Sipple's syndrome: a case report

A 41-year-old woman was hospitalized for evaluation of diabetes mellitus and hypertension. The hormonal and radiological examinations revealed that she had pheochromocytoma of bilateral adrenal gland and medullary carcinoma of thyroid gland. Therefore, she was diagnosed as having Sipple's syndrome. She had no definite familial history, but her two sisters, already dead, had been strongly suspected of having had pheochromocytoma. First, bilateral adrenalectomy was performed and secondly, total thyroidectomy, excision of parathyroid and cervical lymph node dissection were performed. Histopathological diagnosis was pheochromocytoma of bilateral adrenal gland, medullary carcinoma of thyroid gland and chief cell hyperplasia of parathyroid gland. We report a case of Sipple's syndrome, which probably is the 88th case in Japan, with the review of the previous Japanese literature.     

Early diagnosis of and surgical strategy for adrenal medullary disease in MEN II gene carriers

Sixteen multiple endocrine neoplasia type II (MEN II) gene carriers--12 who had undergone thyroidectomy because of medullary carcinoma of the thyroid and 4 whose thyroid glands had been removed because of C cell hyperplasia--were examined for the presence of pheochromocytomas. No patient had sought medical advice for pheochromocytoma symptoms. Fourteen patients had MEN IIa syndromes, one patient had a MEN IIb and another patient had a mixed syndrome of von Recklinghausen's neurofibromatosis and MEN II. Eight patients had undergone unilateral adrenalectomy for pheochromocytoma 11 +/- 4 years before. The patients underwent clinical examination, determination of the urinary excretion of catecholamines and metabolites, and 131I-metaiodobenzylguanidine (131I-MIBG) and CAT scans. 131I-MIBG scanning was performed with images 1, 4, and 7 days after the radionuclide injection. In seven of eight patients who had undergone unilateral adrenalectomies, the 131I-MIBG scans showed accumulation of the radionuclide in the remaining adrenal gland. Bilateral adrenal accumulation of the radionuclide was demonstrated in seven of eight MEN IIa gene carriers who had not undergone adrenalectomy. Five patients, two of whom had undergone adrenalectomy, were found to have unilateral pheochromocytomas less than 2 cm in diameter. Only one of these five patients had an elevated excretion of urinary catecholamines. Between day 4 and day 7 after 131I-MIBG injection, adrenal glands with pheochromocytomas increased their relative accumulation of the radionuclide significantly more (p less than 0.02) than did adrenal glands without any demonstrable pheochromocytomas. All the pheochromocytomas were viewed by means of CAT scans. Only one MEN IIa patient had bilateral pheochromocytomas, but our findings indicate that there is a tendency to bilateral adrenal medullary hyperfunction in most MEN II gene carriers. As 131I-MIBG and CAT scans can facilitate the early diagnosis of pheochromocytomas, unilateral adrenalectomy can safely be performed in most MEN IIa patients. Bilateral pheochromocytomas develop in a majority of patients with MEN IIb syndromes. Bilateral adrenalectomy should therefore be performed in these patients.     

Pheochromocytoma in multiple endocrine neoplasia type II: an example of the two-hit theory of neoplasia

Six kindreds in which pheochromocytomas were present as manifestations of the autosomal dominantly inherited multiple endocrine neoplasia (MEN) type II were studied. The patients underwent bilateral total adrenalectomy with the finding that the pheochromocytomas were bilateral, multifocal, and associated with distinct medullary hyperplasia and reduction in the normal corticomedullary ratio-- features not usually seen in patients with sporadic pheochromocytoma. These findings were exemplified in recent cases of a 34-year-old woman and a 40-year-old man who both had undergone total thyroidectomy for medullary carcinoma of the thyroid. Diagnoses of pheochromocytoma were made by catecholamine studies, computerized tomography, and 131I meta-iodobenzylguanidine (MIBG) scan. Bilateral adrenalectomy was performed with the finding of multiple bilateral pheochromocytomas and adrenal medullary hyperplasia. As in hereditary medullary carcinoma of the thyroid, the histologic findings in pheochromocytomas of the MEN II syndrome are consistent with Knudson's two-mutational-event theory for the initiation of neoplasia, with adrenal medullary hyperplasia representing the manifestation of the first or genetic mutational event and being present invariably in the hereditary cases.     

