Roughly 90% of congenital adrenal hyperplasia is categorized as “classical” due to full (70%, cortisol and aldosterone, salt-wasting) or partial (30%, cortisol alone, simple virilizing) deficiency of 21-hydroxylase. Scant or nonfunctioning 21-hydroxylase reduces cortisol synthesis. Lower background cortisol causes persistent ACTH rise, which stimulates chronic adrenal hyperplasia.
This patient case uncovers that constant ACTH stimulation, besides hyperplasia, can also lead to a functional adrenal mass; characterized as a lipid rich structure (myelolipoma) with increased uptake on 18F-FDG PET scan. Alike masses are seen in testicular glands (called testicular adrenal-rest tumors) of male patients with classical congenital adrenal hyperplasia.
Important to be aware of functional myelolipomas as they do not represent a malignant process.
Journal of the Endocrine Society
A 29-year-old Mexican female was referred for evaluation of a left-sided adrenal mass noted at imaging during a medical evaluation for abdominal pain. She received prednisone from age 6 to 16 years, but she was not aware of her diagnosis and had not received glucocorticoid therapy for 13 years. Her history was notable for ambiguous genitalia, primary amenorrhea, and recurrent urinary tract infections. The physical examination was notable for short stature (134 cm, – 4.9 standard deviation), hirsutism (Ferriman-Gallwey score of 13), hyperpigmentation, Tanner stage 2 breasts, left lower quadrant tenderness, and clitoromegaly (clitoral index: 378 mm2; normal: <35 mm2) with a small, single perineal opening.
Adrenal computed tomography showed a lobulated, enhanced left adrenal mass measuring 10 × 7 cm that was compressing the left kidney. The upper portion of the mass was of lower density, suggestive of fat (−64 Hounsfield units). The right adrenal was enlarged with a low-density mass measuring 4 × 5 cm.
An 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) scan revealed bilaterally enlarged adrenals, with masses showing increased uptake. Genetic [CYP21A2 heterozygous for intron 2 IVS2-13A/C>G splice site mutation / p.R483P (c.1451_1452 deletion insertion of C)] and biochemical [17-hydroxyprogesterone: 17,900 ng/dL or 542.4 nmol/L (reference range, 13 to 175 ng/dL or 0.4 to 5.3 nmol/L)] workups were consistent with the diagnosis of classic simple-virilizing congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency.
The patient was initiated on glucocorticoid and mineralocorticoid replacement. Left-sided laparoscopic adrenalectomy was performed along with excision of the adrenal mass. Histopathology of the left adrenal mass was consistent with myelolipoma [Fig. 1(E) and 1(F)].
Lipid-rich adrenal tumors are usually benign, and they rarely demonstrate increased uptake on 18F-FDG PET scans, a sign of a hormone-secreting tumor. Myelolipoma, the most common fat-containing tumor of the adrenal gland, is an admixture of fatty, adenomatous, and hematopoietic tissues. These benign tumors are rare but are seen with increased frequency in patients with CAH, especially in poor disease control states and often bilaterally. This case demonstrates that unlike other fat-containing benign tumors, hormonally inactive myelolipomas rarely show increased uptake on 18F-FDG-PET scan when the metabolically active adenomatous and hematopoietic components are extensive.
Myelolipoma should be in the differential for a large adrenal mass with increased uptake on 18F-FDG PET scan.
The presence of large, metabolically active, bilateral adrenal masses should raise suspicion for CAH, especially in a patient with clinical signs of excess androgen.