SciELO - Scientific Electronic Library Online

vol.54 issue4Is it necessary to reduce the radioiodine dose in patients with thyroid cancer and renal failure?Concomitant thyroid Malt lymphoma and papillary thyroid carcinoma author indexsubject indexarticles search
Home Pagealphabetic serial listing  

Services on Demand



  • English (pdf)
  • Article in xml format
  • How to cite this article
  • SciELO Analytics
  • Curriculum ScienTI
  • Automatic translation


Related links


Arquivos Brasileiros de Endocrinologia & Metabologia

On-line version ISSN 1677-9487

Arq Bras Endocrinol Metab vol.54 no.4 São Paulo June 2010 



Giant adrenal myelolipoma associated with 21-hydroxylase deficiency: unusual association mimicking an androgen-secreting adrenocortical carcinoma


Mielolipoma adrenal gigante associado à deficiência da 21-hidroxilase: associação não usual simulando um carcinoma adrenocortical secretor de androgênios



Lívia Mara MermejoI; Jorge Elias JuniorII; Fabiano Pinto SaggioroIII; Silvio Tucci JuniorIV; Margaret de CastroI; Ayrton Custódio MoreiraI; Paula C. Lamparelli EliasI

IDivisão de Endocrinologia, Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo (FMRP-USP), Ribeirão Preto, SP, Brazil
IIDivisão de Radiologia, Departamento de Clínica Médica, FMRP-USP, Ribeirão Preto, SP, Brazil
IIIDepartamento de Patologia, FMRP-USP, Ribeirão Preto, SP, Brazil
IVDepartamento de Cirurgia e Anatomia, FMRP-USP, Ribeirão Preto, SP, Brazil

Correspondence to




The objective of this study was to describe a case of giant myelolipoma associated with undiagnosed congenital adrenal hyperplasia (CAH) due to 21-hydroxylase (21OH) deficiency. Five seven year-old male patient referred with abdominal ultrasound revealing a left adrenal mass. Biochemical investigation revealed hyperandrogenism and imaging exams characterized a large heterogeneous left adrenal mass with interweaving free fat tissue, compatible with the diagnosis of myelolipoma, and a 1.5 cm nodule in the right adrenal gland. Biochemical correlation has brought concerns about differential diagnosis with adrenocortical carcinoma, and surgical excision of the left adrenal mass was indicated. Anatomopathologic findings revealed a myelolipoma and multinodular hyperplasic adrenocortex. Further investigation resulted in the diagnosis of CAH due to 21OH deficiency. Concluded that CAH has been shown to be associated with adrenocortical tumors. Although rare, myelolipoma associated with CAH should be included in the differential diagnosis of adrenal gland masses. Moreover, CAH should always be ruled out in incidentally detected adrenal masses to avoid unnecessary surgical procedures.


O objetivo deste trabalho foi descrever um caso de mielolipoma gigante associado à hiperplasia adrenal congênita (HAC) por deficiência da 21-hidroxilase (21OH). Paciente do sexo masculino, 57 anos de idade, encaminhado por achado ultrassonográfico de massa adrenal esquerda. Investigação bioquímica revelou hiperandrogenismo e exames de imagem revelaram grande lesão sólida em adrenal esquerda de aspecto heterogêneo, entremeada de tecido gorduroso, compatível com diagnóstico de mielolipoma, e um nódulo de 1,5 cm na adrenal direita. Os achados bioquímicos sugeriam o diagnóstico de carcinoma adrenocortical, indicando cirurgia para retirada da massa adrenal esquerda. O anatomopatológico confirmou mielolipoma e hiperplasia multinodular do córtex adrenal. A investigação subsequente diagnosticou HAC por deficiência da 21OH. Concluiu-se que a HAC tem sido descrita em associação com tumores adrenocorticais. Apesar de raro, o mielolipoma associado à HAC deve ser incluído nas possibilidades diagnósticas de massa adrenal. Adicionalmente, a HAC deve ser sempre afastada nos casos de massa adrenal de achado incidental, evitando cirurgias desnecessárias.




