Case Reports in Medicine to ultrasonography of the abdomen, on which a tumor in the right adrenal was detected. An adrenal CT scan showed a 4 × 4 × 2.5 cm tumor in the right adrenal with high fat content, which was radiologically considered to be a myelolipoma. The left adrenal was evaluated as normal. Further clinical investigation showed height 165 cm, blood pressure 140/80 mmHg, and normal male genitalia with testicular tenderness bilaterally. Biochemical investiga- tion showed high basal level of 17-OH-progesterone, which was suppressible with dexamethasone, and an impaired cortisol response to ACTH stimulation (Table 1). Adrenal iodomethyl-19-norcholesterol scintigraphy showed high uptake in the right adrenal, which however was suppressed by dexamethasone; uptake was normal or low in the left adrenal. DNA sequencing of CYP21 revealed compound heterozygozity for the I172N mutation (c. 515T > A) and the I2 splice mutation (g.655A/C > G, I172N/I2splice). The myelolipoma was not removed and the tumor size did not increase during a four-year observation period. The patient was started on treatment with 5 mg prednisolone daily for one year, later cortisone acetate 12.5 mg twice a day whereupon his condition improved. The patient died suddenly, 73 years old, in his home; the cause of death remains unknown. 4. Discussion We here report two male patients who presented late in life with large adrenal myelolipomas. One was previously treated for CAH, whereas one was diagnosed with 21-hydroxylase deﬁciency after being diagnosed with the adrenal tumor at 68 years of age. Both tumors were left untreated and did not grow over ﬁve- and nine-year observation periods. An adrenal mass normally requires surgical removal if the largest diameter exceeds 3 cm [1]. Undiagnosed CAH must always be considered as a diﬀerential diagnosis to tumor, particularly with bilateral adrenal masses. Adrenal myelolipomas are benign and usually asymptomatic tumors that usually need not to be resected [2, 6, 7, 11]. Many of the cases that have been reported in literature were diagnosed after adrenalectomy [2, 6, 7, 11]. The imaging characteristics of myelolipomas usually allow presumptive diagnosis, but which may be conﬁrmed by percutaneous needle biopsy in cases of extra-adrenal myelolipomas [5]. However, large myelolipomas could be dangerous if they start bleeding and give symptoms with pain, nausea, vomiting, and hypotension [2]. Because of mass eﬀects and the risk of haemorrhage, elective removal of myelolipomas that exceed 10 cm in diameter might be considered. Increased prevalence of adrenal tumors has been reported in CAH patients and in heterozygote mutation carriers, possibly due to increased levels of ACTH which acts as a growth factor [12–15]. It has been suggested that inadequate glucocorticoid coverage in early life or frequent episodes of infection, both resulting in chronic ACTH increase, contribute to the development of adrenal tumors later in life [15, 16]. The aetiology is unknown, but several theories have been proposed, such as development 3 from residual embryonic mesenchymal tissue in the adrenal glands, or metaplasia of reticuloendothelial cells as a result of chronic stress [2]. It was postulated early in the 1950s that ACTH ele- vation might induce transformation of adrenal tissue into myeloid tissue [17], and myelolipomas could thus be par- ticularly associated with CAH. Hagiwara et al. investigated ACTH receptors and androgen receptor in a resected giant myelolipooma in a woman with CAH. They did not ﬁnd that the receptors were overexpressed and suggest a limited direct role for these hormones in the develop- ment of the myelolipoma [18]. However this conclusion is debatable. To our knowledge less than 20 cases of adrenal myelolipo- mas have been reported in patients with CAH to date [7– 10, 16, 18–20]. Jaresch et al. found adrenal masses in 83% of CAH patients and 45% of heterozygous CYP21 mutation car- riers, which is high compared to the general population [13]. However, their study included only 22 homozygous CAH patients and 20 heterozygous siblings. Conversely, series of adrenal incidentalomas have been tested for germline CYP21 mutations, showing inconsistent results which could be due to small samples [12, 13, 15]. Consequently, it appears that adrenal masses are common in CAH, but that CAH is not a common cause of adrenal masses. The diagnosis of CAH in a patient with an incidental adrenal mass is important as the patient is at risk of adrenal crises [21]. Such patients may beneﬁt from glucocorticoid therapy and should at least be equipped with emergency medication and a medical alert card. Patient 1 had a blunted cortisol response to ACTH stimulation, but he had managed well for 30 years without steroids, working full- time and did not want to take steroids because of the psychological side eﬀects he experienced during adolescence. He was nonetheless advised to take steroids under stressful situations. Patient 2 had higher basal level of cortisol, but suboptimal cortisol response to ACTH stimulation. He had symptoms of cortisol deﬁciency, and his condition improved considerably after treatment with prednisolone was commenced. He had a low normal testosterone level and tenderness of the testicles. This could be the result of testicular adrenal rest tumors but was not investigated further. Whether glucocorticoid suppression therapy in adult age halts further growth of the tumor is uncertain. In our patients the tumors did not grow over four to nine year observation periods despite high ACTH levels. Conversely, Rajput et al. described progressive evolution of an adrenal myelolipoma in a woman with CAH who was treated with prednisolone, although taken irregularly, ren- dering the level of 17-OH-progesterone persistently elevated [19]. In conclusion, congenital adrenal hyperplasia, per se, should be included in the diﬀerential diagnosis of adrenal masses. If suspected clinically, assay of cortisol, ACTH, and 17OH-progesterone should be performed. Adrenal tumors are common in CAH and might require surgical removal, but myelolipomas are benign tumors that usually can be left untreated. Whether, treatment of CAH halts myelolipoma growth is uncertain.