Duodenal carcinoid tumours, phaeochromocytoma and neurofibromatosis: islet cell tumour, phaeochromocytoma and the von Hippel-Lindau complex: two distinctive neuroendocrine syndromes

To clarify neuroendocrine syndromes we have reviewed the association of neurofibromatosis with carcinoid tumours and of neurofibromatosis, phaeochromocytoma or von Hippel-Lindau complex with either carcinoid or islet cell tumours. In nine cases of neurofibromatosis with a carcinoid tumour studied all carcinoid tumours were in the duodenum, were distinctive histologically and had widespread somatostatin immunoreactivity. The duodenum was the primary site in 18 of 20 further published cases of carcinoid tumour and neurofibromatosis. Phaeochromocytoma was also present in six of these 27 cases with neurofibromatosis and duodenal carcinoid tumour. Six patients have been reported with Von Hippel-Lindau complex, phaeochromocytoma and islet cell tumour. A further 11 patients showed phaeochromocytoma and islet cell tumour. No cases of Von Hippel-Lindau complex had a carcinoid tumour, and no cases of neurofibromatosis had an islet cell tumour. We conclude that the association of neurofibromatosis, duodenal carcinoid tumour and phaeochromocytoma forms a distinctive neuroendocrine syndrome, sharply separated from the association of Von Hippel-Lindau complex with islet cell tumour and phaeochromocytoma. This separation is important in pathogenesis, diagnosis and clinical management.     

Phaeochromocytoma: a case study

Phaeochromocytoma is a rare adrenal tumour. The early diagnosis of phaeochromocytoma is important, not only because it offers the possibility of the risks associated with undetected secondary hypertension, but also because unrecognised phaeochromocytoma is a potentially lethal condition. This paper presents a typical case in which the symptoms of a pheochromocytoma mimicked common musculoskeletal syndromes. A diagnosis can be determined through biochemical analysis in conjunction with localising imaging modalities. Ten percent of these rare tumours may develop malignancy and long-term follow up has been shown to be essential in detecting reoccurrence.     

The Frequency of Gastrointestinal Endocrine Tumours in a Well-defined Population - Northern Ireland 1970-1985

The reported incidence of gastrointestinal endocrine tumoursis variable. In Northern Ireland circumstances allowing suchan assessment are favourable with a central diagnostic laboratoryand register established to collect data on tumours from a well-definedpopulation of 1.5 million people. From 1970 to 1985, 368 caseswere recorded of which 85 per cent were carcinoid tumours. Theannual incidence of carcinoid tumours was 1.3 per 100 000 ofthe population and the majority occurred in the appendix (61per cent). No patients presented with the carcinoid syndrome.The annual incidence for other tumours was 0.12 per 100 000for insulinomas; islet cell tumours of unknown type 0.07; Zollinger-Ellisonsyndrome 0.05; and multiple endocrine neoplasia (MEN) 0.05.There were two cases of VIPoma, one glucagonoma, one neurotensinomaand one tumour producing ACTH. It is possible that some tumoursare more uncommon than others because of difficulty in diagnosis.     

Phaeochromocytoma presenting as dilated cardiomyopathy

Phaeochromocytomas are rare endocrine tumours that secrete excessive amounts of catecholamines and can lead to myocarditis and cardiomyopathy. We report a 63-year-old man with long-standing hypertension and diabetes who presented with dilated cardiomyopathy, which was initially thought to be secondary to ischaemic heart disease. Subsequent coronary angiography was normal. Carvedilol therapy unmasked the characteristic features of phaeochromocytoma. Surgical resection of a right adrenal tumour cured his symptoms, hypertension and diabetes, as well as causing a substantial improvement in cardiac function. Phaeochromocytoma should be considered as a rare cause of dilated cardiomyopathy of uncertain aetiology.     

