Multiple Endocrine Neoplasia Type IIb Research Articles

Cancer médullaire de la thyroïde, à propos de 12 observations concernant les différentes formes cliniques

The authors report 12 cases of medullary thyroid carcinoma (MTC). Seven patients suffered from sporadic form of MTC and 5 from familial MCT: 2 isolated MTC, 1 multiple endocrine neoplasia (MEN) type IIa, and 1 MEN type IIb. The calcitonine assay and the pentagastrin test allow an early diagnostic, and must be performed in the family members at risk for hereditary MTC and in the cases of suggestive clinical signs and syndroms, and perhaps in all cold nodules.

Bilateral Localized Orbital Neurofibromas

The authors report on a 30-year-old man who presented with progressive bilateral exophthalmos over a 2-year period. Computed tomography showed large heterogeneous masses in the superior aspect of both orbits. Excisional biopsy via bilateral lateral orbitotomies showed the tumors to be well-circumscribed, relatively avascular, localized neurofibromas. The patient had several features suggestive of multiple endocrine neoplasia type IIB, including Marfanoid habitus, enlarged corneal nerves, thickened lips, and mucosal neuromas. Localized neurofibromas are rare in the orbit and, unlike plexiform neurofibromas, are not typically associated with von Recklinghausen's neurofibromatosis. Bilaterality of such localized neurofibromas has not been previously reported. Recognition of ophthalmic lesions suggestive of multiple endocrine neoplasia IIB should prompt evaluation for systemic manifestations of this disorder.

The Natural Course of Multiple Endocrine Neoplasia Type iib

Multiple endocrine neoplasia (MEN) type IIb is an autosomal dominantly inherited disorder associated with medullary thyroid cancer, pheochromocytoma, and a characteristic phenotype. The present study was performed to investigate the natural course of the syndrome and to describe its expression. The medical records of 18 patients with MEN IIb, seven male and 11 female, were reviewed. The mean age at diagnosis of MEN IIb was 18 years (range, 8 to 41 years). All 18 patients had medullary thyroid cancer. In three patients, medullary thyroid cancer was diagnosed via screening. In two of these patients, the calcitonin value normalized after thyroidectomy. One patient died of metastases from medullary thyroid cancer at the age of 20 years (median duration of follow-up, 10 years). Eight of the 18 patients had pheochromocytomas. All of our patients had neuromas and bumpy lips, and all but one had a marfanoid habitus. A large proportion of the patients had intestinal abnormalities (75%), thickened corneal nerves (69%), skeletal abnormalities (87%), and delayed puberty (43%). The course of medullary thyroid cancer in MEN IIb is not always as aggressive as is generally thought. Periodic examination of relatives who are at risk may lead to early diagnosis and curative treatment. Intestinal abnormalities, skeletal abnormalities, and delayed puberty are commonly found in association with MEN IIb.

The natural course of multiple endocrine neoplasia type IIb. A study of 18 cases

The natural course of multiple endocrine neoplasia type IIb. A study of 18 cases

Autonomic involvement in inherited neuropathies

The inherited peripheral neuropathies constitute a large group of disorders, in some of which the causative metabolic defect has been identified whereas in the majority it is still unknown. Amongst the former, autonomic involvement is an important component in porphyric neuropathy, in the familial amyloid polyneuropathies, in Fabry's disease and in dopamine beta-hydroxylase deficiency. The latter group includes the hereditary sensory and autonomic neuropathies in some of which, such as the Riley-Day syndrome, autonomic disturbances are prominent, whereas in others they constitute only a minor component of the symptomatology. Autonomic dysfunction is an important component of the neurological manifestations in multiple endocrine neoplasia type IIB.

