SEARCH · PubMed Health

Results for “Multiple Endocrine Neoplasia Type 2b”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 55 records · Page 3Linked to original sources

PubMed1998

Ocular manifestations in multiple endocrine neoplasia type 2b.

PURPOSE: To describe the clinical and laboratory findings in a patient with multiple endocrine neoplasia type 2b. METHOD: Case report. An 8-year-old boy underwent ophthalmic examination, genetic evaluation, total thyroidectomy, and biopsy of a tongue nodule. RESULTS: Ocular features, including previously unreported iris changes, and their probable origin are discussed. Genetic testing detected the point mutation at codon 918 within the RET protooncogene on chromosome 10, characteristic of multiple endocrine neoplasia type 2b. Histologic analysis of excised thyroid tissue disclosed medullary carcinoma. A tongue nodule proved to be neuromatous. CONCLUSION: Ophthalmologists can play an important role in the recognition of multiple endocrine neoplasia type 2b, a potentially lethal condition.

Carcinoma, Medullary↗

PubMed1983

Multiple endocrine neoplasia, type 2b, as a cause of megacolon.

A case of multiple endocrine neoplasia, type 2b, is reported presenting with weight loss, neck masses, and constipation. A medullary thyroid carcinoma was found to be present together with a megacolon. In this syndrome, the diagnosis of the thyroid tumor is rarely made before it is well established; hence an appreciation of the accompanying gastrointestinal symptoms and signs may lead to early diagnosis. The case had many classical features, such as ganglioneuromata involving the tongue, lips, and eyelids and typical biochemical findings. However, several unusual findings were present, such as the absence of any skeletal abnormalities, an acute onset of constipation, and the presence of bony metastases and the case is reported to illustrate the complexity of this uncommon entity.

Adult↗

PubMed2002

Medullary thyroid carcinoma as part of a multiple endocrine neoplasia type 2B syndrome: influence of the stage on the clinical course.

BACKGROUND: Multiple endocrine neoplasia type 2B (MEN 2B) is an exceptional syndrome, for which the optimal age of thyroidectomy is poorly established and the course of medullary thyroid carcinoma (MTC) is ill-defined. PATIENTS: All the 18 patients with a MEN 2B syndrome examined at the Institut Gustave Roussy were included in a single-center retrospective study. RESULTS: There were 9 men and 9 women with a mean age of 13 years (range, 2-27 years) at diagnosis. The diagnosis of MTC was based on the presence of a thyroid nodule or involved neck lymph nodes and on dysmorphic features of MEN 2B in 60% and 40% of the cases, respectively. The classic M918T mutation in exon 16 was found in the 16 patients in whom it was investigated. At diagnosis, 2 patients had Stage I MTC, 15 patients had Stage III, and 1 patient had Stage IV disease. T1 MTC was found in 4 patients aged 2.1-3.7 years. However, two of these patients already had N1 disease. One patient with Stage I MTC, aged 3.4 years and 2 patients with Stage III disease, aged 14 and 25 years, had undetectable basal calcitonin (CT) after initial surgery. During follow-up, basal CT became detectable in one of three patients. Among the 15 other patients with an elevated postoperative CT level, metastases were demonstrated in 5 patients after a mean follow-up of 2 years. Five patients died, three of MTC, one of the MEN 2B syndrome, and one of intercurrent disease. Five- and 10-year overall survival rates were 85% and 75%, respectively. CONCLUSIONS: This study confirms the need for early treatment of MTC in patients with the MEN 2B syndrome, preferably within the first 6 months of life. The phenotype of MTC occurring in the MEN 2B syndrome was not more aggressive than sporadic MTC or MTC occurring in other familial syndromes.

Adolescent↗

PubMed1990

Multiple endocrine neoplasia type 2b: long-term follow-up of a case.

Multiple endocrine neoplasia type 2b is a rare inherited syndrome which comprises the association of medullary thyroid carcinoma, phaeochromocytoma, widespread neuromatous proliferation and a characteristic body habitus. In this report we present the late clinical course and autopsy findings of the first patient with this syndrome described in Australia. At presentation she was found to have a right adrenal phaeochromocytoma and medullary thyroid carcinoma which were resected in separate operations. No clinical or biochemical evidence of residual medullary thyroid carcinoma was identified in life. However, in spite of serial vanillylmandelic acid estimations, which showed normal or only mildly elevated levels, and normal results of urinary catecholamine studies, a left adrenal phaeochromocytoma was identified in a metaiodobenzylguanidine (MIBG) study performed 14 years after presentation. Her late clinical course was dominated by progressive dysphagia, intestinal dysmotility and megacolon associated with unrelenting malnutrition. After her death due to an intracerebral haemorrhage, an autopsy confirmed the presence of a left adrenal phaeochromocytoma and revealed diffuse intestinal ganglioneuromatosis to be the cause of her intestinal dysmotility. No residual medullary thyroid carcinoma was found. This case emphasises the propensity for multiple endocrine tumours in these patients and highlights the potentially significant role of intestinal ganglioneuromatosis in the natural history of this condition.

