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

Straub, Rainer H.
Härle, Peter
Kriegel, Martin
Schölmerich, Jürgen
Lorenz, Hanns-Martin

Laboratory of Neuroendocrinoimmunology (R.H.S., P.H., J.S.), Department of Internal Medicine I, Division of Rheumatology, University Hospital, 93042 Regensburg, Germany; Department of Medicine V (H.-M.L.), Division of Rheumatology, University of Heidelberg, 69115 Heidelberg, Germany; and Section of Immunobiology (M.K.), Yale University School of Medicine, New Haven, Connecticut 06520

Received May 6, 2005. Accepted July 11, 2005.

Address all correspondence and requests for reprints to: Rainer H. Straub, M.D., Professor of Experimental Medicine, Laboratory of Neuroendocrinoimmunology, Department of Internal Medicine I, University Hospital, 93042 Regensburg, Germany. E-mail: [email protected].

Conflict of interest: No conflict of interest has been declared by the authors.

First Published Online July 19, 2005

Abbreviations: ASD, Androstenedione; DHEA, dehydroepiandrosterone; RA, rheumatoid arthritis; TNFRSF1A, TNF-receptor superfamily 1A; TRAPS, TNF-receptor-associated periodic syndrome.

Journal of Clinical Endocrinology & Metabolism 90(10):p 5884-5887, October 2005.

Context:

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.

Objective:

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.

Design:

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.

Results:

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 17β-estradiol demonstrated a marked increase during the attack phase.

Conclusion:

This study suggests that some important steroid hormone-conversion steps are activated (aromatase) and inhibited (second step of the P450c17 and the 3β-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.