肾上腺髓质增生症(附八例报告)

目的 提高肾上腺髓质增生症（ＡＭＨ）的诊断水平和治疗效果。方法 回顾总结１９９３年１２月～１９９９年６月收治８例ＡＭＨ患者的临床资料。结果 经景像学检查，８例中５你肾上腺和肾上腺外未发现肿瘤，诊断为ＡＭＨ；３例因肾上腺占位性病变诊断为嗜铬细胞。７例行单侧肾上腺切除术。５例痊愈，２例病情改善，１例行双侧 腺全切除，带血管去髓质自体肾上腺移植术，术后痊愈。结论 Ａ在首先排除嗜铬细胞瘤，确诊需经病理检查     

Diagnosis of adrenal medullary diseases in patients with sporadic or hereditary medullary thyroid carcinoma. A report of 37 cases with 8-year follow-up study

Thirty-seven patients with medullary thyroid carcinoma were investigated to determine the status of adrenal medulla by computed tomography and 131I-metaiodobenzylguanidine (131I-MIBG) scintigraphy as well as measurements of urinary catecholamine excretion. Patients were followed up for 8 years in maximum. Fifteen patients belonged to multiple endocrine neoplasia type 2 including patients with incomplete phenotype. Computed tomography demonstrated adrenal tumors or enlargement in all 6 patients with urinary epinephrine (E) more than 30 micrograms/day, 4 of them were confirmed to have pheochromocytoma or adrenal medullary hyperplasia by surgery. In 2 patients with E less than 30 micrograms/day and epinephrine to norepinephrine (E/N) ratio more than 0.3 suggesting adrenal medullary hyperfunction, computed tomography revealed small adrenal tumors. Three of the remaining 7 patients with E less than 30 micrograms/day and E/N ratio less than 0.3 had equivocal enlargement of unilateral gland on computed tomography. 131I-MIBG scintigraphy demonstrated tracer uptake in adrenal glands with tumor more than 1cm in diameter. One of 2 adrenal glands with medullary hyperplasia showed a faint adrenal image on the scintiscan, but the other showed no tracer uptake. Pheochromocytoma became manifest in 4 patients during the follow-up period, 4, 13, 14 and 34 years after thyroid surgery. None of 22 patients with sporadic medullary thyroid carcinoma showed adrenal abnormalities on the examinations mentioned above.     

A case of Sipple syndrome whose bilateral pheochromocytomas were resected separately after a 3-year interval

A 23-year-old woman who had undergone total thyroidectomy and parabronchial lymphadenectomy at the Department of Otolaryngology in our hospital was suspected to have a thyroid carcinoma. Histological examination revealed a medullary carcinoma of the thyroid and normal parathyroid glands. Because a computed tomographic scan after surgery revealed a tumor of the left adrenal gland, the patient was examined at our department two months after the thyroidectomy, 1994. Endocrinic examinations and 123I-MIBG scintigraphy revealed a left adrenal pheochromocytoma of Sipple syndrome. She then underwent left adrenalectomy. Histological diagnosis was pheochromocytoma of the left adrenal gland. Three years after the surgery, a right adrenal tumor was detected by computed tomography. Although results of endocrine examinations were normal, 131I-MIBG scintigraphy showed a hot spot in the right adrenal gland. Right adrenal pheochromocytoma was diagnosed 3 years after surgery for a contralateral adrenal pheochromocytoma. Although surgery was recommended, the patient consented to right adrenalectomy, 1 year later after marriage and before becoming pregnant. Histological examination of the resected specimen revealed pheochromocytoma of the right adrenal gland.     

儿茶酚胺症诊治（附182例报告）

目的 提高儿茶酚胺症的诊断和治疗水平。方法 报告182例儿茶酚胺症患者的临床资料,其中嗜铬细胞瘤173例,髓质增生9例。临床表现为阵发性高血压103例（57％）,持续性高血压69例（38％）,血压正常10例（5％）。159例行尿VMA检查,异常150例（94％）。腹膜后充气造影53例,阳性46例（87％）;B超检查146例,阳性133例（91％）;CT检查109例,阳性103例（95％）;MRI检查22例,均为阳性。结果 182例均行手术治疗并经病理证实,良性163例（90％）,恶性19例（10％）;肿瘤位于肾上腺151例（83％）,异位嗜铬细胞瘤22例912％）,肾上腺髓质增生9例（5％）。165例随访－24年,19例恶性嗜铬细胞瘤均死亡,余146例129例（88％）术后无需药物治疗,血压恢复正常。17例（12％）术后仍需持续用药控制血压,其中多发性肿瘤7例,肾上腺外肿瘤4例,非儿茶酚胺依赖性高血压6例。结论 尿VMA检查是儿茶酚胺症定性诊断的主要依据,B超、CT、MRI检查为定位诊断的主要依据。根本治疗方法为手术切除,充分的术前准备和正确的围手术期处理十分重要。     

Sipple's syndrome. A urologist's viewpoint.

