Endocrine Abstracts

Background: Diamond Blackfan anaemia (DBA) is a condition caused by mutations in ribosomal protein genes. After the first year of life, the mainstay of treatment is corticosteroids whilst red blood cell transfusions are used for patients who do not respond.

Case: We present a case of a 20-year-old woman with a history of DBA (RPS19 mutation), initially treated with courses of prednisolone, who aged 3 developed steroid-induced adrenal insufficiency. Aged 4, hydrocortisone replacement was commenced. At age 19, there was a loss of clinical response of the DBA to increased hydrocortisone doses. Prednisolone 40mg daily failed to induce a clinical response and it was noted that there were no cushingoid features despite a prolonged course. A prednisolone challenge resulted in serum prednisolone level <5 mg/l with non-suppressed ACTH. Urinary steroid profiling showed metabolised prednisolone at 15-40% of the expected levels, suggesting malabsorption. A hydrocortisone absorption curve was normal. A methylprednisolone challenge resulted in ACTH suppression to 4ng/l at 3 h. Treatment with steroids was preferred over a transfusion strategy due to patient preference and finding of severe hepatic iron loading. A course of high dose methylprednisolone (64mg per day) was commenced, resulting in improvement of haemoglobin from 105g/l to 142g/l and reticulocyte count from 46 x109/l to 149 x109/l. The dose has since been weaned to 36mg/20mg on alternate days.

Discussion: This case demonstrates isolated malabsorption of prednisolone but improved absorption and clinical response with methylprednisolone. The mechanism behind this is not clear but there are no previously known methylation defects in DBA. Finding a suitable steroid has prevented transfusion-dependence for now. A future challenge may be the choice between high doses of methylprednisolone or transfusion-dependence if the disease becomes uncontrolled on low doses of methylprednisolone.