dc.date.accessioned | 2013-11-01T13:59:35Z | |
dc.date.available | 2013-11-01T13:59:35Z | |
dc.date.issued | 2013 | |
dc.identifier.uri | http://hdl.handle.net/10852/37515 | |
dc.description.abstract | Background: Congenital adrenal hyperplasia (CAH) is an inherited recessive disorder, in which enzymes in the adrenal cortex are mutated. The most common form is caused by alterations in CYP21A2, the gene encoding the adrenal steroid 21-hydroxylase enzyme. The consequences are impaired production of cortisol and aldosterone, leading to increased ACTH driven production of adrenal androgens, resulting in virilisation of the female. The patients require life-long treatment with glucocorticoid and mineralocorticoid tablets.<br>
Objective: No published data on CAH in Norway existed when we started our survey. Our aim was to obtain confident epidemiological data from Norway and to describe clinical and genetic aspects in adults with CAH due to 21-hydroxylase deficiency. Specific aims were to describe health-related quality of life and working ability, and the frequency of testicular and adrenal tumours.<br>
Material and methods: Epidemiological data were obtained by scrutiny medical reports at all the University Hospitals in Norway and by contacting endocrinologists throughout the country. First, the patients were invited to a questionnaire survey including medical history, and the Short Form-36 and Quality of Life Scale questionnaire. Second, they were invited to participate in clinical, biochemical and radiological investigations at four University Hospitals, including anthropometric measurements, that is, dual X-ray absorptiometry scanning, adrenal computed tomography, testicular ultrasound, DNA sequencing of CYP21A2 and hormone analyses.<br>
Results: We showed lower incidence of CAH than expected and especially than that of our neighbouring country Sweden. Fewer males than females with CAH were identified although equal sex ratio was expected. As a group the patients had increased working disability and reduced physical and mental health as compared with the normal population. The women had decreased fertility. We found a high frequency of adrenal tumours, particularly myelolipomas, and testicular adrenal rest tumours only associated with salt wasting. The patients had normal BMI but markedly higher fat mass, higher diastolic blood pressure and lower bone mineral density than the general population. We showed higher frequency of osteopenia among the men than the women. Near half of the women had testosterone levels above the normal range and half of the subjects had 17-hydroxyprogesterone (17-OHP) levels above the upper recommended target.We identified four novel and plausibly disease-causing CYP21A2 mutations and, as expected, high correspondence between genotype and clinical phenotype. The frequency of the underlying genetic defects was similar to published results from other Western European countries.<br>
Conclusion: Adult men with CAH were missing and perhaps never diagnosed. Androgen levels and 17- OHP-levels were poorly controlled. We found reduced BMD, impaired quality of life, and increased frequency of adrenal tumours, and in females impaired fertility. These findings may reflect inappropriate glucocorticoid and mineralocorticoid therapy and need for improvement of the medical treatment and general care of adults with CAH. | en_US |
dc.language.iso | en | en_US |
dc.relation.haspart | Paper I: Nermoen I, Følling I, Vegge K, Larmo A, Nedrebø G, Husebye ES, Løvås, K. Two Adults with Adrenal Myelolipoma and 21-Hydroxylase Deficiency. Case Reports in Medicine 2009; 2009:916891. Creative Commons Attribution License. https://doi.org/10.1155/2009/916891 | |
dc.relation.haspart | Paper II: Nermoen I, Husebye ES, Svartberg S, Løvås, K. Subjective health status in men and women with congenital adrenal hyperplasia: a population-based survey in Norway. European Journal of Endocrinology 2010; 163(3):453-459. The paper is removed from the thesis in DUO due to publisher restrictions. The published version is available at: https://doi.org/10.1530/EJE-10-0284 | |
dc.relation.haspart | Paper III: Nermoen I, Rørvik J, Holmedal SH, Hykkerud DL, Fougner KJ, Svartberg S, Husebye ES, Løvås, K. High frequency of adrenal myelolipomas and testicular adrenal rest tumours in adult Norwegian patients with classical congenital adrenal hyperplasia because of 21-hydroxylase deficiency. Clinical Endocrinology 2011; 75(6):753-759. The paper is removed from the thesis in DUO due to publisher restrictions. The published version is available at: https://doi.org/10.1111/j.1365-2265.2011.04151.x | |
dc.relation.haspart | Paper IV: Nermoen I, Brønstad I, Fougner KJ, Svartberg S, Øksnes M, Husebye ES, Løvås, K. Genetic, anthropometric, and metabolic features of adult Norwegian patients with 21-hydroxylase deficiency. European Journal of Endocrinology 2012; 167(4):507-516. The paper is removed from the thesis in DUO due to publisher restrictions. The published version is available at: https://doi.org/10.1530/EJE-12-0196 | |
dc.relation.uri | https://doi.org/10.1155/2009/916891 | |
dc.relation.uri | https://doi.org/10.1530/EJE-10-0284 | |
dc.relation.uri | https://doi.org/10.1111/j.1365-2265.2011.04151.x | |
dc.relation.uri | https://doi.org/10.1530/EJE-12-0196 | |
dc.title | Congenital Adrenal Hyperplasia in Adults: Epidemiological, Genetic, Clinical and Endocrine Features of CYP21A2 Deficiency in Norway | en_US |
dc.type | Doctoral thesis | en_US |
dc.creator.author | Nermoen, Ingrid | |
dc.identifier.urn | URN:NBN:no-39111 | |
dc.type.document | Doktoravhandling | en_US |
dc.identifier.fulltext | Fulltext https://www.duo.uio.no/bitstream/handle/10852/37515/1/dravhandling-nermoen.pdf | |