体前叶瘤(以泌乳素瘤常见)。MEN2A主要表现为甲状腺髓样癌(MTC)、嗜铬细胞瘤和甲状旁腺增生; MEN2B为MTC、黏膜神经纤维瘤和嗜铬细胞瘤。Wermer于1954年首先描述了垂体前叶腺瘤、     

多发性内分泌腺瘤2A型

多发性内分泌腺瘤2型（MEN2）又称Sipple综合征，其病理学特征为甲状腺髓样癌（MTC）或甲状腺C细胞增生。根据不同的临床表现可分为MEN2A、MEN2B、家族性甲状腺髓样癌（FMTC）及其他型。文献报告MEN2A占MEN2的60％，以MTC为主要临床表现，约50％伴有嗜铬细胞瘤（PCC），30％-40％伴有甲状旁腺增生或腺瘤（HPT）。MEN2B以黏膜多发性神经瘤、MTC和（或）PCC为特点，可有类马凡体征，少数患者还伴有肠道神经节母细胞瘤，角膜神经粗大，骨骼发育异常及发育延缓等，无甲状旁腺疾病。FMTC则仅有MTC，且患有MTC的家族成员不少于4个。     

垂体促甲状腺素瘤的临床特点与诊治分析

目的 分析TSH瘤的临床特点和诊治经验.方法 对2006年1月至2011年9月在本院确诊治疗的16例垂体TSH分泌瘤患者的临床表现、实验室检查以及辅助检查和手术治疗效果进行分析.结果 (1)男性9例,女性7例,年龄(51.63±13.23)岁.就诊原因为甲状腺毒症症状占87.5％(14/16),仅2例分别因视物障碍和体检发现甲状腺功能异常.16例患者均无突眼、杵状指、胫前黏液性水肿.(2)血清FT4和FT3水平均高于正常,血清TSH(4.37±2.77)μIU/ml,25％(4/16)的患者同时合并血清甲状腺球蛋白抗体和(或)甲状腺过氧化物酶抗体阳性,促甲状腺素受体抗体全部阴性.9例行TRH兴奋试验:3例有反应(TSH高峰较基线上升5.45～9.20μIU/ml),6例无反应(TSH高峰较基线上升-0.01～3.15μIU/ml).11例患者行生长抑素试验:TSH平均被抑制到基线的27.15％(5.19％～99.15％).有2例患者分别合并血清催乳素和胰岛素样生长因子Ⅰ升高.垂体MRI显示垂体占位15例,其中微腺瘤10例,垂体大腺瘤5例;1例患者垂体未见异常,但见鼻腔内占位.(3)11例患者行手术治疗:9例行经蝶垂体瘤手术,1例行经额垂体瘤手术,1例行内镜下鼻中隔肿瘤手术.术后病理均为垂体腺瘤(11/11).结论 TSH不被抑制的甲状腺毒症需警惕TSH瘤,联合多种动态功能试验更有助于本病的早期诊断;另外在定性诊断符合TSH瘤,垂体影像未见异常的病例还需警惕异位TSH瘤.     

多发性内分泌腺瘤2A型

多发性内分泌腺瘤2型(MEN2)又称Sipple综合征,其病理学特征为甲状腺髓样癌(MTC)或甲状腺C细胞增生。根据不同的临床表现可分为MEN2A、MEN2B、家族性甲状腺髓样癌(FMTC)及其他型。文献报告MEN2A占MEN2的60%,以MTC为主要临床表现,约50%伴有嗜铬细胞瘤(PCC),30%～40%伴有甲状旁腺增生或腺瘤(HPT)。MEN2B以黏膜多发性神经瘤、MTC和(或)PCC为特点,可有类马凡体征,少数患者还伴有肠道神经节母细胞瘤,角膜神经粗大,骨骼发育异常及发育延缓等,无甲状旁腺疾病。FMTC则仅有MTC,且患有MTC的家族成员不少于4个。MEN2A患者的发病…     

多发性内分泌腺瘤病

多发性内分泌腺瘤病分为1型(MEN1)和2型(MEN2),其中MEN2又可分为MEN2A和MEN2B。MEN1主要临床表现为甲状旁腺腺瘤、胃肠胰肿瘤(以胃泌素瘤和胰岛素瘤常见)和垂体前叶瘤(以泌乳素瘤常见)。MEN2A主要表现为甲状腺髓样癌、嗜铬细胞瘤和甲状旁腺增生,MEN2B为甲状腺髓样癌、黏膜神经纤维瘤和嗜铬细胞瘤。1997年,美国国立卫生研究院(NIH)和欧洲MEN1研究联合体(ECMEN1)成功地克隆到MEN1的致病基因men1[1-2]。之后,在绝大部分MEN1家系病人中都发现了该基因的突变,从而确定了men1基因与MEN1之间的因果关系。MEN2由原癌基因ret突…     