Adrenal Gland Neoplasms↗

PubMed2006

De novo multiple endocrine neoplasia type 2B with noncardiogenic pulmonary edema as the presenting symptom.

Multiple endocrine neoplasia (MEN) type 2B is a rare hereditary disorder characterized by medullary thyroid carcinoma, pheochromocytoma, and neuroma. Early signs of MEN 2B are usually neuroma, gastrointestinal problems, and medullary thyroid carcinoma. Noncardiogenic pulmonary edema is rare as a presenting symptom. We report a 31-year-old male who was admitted to our hospital because of noncardiogenic pulmonary edema. He was 168 cm in height, weighed 55 kg, and had an arm span of 166 cm. No marfanoid habitus was evident, but thickened lips and tongue neuroma were present. Chronic constipation had been present since childhood, and the patient had a two-year history of untreated hypertension. Noncardiogenic pulmonary edema and toxic megacolon were noted, and abdominal computed tomography revealed bilateral adrenal tumors. Ultrasonography of the thyroid showed two mass lesions. Intubation and mechanical ventilation were performed because of severe hypoxemia. Endocrinological examinations showed high levels of serum and urinary fractionated catecholamines, serum calcitonin, serum carcinoembryonic antigen, and serum intact parathyroid hormone. It was suggested that the high level of catecholamine from pheochromocytoma had caused the pulmonary edema. RET gene analysis showed a codon 918 mutation in exon 16 resulting in an ATG (methionine) to ACG (threonine) substitution, but analysis of the patient's parents showed the wild type. Therefore, the patient was diagnosed as having de novo MEN 2B. He underwent laparoscopic bilateral adrenectomy and total thyroidectomy. However, the values of serum calcitonin and CEA did not decrease to the normal ranges. Patients with early-stage MEN 2B have distinct characteristics that can aid early detection of the disease, thus possibly allowing them to be saved.

Adrenal Gland Neoplasms↗

PubMed1997

Germline dinucleotide mutation in codon 883 of the RET proto-oncogene in multiple endocrine neoplasia type 2B without codon 918 mutation.

The autosomal dominant multiple endocrine neoplasia type 2 syndromes (MEN 2) comprise three clinically distinct entities, MEN 2A, familial medullary thyroid carcinoma and MEN 2B, which share a common clinical feature: medullary thyroid carcinoma (MTC). MEN 2B is considered to have the most aggressive form of MTC. Therefore, early detection of MEN 2B in order to prevent potentially lethal MTC is important. More than 95% of all MEN 2B cases are caused by germline mutation at codon 918 (M918T) in exon 16 of the RET proto-oncogene. In this study, we demonstrate the presence of germline codon 883 mutation (A883F) in 2 of 3 unrelated MEN 2B cases without codon 918 mutation. Our data demonstrate a novel etiologic event which may have roles in predisposition to MEN 2B when present in the germline and in the pathogenesis of sporadic MTC when somatic.

Alanine↗

PubMed1992

A kindred of multiple endocrine neoplasia type 2B.

We describe familial cases of multiple endocrine neoplasia (MEN) 2B: A 48-year-old man is the proband. He had pheochromocytoma, medullary thyroid carcinomas (MTCs), parathyroid hyperplasia, mucosal neuromas, eversion of eyelids and Marfanoid appearance, and then underwent adrenalectomy and total thyroidectomy. Family screening revealed that his two daughters (10 and 8 years old) had mucosal neuromas and increased serum calcitonin (CT). Both of them had MTCs but no pheochromocytoma, and their MTCs were surgically removed. The father and his children have been in favorable condition since the operations. Southern blot analysis with 33 polymorphic DNA probes was done in MTCs obtained from two daughters. An RBP3 (10q11.2) locus linked to a predisposing gene on chromosome 10 was uninformative in either patient because of constitutional homozygosity. Loss of heterozygosity at the MYCL1 locus on chromosome 1p32 was observed in MTC from the younger sister, but no loss of heterozygosity was recognized in other loci examined. Deletion of the 1p32 locus may play a role in the development of MEN 2B.

Adrenal Gland Neoplasms↗

PubMed1987

Multiple endocrine neoplasia type 2b with a good prognosis.

