Endocrine Abstracts

Case history: A 66 year old lady presented with abdominal pain, new onset diabetes and hypertension. She was diagnosed with Cushing’s syndrome and was found to have a large heterogeneous left adrenal mass of 11.4 × 9.3 cm in size with no disease elsewhere. She underwent a left open adrenalectomy and the histology confirmed an adrenocortical carcinoma (Weiss score of 7) with focal vascular invasion, no extra-capsular spread and clear resection margins. Following surgery she was commenced on 4 mg of prednisolone as steroid replacement. With her low-moderate risk of recurrence different management options were discussed including adjuvant mitotane treatment. Two months postoperatively, mitotane was started with a plan to escalate the dose.

Investigations: We have shown previously that once-daily prednisolone can be used as steroid replacement instead of three times a day hydrocortisone. Most patients require between 3 to 4 mg of prednisolone per day which can be adjusted according to the 8-hour prednisolone level aiming for 15 mcg/l to 25 mcg/l. Keeping in mind that mitotane leads to CYP3A4 induction of which prednisolone is one of its substrate, we carried out three prednisolone day curves (at 1, 2 and 7 months after starting Mitotane) with parallel ACTH measurements to find the optimal prednisolone replacement dose using ACTH as marker of adequate replacement.

Results and treatment: Our results showed that prednisolone levels at different time points correlate well with ACTH levels. With increasing duration of Mitotane treatment, increasing prednisolone doses were required to achieve normalisation of ACTH at 8 hours. Cortisol binding globulin levels predictably increased from 55.7 mg/L to 158.9 mg/L within two months of Mitotane treatment. Our patient required 20 mg of prednisolone at 7 months of treatment.

Conclusions and points of discussion: Mitotane increases cortisol clearance and increases cortisol binding globulin concentration. There is no reliable laboratory marker to guide the optimal dose of steroid replacement. Hydrocortisone needs to be given three times daily and the dose adjustment can be difficult in this scenario. Clinical symptoms, 24-hour urinary free cortisol levels and serial ACTH measurements are being used. With once-daily prednisolone as steroid replacement, a single 8-hour ACTH level can be used to adjust the prednisolone dose with patients receiving Mitotane.