Lack of dehydroepiandrosterone in type I and II hereditary angioedema and role of danazol in steroid hormone conversion

Thon,  Vojtěch; Harle, P.; Scholmerich, J.; Kuklinek, P.; Lokaj,  Jindřich; Straub, RH

Lack of dehydroepiandrosterone in type I and II hereditary angioedema and role of danazol in steroid hormone conversion

Authors	THON Vojtěch HARLE P. SCHOLMERICH J. KUKLINEK P. LOKAJ Jindřich STRAUB RH
Year of publication	2007
Type	Article in Periodical
Magazine / Source	Allergy
MU Faculty or unit	Faculty of Medicine
Citation
Field	Immunology
Keywords	C1 INHIBITOR; C1-INHIBITOR DEFICIENCY; MONONUCLEAR CELLS; BETA ENDORPHIN; EXPRESSION; WOMEN;
Description	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 17 beta-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 17 beta-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 17 beta-oestradiol. In HAE, there seems to be a primary lack of the adrenal androgen DHEA.