A case of Sipple's syndrome, a triad of medullary carcinoma of the thyroid, pheochromocytoma, and parathyroid hyperplasia is presented. The cause, laboratory diagnosis, and operative management of the syndrome are discussed. The need for thorough endocrine screening of patients with pheochromocytoma and family screening of patients with the full syndrome is stressed.     

2型多发内分泌腺瘤病的诊断及外科治疗

目的探讨2型多发内分泌腺瘤病的临床特点、治疗方法及疗效。方法回顾分析我院1980～2002年诊治的8例2型多发内分泌腺瘤病患者的临床特点、诊断及治疗方法与疗效。结果7例有阵发性高血压,5例最高血压超过200mmHg(1mmHg=0．133kPa),3例查体发现肿瘤。经B超、CT及24h尿儿茶酚胺检查确定诊断,2A型6例,2B型2例;表现为甲状腺髓样癌合并嗜铬细胞瘤伴或不伴甲状旁腺腺瘤或增生(6例),1例伴多发黏膜神经瘤,1例为嗜铬细胞瘤伴有马凡综合征;双侧肾上腺肿瘤7例;分期行肾上腺与甲状腺、甲状旁腺结节切除或次全切除术。术后平均随访9年,效果良好。结论2型多发内分泌腺瘤病的诊断主要依赖相应的内分泌检查及B超和CT检查,手术是主要的治疗手段,当嗜铬细胞瘤与其他肿瘤同时存在时,宜首先切除嗜铬细胞瘤。     

Medullary thyroid carcinoma and pheochromocytoma accompanied with nodular hyperplasia in multiple endocrine neoplasia type 2

Three patients with familial multiple endocrine neoplasia type 2 underwent total adrenalectomy and subsequently near-total or total thyroidectomy. The overt pheochromocytomas were present bilaterally in two patients and unilaterally in another patient. In addition, multiple nodules measuring a few mm in diameter were demonstrated in all adrenal medullas examined. All patients exhibited bilateral medullary thyroid carcinomas which varied in size from a few minute nodules accompanied by the microscopic C-cell hyperplasia to distinct large tumors. The thyroid C-cell hyperplasia appeared to be confined to the upper and middle thirds of the lateral lobe, and micronodules of the C-cell hyperplasia enlarged to coalesce, forming one large carcinoma mass. On the other hand, nodular hyperplasia of the chromaffin cells was distributed diffusely throughout the adrenal medulla and each nodule appeared to develop individually into a large pheochromocytoma. These findings suggested that, at least in the family members at a high risk for multiple endocrine neoplasia type 2, the development of both medullary thyroid carcinoma and pheochromocytoma was always preceded by a multicentric nodular hyperplasia. On the basis of the pathogenesis of these tumors, the most rational surgical approach was presented.     

Medullary thyroid carcinoma and pheochromocytoma accompanied with nodular hyperplasia in multiple endocrine neoplasia type 2

Three patients with familial multiple endocrine neoplasia type 2 underwent total adrenalectomy and subsequently near-total or total thyroidectomy. The overt pheochromocytomas were present bilaterally in two patients and unilaterally in another patient. In addition, multiple nodules measuring a few mm in diameter were demonstrated in all adrenal medullas examined. All patients exhibited bilateral medullary thyroid carcinomas which varied in size from a few minute nodules accompanied by the microscopic C-cell hyperplasia to distinct large tumors. The thyroid C-cell hyperplasia appeared to be confined to the upper and middle thirds of the lateral lobe, and micronodules of the C-cell hyperplasia enlarged to coalesce, forming one large carcinoma mass. On the other hand, nodular hyperplasia of the chromaffin cells was distributed diffusely throughout the adrenal medulla and each nodule appeared to develop individually into a large pheochromocytoma. These findings suggested that, at least in the family members at a high risk for multiple endocrine neoplasia type 2, the development of both medullary thyroid carcinoma and pheochromocytoma was always preceded by a multicentric nodular hyperplasia. On the basis of the pathogenesis of these tumors, the most rational surgical approach was presented. Presented at the 14th Annual Congress of the Japan Society for Cancer Therapy, Sendai, September 30, 1976.     

