1/19. Normal thyroid pathology in patients undergoing thyroidectomy for finding a RETgene germline mutation: a report of three cases and review of the literature.Genetic screening for germline RET proto-oncogene mutation in hereditary medullary thyroid cancer (MTC) is accurate and allows for preventive total thyroidectomy to be performed early in patients who are gene carriers. We report 3 children who underwent preventive total thyroidectomy based on the finding of a RETgene germline mutation, but who had no evidence of MTC or C-cell hyperplasia on permanent histology, even after calcitonin immunostaining. review of the English literature of patients undergoing preventive thyroidectomy for a positive RETgene germline mutation, shows that 3.4% of these patients (a total of 209 patients) had normal thyroid glands. Also, 8.6% of patients undergoing preventive total thyroidectomy with prophylactic central neck node dissection had cervical node metastases. We conclude that preventive thyroidectomy in patients screened early for germline RETgene mutation allows for earlier diagnosis and treatment of patients, sometimes even before any hyperplasia or neoplasia can be demonstrated because cervical node metastases can occur early and be demonstrated even with small tumors (< 1 cm), we recommend prophylactic central neck node dissection at the time of preventive thyroidectomy.- - - - - - - - - - ranking = 1keywords = gland (Clic here for more details about this article) |
2/19. A novel case of multiple endocrine neoplasia type 2a associated with two de novo mutations of the RET protooncogene.We report a novel case of multiple endocrine neoplasia type 2a (men 2A) associated with two mutations of the protooncogene RET. One affects codon 634 and causes a cysteine to arginine substitution; the second at codon 640 causes an alanine to glycine substitution in the transmembrane region. The two mutations were present on the same RET allele and were detected in germline and tumor dna. Both mutations were de novo, i.e. they were not found in the dna of the parents or relatives. Immunohistochemical and RT-PCR analysis showed that the pheochromocytoma expressed calcitonin as well as both RET alleles. A cell line established from the tumor and propagated in culture sustained the expression of RET and calcitonin, as did the original pheochromocytoma. Because the patient presented with medullary thyroid carcinoma and pheochromocytoma without parathyroid gland involvement, we speculate that this clinical picture could be correlated with the two RET mutations and to the unusual calcitonin production. This is the first report of a men 2A case due to two mutations of the RET gene and associated with a calcitonin-producing pheochromocytoma.- - - - - - - - - - ranking = 1keywords = gland (Clic here for more details about this article) |
3/19. paraganglioma as a systemic syndrome: pitfalls and strategies.Tumours of the neuroendocrine system in the head and neck region are mostly paragangliomas of the glomus tympanicum or jugulare, or of the carotid body. The majority of these tumours are benign, and the coexistence of multiple paragangliomas seems to be rare. Pre-operative embolization and surgery are regarded as primary therapy for these tumours. The treatment regimen in any patient depends on age, general health, hearing status and the function of the lower cranial nerves. Several presentations are possible in which paragangliomas occur as systemic disease. 1. Paragangliomas may occur bilaterally, or, in rare cases, in multiple areas. Pre-operative bilateral angiography is of utmost importance. In case of multicentricity, it might be necessary to proceed without, or just with, unilateral surgery for preservation of adjacent structures. In surgery of jugular vein paraganglioma, we usually perform a modified transmastoidal and transcervical approach with preservation of middle-ear structures and the ossicles. As an alternative or supplement to surgery, radiotherapy or definitive embolization may be used in the treatment of paragangliomas. 2. Paragangliomas may occur as multiple endocrine neoplasia (men) syndrome combined with medullary thyroid gland carcinoma, and, facultatively, pheochromocytoma. In these cases, endocrinological examination and magnetic resonance imaging (MRI) of the adrenal region, the thorax and the neck are required for an adequate therapeutic strategy. As men may be inherited, family history should be evaluated. 3. Paragangliomas can became malignant and metastasize. Thus, cervical lymph node metastases or distant metastases may occur. We recommend the removal of all ipsilateral lymph nodes and their histological examination.- - - - - - - - - - ranking = 1keywords = gland (Clic here for more details about this article) |