Three patients with the multiple endocrine neoplasia syndrome type 2b (MEN 2b) and a good prognosis are described. During a follow-up period of 41 to 84 months, only little progression of metastases of medullary carcinoma of the thyroid was observed. In one of the patients, liver metastases of medullary carcinoma of the thyroid were already present in biopsy specimens taken 22 years earlier. In two patients bilateral pheochromocytomas were completely removed. These observations show that, in contrast to the general view, the clinical course of MEN 2b can be as indolent as that of MEN 2a or sporadic forms of the tumors involved, despite the presence of metastases. This may indicate that factors other than the type of inheritance contribute to the outcome of the disease.

Adult↗

PubMed1995

Relationship of familial prominent corneal nerves and lesions of the tongue resembling neuromas to multiple endocrine neoplasia type 2B.

PURPOSE: We studied a two-generation family with an inherited syndrome of prominent corneal nerves and lesions of the tongue resembling neuromas without the characteristic neoplasms of the multiple endocrine neoplasia type 2B syndrome. Several different point mutations in the RET proto-oncogene on chromosome 10 have been associated with the multiple endocrine neoplasia type 2 syndromes. Molecular genetic studies of families with partial phenotypic expression of these syndromes may aid in further understanding the origin of the variety of clinical manifestations observed in multiple endocrine neoplasia type 2. METHODS: A family consisting of an 8-year-old male proband, his 10-year-old sister, and 40-year-old mother was identified as having prominent corneal nerves and lesions of the tongue resembling neuromas. Pentagastrin-stimulated serum calcitonin levels were measured in the mother and sister. Molecular genetic studies were performed on all three affected members, to look for the specific point mutation seen in over 95% of patients with multiple endocrine neoplasia type 2B. RESULTS: Serum calcitonin levels were normal, indicating no C-cell hyperplasia or medullary thyroid carcinoma. Molecular genetic studies on these individuals did not disclose the specific point mutation seen in multiple endocrine neoplasia type 2B. CONCLUSIONS: This family demonstrates some of the phenotypic features of the multiple endocrine neoplasia type 2B syndrome without the characteristic neoplasms or the mutation in the RET proto-oncogene associated with multiple endocrine neoplasia type 2B. Their physical findings may be caused by genetic alterations within the RET proto-oncogene on chromosome 10 at yet undetermined sites.

Adult↗

PubMed1983

Multiple endocrine neoplasia type 2b (MEN 2b). Report of 2 pediatric cases.

Two new sporadic cases of multiple endocrine neoplasia type 2b (MEN 2b) are described. Both patients were diagnosed in pediatric age and presented the characteristic features of the syndrome (facies "sui generis", Marfanoid habitus, mucosal neuromas, history of chronic gastrointestinal disturbances) and developed medullary thyroid carcinoma (MTC). In the former case, metastatic neck adenopathies were the first sign by which the disease was recognized. Antitumor treatment consisted of total thyroidectomy, cervical node dissection, administration of I131 and neck irradiation. This patient is alive and well 20 months from diagnosis, still having high serum levels of thyrocalcitonin (TC). In the latter case, the syndrome was diagnosed on clinical grounds before the development of a MTC. The patient was then strictly followed-up and thyroidectomy performed only when serum TC levels rose to abnormally high values: no tumor spread was documented at that time. She is alive and well 4 years from diagnosis.--Early recognition of MEN 2b syndrome is necessary in order to detect and properly treat MTC.

Adolescent↗

PubMed2000

Multiple endocrine neoplasia type 2B mutation in human RET oncogene induces medullary thyroid carcinoma in transgenic mice.

Multiple endocrine neoplasia type 2B (MEN 2B) is a familial cancer syndrome, in which the cardinal feature is medullary thyroid carcinoma (MTC), a malignant tumor arising from the calcitonin producing thyroid C-cells. MEN 2B is associated with a germline point mutation in the RET proto-oncogene, leading to a Met-->Thr substitution at codon 918 in the kinase domain, which alters the substrate specificity of the protein. We used the human calcitonin gene (CALC-I) promoter to generate transgenic mice expressing either the human RET oncogene with the MEN2B-specific 918 Met-->Thr mutation (CALC-MEN2B-RET) or the human non-mutated RET proto-oncogene (CALC-WT-RET) in the C-cells. At 20 - 22 months of age three out of eight CALC-MEN2B-RET transgenic founders presented with macroscopic bilateral MTC. In two founders nodular C-cell hyperplasia (CCH) was observed. Thyroid abnormalities were never observed in CALC-WT-RET transgenic mice or control non-transgenic mice analysed at this age. In some mice from established CALC-MEN2B-RET transgenic lines nodular CCH was observed from 8 months on whereas MTC was detected in 13% of mice from one CALC-MEN2B-RET line, from the age of 11 months on. These results show for the first time that the MEN2B mutation in the RET oncogene predisposes mice for MTC.

