Correspondence

Ovarian Adrenal-Like Tissue in Congenital Adrenal Hyperplasia

N Engl J Med 1998; 339:853-854September 17, 1998

Article

To the Editor:

Testicular lesions containing adrenal-like tissue can be found in some males with congenital adrenal hyperplasia.1 These lesions are often multifocal and bilateral.2 A young woman with congenital adrenal hyperplasia in whom virilization persisted after adrenalectomy was assumed to have adrenal-like cells in her ovaries, but their presence was not confirmed.3

We report here on a girl with congenital adrenal hyperplasia in whom ovarian tissue was found to contain adrenal-like tissue whose function was inhibited by dexamethasone. The patient was a 15-year-old girl with simple, virilizing congenital adrenal hyperplasia due to 21-hydroxylase deficiency in whom control was poor, as documented by primary amenorrhea and high serum 17-hydroxyprogesterone and corticotropin concentrations, during treatment with high doses of cortisone. Ultrasonography showed normal adrenal glands and bilaterally enlarged ovaries (4.5×2.5 cm) with small hypogenic nodules (about 1.5 cm in diameter) surrounded by hyperechogenic borders.

Laparoscopy with biopsy of both ovaries was performed. One biopsy specimen contained a small, ill-defined nodule composed of medium-size polygonal cells, with round or oval monomorphic nuclei and abundant cytoplasm organized in irregular cords and nests (Figure 1AFigure 1Results of Ovarian Biopsy in a 15-Year-Old Girl with Congenital Adrenal Hyperplasia.). Electron microscopy revealed abundant smooth endoplasmic reticulum and many mitochondria and lipid droplets (Figure 1B). These findings are characteristic of the cytoarchitectural features and ultrastructural phenotype of adrenocortical tissue. The extranodular ovarian tissue showed mild sclerosis with some microscopical inclusion cysts and no evidence of primary follicles.

The patient was treated with 0.75 mg of dexamethasone daily, with a rapid decrease in serum 17-hydroxyprogesterone and corticotropin concentrations. She had her menarche and during the following year had regular menses. Repeated ultrasonography revealed physiologic follicles in the ovaries with small remnants of adrenal-like tissue.

Ovarian and testicular adrenal-like tissue can function like adrenal tissue, with its function increased by corticotropin and decreased by high doses of glucocorticoids.4 We recommend ultrasonography of the gonads in patients with congenital adrenal hyperplasia that is not adequately controlled by glucocorticoid therapy, in order to rule out the presence of gonadal adrenal-like tissue.

Gianni Russo, M.D.
Pierluigi Paesano, M.D.
Gianluca Taccagni, M.D.
Alessandro Del Maschio, M.D.
Giuseppe Chiumello, M.D.
University of Milan, 20132 Milan, Italy

4 References

1. 1

   Urban MD, Lee PA, Migeon CJ. Adult height and fertility in men with congenital virilizing adrenal hyperplasia. N Engl J Med 1978;299:1392-1396
   Full Text | Web of Science | Medline

2. 2

   Rutgers JL, Young RH, Scully RE. The testicular “tumor“ of the adrenogenital syndrome: a report of six cases and review of the literature on testicular masses in patients with adrenocortical disorders. Am J Surg Pathol 1988;12:503-513
   CrossRef | Web of Science | Medline

3. 3

   Zachmann M, Manella B, Kempken B, Knorr-Muerset G, Atares M, Prader A. Ovarian steroidogenesis in an adrenalectomized girl with 21-hydroxylase deficiency. Clin Endocrinol (Oxf) 1984;21:575-582
   CrossRef | Web of Science | Medline

4. 4

   Combes-Moukhovsky ME, Kottler ML, Valensi P, Boudou P, Sibony M, Attali JR. Gonadal and adrenal catheterization during adrenal suppression and gonadal stimulation in a patient with bilateral testicular tumors and congenital adrenal hyperplasia. J Clin Endocrinol Metab 1994;79:1390-1394
   CrossRef | Web of Science | Medline

Citing Articles (11)

Citing Articles

1. 1

   T. H. Johannsen, C. P. L. Ripa, E. Carlsen, J. Starup, O. H. Nielsen, M. Schwartz, K. T. Drzewiecki, E. L. Mortensen, K. M. Main. (2010) Long-Term Gynecological Outcomes in Women with Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency. International Journal of Pediatric Endocrinology 2010, 1-7
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2. 2

   Todd D. Nebesio, Erica A. Eugster. (2010) Growth and Reproductive Outcomes in Congenital Adrenal Hyperplasia. International Journal of Pediatric Endocrinology 2010, 1-10
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3. 3

   TH Johannsen, CPL Ripa, E Carlsen, J Starup, OH Nielsen, M Schwartz, Drzewiecki, EL Mortensen, KM Main. (2010) Long-Term Gynecological Outcomes in Women with Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency. International Journal of Pediatric Endocrinology 2010:1, 784297
   CrossRef

4. 4

   ToddD Nebesio, EricaA Eugster. (2010) Growth and Reproductive Outcomes in Congenital Adrenal Hyperplasia. International Journal of Pediatric Endocrinology 2010:1, 298937
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5. 5

   H.L. Claahsen-van der Grinten, B.J. Otten, M.M.L. Stikkelbroeck, F.C.G.J. Sweep, A.R.M.M. Hermus. (2009) Testicular adrenal rest tumours in congenital adrenal hyperplasia. Best Practice & Research Clinical Endocrinology & Metabolism 23:2, 209-220
   CrossRef

6. 6

   Anne Bachelot, Zeina Chakthoura, Agnès Rouxel, Jérome Dulon, Philippe Touraine. (2008) Classical Forms of Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency in Adults. Hormone Research 69:4, 203-211
   CrossRef

7. 7

   Deborah P Merke, Stefan R Bornstein. (2005) Congenital adrenal hyperplasia. The Lancet 365:9477, 2125-2136
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8. 8

   Nike M.M.L Stikkelbroeck, C.G.J.(Fred) Sweep, Didi D.M Braat, Ad R.M.M Hermus, Barto J Otten. (2003) Monitoring of menstrual cycles, ovulation, and adrenal suppression by saliva sampling in female patients with 21-hydroxylase deficiency. Fertility and Sterility 80:4, 1030-1036
   CrossRef

9. 9

   Nike M.M .L. Stikkelbroeck, Ad R.M .M. Hermus, Didi D.M . Braat, Barto J. Otten. (2003) Fertility in Women With Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency. Obstetrical & Gynecological Survey 58:4, 275-284
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10. 10

    Hikmat A. Al-Ahmadie, Jerzy Stanek, James Liu, Padma N. Mangu, Ted Niemann, Robert H. Young. (2001) Ovarian `Tumor' of the Adrenogenital Syndrome. The American Journal of Surgical Pathology 25:11, 1443-1450
    CrossRef

11. 11

    D. Schiller, K. Böhm-Jurkovic, H. Bösmüller, R. Cihal. (2001) Tumeurs testiculaires : le patient garde le secret !. La Revue de Médecine Interne 22, 277-278
    CrossRef