促甲状腺激素垂体瘤病例报道并文献复习

对2例促甲状腺激素(TSH)垂体瘤患者的临床资料进行回顾性分析,并进行文献复习.2例患者都存在甲状腺毒症,均有甲状腺激素水平增高同时不伴TSH抑制,1例大腺瘤患者存在视野缺损.2例患者在确诊之前均误诊为原发性甲状腺功能亢进而接受抗甲状腺药物治疗4～7年,1例患者还曾行甲状腺大部切除术.确诊后大腺瘤患者行垂体瘤手术联合垂体放射治疗,另1例为微腺瘤患者,行垂体放射治疗.术后随访,2例患者的甲状腺功能亢进均较前改善.甲状腺毒症患者血清TSH水平不被抑制时应警惕TSH垂体瘤的存在,鞍区影像学检查可以进一步明确诊断,早期诊断和手术联合放射治疗可以取得较好的治疗效果.     

生长抑素类似物在垂体促甲状腺激素瘤诊断和治疗中的作用

目的探讨生长抑素类似物奥曲肽在垂体促甲状腺素(TSH)瘤诊断和治疗中的作用。方法系统报告北京协和医院诊治的1例垂体TSH大腺瘤患者临床特点,采用99mTc-奥曲肽显像和鞍区MRI对肿瘤进行准确定位诊断。给予奥曲肽0.1mg,每8h皮下注射,10d,观察TSH水平和肿瘤大小的变化,经口鼻蝶窦行垂体瘤切除术,观察手术效果,并进行相关文献复习。结果TSH瘤奥曲肽显像呈阳性。单纯抗甲状腺药物治疗难以使甲状腺功能完全正常。奥曲肽治疗能快速有效使甲状腺功能控制至正常,经10d奥曲肽治疗,垂体肿瘤由3.0cm×2.0cm×2.5cm缩小至2.0cm×2.0cm×1.5cm,甲状腺肿大由Ⅲ度缩小为Ⅱ度。结论99mTc-奥曲肽显像可作为TSH瘤定位诊断的方法之一。奥曲肽治疗能有效控制继发性甲状腺功能亢进并缩小TSH瘤体积,可用作TSH瘤的常规手术前准备。     

垂体促甲状腺激素腺瘤的临床特征和术前短效奥曲肽治疗的临床疗效

目的归纳分泌促甲状腺激素(TSH)垂体腺瘤(TSH腺瘤)的临床特征,评价术前短效奥曲肽治疗的临床疗效。方法回顾性分析首都医科大学附属北京天坛医院2008年1月至2018年1月明确诊断的垂体TSH腺瘤患者共40例。采集一般资料、实验室及影像学检查等临床资料;评价患者术前奥曲肽治疗的临床疗效。结果40例患者(男:女=24∶16),发病年龄(30.5±5.1)岁,大腺瘤35例(87.5%);最常见症状为甲状腺高代谢症候群,共32例(80.0%),其次是头疼、头晕,视力、视野受损和性腺功能减退。30例(75%)患者奥曲肽治疗3~5d甲状腺功能即恢复正常,总有效率90.0%;有效累计剂次超过10次的患者其治疗前游离甲状腺素(FT4)水平明显高于10次以下者。结论甲状腺高代谢症候群、垂体占位效应是垂体TSH腺瘤最常见的临床表现,术前奥曲肽治疗可有效控制甲状腺功能亢进,治疗前FT4水平是影响奥曲肽疗效的重要因素。     

Hyperthyroidism due to a thyroid-stimulating hormone (TSH)-secreting pituitary adenoma associated with functional hyperprolactinaemia. A case report

This paper reports the case of a 31-year-old woman with hyperthyroidism, increased TSH and thyroid hormone levels, evidence of a pituitary adenoma, hyperprolactinaemia, amenorrhoea, and galactorrhoea. Following trans-sphenoidal pituitary adenomectomy, mild hyperthyroidism and increased TSH and alpha subunit levels persisted, whereas hyperprolactinaemia, amenorrhoea, and galactorrhoea disappeared. Serum TSH levels were not affected by administration of TRH, metochlopramide, domperidone, l-dopa or somatostatin. Serum TSH chromatography showed a normal pattern. Following a second trans-sphenoidal pituitary adenomectomy and radiotherapy, hyperthyroidism disappeared, and the TSH and alpha subunit levels returned to normal. Light microscopy showed no specific TSH immunostaining although electron microscopy revealed numerous secretory granules alined along the plasma membrane. The post-operative follow-up confirmed the presence of a TSH-secreting pituitary adenoma associated to functional hyperprolactinaemia.     

