Malignant paraganglioma presenting as Cushing syndrome with virilism in childhood. Production of cortisol, androgens, and adrenocorticotrophic hormone by the tumor

Abstract

Background: A 12-year-old girl with intractable retroperitoneal paraganglioma experienced increased appetite, acne, obesity, "moon face," and enlargement of the clitoris during the course of the tumor. Plasma cortisol, serum testosterone, and dehydroepiandrosterone sulfate (DHEA-S) levels were increased to 34.1 micrograms/dl, 2.0 ng/ml, and 6.628 ng/ml, respectively. Adrenocorticotrophic hormone (ACTH) levels were not increased, and results of dexamethasone suppression tests were negative. Her condition was diagnosed as Cushing syndrome with virilism. Plasma cortisol levels were increased to a level of 107.1 micrograms/dl before death.

Methods: Tumor samples were obtained at the time of autopsy. The concentrations of cortisol, androgens, ACTH, and catecholamines were assayed in the tumor extracts. The indirect immunoperoxidase procedure was performed on fixed tissues for cortisol, DHEA-S, testosterone, and ACTH.

Results: Extracts of the tumor masses contained steroid hormones: the amount of immunoreactive cortisol was 1.64 micrograms/g wet weight; the amount of immunoreactive testosterone was 25.60 ng/g wet weight; immunoreactive DHEA-S, 579.00 ng/g wet weight; and immunoreactive ACTH, 891.00 pg/g wet weight in the metastatic mass of the lung. Immunohistochemically, immunoreactive cortisol, testosterone, and DHEA-S were detectable in the tumor cells. The adrenal gland was atrophic.

Conclusions: The patient is the first reported with malignant paraganglioma with the capacity to produce cortisol, androgens, and ACTH.