Clinical Endocrinology (2008) 69, 117–122 doi: 10.1111/j.1365-2265.2007.03168.x © 2008 The Authors Journal compilation © 2008 Blackwell Publishing Ltd 117 ORIGINAL ARTICLE Blackwell Publishing Ltd Role for postoperative cortisol response to desmopressin in predicting the risk for recurrent Cushing’s disease Daniella Jesus Patrick Carminatti Romanholi* , †, Marcio Carlos Machado* , † , ‡, Camila Canteiro Pereira§, Debora Seguro Danilovic§, Maria Adelaide Albergaria Pereira§, Valter Angelo S. Cescato¶, Malebranche Berardo C. Cunha Neto¶, Nina Rosa Castro Musolino¶, Berenice Bilharinho de Mendonça§ and Luiz Roberto Salgado† †Neuroendocrine Unit, Division of Endocrinology and Metabolism, University of Sao Paulo School of Medicine, Sao Paulo, SP, Brazil, ‡Neuroendocrine Unit, Service of Endocrinology and Metabolism, Hospital de Clinicas, Federal University of Parana (SEMPR), Curitiba, PR, Brazil, §Division of Endocrinology and Metabolism and ¶Neuroendocrine Unit, Division of Neurosurgery, University of Sao Paulo School of Medicine, Sao Paulo, SP, Brazil Summary In the early postoperative period of Cushing’s disease patients, desmopressin may stimulate ACTH secretion in the remnant corticotrophic tumour, but not in nontumour suppressed cells. Objective The aim of this study is to evaluate the serum cortisol responses to desmopressin after pituitary surgery, establishing an optimal cut-off for absolute increment (Δ) of serum cortisol (F) suitable to predict recurrence risk. Design Retrospective case record study. Patients Fifty-seven Cushing’s disease patients submitted to pituitary surgery and desmopressin stimulation in the early postoperative with a long-term follow-up (20–161 months) were studied. Methods and measurements Serum cortisol levels after desmo- pressin test (10 μg IV) 15–30 days after adenomectomy were used to determine ΔF (absolute increment of F: F peak - F baseline). Sensitivity and specificity of ΔF were calculated and a ROC curve was performed to establish an optimal cut-off for ΔF to predict recurrence risk. Results Fifteen patients had immediate postoperative failure (basal F > 165 nmol/l; 6 μg/dl) and one patient was lost during the follow- up. Forty-one patients achieved initial remission and were followed- up. Five of 11 patients who recurred had ΔF > 193 nmol/l (7 μg/dl), but none of 30 patients who remained in prolonged remission showed ΔF > 193 nmol/l after postoperative desmopressin stimulation. Conclusions Persistence of cortisol response (ΔF > 193 nmol/l) to desmopressin in the early postoperative period can help to identify Cushing’s disease patients with initial remission who present risk for later recurrence. (Received 29 June 2007; returned for revision 21 July 2007; finally revised 11 December 2007; accepted 11 December 2007) Introduction Transsphenoidal surgery (TSS) has become the first choice for the treatment of Cushing’s disease patients. 1,2 It is the only form of treatment that allows removal of an ACTH-producing adenoma without the need for lifetime replacement therapy. Selective pituitary adenomectomy produces sustained remission in about 70%–80% of patients with Cushing’s disease, while recurrence, defined as the reappearance of tumour and/or hormonal hypersecretion in previously cured patients, occurs in 13%–25% of the cases. Hence, the term ‘remission’ should be used rather than ‘cure’. Part of this variability may be due to the fact that the definition of remission criteria is highly variable in the literature. 2–7 Parameters that may herald recurrence after a successful surgery are still debatable, but it is widely accepted that low postoperative serum cortisol (F) values are associated with the best long-term outcome. 7–10 Additionally, it has been clearly shown that transient secondary hypoadrenalism is consistent with clinical remission and reversal of hypercortisolism. However, recurrence may also occur after an undetectable basal F and long-term remission has been observed when normal F has been obtained in the immediate post- operative period. 8,10–16 In a large European multicentre study, it was shown that recurrence occurred during the follow-up in 4·3% of those patients with undetectable F levels in the postoperative period. 8 Cyclical cortisol production, which has been previously carefully documented, may explain some of the discordant results of the suppressed cortisol value in the immediate postoperative period and later recurrence. 17,18 Several investigators have shown that patients with evidence of recurrence presented normal cortisol and ACTH responses to ovine CRH in the early postoperative period, whereas those patients with Correspondence: Luiz Roberto Salgado, Neuroendocrine Unit, Division of Endocrinology and Metabolism, University of Sao Paulo School of Medicine, Av. Dr Eneas de Carvalho Aguiar #155, 8th floor, Cerqueira Cesar, Sao Paulo, SP 05403–060, Brazil. Tel./Fax: +55 11 3069 7694; E-mail: salga@uol.com.br *Daniella J.P.C. Romanholi and Marcio C. Machado contributed equally to this work.