Lack of dehydroepiandrosterone in type I and II hereditary angioedema and role of danazol in steroid hormone conversion.
BACKGROUND
Hereditary angioedema (HAE) is successfully treated with danazol, a therapeutic steroid compound. To investigate hormones of the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axis in patients with HAE with and without danazol.


METHODS
We included 16 patients with type I HAE, nine patients with type II HAE, and 16 healthy subjects. Serum levels of adrenocorticotropic hormone (ACTH), cortisol, androstenedione, dehydroepiandrosterone (DHEA), free testosterone, and 17beta-oestradiol were measured.


RESULTS
Serum levels of ACTH were markedly decreased in patients with type II HAE compared to the other groups (P < 0.001). Serum cortisol was similar between groups but danazol treatment decreased cortisol levels, particularly in women (P = 0.019). Serum levels of DHEA were significantly decreased in all patients with type I and II HAE compared to controls (P < 0.05), which was only partly dependent on prior danazol therapy as patients without danazol had also decreased serum levels of DHEA (P < 0.05). Furthermore, free testosterone serum levels were markedly increased in patients under danazol (P < 0.005) and the ratio of 17beta-oestradiol/free testosterone was significantly decreased in these patients (P < 0.005).


CONCLUSIONS
This study demonstrated decreased DHEA in patients with type I and II HAE independent of danazol therapy, which was particularly evident in women. It also demonstrates that danazol induced a marked up-regulation of free testosterone in relation to precursors and downstream 17beta-oestradiol. In HAE, there seems to be a primary lack of the adrenal androgen DHEA.
Thon
V
V
Department of Clinical Immunology and Allergology, Masaryk University, St Anne Faculty Hospital, Brno, The Czech Republic.
Härle
P
P
Schölmerich
J
J
Kuklinek
P
P
Lokaj
J
J
Straub
R H
RH
D000293:Adolescent; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D000735:Androstenedione / Q000097:blood; D054179:Angioedemas, Hereditary / Q000097:blood* / Q000188:drug therapy*; D002648:Child; D003613:Danazol / Q000627:therapeutic use*; D003687:Dehydroepiandrosterone / Q000097:blood*; D004958:Estradiol / Q000097:blood; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D008875:Middle Aged; D013739:Testosterone / Q000097:blood
D013739:Testosterone; D000735:Androstenedione; D003687:Dehydroepiandrosterone; D004958:Estradiol; D000324:Adrenocorticotropic Hormone; D003613:Danazol; D006854:Hydrocortisone