Endocrine Pathology

, 19:122 | Cite as

Lack of ACTH and Androgen Receptor Expression in a Giant Adrenal Myelolipoma Associated with 21-hydroxylase Deficiency

  • Hanae Hagiwara
  • Takeshi Usui
  • Takashi Kimura
  • Tetsuya Tagami
  • Mitsuhide Naruse
  • Sachiko Minamiguchi
  • Takuma Kato
  • Hiroshi Okuno
  • Akira Shimatsu


Myelolipomas of the adrenal gland are benign, nonfunctioning tumors. Patients with congenital adrenal hyperplasia sometimes develop large and bilateral myelolipomas. Although the precise pathogenesis of myelolipomas remains unclear, prolonged stimulation with high levels of adrenocorticotropic hormone (ACTH) or adrenal androgens are assumed to have a causative role. To clarify the role of ACTH and androgen in the pathogenesis of myelolipoma, we report a case of giant adrenal myelolipoma in a patient with poorly controlled congenital adrenal hyperplasia. A 43-year-old female was diagnosed with congenital adrenal hyperplasia at 6 years of age because of ambiguous genitalia. She had high plasma ACTH and 17-hydroxyprogesterone levels. Abdominal computed tomography showed a huge mass on the left adrenal gland, and an enlarged right adrenal mass. Genetic testing for CYP21A2 was performed and revealed that her genotype was IVS2–13A/C>G/I172N. Adrenalectomy for the left-side tumor was performed. Histological study revealed that the tumor consisted of fat cells and myeloid components, findings compatible with adrenal myelolipoma. Neither ACTH receptors nor androgen receptor was over-expressed in the tumor. Our finding that the tumor did not over-express ACTH or androgen receptor suggests a limited direct role for these hormones in the development of the myelolipoma.


myelolipoma 21-hydroxylase deficiency melanocortin receptors (MCRs) androgen receptor (AR) 



We are grateful to Ms. Matsuda for excellent technical assistance with the RT-PCR.

Disclosure information

None of the authors have anything to declare.