Multiple endocrine neoplasia type IIb: A clinicopathological report

The clinicopathological findings in a 12-year-old boy with multiple endocrine neoplasia type IIb (MEN-IIb) are presented. He demonstrated the characteristics of a Marfanoid habitus and had mucosal neuromas of the lips, tongue, eyelids, and cornea. The enlarged right thyroid lobe showed an increased thallium-201 chloride uptake, and the serum calcitonin level was markedly raised. A total thyroidectomy was performed. Histopathological examination showed an infiltrating medullary carcinoma of the thyroid (MCT) and metastatic spread to supraclavicular lymph nodes. Special stains, immunocytochemistry, and electron microscopy revealed mucin-containing follicular structures lined by calcitonin-positive and thyroglobulin-negative tumour cells. Ultrastructurally the mucosal neuromas consisted of proliferating perineurial and Schwann cells. The serum calcitonin level fell below 300 pmol/L, and his stools returned to normal postoperatively. Because the incidence of MCT in MEN-IIb is virtually 100%, a total thyroidectomy in high risk patients--even before clinical evidence of malignant tumours--may be the only hope of cure.

Evaluation of children with multiple endocrine neoplasia type IIb following thyroidectomy

Medullary thyroid carcinoma (MTC) develops in all patients with multiple endocrine neoplasia type IIb (MEN IIb), a rare syndrome that either occurs sporadically or is inherited in an autosomal dominant pattern. The MTC in patients with MEN IIb has been reported to be biologically aggressive with onset at a young age and rapid progression as evidenced by widespread metastases and death, frequently in the teenage years. Seven children, aged 2 to 11 years (mean, 7 years), from three kindreds with MEN IIb were evaluated for evidence of tumor recurrence 3 to 10 years following thyroidectomy. In one child, age 11, a thyroid mass was palpable preoperatively. However, in the remaining six children (aged 2 to 10 years), the diagnosis of MTC was established by an increased concentration of plasma calcitonin (CT), either basally or following pentagastrin (Pg) stimulation. All patients underwent total thyroidectomy with removal of central lymph nodes from the neck. At the time of surgery, six children were found to have bilateral macroscopic MTC, five without and one with cervical metastases. One child (age 2 years) had C-cell hyperplasia, a premalignant precursor of MTC. Currently, five of the seven children are without evidence of recurrent disease clinically and have normal plasma CT levels (less than 0.3 ng/mL) following calcium (Ca) and Pg stimulation 3, 3, 10, 10, and 10 years after thyroidectomy. Two of the seven children have biochemical evidence of residual MTC.(ABSTRACT TRUNCATED AT 250 WORDS)

Multiple Endocrine Neoplasia Type IIB Identified by Magnetic Resonance Imaging

Ectopic, epinephrine-secreting pheochromocytomas are rare and difficult to diagnose. In our case, MRI was able to show the lesion, which could not be clearly identified by CT. The histologic specificity provided by T2-weighted images confirmed the biochemical diagnosis of pheochromocytoma. MRI should be considered as an alternative to CT in the diagnosis of familial pheochromocytomas.

Pathological Features of Multiple Endocrine Neoplasia Type IIb in Childhood

The features of two patients with multiple endocrine neoplasia type IIb are described. Patient 1, a 9-year-old boy with marfanoid features, presented with chronic constipation and failure to thrive since infancy. Patient 2, a 12-year-old boy with marfanoid features, presented with a five-year history of persistent cervical lymphadenopathy. In patient 1, the myenteric and submucosal nerve plexuses at all levels of the small and large intestines were comprised of diffusely disorganized, hyperplastic, mature ganglion cells and nonmyelinated nerve fibers. Nerve plexus dissection with morphometric analysis showed marked thickening of the myenteric plexus with a quantitative increase in neural tissue. Patient 2 had a submucosal neuroma of the tongue. Both patients had occult medullary thyroid carcinoma, and patient 2 had cervical lymph node metastases. Both neoplasms showed positive staining for cytokeratin, carcinoembryonic antigen, calcitonin, bombesin, chromogranin, serotonin, and Leu 7. Electron microscopy showed membrane-bound, intermediate-sized, dense-core neurosecretory granules in tumor cells. In patient 2, calcitonin-positive amyloid was present with localization of calcitonin by immunoelectron microscopy to cytoplasmic secretory granules and to extracellular amyloid fibrils. These cases illustrate the potential for missed or delayed diagnosis in multiple endocrine neoplasia syndromes.

