ESPE Abstracts

Background: iMAD is a very rare cause of ACTH-independent Cushing´s syndrome in young children. Bilateral adrenalectomy is a definitive treatment, but poses young children at a high risk due to life-long adrenal insufficiency. Therefore, pharmacological treatment with metyrapone seems an alternative bridging option for a limited period of time.

Case report: A 3 6/12 year old boy presented with a history of rapid weight gain and growth failure for four months. At first presentation, the boy demonstrated clinical symptoms of Cushing´s syndrome, including arterial hypertension and increased irritability. Serum cortisol was markedly increased (366 ng/ml) and could not be suppressed by low dose dexamethasone (1 mg). ACTH was suppressed (<1 pg/ml) and 24-h-urinary excretion of free cortisol (UFC) increased (585 µg/d). The high-dose dexamethasone test (2 days: 0.5 mg/4 times daily, 3 days: 2 mg/4 times daily) showed a paradox increase in excretion of UFC up to 1734 µg/d. Abdominal ultrasound, abdominal MRI and PET-CT failed to identify a localised mass, visible adrenal hyperplasia or other adrenal pathology as a cause of hypercortisolism. Cranial MRI showed a generalised brain atrophy and signs of posterior reversible encephalopathy syndrome (PRES). Initially, the boy exhibited hypercalcemia; sonography revealed bilateral nephrolithiasis. Exome analysis revealed a variant in the PDE11A gene (c.919C>T) that has already been described in patients with Cushing´s syndrome; thus iMAD was suspected as cause of hypercortisolism. High blood pressure was managed with amlodipin and atenolol. Nephrolithiasis was successfully treated with increasing fluid intake and alkalisation of urine using calcium-sodium-hydrogen citrate. To avoid immediate bilateral adrenalectomy, oral medication with metyrapone (40 mg/kg/d) and hydrocortisone replacement was started. Six months later, catch-up growth and normalisation of body-mass index were observed. Serum cortisol and daily profile of salivary cortisol were within normal limits. The patient´s parents describe normalisation of his behaviour and mood. Blood pressure and cardiologic findings are within age-specific limits under ongoing medication.

Conclusion: Oral metyrapone is effective in normalising hypercortisolism, growth and weight in our patient with suspected iMAD due to a mutation in PDE11A gene. Nevertheless, the best timing of bilateral adrenalectomy, which can provide both definitive therapy and additional information through histological findings, has to be discussed.