Classification and histogenesis of gastroenteropancreatic endocrine tumours

Abstract. A series of 267 gastroenteropancreatic endocrine tumours has been revised from the point of view of histopathologic diagnosis, hormonal profile and clinical behaviour. Results of this investigation, together with revised concepts on the histogenesis of gastroenteropancreatic endocrine growths, allowed to develop detailed classification systems which proved useful for precise tumour diagnosis and for clinico-pathologic correlation, with special reference to tumour function, prognosis and therapy. Among 132 pancreatic growths, various types of islet cell tumours (61 cases), with (45 cases) or without (16 cases) hyperfunctional syndrome, were separated from different types of gut-related (38 cases) and 'ectopic' (three cases) tumours, as well as from 25 non-functioning, locally symptomatic tumours, three small cell carcinomas and two mixed endocrine-exocrine tumours. Among 97 intestinal tumours, 39 argentaffin EC cell carcinoids, mostly from the appendix and ileum, were separated from 23 hindgut-type carcinoids, mostly from the rectum, 22 gastrin cell tumours, mainly from the duodenal bulb, five somatostatin cell tumours, mostly from the periampullary region of the duodenum, and two gangliocytic paragangliomas. Among 38 gastric tumours, five small cell 'neuroen-docrine' carcinomas were separated from three gastrin cell tumours and 30 argyrophil carcinoids, 27 of which arose in the body fundus, 16 associated with chronic atrophic gastritis and four with combined Zollinger Ellison/Multiple Endocrine Neoplasia Syndrome.     

The Biochemical Diagnosis, Localization and Follow up of Phaeochromocytoma: The Role of Plasma and Urinary Catecholamine Measurements

The diagnosis of phaeochromocytoma is dependent on combinedbiochemical and radiological investigation, the biochemicalstudies being performed initially and followed later by bothnon-invasive and invasive radiological techniques. In 23 patientsstudied, a selection of biochemical studies allowed diagnosisand accurate localization of phaeochromocytoma in 16. In somepatients, tumour localization was confirmed by radiographicmethods. Biochemical estimations of catecholamines and/or metabolitesin urine and/or plasma were also performed during and afteroperation, and these measurements allowed monitoring of thecompleteness of tumour excision, and of the possibility of recurrence,in both the short term and long term follow up of patients. ^* Present address: Department of Materia Medica, Stobhill GeneralHospital, Glasgow, G21 3UW.     

A Predominantly Adrenaline-secreting Phaeochromocytoma

A 61-year-old woman who presented with diabetes, nausea, weightloss and sweating was found to have a phaeochromocytoma secretingadrenaline, with a small amount of N-methyIadrenaline. Therewas no significant increase in noradrenaline secretion. Shewas normotensive, and developed profound hypotension in responseto the -adrenergic antagonist phenoxybenzamine. These featuresare unusual in phaeochromocytoma, but similar features occurredin the very few previous reported cases of pure adrenaline-secretingphaeochromocytoma. We conclude that it is important to identifysuch patients, so that they should not be given -adrenergicantagonist drugs.     

Contrast-enhanced ultrasound (CEUS) appearances of an adrenal phaeochromocytoma in a child with Von Hippel-Lindau disease

A phaeochromocytoma is a rare catecholamine-secreting tumour arising from the chromaffin cells. We describe a case of a child with Von Hippel-Lindau disease, with an adrenal phaeochromocytoma who presented with severe dilated cardiomyopathy driven by secondary hypertension. Contrast-enhanced ultrasound findings are described and compared with both magnetic resonance imaging and computed tomography imaging.     

Coeliac Disease and Malignancy

Studies of small-bowel epithelial-cell turnover have been performedon 18 cases who had been diagnosed as having adult ‘coeliacdisease’. These patients seem to be divisible into twogroups on the basis of their mucosal dynamics. The associationof subtotal villous atrophy with a lower cell turnover seemsto carry a particularly grave prognosis. The significance ofthese findings is discussed in relation to the reported associationbetween coeliac disease and abdominal lymphoma.     

22例不典型肾上腺嗜铬细胞瘤的临床分析

目的回顾性分析22例不典型肾上腺嗜铬细胞瘤的临床诊断资料,以提高不典型嗜铬细胞瘤的诊断水平。方法纳入1998年～2004年在我院诊治的肾上腺嗜铬细胞瘤患者90例,根据临床表现分为典型组和不典型组,研究不典型嗜铬细胞瘤患者年龄、肿瘤部位、肿瘤最大径、高血压、血浆儿茶酚胺等方面和典型组患者的差异。结果90例患者中有22例（24．4%）为不典型肾上腺嗜铬细胞瘤,68例（75．6％）为典型肾上腺嗜铬细胞瘤。两组患者年龄、肿瘤平均最大径均无显著差异;不典型组肾上腺肿瘤主要位于右侧肾上腺,其去甲肾上腺素浓度显著低于典型组,且不典型组去甲肾上腺素阳性率也明显低于典型组。结论本组资料显示,和典型肾上腺嗜铬细胞瘤相比,不典型肾上腺嗜铬细胞瘤主要位于右侧,且血浆去甲肾上腺素的检出率低于前者,从肿瘤大小上无法鉴别出不典型肾上腺嗜铬细胞瘤,但综合患者的临床表现、CT检查、血浆儿茶酚胺检测,大多数不典型嗜铬细胞瘤都可在术前正确诊断。     

