Pheochromocytomas and paragangliomas are tumors of the autonomic nervous system; pheochromocytomas are tumors of the adrenal medulla, and paragangliomas are extra-adrenal tumors arising from either the sympathetic nervous system or parasympathetic ganglia. It has previously been estimated that approximately 10%-15% of pheochromocytomas are due to hereditary causes. However, our increased understanding of the three hereditary syndromes (neurofibromatosis 1, multiple endocrine neoplasia type 2, and von Hippel-Lindau syndrome) in which pheochromocytoma is found and the recent discovery that mutations in genes in the succinate dehydrogenase family (SDHB and SDHD) predispose to pheochromocytoma have necessitated a re-evaluation of the genetic basis of pheochromocytoma. These studies indicate that the frequency of germline mutations associated with isolated pheochromocytoma is higher than previously estimated, with both hospital-based series and a large population-based series indicating that the frequency of germline mutations in RET, VHL, SDHB, and SDHD taken together approximates 20%. In all patients with pheochromocytoma, including those with known hereditary syndrome or a positive family history, the frequency of germline mutations in these four genes together approaches 30%. Given the frequency of germline mutations, consideration should be given to genetic counseling for all patients with pheochromocytoma and is particularly important for individuals with a positive family history, multifocal disease, or a diagnosis before age 50. Identification of patients with hereditary pheochromocytoma is important because it can guide medical management in mutation-positive patients and their families. This review provides an overview of the known genetic syndromes that are commonly associated with pheochromocytoma, examines recent data on the association of germline mutations in the succinate dehydrogenase gene family with pheochromocytoma, and suggests guidelines for the genetic evaluation of pheochromocytoma patients.

Alopecia in women is a common problem, and conflicting observational data have failed to determine whether an association exists between alopecia and iron deficiency in women. We therefore utilized an analytical cross-sectional methodology to evaluate whether common types of alopecia in women are associated with decreased tissue iron stores, as measured by serum ferritin. We studied patients with telogen effluvium (n = 30), androgenetic alopecia (n = 52), alopecia areata (n = 17), and alopecia areata totalis/universalis (n = 7). The normal group consisted of 11 subjects without hair loss from the same referral base and source population as those patients with alopecia. We analyzed the data utilizing the unpaired Student's t test assuming unequal variances with an alpha adjustment for multiple comparisons to assess whether the mean ages, ferritin levels, and hemoglobin levels of women without hair loss differed from the means in each alopecia group. The mean age of patients and normals did not differ significantly. We found that the mean ferritin level (ng per ml [95% confidence intervals]) in patients with androgenetic alopecia (37.3 128.4, 46.1]) and alopecia areata (24.9 [17.2, 32.6]) were statistically significantly lower than in normals without hair loss (59.5 [40.8, 78.1]). The mean ferritin levels in patients with telogen effluvium (50.1 [33.9, 66.33]) and alopecia areata totalis/universalis (52.3 [23.1, 81.5]) were not significantly lower than in normals. Our findings have implications regarding therapeutics, clinical trial design, and understanding the triggers for alopecia.

Purpose: This study evaluated rates of BRCA1 and BRCA2 (BRCA1/2) test result acceptance among African American women and identified determinants of test result acceptance. Methods: Acceptance of BRCA1/2 test results was evaluated among 157 African American women at high and moderate risk for having a BRCA1/2 mutation who were offered genetic testing as part of a clinical genetic counseling research program. Results:Twenty-two percent of women received BRCA1/2 test results. Test result acceptance differed between women with Ն10% prior probability of having a BRCA1/2 mutation (34%) and those who had a 5% prior probability (8%). Among women with Ն10% prior probability, test result acceptors were most likely to be married (OR ϭ 5.29, 95% CI ϭ Recently, epidemiological studies have shown that the prevalence of BRCA1 and BRCA2 (BRCA1/2) mutations range from 16 -28% among African American women who have a personal and family history of breast and/or ovarian cancer suggestive of hereditary disease. [1][2][3][4] If found to carry a BRCA1/2 mutation, women have an estimated 60 -80% lifetime risk of developing breast cancer and a 10 -45% lifetime risk of developing ovarian cancer. [5][6][7] Because of the excess rates of breast cancer mortality among African American women, 8,9 participation in genetic counseling and testing may be beneficial to women at increased risk for hereditary cancer to increase knowledge about cancer risks and options for risk reduction. Efforts are now being made to enhance access to genetic counseling and testing for BRCA1/2 mutations among African American women at increased risk for hereditary disease. Recent research has shown that as many as 50% of African American women may participate in genetic counseling for breast cancer susceptibility, 10 but little is known about rates of acceptance of BRCA1/2 test results or determinants of test result acceptance.To address this gap in our knowledge, we evaluated rates of BRCA1/2 test result acceptance among African American women at increased risk for hereditary breast and ovarian cancer and identified sociodemographic, clinical, and psychological barriers and facilitators to receiving genetic test results. Because prior studies have shown that cancer-specific worry may influence decisions about participating in genetic counseling among African American women 11 we were interested in exploring the relationship between BRCA1/2 test result acceptance and cancer-specific worry. Other reports have shown that many African American women would want to have genetic testing to be reassured about their cancer risk 12 ; however, it is possible that women who are uncertain about their risk of developing cancer may be most likely to receive test results to better define their risk of disease. Thus, we were also interested in determining whether certainty about one's risk of developing breast cancer is associated with genetic test acceptance. Since previous research has shown that responses to education about hereditary breast cancer and genetic testing may diffe...

Despite receiving a large number of referrals, only a small subset of women were eligible for enrollment. Oncology settings were the most effective at identifying eligible African American women and general medical practices were the least effective. Factors associated with enrollment included having a stronger family history of cancer and being referred from oncology clinics and community oncology resources. Referral from oncology clinics was the only factor associated significantly with participation in genetic counseling. Education about hereditary breast cancer may be needed among primary care providers to enhance appropriate referral of African American women to genetic counseling for BRCA1/2 mutations.

Purpose: To evaluate attitudes about the benefits, limitations, and risks of genetic testing for BRCA1 and BRCA2 (BRCA1/2) mutations and explore testing intentions in African American women at increased risk for hereditary breast cancer. Methods: Attitudes and intentions were evaluated by telephone in African American women (n ϭ 74) at moderate and high risk for having a BRCA1/2 mutation. Results: Attitudes about the benefits of genetic testing were endorsed at a higher rate relative to limitations and risks; however, only 30% of respondents indicated that they would definitely have testing. In regression analysis, women most likely to be considering testing were those with fatalistic beliefs about cancer and those who believed they had a BRCA1/2 mutation. Women who had two or more affected relatives were also most likely to be considering testing. Women who had a personal history of cancer and those who believed they were at high risk for developing breast cancer were most likely to report greater limitations and risks. Pros scores were higher among women older than age 50 and those who were unemployed.Conclusion: Although African American women at moderate and high risk for BRCA1/2 mutations report favorable attitudes about genetic testing, interest in testing may be limited. Women affected with cancer and those who believe they are at a higher risk for developing breast cancer may be most concerned about the negative consequences of testing. Increased attention may need to be given to beliefs about genetic testing and testing motivations during genetic counseling with African American women. Genet Med 2005:7(4):230 -238.