A CASE OF MULTIPLE ENDOCRINE NEOPLASIA TYPE IIb (MENIIb)

A case of multiple endocrine neoplasia type IIb (MENIIb) frequently consisting of medullary thyroid carcinoma (MTC), multiple mucosal neurinoma, megacolon and gastric diverticulum is reported. A 30-year-old male was hospitialized with a neck tumor. Aspiration biopsy, neck roentgenography and serum calcitonin measurement indicated that the tumor was MTC. The patient was diagnosed to have MENIIb based on MTC, characteristic face with thickened lips, multiple mucosal neurinoma and megacolon. We attempted total thyroidectomy, but the MTC was too invasive around tissues to resect. The removed pretracheal lymphonodes revealed medullary carcinoma metastasis. For the moment the presence of a pheochromocytoma is not confirmed by CT and serum and urine catecholamine mesurements.

Medullary carcinoma in children. Results of early detection and surgery.

Early diagnosis and surgical treatment of medullary carcinoma of the thyroid (MCT) in children is essential to decrease the likelihood of metastatic spread. To determine the optimal timing of screening and surgery, we reviewed all children younger than 16 years old who were undergoing surgical treatment. From 1970 to 1988, 33 children 6 months old to 15.9 years old (mean, 9 years old) with MCT or C-cell hyperplasia or both underwent total thyroidectomy. Follow-up was 4 months to 15 years after surgery (mean, 9 years). Six of 31 patients presented with a neck mass. Basal immunoreactive calcitonin level was increased in 3 of 7 patients with C-cell hyperplasia alone, in 10 of 18 patients with nonmetastatic MCT, and in all 5 patients with metastatic MCT. At the time of surgery, 7 patients had C-cell hyperplasia, 19 patients had MCT without metastasis, and 7 patients had MCT with metastases. All children with metastasis were more than 12 years old. Medullary carcinoma of the thyroid was seen as early as age 6 months in a child with multiple endocrine neoplasia type IIb (MEN-IIb) and age 3 years in a child with MEN-IIa. At follow-up, 25 patients were free of disease and 8 had had recurrent disease. Two of the 8 patients with MEN-IIb had died. All 6 children with a neck mass at presentation had recurrent disease. Of 27 patients diagnosed by screening, 25 had no evident disease and 2 had persistent disease. Thus, in children with MEN-II syndromes, screening studies are highly effective in detecting MCT. All children with MEN-IIb should be studied shortly after birth, and those with MEN-IIa should be studied by 1 year old.

The occurrence of multiple endocrine neoplasia type IIb, in two children of an affected mother

The occurrence of multiple endocrine neoplasia type IIb, in two children of an affected mother

Gastrointestinal manifestations of sipple syndrome in children

The diagnosis and management of patients with multiple endocrine neoplasia (MEN) type IIA and type IIB are of special challenge to pediatric surgeons. Patients characteristically present early in life with significant intestinal symptoms at a time when the characteristic phenotypic features of MEN IIB are frequently absent. We are reporting 12 patients with MEN type II (9 with type IIA and 3 type IIB or Sipple's syndrome), all of whom presented with gastrointestinal manifestations. All 12 patients had signs and symptoms of bowel obstruction during the neonatal period. An unusual association of Hirschsprung's disease and MEN IIA was noted in our nine patients found among a kindred of 92 individuals. All three patients with Sipple's syndrome (MEN IIB) had severe gastrointestinal symptoms since birth, including recurrent pseudoobstruction. The possibility of MEN type II should be considered in all cases of bowel obstruction in the newborn period. Screening for medullary carcinoma of the thyroid must be carried out from infancy. A detailed family history is very important to avoid unnecessary surgery for bowel obstruction in Sipple's syndrome.

