In a prospective study of 103 patients with carcinoid tumors consecutively referred for medical treatment, the most common sites of the primary tumors were the ileum (73%), bronchi (7%), and jejunum (4%). All patients had local metastases, and 96 (93%) also had liver metastases. The most common initial symptoms were diarrhea (32%), ileus (25%), and flush (23%). The overall frequency of diarrhea was 84% and of flush was 75%. Heart insufficiency caused by cardiac valve disease was seen in 33% of the patients. The carcinoid syndrome, including flush, diarrhea, and elevated urinary 5-hydroxyindole acetic acid (5-HIAA) concentrations, was manifested by 69 patients (67%), 64 of whom (93%) had carcinoid tumors of mid-gut origin. Elevated urinary 5-HIAA was found in 91 patients (88%), of which 89 displayed liver metastases. The plasma concentration of the tachykinin neuropeptide K (NPK) was elevated in 67 patients (66%), 63 of whom had tumors of the mid-gut region. Serum pancreatic polypeptide (PP) and human chorionic gonadotrophin alpha levels were elevated in 43% and 28% of the patients, respectively, and the highest levels were found in patients with metastatic bronchial carcinoid tumors. Thirty-nine of the 103 patients are now dead; 18 died of tumor progression, whereas 14 patients died of heart failure secondary to a carcinoid tricuspidal valve insufficiency. The estimated median survival from the time of histologic diagnosis was 14 years, and from the time of carcinoid syndrome was 8 years.

In multiple endocrine neoplasia type 1 (MEN-1), benign enlargement of the adrenal cortex has been found in about one third of necropsy cases. To elucidate the clinical and genetic characteristics of the MEN-1 adrenal lesion, we have investigated 33 MEN-1 patients. Twelve individuals (37%) demonstrated adrenal enlargement, which was bilateral in 7 of them. Histopathology revealed diffuse and nodular cortical hyperplasia, adenomas, and a single case of adrenocortical carcinoma. The apparently benign adrenal enlargements were not associated with presently ascertainable biochemical disturbances in the hypothalamic-pituitary-adrenocortical axis, and they were without radiological signs of progression during follow-up. The individual developing unilateral adrenocortical carcinoma showed rapid adrenal expansion, feminization, and an abnormal urinary steroid profile after 4 yr of observation for bilateral minor adrenal enlargements. Pancreatic endocrine tumors were significantly overrepresented and present in all MEN-1 individuals with adrenal involvement. In agreement with findings in sporadic cases, the MEN-1 adrenocortical carcinoma genome showed loss of constitutional heterozygosity for alleles at 17p, 13q, 11p, and 11q. The benign adrenal lesions retained heterozygosity for the MEN-1 locus at chromosome 11 q 13. Despite its prevalence and malignant potential, the pituitary-independent adrenocortical proliferation does not appear to be a primary lesion in MEN-1, but might represent a secondary phenomenon, perhaps related to the pancreatic endocrine tumor.

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A prospective study has been performed on 84 patients with endocrine pancreatic tumours evaluated at the Medical Department in Uppsala. Available information concerning the patients' presenting symptoms, age at diagnosis, clinical syndrome, tumour location, location of metastases, diagnostic radiology, biochemical and histopathological findings has been analysed. Our results indicate that most patients initially show rather vague and non-specific symptoms, with dyspepsia and pain being the most frequent presenting features. The median delay between appearance of the first symptom and diagnosis was 2 years; the delay was 35 months in sporadic cases and 14.5 months in familial cases. In spite of improvements in diagnostic methods, the median age at diagnosis (53 years) has not been reduced, and most patients are encountered when the tumour has reached an advanced stage. There is a need for a method of screening patients with still uncharacteristic abdominal symptoms for a neuroendocrine tumour. The presence of elevated levels of plasma chromogranin in all patients with a proven tumour suggests that such possibilities exist, and the use of this biochemical marker in the future might reduce the age at diagnosis and thus improve the likelihood of cure and survival of patients with endocrine pancreatic tumours.

Study results support the use of US as a first-line diagnostic examination in patients suspected of having pancreatic tumor. Dependency on the investigator's experience with US mandates continuous evaluation of its performance.