Adrenal myelolipomas are relatively uncommon benign tumors, usually small and unilateral. They are usually found incidentally and rarely present as giant myelolipomas (1). They are composed of mature adipose cells and haematopoietic myeloid cells (2,3). Although usually asymptomatic, myelolipomas can cause pain upon the occurrence of hemorrhage, necrosis or compression. Occasionally, they can occur concomitantly with other lesions such as cortical adenoma (2-4), ganglioneuroma (5), carcinoma (6), pheochromocytoma (7), or CAH (8). Although characteristically non-functioning, there have been a few reports of myelolipomatous masses associated with adrenocortical hypersecretion (8,9). On radiologic evaluation, they typically present a high fat content that gives them a pathognomonic appearance on CT and MRI images (10,11). On CT, the presence of low attenuation fat in the lesion, which has a density of -30 HU, is a specific and diagnostic finding. On MRI, the fat components in the lesion demonstrate high signal on T1- and T2-weighted images and lose signal on T1-fat-saturated images resembling intra-abdominal fat (10,12). However, the presence of hemorrhage and necrosis features can emulate the radiological aspect of adrenocortical carcinoma (10).

In this report, we describe an uncommon case of a 57-year-old man with a giant myelolipoma presented as an adrenal mass with a heterogeneous appearance on radiologic evaluation associated with hyperandrogenism resulting in preoperative diagnosis of adrenocortical carcinoma. The anatomopathologic findings revealed a myelolipoma, and further investigation resulted in the associated diagnosis of CAH due to 21OH deficiency.



A 57-year-old Brazilian male patient was referred to the Endocrine Division in June 2008 with abdominal pain and an abdominal ultrasound revealing a left adrenal mass of 12 x 9 x 12 cm. He was father of two daughters aged 32 and 34 years. At admission, the patient weighed 56.8 kg and was 160 cm tall, with a body mass index of 22 kg/m2. He had a blood pressure of 100/70 mmHg and a heart rate of 72 beats/min. Other physical examination was unremarkable, except by slightly decreased and hard testis (3.5 x 2 cm bilaterally). There was no clinical evidence of Cushing's syndrome, hyperaldosteronism or pheochromocytoma. A laboratory screening for adrenal incidentaloma demonstrated suppressed plasma cortisol levels after 1 mg overnight dexamethasone (33 nmol/l; normal < 50); normokalemia (4.3 mmol/L; normal range 3.5-5); normal urinary metanephrines (502 nmol/24h; normal range 31-1167) and urinary normetanephrines (1147 nmol/24h; normal range 240-2459), and plasma catecholamines (3.6 nmol/L; normal range 0.7-3.9); normal DHEAS (4 mmol/L; normal range 6.5-9.1); normal testosterone (13 nmol/L; normal 8.7-31.2 range), and elevated androstenedione (74 nmol/L; normal range 2.1-8.7). CT and MRI exams have characterized the lesion as a large heterogeneous left adrenal soft tissue mass with substantial amount of interweaving free fat tissue. There was also a 1.5 cm nodule with similar features in the right adrenal gland (Figure 1).



Although the imaging features were typical for myelolipoma, the biochemical findings showing androstenedione hypersecretion associated with a large adrenal mass led to a preoperative diagnosis hypothesis of androgen secreting adrenocortical carcinoma. Patient underwent open left adrenalectomy. The intraoperatory findings demonstrated a 15 x 10 cm left adrenal circumscribed mass which was completely excised, and a small pigmented right adrenal mass of around 1.5 cm, that was not removed due to its benign appearance. Pathological findings revealed an enlarged left adrenal gland with a yellow and tan circumscribed mass of 15 cm in its largest diameter that weighed 585 g. At the microscopy the tumor was characterized as a myelolipoma that rose on a multinodular hyperplasic adrenocortex (Figure 2).

The patient postoperative recovery was unremarkable, but the androgens remained elevated on the fifth day after surgery (Table 1). To rule out a potentially unsuccessful surgery and to diagnose a suspected CAH, measurement of basal and post ACTH1-24 stimulation test 17OHP was performed, followed by a 2 mg/day dexamethasone suppression test during 5 days. Basal 17OHP was 261 nmol/L, reaching 342 nmol/L 60 minutes after ACTH1-24 (Table 1). All androgens showed a marked suppression after 5 days of the dexamethasone suppression test, thus confirming the diagnosis of CAH (Table 1).