Animals↗

PubMed1977

Alimentary tract manifestations of multiple endocrine neoplasia, type 2b.

Alimentary tract manifestations were found in all of 17 patients with multiple endocrine neoplasia, type 2b. The manifestations are important because (1) they were chronic, (2) they were severe and led to abdominal operation in 5 patients, (3) they antedated detection of the endocrine neoplasms in the syndrome in 16 patients (94%), and (4) they provided clinical clues that stimulated search for thyroidal C-cell and adrenal medullary disease in 6 patients. The alimentary tract manifestations were diverse: symptoms included constipation, diarrhea, difficulty with feeding, projectile vomiting, crampy abdominal pain, and loud borborygmi; findings included thickened lips, nodules on the anterior third of the tongue, abdominal distention, visible peristaltic waves, and roentgenographic evidence of megacolon or diverticulosis of the colon or of dilatation of the small intestine and stomach. Initial misinterpretation or failure to realize the significance of one or more of these alimentary tract manifestations led to suspicion of aganglionic megacolon (three patients), malabsorption syndrome (two patients), and tracheal ring (one patient).

Abdomen↗

PubMed2006

Phenotypic multiple endocrine neoplasia type 2B, without endocrinopathy or RET gene mutation: implications for management.

The multiple endocrine neoplasia (MEN) type 2B is an autosomal dominant condition characterized by aggressive medullary C-cell tumors, pheochromocytoma, and a discrete physical appearance (marfanoid habitus, prominent corneal nerve fibers, thick lips, and mucosal and intestinal neuromas). A specific point mutation in the RET proto-oncogene is present in 95% cases. Occasionally cases present with the characteristic physical appearance of MEN 2B but no identifiable germline mutation or endocrinopathy, and it has been suggested that these patients may represent a discrete subgroup termed pure mucosal neuroma syndrome (MNS). We present a patient with MNS, who had a thyroidectomy at age 14.5 years with normal thyroid histology. Direct sequencing of all 20 exons of the RET gene showed no mutation. This case supports the suggestion that pure MNS can exist in the absence of an identifiable RET gene mutation. We suggest that prophylactic thyroidectomy is unnecessary in these patients although they should still be screened for endocrinopathy on a regular basis.

Adolescent↗

PubMedDate not supplied

Prolonged survival of a patient with multiple endocrine neoplasia type 2b and stage IV medullary thyroid carcinoma.

OBJECTIVE: To present a case of multiple endocrine neoplasia type 2B (MEN2B) with a prolonged course. METHODS: We describe the clinical, laboratory, and radiologic findings in a patient with MEN2B and review the various interventions during a period of approximately 3 decades. RESULTS: In 1962, a 19-year-old man with a marfanoid body habitus presented with multiple thyroid nodules and neurofibromas of the tongue. Total thyroidectomy demonstrated multicentric medullary thyroid carcinoma with cervical lymph node metastatic involvement. At the time of the first description of the MEN2B syndrome, the patient was enrolled in a surveillance program. An increase in urinary metanephrines resulted in bilateral adrenalectomy for multinodular pheochromocytoma in 1972. Increased serum calcitonin levels and the appearance of cervical lymphadenopathy led to modified radical neck dissection 12 years after the initial diagnosis of medullary thyroid carcinoma. In 1975, angiography revealed extensive hepatic lesions metastatic from the medullary thyroid carcinoma; this finding was confirmed by open liver biopsy in 1988. The patient lived 16 years after the initial diagnosis of liver metastatic disease and died 29 years after the initial examination. CONCLUSION: The 3-decade course of this patient not only represents a classic case of MEN2B but also allows us to present the history of this disease from its discovery to the current era of genetic testing and exemplifies the possibility of long-term survival in a patient with liver metastatic involvement from medullary thyroid carcinoma.

Adult↗

PubMed1990

Linkage of the multiple endocrine neoplasia type 2B gene (MEN2B) to chromosome 10 markers linked to MEN2A.