4/19. Multiple endocrine neoplasia (men)--an overview and case report--patient with sporadic bilateral pheochromocytoma, hyperparathyroidism and marfanoid habitus.The multiple endocrine neoplasia syndromes are divided into two categories: men type I and men type II. The men type II syndrome is further divided into men IIa and men IIb. The syndromes are characterized by benign and malignant changes in two or more endocrine organs, as well as incidental changes in nervous, muscular and connective tissue. Two main forms can be distinguished: the men-I syndrome with hyperplasia of the parathyroid gland, accompanied by islet cell tumor and pituitary adenoma; the men-II syndrome with medullary thyroid carcinoma in combination with bilateral pheochromocytoma and hyperplasia of the parathyroid gland (men IIa), while type IIb is characterized by the additional appearance of neurocutaneous manifestations without primary hyperparathyroidism. Characteristics shared by these syndromes include the involved cell type, most of the tumors are composed of one or more specific polypeptide- and biogenic amine-producing cell types (APUD--amine precursor uptake and decarboxylation). The second characteristic is the increased incidence in certain families. The hereditary component is autosomal dominant with variable expression but high penetrance. Mechanisms of tumorigenesis differ in these syndromes. While men I is caused by an inherited mutation of a tumor suppressor gene, menin, located on the long arm of chromosome 11, men II is caused by activation of the RET proto-oncogene. We have reported the case of a young man exhibiting bilateral pheochromocytoma. In addition, the patient showed mild primary hyperparathyroidism and marfanoid habitus, all these stigmata usually being part of the men-II syndrome. Although this described patient showed a phenotypic mixture of the men-IIa and men-IIb syndrome, the genetic analysis for men II and von-Hippel-Lindau gene did not reveal any pathologic mutations, the endocrine disorders described here are not related to multiple endocrine neoplasia syndromes.- - - - - - - - - - ranking = 2keywords = gland (Clic here for more details about this article) |
5/19. A family of multiple endocrine neoplasia type 2a with the RET proto-oncogene mutation in codon 618 (Cys-->Arg).Multiple endocrine neoplasia type 2 (men-2) is a hereditary syndrome characterized by medullary thyroid carcinoma (MTC), pheochromocytoma and hyperplasia or adenoma of the parathyroid gland with hyperparathyroidism. Recent genetic studies have identified the presence of germline missense mutations in the RET proto-oncogene in almost 100% of men-2 patients. We report here three generations of one men-2 family with rare missense mutation at codon 618 (Cys-->Arg) of the RET proto-oncogene. The first patient was surgically treated at the age of 63 years but died of bone metastasis. His two children (29-year-old daughter and 25-year-old son) were treated surgically for MTC and neck lymph node metastasis. Germline mutations of the RET proto-oncogene of these three MTC patients and two children of the 29-year-old daughter (9-year-old female and 7-year-old male) were examined. Three MTC patients and the 9-year-old female possessed the mutation. The phenotype of the family with this rare point mutation of the RET proto-oncogene is reported.- - - - - - - - - - ranking = 1keywords = gland (Clic here for more details about this article) |
6/19. Prophylactic total thyroidectomy in an 8-year-old girl with multiple endocrine neoplasia type 2a.We report a genetic carrier of multiple endocrine neoplasia type 2a (men 2A) who underwent prophylactic total thyroidectomy. The asymptomatic carrier of men 2A, an 8-year-old Taiwanese girl, was admitted for early thyroidectomy. Preoperative basal plasma concentrations of calcitonin and intact parathyroid hormone, and urine vanillylmandelic acid excretion, were normal. ultrasonography of the thyroid was also normal. pathology did not reveal any gross lesion but C-cell hyperplasia of the thyroid gland was found microscopically. Prophylactic total thyroidectomy is encouraged and is justified during the first decade of life for men 2A carriers.- - - - - - - - - - ranking = 1keywords = gland (Clic here for more details about this article) |
7/19. Familial isolated parathyroid adenoma in a consanguineous family.The 23-year-old Caucasian male propositus presented with symptomatic hypercalcemia, hypophosphatemia and normocalciuria for 2 months. His 29-year-old brother had undergone an operation for recurrent parathyroid adenoma at age 26 and 28. No other member of the family was affected. His father and mother were second-degree relatives. Laboratory studies showed primary hyperparathyroidism (pHPT), while the remaining endocrine studies and genetic testing for multiple endocrine neoplasia 1 and 2A were normal. technetium-cardiolite scintigraphy and ultrasound scans revealed a parathyroid mass at the left lower neck. Apart from bilateral hearing loss due to gentamicin treatment as a pre-term child, the patient was in of good health. Signs or symptoms of other endocrinopathies were absent. The patient was referred for parathyroidectomy with subsequent autotransplantation of the remaining glands into his sternocleidomastoid muscle. Histological examination revealed an adenoma with oncocytic differentiation, similar to that seen in his brother. The disease may follow a recessive mode of inheritance or may be due to a dominant germ-cell mutation in one of the parents. The presented case may ultimately help in elucidating the molecular genetic basis of this rare form of pHPT.- - - - - - - - - - ranking = 1keywords = gland (Clic here for more details about this article) |