Differences between sporadic pheochromocytoma and pheochromocytoma in multiple endocrime neoplasia, type 2

We studied the gross and microscopic pathology of the adrenal gland in 69 cases of sporadic phenochromocytoma in order to develop a profile of the neoplasm to compare with that of pheochromocytoma observed in the syndrome of multiple endocrine neoplasia, type 2 (MEN 2). The results showed that sporadic pheochromocytoma was a unicentric (93%), unilateral (100%) neoplasm, which was associated with normal extratumoral adrenal medulla (100%). The findings contrast with those encountered in the adrenal gland in MEN 2, in which the tumor involvement is frequently multicentric, usually bilateral, and associated with extratumoral medullary hyperplasia in cases of early involvement. Therefore, the interpretation of the results of pathologic examination of a pheochromocytoma should be immediately communicated to the surgeon.     

Medullary carcinoma of the thyroid gland

Nine cases of medullary carcinoma of the thyroid gland (MTC) are reported. Four of the carcinomas were of the familial type. Five of the patients were men and four were women. Patient age ranged from 23 to 66 years, with a mean age of 40 years. The median age of the four patients with the familial MTC was 32 years. A total or a subtotal thyroidectomy was performed in four and five patients, respectively, associated with a modified neck dissection in six patients with involved cervical lymph nodules. An underlying pheochromocytoma of the left adrenal was excised in one patient prior to thyroidectomy. In all cases the parathyroid glands were identified, and in two cases of familial MTC, in which they were grossly enlarged, the parathyroid glands were removed. Four patients died as a result of their disease within 3 years, whereas patients are well 4 to 12 years after surgery. The best chance of cure lies in early diagnosis and an aggressive surgical removal of the primary tumor and any cervical metastases.     

儿茶酚胺症（附86例报告）

报告８６例儿茶酚胺症。其中肾上腺嗜铬细胞瘤７４例（８６％），肾上腺外嗜铬细胞瘤１０例（１１．６％＿，肾上腺髓质增生（ＡＭＨ）２例（２．３％）。ＣＡ及ＶＭＡ测定对诊断有特异性，Ｂ超及ＣＴ对肾上腺嗜铬细胞瘤的诊断率分别为９３％和９５％。肾上腺外嗜铬细胞瘤有多发性、复发性、恶性率明显增高，无症状嗜铬细胞瘤占８．１％。对无功能肾上腺肿瘤及源于腹膜后的上腹部肿物，要注意嗜铬细胞瘤的可能。ＡＭＨ最可靠的诊断是     

Diagnostic and operative problems in multiple pheochromocytomas.

Two children, aged 14 yr, with multiple pheochromocytomas are presented. Both patients had a positive family history. In the preoperative aortographies the intra-adrenal pheochromocytomas of both patients were well visualized, but not the extra-adrenal tumors of the first case. Chlorpromazine as an adrenergic blocking agent was successfully used in the preoperative treatment. Postoperative catecholamine excretion in the first case was repeatedly slightly increased indicating residual pheochromocytoma. In addition to the bilateral adrenal pheochromocytomas, multiple islet cell adrenomas and cholecystolithiasis were revealed at the operation of the second case. After bilateral adrenalectomy and total pancreaticoduodenectomy, regular follow-up examinations were carried out for 28 months. Hyperparathyroidism and signs of possible medullary thryoid carcinoma were discovered. Thus the patient had an unique pattern of MEA syndrome.     

Multiple endocrine adenomatosis type IIB. Report of two cases and review of the literature.

The combination of bilateral medullary thyroid cancer, bilateral pheochromocytoma, Marfanoid body habitus with arachnodactyly, pectus excavatum, mucosal neuromas, and hyperplastic corneal nerves has become recognized as a definite entity, multiple endocrine adenomatosis (MEA) Type IIB. Two cases of MEA Type IIB are described, along with diagnosis, treatment, pitfalls in management, and related syndromes. When this syndrome is suspected, a careful search for other hyperfunctioning endocrine glands, particularly pheochromocytoma, must be made. Failure to recognize pheochromocytoma may prove a serious hazard if thyroidectomy is the initial procedure. The value of thyrocalcitonin as an indicator of the presence of medullary thyroid cancer and its value as a familial screening test are discussed.     

