Human Reproduction, Vol. 18, No. 5, 1132-1133,
May 2003
© 2003 European Society of Human Reproduction and Embryology
Adrenal antibiotics detect asymptomatic auto-immune adrenal insufficiency in young women with premature ovarian failure
Jungfrudansen 34, SE-171 56 SOLNA, Sweden e-mail: susanne{at}merz.as
Dear Sir,
A total of 2–10% of women with spontaneous premature ovarian failure (POF) develop primary adrenal insufficiency (Bakalov et al., 2002
). Since Addison’s 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 Addison’s disease in an early stage (Krohn et al., 1992; Winqvist et al., 1992; 1993). Bakalov et al. could diagnose Addison’s 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 Addison’s disease (Winqvist et al., 1992; Silva et al., 2000). Antibodies to 21-hydroxylase have been found in 64–86% 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 Addison’s 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)
|
The autoimmune attack in Addison’s disease in combination with gonadal autoimmunity is directed against SCC (CYP 11A) or 17
-hydroxylase (CYP 17) respectively. Investigations have shown that patients with antibodies to SCC or 17-hydroxylase commonly have antibodies to 21-hydroxylase as well (Winqvist et al., 1995; Silva et al., 2000). That explains Bakalov’s result. But there are also patients with antibodies to SCC or 17-hydroxylase that do not have antibodies to 21-hydroxylase (Winqvist et al., 1995; Silva et al., 2000). This last group of high-risk patients for Addison’s disease are missed if antibodies to SCC and 17-hydroxylase are not assayed in patients with POF.
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, 2096–2100.
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 Addison’s disease as steroid 17-hydroxylase. Lancet, 339, 770–773.[CrossRef][Web of Science][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 Addison’s disease and autoimmune polyendocrine syndrome type III. Eur. J. Endocrinol., 142, 187–194.[Abstract]
Winqvist, O., Karlsson, F.A. and Kämpe, O. (1992) 21-hydroxylase, a major autoantigen in idiopathic Addison’s disease. Lancet, 339, 1559–1562.[CrossRef][Web of Science][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 Addison’s disease. J. Clin. Invest., 92, 2377–2385.[Web of Science][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, 1717–1723.
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||