| 1. |
- Brauckhoff, Michael, et al.
(författare)
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Premonitory symptoms preceding metastatic medullary thyroid cancer in MEN 2B : An exploratory analysis
- 2008
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Ingår i: SURGERY. - : Elsevier BV. - 0039-6060. ; 144:6, s. 1044-1050
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Tidskriftsartikel (refereegranskat)abstract
- Background. More than 90% of M918T carriers with multiple endocrine neoplasia type 2B (MEN 2B) harbor de novo mutations in the REarranged during Transfection (RET) protooncogene. DNA-based screening for RET germline mutations is rarely useful for early diagnosis, which thus is contingent on the clinical ascertainment of MEN 2B-specifitc symptoms as soon as they emerge. Little information exists about the presence of these symptoms in infancy.Methods. Detailed information was gathered regarding the development of MEN 2B-associated symptoms from the parents of 25 M918T RET carriers and 50 age- and sex-matched, controls with the use of a disease-specific questionnaire.Results. Until the end of the study, at a median age of 16 2 (range, 0.5-34.9 years), all 25 M918T RET carriers had developed medullary thyroid cancer. By that time, 96%, 91%, 71%, 75%, and 28% Of carriers displayed oral manifestations, ocular abnormalities, intestinal symptoms, musculoskeletal malformations, and pheochromocytoma, respectively. During the first year of life, fewer than 20% of carriers were found to express the typical MEN 2B phenotype, whereas 86% and 61% of these children, but none of the controls, were noted for their inability to cry tears and for constipation.Conclusion. Because the classic MEW 2B phenotype is rare during the first year of life, more emphasis should be placed on the more subtle features of the syndrome. Additional studies are needed to validate the usefulness of the symptoms "inability to cry" and "constipation" for earlier diagnosis of MEAT 2B.
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| 2. |
- Machens, Andreas, et al.
(författare)
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Risk-oriented approach to hereditary adrenal pheochromocytoma.
- 2006
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Ingår i: Annals of the New York Academy of Sciences. - : Wiley. - 0077-8923 .- 1749-6632. ; 1073, s. 417-28
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Tidskriftsartikel (refereegranskat)abstract
- Hereditary adrenal pheochromocytoma is caused by germline mutations in RET, VHL, SDHB, SDHD, and NF1. As these genes differ in function, so may their pheochromocytoma phenotypes, suggesting gene-specific patterns of age-related progression to pheochromocytoma. This possibility was explored for gene carriers with a lifetime risk of pheochromocytoma in excess of 50%. Published age-standardized penetrance rates of VHL-, SDHB-, and SDHD-associated pheochromocytoma were gauged against age-standardized penetrance rates of MEN2-associated pheochromocytoma in 219 institutional carriers of RET mutations conferring highest (codon 918), high (codons 609, 611, 618, 620, 630, and 634) and least high risk (codons 768, 790, 791, 804, and 891). The highest-risk category included SDHB, SDHD, and the highest-risk RET genotype; the high-risk category VHL missense mutations and the high-risk RET genotypes; and the least-high risk category VHL truncating mutations and least-high risk RET genotypes. Detailed information on recurrence rates and intervals was available only for the RET carriers (19-31% and means of 4.3-5.5 years; all RET risk categories combined). Ipsilateral recurrences in adrenal remnants, and contralateral recurrences in virgin adrenals were comparable in incidence (27% and 39%, P=0.69; high-risk RET category) and time to recurrence (means of 4.3 vs. 5.4 year; P>0.99; high-risk RET category), discounting a major effect of tumor spillage at primary subtotal adrenalectomy on pheochromocytoma recurrence. The risk of malignancy usually is low, except for SDHB (38%). For most hereditary pheochromocytomas, endoscopic subtotal adrenalectomy is the procedure of choice. Grouping hereditary pheochromocytoma into preliminary risk categories may improve the management of gene carriers at risk of developing pheochromocytomas.
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