8/19. Cortical-sparing laparoscopic adrenalectomy in a patient with multiple endocrine neoplasia type IIA.We describe the case of a patient affected by multiple endocrine neoplasia type IIA with a new diagnosis of an asymptomatic right pheochromocytoma. The patient underwent laparoscopic adrenalectomy with adrenal sparing. The removal of the tumor was successful with preservation of about one third of the adrenal gland. At the time of the last follow-up, the patient is well with partial hypoadrenalism without replacement therapy. The limitations to cortical-sparing adrenalectomy imposed by traditional open surgery (small tumor with peripheral location) can be reconsidered using the laparoscopic approach. Laparoscopic cortical-sparing adrenalectomy should become the gold standard for treatment of bilateral pheochromocytoma. The advantages of this technique are its efficacy and its reduced invasiveness with a low rate of complications either during the operation or in the postoperative period. Moreover, the preservation of a portion of the adrenal cortex may prevent the need for a life-long steroid replacement therapy.- - - - - - - - - - ranking = 1keywords = gland (Clic here for more details about this article) |
9/19. Primary diagnosis of multiple pheochromocytomas in the brother of a men-2 patient by simultaneous MIBG scintigraphy and low-dose computed tomography.Metaiodobenzylguanidine (MIBG) scintigraphy is a well-established functional imaging method for localizing pheochromocytomas. However, the morphologic information revealed on the scintigram is often too sparse and thus, accordingly, supplemental computed tomography (CT) or magnetic resonance imaging are often performed. Recently, gamma cameras with built-in low-dose CT were introduced. The authors describe a patient with a high likelihood of pheochromocytoma who had simultaneous MIBG scintigraphy and low-dose CT performed as the primary examinations. The scan revealed pheochromocytomas in both adrenal glands and one extra-adrenal pheochromocytoma located in the liver. The combined imaging ensured the final diagnosis without any need for further imaging. Based on the findings of this case, the authors believe that combined MIBG scintigraphy and low-dose CT is a promising future single imaging technique for pheochromocytomas.- - - - - - - - - - ranking = 1keywords = gland (Clic here for more details about this article) |
10/19. Adrenal ganglioneuromas in children with multiple endocrine neoplasia type 2: a report of two cases.CONTEXT: Pheochromocytomas of the adrenal gland are a common component of the multiple endocrine neoplasia type 2 (MEN2) syndromes. However, pure adrenal ganglioneuromas, an extremely rare pediatric tumor of neural crest origin composed of mature ganglion cells, have never been reported in association with MEN2 in humans. MEN2A is comprised of medullary thyroid carcinoma (MTC), pheochromocytoma, and parathyroid hyperplasia. MEN2B is characterized by MTC, pheochromocytoma, neural abnormalities of the gastrointestinal tract, and mucosal neuromas. EVIDENCE ACQUISITION: We report two pediatric patients, one with MEN2A and one with MEN2B, who developed isolated adrenal ganglioneuromas without evidence of pheochromocytomas. EVIDENCE SYNTHESIS: MEN2A and MEN2B are caused by activating mutations in the RET proto-oncogene, which encodes a tyrosine kinase receptor essential for signal transduction in neural crest-derived tissues, including the peripheral and enteric nervous systems, C cells of the thyroid gland, and chromaffin cells of the adrenal gland. Both pheochromocytomas and ganglioneuromas originate from neural crest cells. Interestingly, two mouse models of MEN2B exhibit adrenal ganglioneuroma formation. One mouse model develops only ganglioneuromas (but not pheochromocytomas) and expresses only one of the oncogenic RET isoforms. The other mouse model, created by site-directed mutagenesis to simulate the most common human mutation, develops both ganglioneuromas and pheochromocytomas. CONCLUSIONS: Given our two cases, our current understanding of the mouse models, and the common origins of all these tumor cell types, we recommend including ganglioneuromas as a rare, but not unexpected, component of the MEN2 syndromes.- - - - - - - - - - ranking = 3keywords = gland (Clic here for more details about this article) |
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