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

Abstract

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%, PZ0.02), and later (mean 44.7 months, median 43, range 7-94 vs mean 21.5 months, median 17, range 3-61, PZ0.05), 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.

Performance of salivary cortisol in the diagnosis of Cushing's syndrome, adrenal incidentaloma, and adrenal insufficiency

“…There are data about the efficacy in relapse prediction of stimulatory tests (22,25,26) and fewer about salivary cortisol (27). We demonstrated higher LNSC levels in active CD patients than in those with CD in remission and also in those with non-CS than in those with CD in remission, confirming the data published by Carrasco et al (27) and suggesting salivary cortisol as a simple and reliable tool to follow up patients with CD in remission.…”

“…The LNSC test, as proposed recently (5,6,7,10,11,12,14), is a reliable, noninvasive, stress-free, and low-cost procedure to diagnose CS. Moreover, elevation of LNSC levels might be the first abnormality to be checked in the follow-up after surgery (22).…”

Treatment of Cushing's Syndrome: An Endocrine Society Clinical Practice Guideline

“…Early recovery (within 6 mo) of HPA axis function may indicate an increased risk of recurrence (66). Two longitudinal studies demonstrated that elevated late-night serum/salivary cortisol is one of the earliest biochemically detectable signs of recurrence and almost always precedes elevated urine cortisol (75,76). Although many such patients evolve to significant hypercortisolism, it is uncertain whether there is any benefit to treating patients with a mild early recurrence if they are asymptomatic.…”

The diagnostic performance of urinary free cortisol is better than the cortisol:cortisone ratio in detecting de novo Cushing's syndrome: the use of a LC–MS/MS method in routine clinical practice

“…We also found normal UFF excretion in two out of ten recurrent CD patients. One study in the literature, in fact, reported that elevated UFF levels appear later with respect to other tests in recurrent CD patients (20). During the routine follow-up of these patients, early diagnosis of recurrence (based on pathological results of two other screening tests) can be made even in the event that UFF levels are normal or only slightly elevated, due to lower sensitivity and specificity of UFF in this particular clinical setting.…”