To further confirm CAH diagnosis, a genomic analysis was performed from the DNA of the peripheral blood leukocytes and the patient was found to be a compound heterozygous carrier of the Q318X and intron2 splicing (Sp2) mutation in the CYP21A2 gene. Later on, therapy was initiated with 5 mg of prednisone and 0.1 mg of fludrocortisone daily, with the androstenedione level falling into normal range (Table 1). A low testosterone level (3.2 nmol/L) and slightly high levels of LH and FSH (20 and 13.2 IU/L, respectively), indicate an actual primary gonadal dysfunction most likely due to long-term suppression of hypothalamic-pituitary-gonadal axis.



The pathogenesis of adrenal myelolipomas remains unclear. A variety of mechanisms are proposed to underlie the etiology of adrenal myelolipomas, such as the presence of embryonic bone marrow in adrenal tissue (3). Some evidences indicate that ACTH may have a role in the development of these tumors, demonstrated by an increase in the relative frequency of myelolipomas in patients with excessive ACTH secretion, such as in CAH (13,14), Nelson's syndrome (15), and Addison's disease (3). Moreover, myeloid metaplasia in the adrenal cortex is observed in severely burned and cancer patients, two groups that are subject to long periods of intense stress (16). Indeed, myelolipomas have been associated with various forms of CAH like 21OH deficiency, 17-hydroxylase (17OH) deficiency and recently with 11b-hydroxylase deficiency (17). It is worth pointing out that most of these patients were either untreated or had stopped taking their medication for an extended period and were exposed for many years to chronically elevated ACTH and androgen levels which have been shown to induce transformation of adrenal cortical precursor cells into mature fat cells (17,18).

To date, approximately 25 cases of myelolipomas associated with CAH have been reported. The mean age of these patients was 48 years (range 23-82 years). The characteristics of each patient and tumor are shown in table 2. The majority of them, 19 (76%), was associated with CAH due to 21OH deficiency, 4 (16%) with CAH due 17OH deficiency and 1 (4%) with CAH due to 11b-hydroxylase deficiency. Our patient presents CAH due to 21OH deficiency, with a genotype Q318X / Sp2. Considering size and localization, the mean tumor size was 12.4 cm (range 1-43 cm) and bilateral lesions were reported in ten cases (40%). Jaresch and cols. (37) previously described a positive correlation between the age of CAH patients and the age at onset of therapy, and adrenal size; with older patients and patients who were untreated for a long period presenting the most hyperplastic adrenal glands with no correlation between tumor size and serum 17OHP concentrations. In these cases, chronic ACTH excess could induce diffuse or nodular adrenocortical hyperplasia which would later become autonomous because of oncogenic mutations in the tissue. Although under-diagnosis of CAH due to 21OH deficiency is more frequent in male patients, as observed in our case, there was no difference in gender prevalence of myelolipomas associated with CAH described thus far in the literature, with 13 women and 12 men accounting for the casuistics. The great majority of myelolipomas associated with CAH are localized in the adrenal gland, however there are descriptions of myelolipomas in other locations, such as the testis (38). There was also an increase in reports of myelolipomas in more recent years (12 reports in the last decade versus 13 from 1975 to 1997) explained by the widespread use of radiologic evaluation resulting in more diagnosis of adrenal incidentalomas (39).



In conclusion, we describe a rare case of giant myelolipoma associated to CAH due to 21OH deficiency. The excessive ACTH and/or androgen secretion over a long period of time could have had a stimulatory role in the development of the adrenal myelolipoma in the present patient. However, the mechanism underlying the reduced 21OH reserve among incidentaloma patients and the increased occurrence of adrenal tumors in simple virilizing or late-onset CAH forms remains a matter of speculation. Additionally, although surgery was mandatory in the present case due to tumor symptoms and size, CAH should always be ruled out in incidentally detected adrenal masses to avoid unnecessary surgical procedures.

Acknowledgements: This work was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (Fapesp) (grant numbers 08/09276-0 and 07/58365-3).

Disclosure: no potential conflict of interest relevant to this article was reported.