A TSH secreting pituitary tumour causing hyperthyroidism: presentation of a case and review of the literature.

A 45 year old male with a 12 year history of mild hyperthyroidism and a pituitary tumour is presented. He had both clinical and laboratory evidence of hyperthyroidism and his serum TSH was persistently and markedly elevated. A TRH test resulted in no further rise in serum TSH. No evidence of pituitary or peripheral endocrine deficiencies existed and prolactin levels were normal. Craniotomy was performed and a pituitary adenoma was removed. On light microscopy, it was mostly composed of chromophobes. However, occasional granulated cells were observed, and on electron microscopy, most of the cells contained fine granules, which suggested possible thyrotroph origin of the tumour. One week post-operatively the patient's serum TSH returned to normal. Again, TRH produced no response in TSH. The patient became hypothyroid by clinical and laboratory findings and is currently on thyroid replacement therapy. The previously reported TSH secreting tumours associated with hyperthyroidism are reviewed.     

Hyperthyroidism due to a TSH-secreting pituitary tumor

A 28-year-old female with a 12-year history of goiter is presented. She had both clinical and laboratory evidence of hyperthyroidism, and her serum TSH was persistently and markedly elevated after treatment with antithyroid drugs. A TRH stimulation test resulted in no further rise in serum TSH after cessation of medication. Menses were regular and serum prolactin levels were normal. Serum LH and FSH responses to LHRH stimulation test were normal. No other evidence of pituitary or peripheral endocrine deficiencies existed. She underwent a subtotal thyroidectomy followed by 131I therapy three years later. A pituitary adenoma with sphenoidal and suprasellar extension was completely removed by transphenoidal approach. On light microscopy, it was mostly composed of chromophobic cells with occasional calcification showing sinusoidal pattern. On electron microscopy, most of the cells contained fine granules, which suggested thyrotroph. The immunoperoxidase technique revealed TSH beta in the cytoplasm of some adenoma cells. Three days postoperatively the patient's serum TSH levels returned to normal. TRH stimulation test produced a normal response in serum TSH. The patient was diagnosed hypothyroid by laboratory findings and is currently on thyroid replacement therapy. The patient became pregnant and delivered twice prior to the operation for pituitary adenoma. The previously reported TSH secreting adenomas associated with hyperthyroidism were reviewed.     

Coincidence of hot thyroid nodules and primary hyperparathyroidism.

Hyperthyroidism is frequently associated with hypercalcemia, which usually subsides after successful treatment of hyperthyroidism. Moreover, thyroid nodules are frequently detected by preoperative thyroid ultrasound in patients with primary hyperparathyroidism. Sensitised by the observation of a patient with coexisting hyperthyroidism and hyperparathyroidism we prospectively evaluated thyroid nodules in euthyroid patients with hyperparathyroidism by thyroid scintigraphy. Whereas the first patient with hyperparathyroidism was hyperthyroid the subsequent four patients with hyperparathyroidism and thyroid nodules had normal fT3 and fT4. Two patients had hypercalcemia and nephroureterolithiasis. Three patients suffered from hypercalcemia and bone pain due to osteoporosis. In the hyperthyroid patient hypercalcemia persisted after euthyroidism was achieved intact parathyroid hormone was found to be elevated. Subsequently, thyroid nodules, detected by preoperative ultrasound in four euthyroid patients with primary hyperparathyroidism, were identified as compensated hot nodules by thyroid scintigraphy. All patients underwent combined subtotal thyroidectomy and parathyroid resection. Histology showed hyperplastic parathyroid glands in one patient and a single parathyroid adenoma in four cases. Postoperatively calcium and PTH levels returned to normal and TSH levels increased in all patients. Persistence of hypercalcemia after successful treatment of hyperthyroidism should be reason for the determination of parathyroid hormone. Thyroid nodules detected by preoperative ultrasound in patients with hyperparathyroidism living in areas of iodine deficiency should be further evaluated by scintigraphy even if TSH is normal. In the case of hot thyroid nodules both parathyroid and partial thyroid resection should be performed.     

