Bilateral adrenal incidentaloma caused by 21-hydroxylase deficiency in an adult

A 46-year-old patient was referred to our hospital due to incidental detection of an intraabdominal mass on ultrasound during work-up for abdominal discomfort. When the patient was seen, she was asymptomatic with the exception of mild non-specific weakness experienced over the previous 3 years. There was no history of chronic disease or acute medical conditions. She had never menstruated, been married, or had children. The patient’s blood pressure was 95/65 mmHg. Her height was 156 cm and her weight was 65 kg; moderate hirsutism of the face and chin was observed. Magnetic resonance imaging of the abdomen revealed that both adrenal glands were enlarged (Fig. 1), and the uterus, vagina, and the root of the penis were seen. Blood tests revealed normal electrolyte levels, marked elevation of baseline and 60-min 250-lg synthetic adrenocorticotropic hormone (ACTH)-stimulated 17-hydroxyprogesterone (33,867 ng/dL and 34,454 ng/dL, respectively, reference, 20–100 ng/dL and 42–250 ng/dL), baseline, 30and 60-min 250-lg ACTH-stimulated cortisol (5.4 lg/dL, 5.0 lg/dL, and 5.1 lg/dL, respectively), high basal ACTH (529.3 pg/mL, reference, 10–90 pg/mL), dehydroepiandrosterone sulfate (148 lg/dL, reference, 80–560 lg/dL), estradiol (14.0 pg/ml, reference 19.5–144.2 pg/ml), total testosterone (3.82 ng/ml, reference 0.08–0.95 ng/ml), and decreased FSH and LH levels (\0.3 and \0.7 IU/L, respectively, reference, 1.4–18.1 and 1.5–9.3 IU/L). Chromosomal analysis confirmed a normal female karyotype. Informed consent was obtained for genetic study. Gene analysis of CYP21A2 revealed compound heterozygous mutations: c.293-13A[G (IVS2(-13)A[G) and c.1069C[T (p.R357W). These findings were consistent with simple virilizing congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD), in which ineffective cortisol synthesis increases the production of corticotropin-releasing hormone and ACTH, leading to adrenal gland hyperplasia. There was no family history of CAH. After diagnosis of CAH in the patient, one of her siblings, a 44-year-old male with two children, provided informed consent for genetic testing. He harbored a heterozygous mutation of c.293-13A[G on CYP21A2, which is one of the two mutant alleles carried by the patient. This suggests that their parents may be heterozygous. 21OHD is the most common genetic disease in human beings [1]. Chronic enlargement of the adrenal glands in 21OHD is associated with an increased prevalence of adrenal tumors, including massive myelolipomas [1, 2]. A recent study suggested that patients with multiple adrenal incidentalomas with hyperandrogenism or those of Middle Eastern origin may benefit from screening for CAH or carrier status [3]. This image shows the changes in the adrenal glands that occurred in a case of CAH that remained untreated until the fifth decade of life. This case also brings into question the need for medical management of gland enlargement beyond the replacement of physiologically deficient glucocorticoid, and what parameters will be useful in the management of gland enlargement. S. H. Kim J. H. Park (&) Division of Endocrinology and Metabolism, Department of Internal Medicine, Chonbuk National University Medical School/Chonbuk National University Hospital, Geonji-Ro 20, Deokjin-Gu, Jeonju 561-712, Republic of Korea e-mail: parkjh@jbnu.ac.kr