Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Since the discovery that germ-line mutations in the RET protooncogene are responsible for the multiple endocrine neoplasia (MEN) syndromes types 2A and 2B, prophylactic thyroidectomy has been recommended for MEN patients to prevent medullary thyroid carcinoma (MTC). In this report, we present the medium-term follow up results on the earliest group of 18 patients having prophylactic thyroidectomy for MEN 2A. There were no operative complications. Microscopic or grossly evident MTC was present in 14 (78%) of the resected patients. None of the patients had metastasis of their MTC to regional lymph nodes. At three years' follow up, there is no evidence of residual or recurrent MTC, based on biochemical testing. We conclude that prophylactic thyroidectomy, based on direct DNA testing for RET gene mutations, is an effective and safe way to manage MTC in patients with MEN 2A.
Exp Clin Endocrinol Diabetes 1998
PMID:Prophylactic thyroidectomy, based on direct genetic testing, in patients at risk for the multiple endocrine neoplasia type 2 syndromes. 951 56

In the present study, we retrospectively reviewed thirteen consecutive patients with insulinomas including 2 reoperations at our department for insulinomas, from the viewpoint of preoperative localization studies, surgery and long term follow-up. The results of the preoperative localization studies proved to be percutaneous transhepatic portal venous sampling (PTPVS) 6/7, angiography 8/15, ultrasonography (US) 6/11, endoscopic ultrasonography (EUS) 4/4, computed tomography (CT) 3/10, and magnetic resonance imaging (MRI) 2/2. The tumor was visualized by intraoperative ultrasonography (IUS) in 6 of 6 patients (100%). Six patients underwent enucleation, 6 patients underwent distal pancreatectomy, 2 patients underwent subtotal (80%) distal pancreatectomy, and one patient a pylorus preserving pancreaticoduodenectomy (PPPD). Two patients, one of whom belonged to the MEN-I group, underwent reoperations because they had multiple adenomas. The development of iatrogenic diabetes occurred in the case of 3 patients. These results suggest that the use of selected preoperative localization studies (PTPVS and probably EUS) may be very helpful for detecting insulinoma, and that IUS is an essential part of the operative exploration for insulinoma. Our data may further indicate the need for an aggressive surgical procedure in the case of multiple adenoma or insulinoma in MEN-I.
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PMID:Tumor localization studies and surgical treatment in patients with insulinoma. 967 43

Of the rare pancreatic endocrinomas, glu-cagonomas, either with or without diabetico-dermatogenic syndrome (DDS), are probably third in frequency after insulinomas and gastrinomas. This study was carried out to evaluate the present status of glucagonoma/DDS in a statistically reliable number of cases and to provide precise information to investigators actively working in this particular field of research. A total of 407 cases of glucagonoma were collected from the international literature and evaluated according to characteristic clinicopathologic features. Findings were: (1) The incidence of DDS was 57.2% (233/407). (2) The tail of the pancreas was predominantly involved, in 53.7% (213/397). (3) One-third of the tumors (80 of 276 for whom size was recorded; 29.0%) measured 20 mm or less. (4) Metastases occurred in 51.4% (209/407) and malignant tumors in 60.7% (247/407). (5) Multiplicity occurred in 11.8% (48/407), and associated multiple endocrine neoplasia type 1 in 13. 0% (53/407). (6) In the patients with DDS, the rates of hyperglucagonemia, necrolytic migratory erythema, diabetes mellitus, loss of weight, hypo-aminoacidemia, or anemia, as representative constituents of DDS, were all higher than rates in the overall series (P < 0.01). (7) The 10-year survival rate in the 233 patients with DDS was 51.6% in those with metastases and 64.3% in those without metastases (P < 0.001).
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PMID:Glucagonomas/diabetico-dermatogenic syndrome (DDS): a statistical evaluation of 407 reported cases. 988 Jul 81

Familial pituitary tumors are rare. Only 45 cases in 20 families with acromegaly have been reported. A third of the cases (30%) is related to multiple endocrine neoplasia type 1 (MEN 1). We report two cases of acromegaly in one family with pituitary macroadenomas. A 46-year-old woman with elevated serum growth hormone (GH) and insulin-like growth factor (IGF-1) and a failure to supress GH in the glucose tolerance test underwent transsphenoidal surgery 4 years ago. Three years later her 24-year-old son also presented with typical signs of acromegaly. A pituitary macroadenoma was identified by MRT and he also underwent transsphenoidal surgery. There were no symptoms of McCune-Albright syndrome or other forms of endocrine hyperfunction in the two patients. In an attempt to identify the molecular etiology of the tumours DNA was extracted from paraffin fixed tissue from both patients. Exon 7 to 13 of the Gsp-protein and exons 1 to 10 of the menin gene were amplified by PCR. Although Gsp mutations have been identified in 40% of somatotroph tumors, direct sequencing of the PCR products showed no mutations in exons 7 to 13 of Gs alpha. Moreover no mutations were found in exons 1 to 10 of the menin gene. Therefore, molecular causes other than Gsp or menin gene mutations have to be considered as the molecular etiology of acromegaly in this family.
Exp Clin Endocrinol Diabetes 1999
PMID:Acromegaly in a family without a mutation in the menin gene. 1007 64