Twelve-year experience in the investigation and treatment of paragangliomas

We report a 12-year laboratory experience in the diagnosis of 37 patients with phaeochromocytoma, one with malignant paraganglioma and one with ganglioneuroblastoma. Surgery was performed in eight different hospitals, which underlines the difficulty of ensuring uniformity of investigations. Of the 37 with phaeochromocytoma, 15 were in the right adrenal gland, 12 were on the left, seven were bilateral and three were extra adrenal. Twenty-three were male and 15 were female; the median age was 36 years. Four of five patients with von Hippel-Lindau disease had bilateral adrenal tumours and four had neurofibromatosis. None had multiple endocrine neoplasia. Using essential hypertensive patients as a reference population, diagnostic sensitivity was 80% for noradrenaline, 54.4% for adrenaline, 19.1% for dopamine, 93.3% for total normetanephrine, 33.3% for total metanephrine, 78.7% for 3-methoxy-4-hydroxymandelic acid (HMMA) and 23.5% for homovanillic acid (HVA). However, if each patient's results were taken as a package, the sensitivities were 100% for noradrenaline, 63.6% for adrenaline, 30.3% for dopamine and 89% for HMMA. Seven recent patients had gene analysis. There were six (15.4%) deaths due directly or indirectly to the paraganglioma. Postoperative blood pressures were normal in 74%. The decrement in catecholamine values post-surgery is shown. Urinary noradrenaline values fell by a mean of 94.5% and the use of urinary noradrenaline as a tumour marker is also demonstrated.     

Serum neurone-specific enolase levels in patients with neuroendocrine and carcinoid tumours.

We have examined concentrations of neurone-specific enolase (NSE) in sera from 18 patients with various neuroendocrine tumours, 26 patients with carcinoid tumours, 21 patients with non-neuroendocrine tumours and 37 control individuals. No statistically significant difference between the concentrations in patients with neuroendocrine tumours and patients with carcinoid tumours was found. However the NSE concentrations in patients with carcinoid and neuroendocrine tumours, when these two groups were combined, were significantly different from the patients with non-neuroendocrine tumours or the control individuals (P < or = 0.01). 38.5% of the patients with carcinoid tumours had raised NSE concentrations in serum; 55.5% of those with non carcinoid neuroendocrine tumours had raised concentrations. There appeared to be no correlation between the NSE concentrations and the extent of metastases.     

Thoracic epidural analgesia in a patient with von Hippel‐Lindau disease

von Hippel‐Lindau disease (VHLD) is an autosomal dominant disorder characterized by central nervous system hemangioblastomas and renal tumors. Here, we report a case of thoracic epidural placement in a 35‐year‐old woman with VHLD presenting for left open heminephrectomy for renal masses. We also reviewed the literature on this topic.     

A clinical study of type 2 neurofibromatosis.

The clinical features, age at onset of symptoms and survival of 150 patients with type 2 neurofibromatosis were studied. The mean age at onset was 21.57 years (n = 110) and no patients presented after 55 years of age. Patients presented with symptoms attributable to vestibular schwannomas (acoustic neuroma), cranial meningiomas and spinal tumours. In 100 patients studied personally by the authors 44 per cent presented with deafness and this was unilateral in the majority (35/44). Deafness was accompanied by tinnitus in a further 10 per cent and muscle weakness or wasting was the first symptom in 12 per cent. Less common presenting symptoms were seizures (8 per cent), vertigo (8 per cent) numbness and tingling (2 per cent) and blindness (1 per cent). Eleven patients were diagnosed asymptomatically through screening. Café au lait spots occurred in 43 per cent (n = 43) but only one case had six. Skin tumours were detected in 68 per cent (68/100) and 38 per cent (34/90) had an identifiable lens opacity or cataract. The mean age at death in 40 cases was 36.25 years and all but one death was a result of a complication of neurofibromatosis. There are marked inter-family differences in disease severity and tumour susceptibility.     