Hyperthyroidism in a patient with TSH-producing pituitary adenoma coexisting with thyroid papillary adenocarcinoma

A 27-year-old woman who presented with a left thyroid nodule was found to have hyperthyroidism caused by a syndrome of inappropriate secretion of TSH. The levels of free T3, free T4 and TSH were 9.50 pg/mL, 4.05 ng/dL and 2.16 microU/mL, respectively. Magnetic resonance imaging of the head revealed a pituitary macroadenoma. The TSH response to TRH stimulation was normal and responses of other anterior pituitary hormones to stimulation tests were also normally preserved. Administration of octreotide with iodine successfully reversed hyperthyroidism prior to total resection of pituitary adenoma, which was followed by hemithyroidectomy of the left thyroid five months later. Histologically, the resected pituitary adenoma was a TSH-producing adenoma (TSH-oma) and the thyroid nodule was a papillary adenocarcinoma. Serum TSH diminished to undetectable levels immediately following pituitary adenomectomy but gradually normalized over nine months. Coexistence of a TSH-oma with thyroid cancer is very rare and only two similar cases have previously been documented. This combination raises the possibility that TSH may be involved in tumorigenesis in the thyroid gland.     

Hyperthyroidism due to inappropriate secretion of thyrotropin in 10 patients.

PURPOSE: The syndrome of inappropriate thyroid-stimulating hormone (TSH) secretion, characterized by elevated serum free thyroxine and triiodothyronine levels in association with measurable serum TSH concentrations, remains an uncommon cause of hyperthyroidism that is being recognized with increasing frequency. The hyperthyroidism may be due to either neoplastic pituitary TSH secretion or selective pituitary resistance to thyroid hormone. In an effort to better understand this rare cause of hyperthyroidism, we undertook a retrospective analysis of our institution's experience with this condition. PATIENTS: We reviewed our cumulative experience (10 patients) with hyperthyroidism due to the syndrome of inappropriate secretion of TSH. RESULTS: Six patients were diagnosed with TSH-secreting pituitary adenomas and four were found to have selective pituitary resistance to thyroid hormone. One patient with tumor had a TSH-secreting pituitary adenoma in the setting of multiple endocrine neoplasia syndrome. In all patients with tumor, hyperthyroidism was successfully treated with transsphenoidal adenomectomy with or without pituitary radiotherapy. All four patients with pituitary resistance had thyroid ablation or resection prior to their correct diagnosis. Therefore, therapy for this group of patients involved thyroid hormone replacement and efforts to suppress TSH hypersecretion. All 10 patients have done well clinically, with follow-up ranging from 2 weeks to 13 years. CONCLUSIONS: Adequate treatment exists for the two primary causes of TSH hypersecretion. TSH-secreting pituitary adenomas are treated with surgery and, if necessary, adjuvant pituitary radiotherapy. The results are generally good if the tumor is diagnosed and treated at an early stage. Primary therapy for hyperthyroidism due to selective pituitary resistance to thyroid hormone is aimed at suppression of pituitary TSH hypersecretion. The evaluation of any patient with hyperthyroidism must be thorough and, in some cases, should include measurement of TSH to determine the presence of inappropriate secretion. Eliminating this diagnosis will help avoid improper and potentially harmful treatment of hyperthyroid patients.     

Surgical Management of Thyrotropin-Secreting Pituitary Adenomas

The reported cases of hyperthyroidism due to a TSH-secreting pituitary adenoma have steadily increased in previous years; however, information about the results and long term outcome after pituitary surgery is scanty.Twenty-four patients with a TSH-secreting adenoma underwent pituitary surgery at our department in the last 15 years. Hypersecretion of other pituitary hormones was diagnosed in 7 patients. Three patients were euthyroid at the time of surgery because of previous ablative thyroid therapies.The success rate of surgery strictly depends on the criteria used. Normalization of elevated FT₃ and FT₄ levels occurred in 17 of the 21 patients with preoperative hyperthyroidism: however, only those with early postoperative undetectable TSH level (12 cases) had no recurrence of disease during follow-up and no residual tumor tissue on postoperative MRI, whereas recurrence of hyperthyroidism occurred in 3 of the 5 patients without postoperative TSH inhibition. All 3 euthyroid patients had a subtotal removal of the tumor, as judged by postoperative MRI.Surgical removal is the therapy of choice of TSH-secreting adenomas, whereas radiotherapy and medical treatment with somatostatin analogues are usually reserved to patients with incomplete tumor removal. A thorough postoperative evaluation is necessary to discriminate between complete and partial remission of disease.