It is clear that cutaneous lesions of metabolic epidermal necrosis in the dog can occur either with a demonstrable glucagon-secreting tumor or with hepatic disease without any detectable glucagonoma. Additional clinical case reports of the disease in cats are needed to better characterize the disease in this species. The lesions of NME-MEN may not represent a specific physiological mechanism of cutaneous disease but instead a pathophysiological process that can be triggered by several systemic metabolic abnormalities. The fact that NME is observed in association with a variety of conditions supports the theory that an overall metabolic derangement results in the rash. The prognosis for canine MEN is poor; however, some affected dogs have been maintained for many months with dietary management. High-quality protein diets such as Hill's Prescription Diet a/d (Hill's Pet Products) or other "recovery" diets may be helpful. Zinc and essential fatty acid supplementation may help some patients. Dietary supplementation with cooked egg yolks may be helpful. It is prudent to avoid corticosteroids in these cases, as development of diabetes mellitus worsens the prognosis. Histopathological examination of the pancreas coupled with determination of plasma glucagon may help define the characteristics of GS versus HS in dogs. It is possible that some dogs diagnosed with MEN-HS may have an undetected pancreatic tumor. Although the hepatic ultrasound findings in dogs with MEN-HS are becoming well characterized, it is possible for dogs with pancreatic neuroendocrine tumors to also have abnormal hepatic ultrasonography. As the presence of MEN and hepatic disease does not necessarily rule out the presence of a pancreatic tumor, prospective studies correlating plasma glucagon levels with pancreatic histopathology in cases of MEN-GS versus MEN-HS seem warranted.
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PMID:Metabolic epidermal necrosis-hepatocutaneous syndrome. 1056 4

Primary Hyperparathyroidism (PHP) often goes unrecognised. Evidence of the influence of thyroid diseases on parathyroid activity exists. In order to determine the prevalence of primary hyperparathyroidism (PHP) in patients with thyroid diseases, a series of patients referred to an outpatient department for patients with thyroid diseases were examined for additional PHP. In addition to screening for thyroid diseases, serum calcium concentration (S-Ca) was measured in a series of persons who came to our outpatients' service for patients with thyroid diseases during the period 1992 to 1998. 13387 persons, median age 48 y, m = 2367, f = 11020, among them 9017 patients with thyroid diseases and 4370 persons without thyroid dysfunction, were studied. In patients with S-Ca outside the normal range, further diagnostic tests relating to PHP were performed. 106/13387 persons showed S-Ca > or = 2.6 mmol/L, in 31 cases due to PHP. In comparison to persons without thyroid diseases, the occurrence of PHP was significantly higher in patients with thyroid diseases (4/4370 = 0.09% vs. 26/9017 = 0.29%). Furthermore, 2 patients with normal S-Ca were diagnosed as having PHP in addition to another endocrine disease (acromegaly, multiple endocrine neoplasia type IIa, resp.). 31 of the 54 persons with S-Ca > 2.6mmol/L and who showed no other reasons for hypercalcaemia were found to be in a hyperthyroid state. The prevalence of PHP was significantly higher in patients with euthyroid goitre (p < 0.05) and in patients with thyroid carcinoma (p = 0.01) as compared to other persons with thyroid diseases. The groups of patients did not differ with regard to age. However, patients without thyroid diseases were significantly younger (median age 38y). Above the age of 50, the prevalence of PHP became higher in patients with euthyroid goitre or thyroid carcinoma than in those with a healthy thyroid gland. In contrast, in persons of under 50 y, there was no difference between these groups. The percentage of males with PHP was higher than in the total population studied (30% vs. 21.5%). In conclusion, a high occurence of PHP could be demonstrated in patients with thyroid diseases (0.29%) as compared to persons without thyroid dysfunction (0.09%), the highest prevalence being in patients with thyroid carcinoma. A clinically not relevant influence of thyroid function on S-Ca was seen in some patients with hyperthyroidism. Determination of S-Ca is recommended for each patient referred to a thyroid outpatients' department because of the high number of PHP cases in this context.
Exp Clin Endocrinol Diabetes 1999
PMID:Prevalence of primary hyperparathyroidism in 13387 patients with thyroid diseases, newly diagnosed by screening of serum calcium. 1059 98

