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Liberman B; Nogueira KC; Huayllas MC; Goldman J; Cukiert A.
Departments of Endocrinology and Neurosurgery, Hospital Brigadeiro, Sao Paulo SP, Brazil
Rationale: Ketoconazole (KTZ) is an imidazole derivative which inhibits adrenal steroidogenesis and has successfully been used in the control of Cushing’s disease. It could be used in an attempt to reduce hypercortisolemia and improve clinical condition prior to transesphenoidal surgery (TS) or after unsuccessful surgery while waiting for the effects from radiotherapy. There are no data in the literature concerning the effects of ketoconazole on the immediate postoperative cortisol dynamics and on the timing for the development of adrenal insufficiency (AI) after successful surgery. In this paper, we studied whether there was any influence of the preoperative use of KTZ on the timing for the development of adrenal insufficiency after successful transesphenoidal surgery.
Methods: We studied 7 patients with Cushing´s disease submitted to TS who were treated with KTZ for at least XXXX months prior to surgery (mean dose= XXXX) (Group A) and compared them with 15 patients who did not received KTZ (Group B). All patients had successful surgery and developed adrenal insufficiency at the immediate postoperative period. No patient received glucocorticoid replacement therapy during/after surgery. Cortisol level during the first postoperative hours and the timing for adrenal insufficiency development were studied. Adrenal insufficiency was considered when cortisol plasma level was less than 5.0 mcg/dl associated to the classical AI symptoms or when cortisol plasma level was less than 2,0 mcg/dl in asymptomatic patients.
Results: There was no significant difference on the preoperative hormone levels between Group A and B patients. AI occurred 16,86 2,4 hours postoperatively in Group A and after 27,8 3,0 hours in group B (p<0,05).
Discussion: AI developed significantly earlier in patients with Cushing’s disease who had successful adenoma removal and received KTZ preoperatively, when compared to those who did not receive KTZ. Since AI might represent a life-threatening event, special attention should be drawn to those patients receiving KTZ preoperatively for earlier postoperative detection of AI signs and symptoms.