1. Kelekis NL, Alexopoulou E, Brountzos EN, Ladis V, Boussiotou A, Kelekis DA. Giant adrenal myelolipoma with minimal fat content in a patient with homozygous beta-thalassemia: appearance on MRI. J Magn Reson Imaging. 2003;18(5):608-11.         [ Links ]

2. Olsson CA, Krane RJ, Klugo RC, Selikowitz SM. Adrenal myelolipoma. Surgery. 1973;73(5):665-70.         [ Links ]

3. Plaut A. Myelolipoma in the adrenal cortex; myeloadipose structures. Am J Pathol. 1958;34(3):487-515.         [ Links ]

4. Manassero F, Pomara G, Rappa F, Cuttano MG, Crisci A, Selli C. Adrenal myelolipoma associated with adenoma. Int J Urol. 2004;11(5):326-8.         [ Links ]

5. Merchant SH, Herman CM, Amin MB, Ro JY, Troncoso P. Myelolipoma associated with adrenal ganglioneuroma. Arch Pathol Lab Med. 2002;126(6):736-7.         [ Links ]

6. Sun X, Ayala A, Castro CY. Adrenocortical carcinoma with concomitant myelolipoma in a patient with hyperaldosteronism. Arch Pathol Lab Med. 2005;129(6):e144-7.         [ Links ]

7. Ukimura O, Inui E, Ochiai A, Kojima M, Watanabe H. Combined adrenal myelolipoma and pheochromocytoma. J Urol. 1995;154(4):1470.         [ Links ]

8. Hagiwara H, Usui T, Kimura T, Tagami T, Naruse M, Minamiguchi S, et al. Lack of ACTH and androgen receptor expression in a giant adrenal myelolipoma associated with 21-hydroxylase deficiency. Endocr Pathol. 2008;19(2):122-7.         [ Links ]

9. Lamas C, Lopez LM, Lozano E, Atienzar M, Ruiz-Mondejar R, Alfaro JJ, et al. Myelolipomatous adrenal masses causing Cushing's syndrome. Exp Clin Endocrinol Diabetes. 2009;117(8):440-5.         [ Links ]

10. Lockhart ME, Smith JK, Kenney PJ. Imaging of adrenal masses. Eur J Radiol. 2002;41(2):95-112.         [ Links ]

11. McLoughlin RF, Bilbey JH. Tumors of the adrenal gland: findings on CT and MR imaging. AJR Am J Roentgenol. 1994;163(6):1413-8.         [ Links ]

12. Ilias I, Sahdev A, Reznek RH, Grossman AB, Pacak K. The optimal imaging of adrenal tumours: a comparison of different methods. Endocr Relat Cancer. 2007;14(3):587-99.         [ Links ]

13. Miyazaki Y, Yoshida M, Doi J. [A case of adrenal myelolipoma associated with adrenogenital syndrome]. Hinyokika Kiyo. 1990;36(1):35-9.         [ Links ]

14. Oliva A, Duarte B, Hammadeh R, Ghosh L, Baker RJ. Myelolipoma and endocrine dysfunction. Surgery. 1988;103(6):711-5.         [ Links ]

15. Maschler I, Rosenmann E, Ehrenfeld EN. Ectopic functioning adrenocortico-myelolipoma in longstanding Nelson's syndrome. Clin Endocrinol (Oxf). 1979;10(5):493-7.         [ Links ]

16. Delarue J, Monsaingeon A. [Myeloid metaplasia in the adrenal cortex of burned subjects.]. C R Seances Soc Biol Fil. 1950;144(11-12):777-8.         [ Links ]

17. John M, Menon SK, Shah NS, Menon PS. Congenital adrenal hyperplasia 11beta-hydroxylase deficiency: two cases managed with bilateral adrenalectomy. Singapore Med J. 2009;50(2):e68-e70.         [ Links ]

18. Selye H, Stone H. Hormonally induced transformation of adrenal into myeloid tissue. Am J Pathol. 1950;26(2):211-33.         [ Links ]

19. Schindler H. [Myelolipoma of the adrenal gland in adrenogenital syndrome]. Wien Med Wochenschr. 1975;725(48):695-7.         [ Links ]

20. 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. 1979;3(2):109-23.         [ Links ]

21. Barr AB, Giltman LI. Congenital adrenal hyperplasia diagnosed in an 82-year-old: case report. Va Med. 1982;109(12):844-5.         [ Links ]

22. Condom E, Villabona CM, Gomez JM, Carrera M. Adrenal myelolipoma in a woman with congenital 17-hydroxylase deficiency. Arch Pathol Lab Med. 1985;109(12):1116-7.         [ Links ]

23. Sasano H, Masuda T, Ojima M, Fukuchi S, Sasano N. Congenital 17 alpha-hydroxylase deficiency: a clinicopathologic study. Hum Pathol. 1987;18(10):1002-7.         [ Links ]

