Jungfrudansen 34, SE-171 56 SOLNA, Sweden e-mail: susanne{at}merz.as
Dear Sir,
A total of 210% of women with spontaneous premature ovarian failure (POF) develop primary adrenal insufficiency (Bakalov et al., 2002). Since Addisons disease is potentially life threatening, it is important to discover these women with autoimmune polyendocrine syndrome. It is thus fortunate that Bakalov et al. call attention to this problem (Bakalov et al., 2002
). Antibody-based diagnosis has made it possible to discover autoimmune Addisons disease in an early stage (Krohn et al., 1992
; Winqvist et al., 1992
; 1993). Bakalov et al. could diagnose Addisons disease in 3.2% of their POF-patients by demonstrating antibodies to 21-hydroxylase (CYP 21, P450c21) (Bakalov et al., 2002
). 21-hydroxylase is a major auto-antigen in Addisons disease (Winqvist et al., 1992
; Silva et al., 2000
). Antibodies to 21-hydroxylase have been found in 6486% of patients with adrenal autoimmunity (Silva et al., 2000
) but two other cytochrome enzymes which are part of steroid synthesis are also known autoantigens in Addisons disease. These are side-chain cleavage enzyme (SCC, CYP 11A, P450scc) (Winqvist et al., 1993
; 1995) and 17
-hydroxylase (CYP 17, P450c17) (Krohn et al., 1992
). The following overview shows that SCC and 17
-hydroxylase are involved in the synthesis of both cortisol and sex hormones. 21-hydroxylase is only involved in the synthesis of cortisol, not sex hormones (simplified after Hedlund, 2000
) (Figure 1)
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References
Bakalov, V.K., Vanderhoof, V.H., Bondy, C.A. and Nelson, L.M. (2002) Adrenal antibodies detect asymptomatic auto-immune adrenal insufficiency in young women with spontaneous premature ovarian failure. Hum. Reprod., 17, 20962100.
Hedlund, E. (2000) Cytochrome P450 in the rat brain: Characterization and regulation. Department of Medical Nutrition and the Department of Biosciences at Novum, Karolinska Institute, Stockholm, Sweden (Thesis).
Krohn, K., Uibo, R., Aavik, E., Peterson, P. and Savilahti, K. (1992) Identification by molecular cloning of an autoantigen associated with Addisons disease as steroid 17-hydroxylase. Lancet, 339, 770773.[ISI][Medline]
Silva, C.R., Kater, C.E., Dib, S.A., Laureti, S., Forini, A.C. and Falorni, A. (2000) Autoantibodies against recombinant human steroidogenic enzymes 21-hydroxylase, side-chain cleavage and 17 -hydroxylase in Addisons disease and autoimmune polyendocrine syndrome type III. Eur. J. Endocrinol., 142, 187194.[ISI][Medline]
Winqvist, O., Karlsson, F.A. and Kämpe, O. (1992) 21-hydroxylase, a major autoantigen in idiopathic Addisons disease. Lancet, 339, 15591562.[ISI][Medline]
Winqvist, O., Gustafsson, J., Rorsman, F., Karlsson, F.A. and Kämpe, O. (1993) Two Different cytochrome P450 enzymes are the adrenal antigens in autoimmune polyendocrine syndrome Type I and Addisons disease. J. Clin. Invest., 92, 23772385.[ISI][Medline]
Winqvist, O., Gebre-Medhin, G., Gustafsson, J., Ritzén, E.M., Lundkvist, Ö., Karlsson, F.A. and Kämpe, O. (1995) Identification of the main gonadal autoantigens in patients with adrenal insufficiency and associated ovarian failure. J. Clin. Endocrinol. Metab., 80, 17171723.[CrossRef]