Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Three patients with symptomatic metastatic medullary thyroid carcinoma (MTC), one with sporadic form and two with MEN IIa, were treated with the long-acting somatostatin analogue octreotide (SMS 201-995, Sandoz) for 3 to 17 months. Octreotide was administered subcutaneously in a starting dose of 0.6 to 1.0 mg/day by automatic pump (Travax ASH6, Travenol). Symptoms of diarrhoea, weight loss and malaise improved in all patients. Maximal percentage decrease in mean serum calcitonin was 47, 52 and 81% of the basal values, and was observed 1-3 months from the beginning of treatment. Likewise, carcinoembryonic antigen (CEA) levels initially dropped to 45, 60 and 63% of the levels before therapy. A continuing effect was seen in the two patients with MEN IIa after 15 and 17 months of treatment. However, after the initial decrease, calcitonin (CT) levels went up again to 67 and 68% of the basal values and the dose of octreotide had to be increased to 1.5 mg and 2.0 mg/day. CEA also returned to 84 and 105% of the pretreatment titres. Response to 1.5 mg/day octreotide was lost in the patient with the sporadic form of disease after 3 months. Side-effects were minimal. Effects on tumour size could not be evaluated. These suggest that octreotide might be a valuable adjuvant in the long-term management of metastatic MTC. Tachyphylaxis may occur.
 ...
PMID:Long-term treatment of metastatic medullary thyroid carcinoma with the somatostatin analogue octreotide. 197 36

We have reviewed data pertinent to three tumor syndromes that derive from overproduction of three GEP peptide hormones. The clinical syndrome of somatostatin excess remains well defined with diabetes, diarrhea, steatorrhea being predominant features. With the availability of assays and increasing awareness, more cases are being diagnosed in the intestine and these differ somewhat in their presentation with cholecystitis, GI bleeding, or a mass as the cardinal features. An unusual association with MEN II pheochromacytoma and neurofibromatosis is emerging. PPomas remain enigmatic. Although diarrhea is a feature, these tumors are usually silent and present with hypatomegally, abdominal pain, and jaundice because of the large size and malignant nature. Neurotensinomas remain rare and truly difficult to separate from the symptom complex produced by VIP excess. Edema, hypotension, cyanosis and flushing should alert one to the possibility of a neurotensin-secreting tumor.
 ...
PMID:Somatostatinomas, PPomas, neurotensinomas. 282 62

The presence of somatostatin-immunoreactivity in tumor tissue of adrenal pheochromocytoma and thyroid medullary carcinoma identified by peroxidase-antiperoxidase technique is reported in one case of Sipple syndrome. This patient was found to have a high concentration of somatostatin-immunoreactivity in the peripheral blood (40 ng/l, normal 0-20 ng/l). After removal of the tumors, the plasma somatostatin-immunoreactivity fell within normal range (12.5 ng/l). This seems to be the first report of Sipple syndrome that produces somatostatin-immunoreactivity in both: pheochromocytoma and thyroid medullary carcinoma.
 ...
PMID:Coexistence of somatostatin-immunoreactivity in an adrenal pheochromocytoma and a thyroid medullary carcinoma (Sipple syndrome). 290 Jul 71

We have studied the clinical and thyroid immunohistological features of 19 patients with sporadic medullary thyroid carcinoma and 16 patients with the hereditary syndrome multiple endocrine neoplasia 2a (MEN 2a). Both groups were identified by family screening using serum calcitonin determinations before and after pentagastrin stimulation. Pheochromocytoma and hyperparathyroidism were associated both with multiple endocrine neoplasia 2a and some cases of sporadic medullary thyroid carcinoma. Hereditary medullary thyroid carcinoma was invariably associated with C-cell hyperplasia, but C-cell hyperplasia was also associated with some sporadic tumours. All tumours were positive for calcitonin and carcinoembryonic antigen (by immunohistological staining) (CEA) and most tumours stained for somatostatin. C-cell hyperplasia also stained for calcitonin, CEA and somatostatin. We conclude that sporadic and familial medullary thyroid carcinoma cannot always be discriminated by clinical or immunohistological methods. Family screening is essential in the diagnosis of hereditary medullary thyroid carcinoma.
 ...
PMID:Familial and sporadic medullary thyroid carcinoma: clinical and immunohistological findings. 290 73

