Adrenal and Gonadal Hormone Variations during a Febrile Attack in a Woman with Tumor Necrosis Factor Receptor-Associated Periodic Syndrome

Abstract

TNF-receptor-associated periodic syndrome (TRAPS) is a hereditary fever syndrome that results from mutations in the TNF-receptor superfamily 1A gene (TNFRSF1A). It is characterized by periodic fever, arthralgia, abdominal pain, myalgia, headache, and skin lesions. Because adrenal and gonadal hormone cascades are modulated by TNF, this study aimed to investigate specific hormones and enzyme steps during an attack phase in a woman with TRAPS. Morning blood samples were taken from a 38-yr-old woman before, during, and after the febrile episode in the late luteal, menstrual, and early follicular phase of the menstrual cycle, respectively. Serum cortisol levels were markedly increased throughout the entire observation period and demonstrated a dip during the attack phase. In contrast, serum levels of dehydroepiandrosterone and 17-hydroxyprogesterone demonstrated a sharp rise during the febrile episode. Dehydroepiandrosterone in relation to androstenedione or cortisol was increased. Indicative of aromatase activation, estrone and 17beta-estradiol demonstrated a marked increase during the attack phase. This study suggests that some important steroid hormone-conversion steps are activated (aromatase) and inhibited (second step of the P450c17 and the 3beta-hydroxysteroid dehydrogenase) during the inflammatory attack phase in a TRAPS patient. These changes of enzyme pathways are typical on the basis of increased TNF signaling.