Tohoku J. Exp. Med., 2013 October, 231(2)

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

MASAYUKI HAYASHI,¹ YUKO KATAOKA,¹ YOSHIHISA SUGIMURA,² FUMIKO KATO,^3,4 MAKI FUKAMI,³ TSUTOMU OGATA,^3,4 KEIKO HOMMA,⁵ TOMONOBU HASEGAWA,⁶ YUTAKA OISO,² HIRONOBU SASANO⁷ and HIROSHI TANAKA¹

¹Department of Endocrinology and Metabolism, Chukyo Hospital, Nagoya, Aichi, Japan
²Department of Endocrinology and Diabetes, Field of Internal Medicine, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan
³Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan
⁴Department of Pediatrics, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan
⁵Central Clinical Laboratories, Keio University Hospital, Tokyo, Japan
⁶Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan
⁷Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan

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 CYP21A2. 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 CYP21A2 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.

keywords —— adrenocortical carcinoma; cortisol; 21-hydroxylase deficiency; prominent masculinization; testosterone

© 2013 Tohoku University Medical Press

===============================

Tohoku J. Exp. Med., 2013, 231, 75-84

Correspondence: Masayuki Hayashi, Department of Endocrinology and Metabolism, Chukyo Hospital, 1-1-10, Sanjo, Minami-ku, Nagoya, Aichi 457-8510, Japan.

e-mail: masayuki_hayashi@chukyo-hosp.jp