The syndrome of multiple endocrine neoplasia type 2B (MEN 2B) resembles that of MEN 2A in that both include medullary carcinoma of the thyroid, pheochromocytoma, and autosomal dominant inheritance, but is distinct in that MEN 2B patients have neuromas of the mucous membranes. MEN2A has been linked to RBP3, D10S5, FNRB, D10S15, and D10Z1 near the centromere of chromosome 10. We examined linkage between MEN2B and RFLPs on chromosome 10 in all available members in two or three generations of 14 kindreds. The centromere marker D10Z1 was linked to MEN2B with a peak lod score of 5.42 at theta = 0.02. One possible recombinant was observed between D10Z1 and MEN2B. Multipoint analysis of RFLPs at FNRB, D10Z1, RBP3, and D10S15 gave a peak lod score of 7.12 at the midpoint between D10Z1 and RBP3 on the long arm (band q11). The most likely gene order FNRB-D10Z1-MEN2B was 27 times more likely than MEN2B-FNRB-D10Z1 and 31/2 times more likely than FNRB-MEN2B-D10Z1. Additional data will be required to establish the order of these loci with confidence.

Chromosomes, Human, Pair 10↗

PubMed1979

Multiple endocrine neoplasia, type 2b: phenotype recognition; neurological features and their pathological basis.

Sixteen patients affected with multiple endocrine neoplasia, type 2b (MEN 2b), were evaluated by clinical, neurological, nerve conduction and electromyographic, and postmortem examinations. Eight of the 11 patients examined clinically had symptoms: 5, neurogenic constipation; 1, failing vision due to hypertrophied corneal nerves; 1, neuromuscular symptoms and pes cavus; and 1, facial disfigurement. Expression of the dominantly inherited MEN 2b gene is more variable than previously known. When neuromuscular findings are present alone, the features may be those of peroneal muscular atrophy. Because 10 of the 11 patients had sufficiently full expression of the dominantly inherited gene--"Marfanlike" body build, full and fleshy lips, whitish yellow nodules (neuromas) on the tip and edges of the tongue, pes cavus, or peroneal muscular atrophy--the presence of MEN 2b was recognized and a search for the usually associated medullary thyroid carcinoma was instigated. In addition to the recognized involvement of autonomic nerves, we have confirmed that somatic motor and senory neurons may be involved. Findings at postmortem evaluation indicate that symptoms can be attributed to neuroma formation: a characteristic adventitious plaque of tissue composed of hyperplastic, interlacing bands of Schwann cells and myelinated fibers overlay the posterior columns of the spinal cord.

Adolescent↗

PubMed1996

Ligand stimulation of a Ret chimeric receptor carrying the activating mutation responsible for the multiple endocrine neoplasia type 2B.

Inherited activating mutations of Ret, a receptor tyrosine kinase, predispose to multiple endocrine neoplasia (MEN) types 2A and 2B and familial medullary thyroid carcinoma. To investigate the effects induced by acute stimulation of Ret, we transfected both PC12 and NIH 3T3 cells with a molecular construct in which the ligand-binding domain of the epidermal growth factor receptor was fused to the catalytic domain of Ret. Acute stimulation of the chimeric receptor induced PC12 cells to express a neuronal-like phenotype. Moreover, we introduced the dominant mutation, responsible for the multiple endocrine neoplasia type 2B, in the catalytic domain of the Ret chimera. Expression of the mutant chimera, in the absence of ligand stimulation, induces the PC12 cells to acquire a flat morphology with short neuritic processes and transforms the NIH 3T3 cells. Stimulation of the mutant chimera with epidermal growth factor causes a drastic overgrowth of long neuritic processes, with the induction of the suc1-associated protein tyrosine phosphorylation in PC12 cells and higher transforming efficiency in NIH 3T3 cells. These data indicate that the gain-of-function MEN2B mutation does not abrogate ligand responsiveness of Ret and suggest that the presence of Ret ligand could play a role in the pathogenesis of the MEN2B syndrome.

3T3 Cells↗

PubMed2000

Temporal bone findings in multiple endocrine neoplasia type 2B.

To our knowledge, present case is the first published report of temporal bone findings in multiple endocrine neoplasia type 2B (MEN-2B). We describe a 43-year-old Japanese man with medullary thyroid carcinoma (MTC), pheochromocytoma, mucosal neuroma and a Marfanoid body habitus. The collateral adrenal tumors and MTC were removed surgically. However, 14 years after surgery, the MTC and pheochromocytoma recurred and the patient died of intracranial hemorrhage due to hypertension. During the autopsy, metastatic MTC was detected in the liver, lungs, kidneys, pancreas and cervical lymph nodes. Recurrent pheochromocytoma was present in the right kidney. Mucosal neuromas were found in the tongue, gastrointestinal tract and vesical nerve plexus. The following histopathological findings were seen in both temporal bones: metastatic MTC was found as well as neuromas and the cochlear aqueduct was widely patent.

Adult↗