Bilateral subtotal adrenal resection for bilateral pheochromocytomas in multiple endocrine neoplasia, type IIa: a case report

Our treatment philosophy for the management of the adrenal glands in patients with multiple endocrine neoplasia, type IIa has been bilateral total adrenalectomy. In the patient described, exceptional and pressing reasons necessitated preservation of adrenocortical function. Bilateral pheochromocytomas were resected with preservation of the adrenal cortices. Adrenocortical function was normal 36 months after resection. Although the patient remained symptom free, elevated basal immunoreactive plasma calcitonin levels suggested the presence of residual or metastatic medullary thyroid carcinoma. There was no evidence of recurrent pheochromocytoma.     

A case of composite pheochromocytoma-ganglioneuroblastoma in the adrenal gland with primary hyperparathyroidism

We report a case of composite pheochromocytoma-ganglioneuroblastoma in the adrenal gland with primary hyperparathyrodisim. A 55-year-old woman consulted our hospital for an examination of a right adrenal tumor, incidentally found by screening abdominal ultrasound sonography. On the clinical diagnosis of pheochromocytoma in the right adrenal gland from the findings of enhanced abdominal computed tomography, endocrinal examinations and 123I-metaiodobenzyl-guanidine scintigram, right adrenalectomy was performed transperitoneally. Histopathological diagnosis was an adrenal composite pheochromocytoma-ganglioneuroblastoma. This combination of compound adrenal tumor is extremely rare, and to date this case may be the seventh reported in Japan. Moreover, since her serum calcium level and intact parathyroid hormone level were high, so we considered the existence of multiple endocrine neoplasia type 2A. 99mTc-methoxyisobutylisonitrile scintigram and ultrasound of the neck revealed hyperparathyroidism, but medullary thyroid carcinoma was not detected. One year later, she was readmitted for parathyroid tumor excision, and histopathological finding was parathyroid adenoma. We concluded that she had both adrenal composite pheochromocytoma and hyperparathyroidism incidentally.     

U形解剖在后腹腔镜肾上腺及腺瘤切除术中的应用

目的总结后腹腔镜肾上腺及腺瘤切除术的经验和改进方法。方法2003年5月2010年5月,采用后腹腔镜技术行肾上腺及腺瘤切除术447例。男性175例,女性Z72例,平均年龄（39士12．8）岁（15～84岁）。原发性醛固酮增多症128例,柯兴氏综合征112例,嗜铬细胞瘤57例,副神经节瘤10例,髓脂瘤28例,肾上腺囊肿17例,神经鞘瘤11例,肾上腺髓质增生9例,原发性肾上腺结节状增生5例,原发性肾上腺癌3例,转移性肾上腺癌3例,其他单纯无功能皮质腺瘤64例;瘤体平均直径（2．8士2．1）cm（O．5-10cm）。所有病例均采用后腹腔途径,沿肾背侧缘向上游离出肾上极并尽量扩大腹膜后腔,然后在肾上极内上份的Gerota筋膜前层与腹膜反折之间的无血管间隙进行分离,其次再分离肾周脂肪囊和Gerota筋膜后层之间的无血管间隙;将前两个解剖层面在肾上极表面无血管层面连通起来,形成一个“U”形的解剖步骤,最后再离断其上份的附着部分,切下肿瘤或肾上腺,计算其手术成功率、手术时间、术中估计出血量、术后住院时间、手术相关并发症等临床资料。结秉本组手术成功率为97．3％（435／447）。因术中和术后出血、气胸、过度肥胖等而转开放手术12例。单侧手术平均时间（45土22）min（15～140min）,术中估计平均出血量（35士15）mL（15∽200mL）,14例需要术中、术后输血1～2单位,输血率为3．1％（14／447）,术后平均住院时间（5．3士2．5）d（3～10d）。术后伤口延迟愈合、皮下气肿、发热等手术相关并发症发生率为5．6％（25／447）。砖论后腹腔镜手术对腹腔脏器干扰小,依据U形的解剖步骤,解剖层次清楚,可有效地缩短手术时间并减少出血等手术并发症。后腹腔镜手术是治疗肾上腺外科良性疾病的金标准。     

带蒂肾上腺背部皮下移位术治疗肾上腺髓质增生症

目的 进一步探讨肾上腺髓质增生症的手术方法。方法 肾上腺髓质增生患者8例,手术分离并结扎肾上腺下、内侧血管,使肾上腺上组血管形成5.0-6.0cm的蒂,自第11肋间拉至背部皮下,以带蒂肾上腺背部皮下移位术治疗,结果 术后8例均获得随访,随访时间6个月-4年,平均2年,除1例患者伴有神经官能症,症状未减,余7例血压及内分泌检查皆恢复正常。结论 带蒂肾上腺背部皮下移位术治疗髓质增生,操作简单,疗效满意。