24. Murakami C, Ishibashi M, Kondo M, Ohshiro S, Fujita M, Sato S, et al. Adrenal myelolipoma associated with congenital adrenal 21-hydroxylase deficiency. Intern Med. 1992;31(6):803-6.         [ Links ]

25. 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. 1993;84(11):2031-4.         [ Links ]

26. 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. 1996;81(5):1776-9.         [ Links ]

27. Umpierrez MB, Fackler S, Umpierrez GE, Rubin J. Adrenal myelolipoma associated with endocrine dysfunction: review of the literature. Am J Med Sci. 1997;314(5):338-41.         [ Links ]

28. Parenteau C, Mongeau CJ, Benard B, Maheux P. Pigmented adrenal hyperplasia with myelolipomatous changes and bilateral testicular enlargement in an untreated man with 21-hydroxylase deficiency. Endocr Pract. 2000;6(3):260-3.         [ Links ]

29. Nagai T, Imamura M, Honma M, Murakami M, Mori M. 17alpha-hydroxylase deficiency accompanied by adrenal myelolipoma. Intern Med. 2001;40(9):920-3.         [ Links ]

30. Allison KH, Mann GN, Norwood TH, Rubin BP. An unusual case of multiple giant myelolipomas: clinical and pathogenetic implications. Endocr Pathol. 2003;14(1):93-100.         [ Links ]

31. Mathew J, Menon PS, Shah NS. An elderly lady in shock. J Postgrad Med. 2005;51(1):51-3.         [ Links ]

32. Patocs A, Liko I, Varga I, Gergics P, Boros A, Futo L, et al. Novel mutation of the CYP17 gene in two unrelated patients with combined 17alpha-hydroxylase/17,20-lyase deficiency: demonstration of absent enzyme activity by expressing the mutant CYP17 gene and by three-dimensional modeling. J Steroid Biochem Mol Biol. 2005;97(3):257-65.         [ Links ]

33. Kalidindi RS, Hattingh L. Bilateral giant adrenal myelolipomas in a patient with known congenital adrenal hyperplasia-imaging appearances and change in the CT morphology following steroid treatment: a case report. Abdom Imaging. 2006; DOI: 10.1007/s00261-006-9096-x.         [ Links ]

34. Treska V, Wirthova M, Hadravska S, Mukensnabl P, Kuntscher V, Kreuzberg B, et al. [Giant bilateral adrenal myelolipoma associated with congenital adrenal hyperplasia]. Zentralbl Chir. 2006;131(1):80-3.         [ Links ]

35. Sakaki M, Izaki H, Fukumori T, Taue R, Kishimoto T, Kanayama HO. Bilateral adrenal myelolipoma associated with adrenogenital syndrome. Int J Urol. 2006;13(6):801-2.         [ Links ]

36. Nigawara T, Kageyama K, Sakihara S, Takayasu S, Kawahara M, Imai A, et al. A male case of nonclassical 21-hydroxylase deficiency first manifested in his sixties with adrenocortical incidentaloma. Endocr J. 2008;55(2):291-7.         [ Links ]

37. Jaresch S, Kornely E, Kley HK, Schlaghecke R. Adrenal incidentaloma and patients with homozygous or heterozygous congenital adrenal hyperplasia. J Clin Endocrinol Metab. 1992;74(3):685-9.         [ Links ]

38. Adesokan A, Adegboyega PA, Cowan DF, Kocurek J, Neal DE Jr. Testicular "tumor" of the adrenogenital syndrome: a case report of an unusual association with myelolipoma and seminoma in cryptorchidism. Cancer. 1997;80(11):2120-7.         [ Links ]

39. Seppel T, Schlaghecke R. Augmented 17 alpha-hydroxyprogesterone response to ACTH stimulation as evidence of decreased 21-hydroxylase activity in patients with incidentally discovered adrenal tumours ('incidentalomas'). Clin Endocrinol (Oxf). 1994;41(4):445-51.         [ Links ]



Correspondence to:
Paula C. Lamparelli Elias
Divisão de Endocrinologia, Departamento de Clínica Médica, FMRP-USP
Av. Bandeirantes, 3900
14048-900 − Ribeirão Preto, SP, Brazil

Received on Oct/23/2009
Accepted on Jan/13/2010

Creative Commons License All the contents of this journal, except where otherwise noted, is licensed under a Creative Commons Attribution License