The concentration of epinephrine, norepinephrine, dopamine, met-enkephalin-, ACTH-, calcitonin- and somatostatin-like immunoreactivity (IR) were determined in the extracts of 9 adrenal pheochromocytomas from 7 patients. Six of these patients had Sipple's syndrome. There was a close correlation between the amounts of met-enkephalin-IR and of epinephrine present in the tumor tissue (p less than 0.01). Such a correlation was not found between catecholamines and the other polypeptide hormones investigated. The relevance of the close parallel in the occurrence of met-enkephalin-IR and epinephrine in human adrenal pheochromocytoma tissue is unknown, but it underlines earlier observations in the normal bovine and rat adrenal medulla on a co-storage and co-release of these substances in normal circumstances.
 ...
PMID:A close correlation between the amount of met-enkephalin-immunoreactivity and epinephrine in adrenal pheochromocytoma tissue from patients with Sipple's syndrome. 614 10

Neuroendocrine tumours can form in any part of the gastrointestinal tract. The most common types are the ECL cell tumours of the oxyntic mucosa of the stomach, G cell tumours of the duodenum, argentaffin, EC cell tumours of the small intestine and L cell tumours of the large bowel. The only well-defined clinical syndromes associated with hormone hypersecretion are ZES, resulting from duodenal gastrinomas, and carcinoid syndrome, caused by malignant argentaffin tumours. Genetic predisposition has been demonstrated for some tumour types, e.g. duodenal gastrinoma in MEN 1 and duodenal somatostatin cell tumours in MEN 2. Other factors predisposing to the genesis of these lesions include circulating hormone levels and the maintenance of chronic inflammatory states. As with most neuroendocrine tumours, malignant potential is difficult to assess on the basis of histology alone and prognostic evaluation depends more on size and evidence of local invasion and/or distant metastases.
 ...
PMID:Gastrointestinal endocrine tumours. Pathology. 911 12

Selecting the appropriate approach for resection and follow-up of pheochromocytomas (PCCs) is highly dependent upon reliable localization and exclusion of multifocal, bilateral, or metastatic disease. Metaiodobenzylguanidine (MIBG) scintigraphy was developed for functional localization of catecholamine-secreting tissues. Somatostatin receptor imaging (SRI) has a high sensitivity for localizing head and neck paragangliomas, but studies of intraabdominal PCCs are rare. In this study we review our experience of [(123)I]MIBG and SRI, performed since 1983 and 1989, respectively, in the work-up of primary and recurrent PCCs. Scintigraphic results were correlated with catecholamine secretion, size and site, malignancy, associated tumor syndromes, and morphological features. [(123)I]MIBG scans were performed in a total of 75 patients, in 70 cases before resection of primary PCCs and in 5 cases because of recurrent disease. Ninety-one PCCs were resected. The overall detection rates were 83.3% and 89.8% for PCCs larger than 1.0 cm. Multifocal disease was detected in 4 patients with [(123)I]MIBG. [(123)I]MIBG uptake correlated with greater size of PCC (r = 0.33; P = 0.008) and greater concentration of plasma epinephrine (r = 0.32; P = 0.006). [(123)I]MIBG-negative PCCs (n = 14) had significantly (P = 0.01) smaller diameters than [(123I)]MIBG-positive tumors. Furthermore, [(123)I]MIBG uptake was significantly higher in unilateral (P = 0.02), benign (P = 0.02), sporadic (P = 0.02), intraadrenal (P = 0.02), and capsular invasive (P = 0.03) PCCs than in bilateral, malignant, MEN2A/2B-related, extraadrenal, and noninvasive PCCs, respectively. The detection rate of SRI was only 25% (8 of 32) for primary benign PCCs. In 14 patients metastases occurred, which were effectively visualized with [(123)I]MIBG in 8 of 14 cases. SRI was able to detect metastases in 7 of 8 cases, including 3 [(123)I]MIBG-negative metastatic cases. In addition, [(123)I]MIBG and SRI detected 2 recurrences. In conclusion, [(123)I]MIBG uptake is correlated with the size, epinephrine production, and site of PCCs. Its role in bilateral and MEN2A/2B-related PCCs seems limited. In cases of recurrent elevation of catecholamines, localization of metastases and/or recurrence should be attempted with [(123)I]MIBG scintigraphy. In suspicious metastatic PCCs, SRI might be considered to supplement [(123)I]MIBG scintigraphy.
 ...
PMID:[(123)I]metaiodobenzylguanidine and [(111)In]octreotide uptake in begnign and malignant pheochromocytomas. 1115 32

