Rare and severe complications of congenital adrenal hyperplasia due to 21-hydroxylase deficiency: a case report

We report the case of a patient with classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency who presented with unusual anatomical and biochemical features, namely massively enlarged adrenal glands, adrenogenital rest tissue and an unexpected endocrine profile. The contribution of the adrenocortical cells in the adrenals and testicles was determined by a cosyntropin stimulation test before and after adrenalectomy. To the best of our knowledge this is the first report of such a case in the literature.

A 35-year-old Caucasian man was admitted to the emergency room with an Addisonian crisis. He had been diagnosed with congenital adrenal hyperplasia in the neonatal period. He acknowledged poor adherence to treatment and irregular medical assistance. Physical examination revealed marked cutaneous and gingival hyperpigmentation, hypotension, and hard nodules in the upper pole of both testicles. Blood analysis showed mild anemia and hyponatremia and no evidence of acute infection. Endocrine evaluation showed very low cortisol levels, low dehydroepiandrosterone-sulfate and elevated corticotropin, 11-deoxycortisol and delta-4-androstenedione. The concentration of 17-hydroxyprogesterone was 20,400ng/dL. After the cosyntropin stimulation test the pattern was similar and there was no significant increase in cortisol or 17-hydroxyprogesterone. The abdominal computed tomography scan revealed grossly enlarged and heterogeneous adrenal glands (left, 12cm; and right, six cm). A bilateral adrenalectomy was performed and pathologic examination revealed adrenal myelolipomas with nodular cortical hyperplasia. The sonogram showed bilateral heterogeneous masses on the upper pole of both testes which corresponded to the nodular hyperplasia of adrenal rest tissues. The genetic study revealed compound heterozigoty (mutations R124H and R356W), suggestive of a phenotypically moderate disease. We performed a cosyntropin stimulation test after adrenalectomy. The steroidogenic profile displayed the same unusual features, indicating an important contribution from the adrenogenital cells.

This case illustrates that congenital adrenal hyperplasia due to 21-hydroxylase deficiency can progress to severe acute and chronic complications. The masses in the patient’s adrenal glands and testicles resulted from chronically elevated adrenocorticotropic hormone and growth of adrenocortical cells. The basal and stimulated steroid profile, before and after adrenalectomy, revealed an unexpected pattern, suggesting significant contribution of the testicular adrenal cells to the steroidogenesis.