Sequential hormonal changes in 21 patients with recurrent Cushing's disease after successful pituitary surgery

Objective: To describe the sequence of hormonal changes during recurrence of Cushing's disease (CD) after successful transsphenoidal surgery (TSS). Design: Retrospective study in a single center. Patients and methods: We studied 101 of the 127 patients treated by TSS for CD between 1996 and 2009, who had hypocortisolism or eucortisolism for at least 3 months post-TSS. We arbitrarily defined 'overt recurrence', as presence of two classical parameters of excess cortisol (increased midnight - either serum or salivary - and 24 h urinary cortisol (UC)), leading to further specific therapeutic action, and 'mild recurrence', as presence of a single classical parameter, leading to simple surveillance. Results: Of the 101 patients, 21 (20.8%) presented with recurrence, 'mild' or 'overt', during long-term follow-up (median 50.4 months, range 7-99). Recurrence occurred less frequently (16.8 vs 50%, P=0.02), and later (mean 44.7 months, median 43, range 7-94 vs mean 21.5 months, median 17, range 3-61, P=0.05), in patients with early post-TSS hypocortisolism compared with those with eucortisolism. Increase in midnight cortisol occurred in a mean time of 38.2 months, while UC elevation was observed at 50.6 months. Vasopressin analogs and CRH tests were eventually positive in 85 and 93% of all patients respectively; a positive response to one of the two dynamic tests preceded the increase in midnight cortisol or UC in 71 and 64% of the patients respectively. Conclusion: A positive response to vasopressin analogs and/or CRH tests occurs early in recurrence, followed by an increase in midnight cortisol, while UC elevation is at a later stage.