卵巢甲状腺肿类癌

目的　探讨卵巢甲状腺肿类癌的临床及病理组织学特征。方法　应用光镜观察及免疫组化染色对 2例卵巢甲状腺肿类癌进行病理分析 ,同时复习相关文献。结果　肿瘤主要由类癌和甲状腺肿两种成分构成。免疫组化 :类癌细胞CgA、Syn( ) ,Tg和降钙素 (CT) (- )。结论　卵巢甲状腺肿类癌是一种具有独特临床病理学特征的生殖细胞肿瘤 ,伴有甲状腺滤泡分化     

Recent Advances in the Diagnosis and Management of Carcinoid Syndrome

Carcinoid syndrome, a paraneoplastic condition linked with the release of multiple humoral factors, affects around 30-40% of patients with well-differentiated neuroendocrine tumours. Carcinoid syndrome has a major and unfavourable impact on patients' quality of life; it raises costs when compared to non-functioning neuroendocrine tumours; and it causes patients' lifestyles to alter, such as food, job, physical activity, and social life. Somatostatin analogues have been the first-line therapy for individuals with neuroendocrine tumours and carcinoid disease for decades. While these drugs give considerable relief from carcinoid syndrome symptoms, clinical progression is unavoidable, necessitating further research into newer treatment measures.Carcinoid tumours are sometimes difficult to diagnose because of their vague or nonspecific symptoms. There have been several advancements in all aspects of carcinoid syndrome, as well as novel therapeutics, in the previous few years. New epidemiological studies show that it is becoming more common; increasing insights into the pathogenesis of its various clinical manifestations and its natural history: definition of prognostic factors; new methods to verify its presence; the development of new drugs to treat its various manifestations, both initially and in somatostatin-refractory cases; and an increased understanding of the pathogenesis, natural history, and management of the disease.An all language literature search was conducted on MEDLINE, COCHRANE, EMBASE, and Google Scholar till November 2021. The following search strings and Medical Subject Headings (MeSH) terms were used: “Recent advances”, “Carcinoid syndrome”, “Neuroendocrine Neoplasms” and “Carcinoid heart disease”. We comprehensively reviewed the literature on the pathogenesis, clinical features, and newer treatment modalities for Carcinoid Syndrome.Recent advancements in research and management have resulted from advances in our understanding of the aetiology of carcinoid syndrome. The development of molecular indicators of aggressiveness improved serum tumour markers, and the molecular aetiology of carcinoid heart disease are all possible because of advances in molecular biology. We conducted a comprehensive review to update knowledge regarding the pathophysiology, diagnostic protocols, and current and newer treatments for carcinoid syndrome, which presently requires a multidisciplinary approach, due to the complexity of the illness's aetiology, diagnosis, and therapy.     

Carcinoid of the duodenum: A report of six cases

Duodenal carcinoid tumors are rare. Six cases of primary duodenal carcinoid tumors are presented. Analysis of these cases indicates that the radiographic appearance can vary from a benign-appearing intramural submucosal mass lesion to a large bulky ulcerating lesion. All cases in this series followed a benign course. One patient has survived over 30 years with proven regional and hepatic metastases. This patient showed regression of the duodenal lesion following embolization for control of severe hemorrhage.     

Endoscopic resection of small rectal carcinoid tumours using an aspiration method with a transparent overcap

Rectal carcinoid tumours are often small and rarely metastatic. Endoscopic resection may, therefore, be the best treatment for small tumours. We diagnosed rectal carcinoid tumours in four women and three men (mean age 53 years; range, 43 - 63) between 1994 and 1999. Tumour depth was evaluated using a high-frequency ultrasonographic probe in five of the seven patients. All tumours were resected by endoscopic mucosal resection using an aspiration method with a transparent overcap. Histologically, all tumours were located within the submucosal layer. Tumour cells were found at the resected margin of the lateral side in one patient, and at the bottom of the margin in another. Both patients were followed up with frequent endoscopy, and no local recurrences have been detected at 1-year or 4-year follow-ups. Ultrasonographic examination before resection is useful to estimate tumour depth. Endoscopic resection by an aspiration method with a transparent overcap is safe and effective for the treatment of small rectal carcinoid tumours.