The diagnosis of entero-neuropancreatic tumours different from Zollinger-Ellison syndrome and carcinoid syndrome require an high index of suspicion and even when they are associated to virulent syndromes such as VIPoma or insulinoma syndrome the mean delay in diagnosis is of 4 years. Symptomatic hypoglycaemia due to inappropriate insulin release from insulinoma and watery diarrhoea leading to dehydration caused by elevated circulant vaso-intestinal peptide levels are present in the 90% and 100% of the patients at presentation of the respective syndrome. Somatostatinoma syndrome has a far more subtle presentation and it tends to present much later during the disease course. The diagnosis is based on the presence of gallstones, diabetes, weight loss, diarrhoea and steatorrhoea. Growth hormone releasing factor neuroendocrine tumours (GRFoma) present with acromegaly and account for less than 2% of the acromegalic patients in which the growth hormone is from an ectopic source located in the pancreas. The Cushing's syndrome diagnosis due to rare ectopic neuroendocrine tumour adrenocorticotropic hormone secretion can be made only with selective angiography, whereas non-functional and pancreatic polypeptide producing neuroendocrine tumours (PPoma) present without any symptoms. Finally, multiple endocrine neoplasia type one occurs more commonly with somatostatinoma or GRFoma, conversely patients with multiple endocrine neoplasia type one can develop insulinoma (20%) or PPoma (60%).
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PMID:Diagnosis of non-Zollinger-Ellison syndrome, non-carcinoid syndrome, enteropancreatic neuroendocrine tumours. 1060 21

Medullary thyroid carcinoma (MTC) occurs sporadically (sMTC) or as part of the inherited cancer syndrome, multiple endocrine neoplasia type 2 (MEN 2). While the occurence of the MEN 2 syndrome is associated with mutations in the RET protooncogene, the reason for carcinogenesis in sMTC still remains unclear. Ras is a frequently mutated oncogene in a broad spectrum of human tumors and has been found in about 50% of follicular, papillary or anaplastic thyroid carcinomas. The purpose of this study was to determine, whether mutations in the ras oncogene could play a possible role in the carcinogenesis of sMTC. In this study we analyzed 15 sMTC for mutations in the hotspots codon 12, 13 and 61 of the H- and K-ras oncogene. We used the direct sequencing technique. In none of the examined tumors we were able to detect a mutation in the codon 12, 13 and 61 of the H-ras and K-ras oncogene. Based upon these results, we conclude that H- and K-ras do not play an important role in the carcinogenesis of sMTC.
Exp Clin Endocrinol Diabetes 2000
PMID:Absence of H- and K-ras oncogene mutations in sporadic medullary thyroid carcinoma. 1076 32

Activating germline mutations of the RET proto-oncogene are found in more than 90% of families with multiple endocrine neoplasia type 2a (MEN 2a) and familial medullary thyroid carcinoma (FMTC). The majority of patients with these hereditary tumors carry germline mutations that result in the substitution of one of five cysteine residues in exon 10 and 11. Different mutations in exons 13, 14 and 15 affecting non-cysteine residues have also been described but are considered to be rare. We now for the first time report a double mutation of the RET proto-oncogene occurring in the germline of a kindred with FMTC. Both mutations occur within the tyrosine kinase domain in exon 14 and lead to the substitution of valine 804 by methionine and arginine 844 by leucine. Since the double mutated allele cosegregated with the disease and was not identified in 200 unrelated normal probands, we conclude that they represent mutations that predispose the individual to the development of FMTC with a mild phenotype.
Exp Clin Endocrinol Diabetes 2000
PMID:A RET double mutation in the germline of a kindred with FMTC. 1114 22

The recent identification of MEN1 gene mutations as the molecular cause of familial multiple endocrine neoplasia type 1 syndrome (MEN1) has had a significant impact on clinical patient care. In the following consensus statement we will present recommendations for clinical screening and follow-up in patients and relatives with suspected or established MEN1 syndrome. MEN1 mutational analysis should be performed in individuals with newly diagnosed MEN1-typical endocrine neoplasia (e.g., primary hyperparathyroidism, gastroenteropancreatic tumor, pituitary adenoma) if additional diagnostic criteria are met (e.g., age <40 years; positive family history; multifocal or recurrent neoplasia; two or more organ systems affected). Genetic family screening is advisable in first degree relatives of MEN1 patients during early adolescence to reliably assess future MEN1 disease risk. In symptomatic individuals carrying MEN1 germ line mutations, annual clinical and biochemical (calcium, PTH, gastrin, prolactin) follow-up as well as routine pancreatic and pituitary imaging may be complemented as individually needed. In contrast, relatives without family-specific MEN1 mutation do not require routine follow-up. Diagnostic procedures and treatment in symptomatic MEN1 mutation carriers and patients may differ from that in sporadic endocrine neoplasia, calling for individual management. Genetic counselling and dedicated endocrine surgery should be integral parts of current medical care in MEN1 syndrome.
Exp Clin Endocrinol Diabetes 2000
PMID:Concepts for screening and diagnostic follow-up in multiple endocrine neoplasia type 1 (MEN1). 1098 49


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