This is a consensus statement from an international group, mostly of clinical endocrinologists. MEN1 and MEN2 are hereditary cancer syndromes. The commonest tumors secrete PTH or gastrin in MEN1, and calcitonin or catecholamines in MEN2. Management strategies improved after the discoveries of their genes. MEN1 has no clear syndromic variants. Tumor monitoring in MEN1 carriers includes biochemical tests yearly and imaging tests less often. Neck surgery includes subtotal or total parathyroidectomy, parathyroid cryopreservation, and thymectomy. Proton pump inhibitors or somatostatin analogs are the main management for oversecretion of entero-pancreatic hormones, except insulin. The roles for surgery of most entero-pancreatic tumors present several controversies: exclusion of most operations on gastrinomas and indications for surgery on other tumors. Each MEN1 family probably has an inactivating MEN1 germline mutation. Testing for a germline MEN1 mutation gives useful information, but rarely mandates an intervention. The most distinctive MEN2 variants are MEN2A, MEN2B, and familial medullary thyroid cancer (MTC). They vary in aggressiveness of MTC and spectrum of disturbed organs. Mortality in MEN2 is greater from MTC than from pheochromocytoma. Thyroidectomy, during childhood if possible, is the goal in all MEN2 carriers to prevent or cure MTC. Each MEN2 index case probably has an activating germline RET mutation. RET testing has replaced calcitonin testing to diagnose the MEN2 carrier state. The specific RET codon mutation correlates with the MEN2 syndromic variant, the age of onset of MTC, and the aggressiveness of MTC; consequently, that mutation should guide major management decisions, such as whether and when to perform thyroidectomy.
 ...
PMID:Guidelines for diagnosis and therapy of MEN type 1 and type 2. 1205 Feb 90

Multiple endocrine neoplasia syndrome type II-A (MEN-IIA) is a rare endocrinological disorder occurring in 0.04% of the general population. The combination of papillary thyroid carcinoma with MEN-IIA appears even less frequently. We describe the case of a 21-year-old woman with pheochromocytoma of the left adrenal gland, medullary thyroid carcinoma, hyperplasia of the parathyroid glands and papillary thyroid carcinoma. MEN II-A syndrome resulted from de novo mutation of the RET proto-oncogene, which was detected in the DNA of peripheral blood leucocytes. Three months postoperatively calcitonin levels were normal, whilst increased serum thyroglobulin values prompted the need for further investigation. Whole body scanning with (131)I and with (99m)Tc-sestamibi and also US test of cervical lymph nodes, were negative. The synthetic analogue of somatostatin (99m)Tc-depreotide was used for whole body scintigraphy, cervical and thoracic tomographic scanning and revealed anterior cervical, upper mediastinal and right hilar foci of pathological uptake[Fig.1 and Table 1: see text]. These findings were compatible with findings from CT and MRI that followed in order to complete the diagnostic evaluation. The patient underwent surgical resection of the metastatic foci with uneventful postoperative course. Histology showed lymph node metastases originating from the papillary thyroid carcinoma. Ratio values >2 were abnormal (Fig. 2). Computer processing of the corresponding ROIs on healthy tissues produced the following normal values: Th/Arm: 1.874,, Med/Arm: 1.699, Hi/Arm: 1.141 (Fig. 3).
 ...
PMID:[A patient with MEN-IIA syndrome due to de novo mutation and papillary thyroid carcinoma; the role of 99m Tc-depreotide in diagnosing metastases and brief review of the literature]. 1584 Dec 92

One hundred fifty-four consecutive patients with pheochromocytoma (PC, n=137) or paraganglioma (PG, n=17) were treated at our unit. Twenty patients had MEN 2, 15 VRD, and 1 VHL tumors. Twelve had malignant tumors and were classified according to mode of presentation: (1) Distant metastases (n=4); three underwent surgical debulking (with chemotherapy in one); and three had 131I-MIBG therapy. Within 4 years two patients died of tumor progression. (2) Locally advanced disease (n=4), all resected for cure. (3) Malignancy disclosed during follow-up after adrenalectomy with "benign" histopathology (n=4). All patients in groups 2 and 3 developed recurrence 9 (1-17) years after primary surgery; four underwent resection, one remains tumor-free. The others were treated chronically with phenoxybenzamine, combined with 131I-MIBG in one. These eight patients were observed 20 (5-35) years after primary surgery and 11 (1-19) years after recurrence. This series is population-based and may better reflect the natural history of malignant PC/PG than the series from national referral centers. Active surgical treatment and phenoxybenzamine resulted in low tumor-related mortality in groups 2 and 3; five patients died 8-30 years after diagnosis, four of PC/PG (three from group 2 and one from group 3) and one of other causes. We propose tumor uptake studies (MIBG- and octreotide scintigraphy) in patients with nonresectable metastases; to select individual radionuclide therapy data on the expression of CA-transporters/somatostatin receptors may be helpful. To diagnose PC/PG early, screening of adrenal incidentalomas has been suggested. In a regional population-based prospective study, 503 incidentalomas were reported during 18 months, but only one patient with PG was identified.
 ...
PMID:Malignant pheochromocytoma in a population-based study: survival and clinical results. 1710 19


1