TREATMENT OF HETASTATIC MEDULLARY THYROID CARCINOMA (MTC) WITH SOMATOSTATIN ANALOG (SMS 201 - 995) RESULTING IN REMISSION OF DIARRHEA AND DECREASE OF VIP AND GRP CONCENTRATIONS

A 15 year old boy was admitted to our department because of intractable diarrhea, flushes and pulmonary restriction over the last 4 years. Final diagnosis was Multiple Endocrine Neoplasia Type IIb (mucosal neuromas, MTC, marfan-like habitus) with pulmonary and lymphatic metastases of MTC secreting excessive amounts of calcitonin (CT: 150 ng/ml, normal: 300 pg/ml, normal: undetectable) and carcino-embryonic antigen (CEA: 150-223 ng/ml, normal: <10 ng/ml). In adults, the long-acting somatostatin analog has been shown to suppress hormonal hypersecretion in many endocrine tumors including carcinoid syndromes and vipomas. Since no effective therapy of metastatic MTC is available so far, we used SMS 201 - 995 in an attempt to control diarrhea and tumor growth. During therapy with s.c. injections the boy experienced clinical improvement by decrease of stool frequency from 4 - 9 to 2 - 4 daily. VIP and GRP fell toward the normal range (9.94 pM and 15 pg/ml, respectively). However, CT and CEA did not change at all. Endocrine side effects were an inhibition of insulin and HGH secretion. SMS 201 - 995 appears to be a promising agent in the symptomatic therapy of intractable diarrhea. The decrease of VIP and GRP might indicate a partial inhibition of tumor activity and growth.

The multiple endocrine neoplasia syndromes.

The Multiple Endocrine Neoplasia syndromes are familial disorders in which neoplastic changes develop in multiple endocrine tissues. Almost all of these diseases are inherited as autosomal dominant traits with complete penetrance but variable expressivity. Classification of the Multiple Endocrine Neoplasias is based on the pattern of endocrine organ involvement. Multiple Endocrine Neoplasia Type I (MEN-I) is characterized by the concurrence of pituitary adenomas, parathyroid hyperplasia and pancreatic islet cell neoplasms. Multiple Endocrine Neoplasia Type II (MEN-II or IIa) consists of medullary thyroid carcinoma (MTC), parathyroid hyperplasia and pheochromocytomas. Multiple Endocrine Neoplasia Type IIb (MEN-IIb) is similar to MEN-IIa in that affected patients have MTC and pheochromocytomas. Multiple mucosal neuromas and ganglioneuromatosis of the gastrointestinal tract are also present in patients with MEN-IIb, but these individuals rarely manifest hyperparathyroidism. The Multiple Endocrine Neoplasia syndromes have attracted a great deal of attention because of their characteristic clinical features and familial pattern of occurrence. By utilizing recently developed provocative tests it is possible through aggressive screening of kindred members at risk to detect certain of these diseases (particularly MTC and pancreatic islet cell neoplasia) at an early stage. Therapeutic intervention in selected patients is associated with a high cure rate.

Hyperplasia of the Myenteric Plexus

An infant with cutaneous criteria for neurofibromatosis had hyperplasia of the intestinal myenteric plexus and a clinical presentation mimicking Hirschsprung's disease. Many of his phenotypic features are also found in multiple endocrine neoplasia type IIb, a condition in which hyperplasia of the myenteric plexus is common. This case illustrates the overlapping nature of neural crest-derived conditions and the variable presentation of megacolon (ganglionic or aganglionic) in infancy.

Histologic Study of the Ocular Lesions in Multiple Endocrine Neoplasia Syndrome Type IIb

We studied the clinical and histopathologic findings in the eyes of two patients with multiple endocrine neoplasia type IIb. A prominent clinical feature of this condition is enlarged nonmyelinated corneal nerves composed of bundles of axons associated with Schwann cells. Prominent corneal nerves within an otherwise normal corneal stroma are an important clinical feature of multiple endocrine neoplasia type IIb. Because of this, ophthalmologists are in a position to make an early diagnosis and hence to recommend diagnostic procedures and treatment for the associated potentially fatal medullary carcinoma of the thyroid and pheochromocytomas.

Multiple Endocrine Neoplasia Type IIb: The Most Aggressive Form of Medullary Thyroid Carcinoma

The combined clinical anomalies and common neuro-ectodermal origin of this most aggressive form of medullary thyroid carcinoma have been recognized. only recently. A description of the syndrome and five case reports sum up the most recent conclusions.