  1. 1.
    Olsson CA, Krane RJ, Klugo RC, Selikowitz SM. Adrenal myelolipoma. Surgery 73:665–70, 1973.PubMedGoogle Scholar
  2. 2.
    Plaut A. Myelolipoma in the adrenal cortex; myeloadipose structures. Am J Pathol 34:487–515, 1958.PubMedGoogle Scholar
  3. 3.
    Barr AB, Giltman LI. Congenital adrenal hyperplasia diagnosed in an 82-year-old: case report. Va Med 109:844–5, 1982.PubMedGoogle Scholar
  4. 4.
    Boudreaux D, Waisman J, Skinner DG, Low R. Giant adrenal myelolipoma and testicular interstitial cell tumor in a man with congenital 21-hydroxylase deficiency. Am J Surg Pathol 3:109–23, 1979.PubMedCrossRefGoogle Scholar
  5. 5.
    Condom E, Villabona CM, Gomez JM, Carrera M. Adrenal myelolipoma in a woman with congenital 17-hydroxylase deficiency. Arch Pathol Lab Med 109:1116–7, 1985.PubMedGoogle Scholar
  6. 6.
    Kalidindi RS, Hattingh L. Bilateral giant adrenal myelolipomas. Abdom Imaging 31:125–7, 2006. doi: 10.1007/s00261-005-0014-4.PubMedCrossRefGoogle Scholar
  7. 7.
    Murakami C, Ishibashi M, Kondo M, Ohshiro S, Fujita M, Sato S, Kako M, Furue H, Mizuguchi K, Yamaji T. Adrenal myelolipoma associated with congenital adrenal 21-hydroxylase deficiency. Intern Med 31:803–6, 1992. doi: 10.2169/internalmedicine.31.803.PubMedCrossRefGoogle Scholar
  8. 8.
    Nagai T, Imamura M, Honma M, Murakami M, Mori M. 17alpha-hydroxylase deficiency accompanied by adrenal myelolipoma. Intern Med 40:920–3, 2001. doi: 10.2169/internalmedicine.40.920.PubMedCrossRefGoogle Scholar
  9. 9.
    Oliva A, Duarte B, Hammadeh R, Ghosh L, Baker RJ. Myelolipoma and endocrine dysfunction. Surgery 103:711–5, 1988.PubMedGoogle Scholar
  10. 10.
    Ravichandran R, Lafferty F, McGinniss MJ, Taylor HC. Congenital adrenal hyperplasia presenting as massive adrenal incidentalomas in the sixth decade of life: report of two patients with 21-hydroxylase deficiency. J Clin Endocrinol Metab 81:1776–9, 1996. doi: 10.1210/jc.81.5.1776.PubMedCrossRefGoogle Scholar
  11. 11.
    Sakaki M, Izaki H, Fukumori T, Taue R, Kishimoto T, Kanayama HO. Bilateral adrenal myelolipoma associated with adrenogenital syndrome. Int J Urol 13:801–2, 2006. doi: 10.1111/j.1442-2042.2006.01406.x.PubMedCrossRefGoogle Scholar
  12. 12.
    Umpierrez MB, Fackler S, Umpierrez GE, Rubin J. Adrenal myelolipoma associated with endocrine dysfunction: review of the literature. Am J Med Sci 314:338–41, 1997. doi: 10.1097/00000441-199711000-00012.PubMedCrossRefGoogle Scholar
  13. 13.
    Wagnerova H, Lazurova I, Bober J, Sokol L, Zachar M. Adrenal myelolipoma. 6 cases and a review of the literature. Neoplasma 51:300–5, 2004.PubMedGoogle Scholar
  14. 14.
    Allison KH, Mann GN, Norwood TH, Rubin BP. An unusual case of multiple giant myelolipomas: clinical and pathogenetic implications. Endocr Pathol 14:93–100, 2003. doi: 10.1385/EP:14:1:93.PubMedCrossRefGoogle Scholar
  15. 15.
    Iwamoto T, Yajima M, Tanaka H, Minagawa N, Osada T. A case report: reversible male infertility due to congenital adrenal hyperplasia. Nippon Hinyokika Gakkai Zasshi 84:2031–4, 1993.PubMedGoogle Scholar
  16. 16.
    Schindler H. Myelolipoma of the adrenal gland in adrenogenital syndrome. Wien Med Wochenschr 725:695–7, 1975.PubMedGoogle Scholar
  17. 17.
    Treska V, Wirthova M, Hadravska S, Mukensnabl P, Kuntscher V, Kreuzberg B, Lisa L, Kozak K. Giant bilateral adrenal myelolipoma associated with congenital adrenal hyperplasia. Zentralbl Chir 131:80–3, 2006. doi: 10.1055/s-2006-921375.PubMedCrossRefGoogle Scholar
  18. 18.
    Bennett BD, McKenna TJ, Hough AJ, Dean R, Page DL. Adrenal myelolipoma associated with Cushing’s disease. Am J Clin Pathol 73:443–7, 1980.PubMedGoogle Scholar
  19. 19.
    Hisamatsu H, Sakai H, Tsuda S, Shigematsu K, Kanetake H. Combined adrenal adenoma and myelolipoma in a patient with Cushing’s syndrome: case report and review of the literature. Int J Urol 11:416–8, 2004. doi: 10.1111/j.1442-2042.2004.00815.x.PubMedCrossRefGoogle Scholar
  20. 20.
    Kanj HA, Noronha J, D'Aguillo AF, Amorosa JK, Amorosa LF. Bilateral adrenal myelolipomas with Cushing’s syndrome. JAMA 259:3034–6, 1988. doi: 10.1001/jama.259.20.3034.PubMedCrossRefGoogle Scholar
  21. 21.
    Maschler I, Rosenmann E, Ehrenfeld EN. Ectopic functioning adrenocortico-myelolipoma in longstanding Nelson’s syndrome. Clin Endocrinol (Oxf) 10:493–7, 1979. doi: 10.1111/j.1365-2265.1979.tb02106.x.CrossRefGoogle Scholar
  22. 22.
    Usui T, Nishisho K, Kaji M, Ikuno N, Yorifuji T, Yasuda T, Kuzuya H, Shimatsu A. Three novel mutations in Japanese patients with 21-hydroxylase deficiency. Horm Res 61:126–32, 2004. doi: 10.1159/000075587.PubMedCrossRefGoogle Scholar
  23. 23.
    Dean G. Myelolipoma of the adrenal gland. Scott Med J 16:513–8, 1971.PubMedGoogle Scholar
  24. 24.
    Nicod JL. Adenoma, lipoma and myelolipoma of the adrenal cortex. Bull Assoc Fr Etud Cancer 50:109–22, 1963.PubMedGoogle Scholar
  25. 25.
    Miyazaki Y, Yoshida M, doi:J. A case of adrenal myelolipoma associated with adrenogenital syndrome. Hinyokika Kiyo 36:35–9, 1990.PubMedGoogle Scholar
  26. 26.
    Delarue J, Monsaingeon A. Myeloid metaplasia in the adrenal cortex of burned subjects. C R Seances Soc Biol Fil 144:777–8, 1950.PubMedGoogle Scholar
  27. 27.
    Selye H, Stone H. Hormonally induced transformation of adrenal into myeloid tissue. Am J Pathol 26:211–33, 1950.PubMedGoogle Scholar
  28. 28.
    Griffon N, Mignon V, Facchinetti P, Diaz J, Schwartz JC, Sokoloff P. Molecular cloning and characterization of the rat fifth melanocortin receptor. Biochem Biophys Res Commun 200:1007–14, 1994. doi: 10.1006/bbrc.1994.1550.PubMedCrossRefGoogle Scholar
  29. 29.
    Berner HS, Lyngstadaas SP, Spahr A, Monjo M, Thommesen L, Drevon CA, Syversen U, Reseland JE. Adiponectin and its receptors are expressed in bone-forming cells. Bone 35:842–9, 2004. doi: 10.1016/j.bone.2004.06.008.PubMedCrossRefGoogle Scholar
  30. 30.
    Considine RV. Regulation of leptin production. Rev Endocr Metab Disord 2:357–63, 2001. doi: 10.1023/A:1011896331159.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 2008

Authors and Affiliations

  • Hanae Hagiwara
    • 1
  • Takeshi Usui
    • 1
    • 4
  • Takashi Kimura
    • 1
  • Tetsuya Tagami
    • 1
    • 4
  • Mitsuhide Naruse
    • 1
    • 4
  • Sachiko Minamiguchi
    • 2
  • Takuma Kato
    • 3
  • Hiroshi Okuno
    • 3
  • Akira Shimatsu
    • 1
    • 4
  1. 1.Department of Endocrinology and MetabolismNational Hospital Organization Kyoto Medical CenterKyotoJapan
  2. 2.Department of Surgical PathologyNational Hospital Organization Kyoto Medical CenterKyotoJapan
  3. 3.Department of UrologyNational Hospital Organization Kyoto Medical CenterKyotoJapan
  4. 4.Clinical Research InstituteNational Hospital Organization, Kyoto Medical CenterKyotoJapan

Personalised recommendations