Endocrine Abstracts

Introduction: Mitotane is an adrenolytic drug which is used in patients with adrenocortical carcinoma (ACC) and leads to adrenal insufficiency (AI). The aim of this study was to evaluate the time to recovery of the hypothalamus-pituitary-adrenal (HPA) axis after adjuvant mitotane treatment and to determine possible predictive factors.

Materials and Methods: In this retrospective study, we included 19 patients with ACC, ENSAT stage I- III, who were treated with mitotane in an adjuvant setting, during a median time of 24 months (3-47). Patients in whom less than 6 months had elapsed after mitotane discontinuation were excluded. HPA recovery was defined by morning cortisol level of ≥350 nmol/l or a cortisol level in the Synacthen test of ≥440 nmol/l. Partial HPA axis recovery was defined by morning cortisol level of 250-350 nmol/l without an adequate (≥440 nmol/l) increase in cortisol in the Synacthen test. The median follow-up time was 84 months (36-136).

Results: The HPA axis completely recovered in 10 (53%) patients after a median time of 27 months (12-41). In another 3 patients (16%) we noticed a partial HPA axis recovery whereas 6 patients (31%) still had AI after 126 months of follow-up. There was a trend to longer period to HPA axis recovery in patients who developed central hypothyroidism (CH) during mitotane treatment (P = 0.067). Of 7 patient who did not develop CH, HPA axis recovered in 5 after a mean time of 18 months after mitotane discontinuation. In contrast, of 12 patients with CH, in 5 HPA axis recovered after mean time of 74 months whereas remaining 7 still had AI after a respective follow-up of 6, 13, 36, 50, 93, 116 and 126 months.

Conclusion: Our study demonstrated that HPA axis do not recover in a considerable number of ACC patients, even after several years of adjuvant mitotane discontinuation. It appears that the development of CH during mitotane treatment might predict delayed HPA axis recovery.