A 68-Year-Old Phenotypically Male Patient with 21-Hydroxylase Deficiency and Concomitant Adrenocortical Neoplasm Producing Testosterone and Cortisol

Access this Article

Search this Article

Author(s)

    • Sasano Hironobu
    • Department of Pathology, Tohoku University Graduate School of Medicine
    • Kataoka Yuko
    • Department of Endocrinology and Metabolism, Chukyo Hospital
    • Sugimura Yoshihisa
    • Department of Endocrinology and Diabetes, Field of Internal Medicine, Nagoya University Graduate School of Medicine
    • Kato Fumiko
    • Department of Molecular Endocrinology, National Research Institute for Child Health and Development|Department of Pediatrics, Hamamatsu University School of Medicine
    • Fukami Maki
    • Department of Molecular Endocrinology, National Research Institute for Child Health and Development
    • Ogata Tsutomu
    • Department of Molecular Endocrinology, National Research Institute for Child Health and Development|Department of Pediatrics, Hamamatsu University School of Medicine
    • Homma Keiko
    • Central Clinical Laboratories, Keio University Hospital
    • Oiso Yutaka
    • Department of Endocrinology and Diabetes, Field of Internal Medicine, Nagoya University Graduate School of Medicine

Abstract

The steroidogenic enzyme 21-hydroxylase is necessary for the synthesis of both glucocorticoids and mineralocorticoids. 21-hydroxylase is a cytochrome P-450 enzyme and is encoded by the gene <i>CYP21A2</i>. Here we report a 68-year-old phenotypically 'male' but genetically female patient with 21-hydroxylase deficiency (21OHD) and the concomitant virilizing adrenocortical carcinoma. This patient grew up as a male and has not encountered any episodes of adrenal insufficiency without glucocorticoid replacement in his lifetime. A chromosome test at admission, however, identified the 46, XX karyotype, and serum 17-hydroxyprogesterone and urine pregnanetriolone and 11β-hydroxyandrostendione were all elevated, consistent with 21OHD. Moreover, serum testosterone was 1.90 ng/ml, much higher than the female standard levels, and serum cortisol was 5.7 µg/ml, slightly lower than standard levels. Genetic analysis identified the patient as a heterozygote of the two pathogenic mutations in the <i>CYP21A2</i> gene: IVS2-13C(A)>G and R356W. Magnetic resonance imaging (MRI) revealed the presence of left adrenal tumor measuring 6 cm, which was subsequently diagnosed as adrenocortical carcinoma based on the criteria of Weiss. Immunohistochemical analysis of the tumor specimens revealed the expression of various enzymes involved in testosterone production, including 3β-hydroxysteroid dehydrogenase, 17α-hydroxylase/17,20-lyase, and 17β-hydroxysteroid dehydrogenase. Importantly, the expression of immunoreactive 21-hydroxylase was detected in these tumor cells. The levels of adrenal tumor-derived steroid metabolites were all markedly decreased following the surgery. This is the first report on a virilized 21OHD patient associated with the adrenocortical tumor that produces testosterone. Moreover, the concomitant adrenocortical tumor may ameliorate adrenocortical insufficiency by producing cortisol.

Journal

  • The Tohoku Journal of Experimental Medicine

    The Tohoku Journal of Experimental Medicine 231(2), 75-84, 2013

    Tohoku University Medical Press

Codes

  • NII Article ID (NAID)
    130004720753
  • Text Lang
    ENG
  • ISSN
    0040-8727
  • Data Source
    J-STAGE 
Page Top