title: Accuracy of Late-Night Salivary Cortisol in Evaluating Postoperative Remission and Recurrence in Cushing's Disease.
abstract: BACKGROUND
  Late-night salivary cortisol (LNSC) is well-validated in the diagnosis of Cushing's disease (CD). The accuracy of LNSC during follow-up of patients undergoing transsphenoidal surgery (TSS) has not been fully characterized.
  
  
  OBJECTIVE
  We examined the accuracy of LNSC in establishing remission and identifying recurrence in postoperative patients with CD.
  
  
  METHODS
  This is a retrospective study.
  
  
  METHODS
  Records of patients with CD who underwent TSS by a single neurosurgeon in our tertiary center (2005-2014) were analyzed (N = 224). Patients were selected for further investigation (n = 165) if there was at least one available LNSC test obtained after TSS (either within 3 months or during long-term follow-up). Extracted data included demographic and clinical characteristics, magnetic resonance imaging and laboratory data (morning serum cortisol, 24-hour urine free cortisol [UFC], LNSC) .
  
  
  METHODS
  Remission was defined as nadir morning serum cortisol less than 5 mcg/dl and nadir 24-hour UFC less than 23 mcg. Recurrence was considered definite if confirmed surgically or prompted radiotherapy.
  
  
  RESULTS
  Surgical remission occurred in 89% of 89 patients with available LNSC data. LNSC, obtained within 3 months of TSS, established remission with 94% sensitivity and 80% specificity at a cutpoint of 1.9 nmol/l (area under the curve [AUC] = 0.90). At a median follow-up of 53.5 months, LNSC established recurrence (75% sensitivity and 95% specificity) at a cutpoint of 7.4 nmol/l (AUC = 0.87), and 24-hour UFC established recurrence (68% sensitivity and 100% specificity) at a cutpoint of 1.6-fold above normal (AUC = 0.82).
  
  
  CONCLUSIONS
  LNSC may accurately establish remission after TSS and identify recurrence more accurately than 24-hour UFC during long-term follow-up.
authors.affiliation: Neuroendocrine Unit (F.G.A., A.T.F., L.B.N., K.K.M., A.K., B.M.K.B., N.A.T.) and Department of Neurosurgery (B.S.), Massachusetts General Hospital, Boston, MA 02114, and Harvard Medical School (F.G.A., B.S., A.T.F., L.B.N., K.K.M., A.K., B.M.K.B., N.A.T.), Boston, MA 02115.
authors.forename: Fatemeh G
authors.initials: FG
authors.lastname: Amlashi
authors.affiliation: Neuroendocrine Unit (F.G.A., A.T.F., L.B.N., K.K.M., A.K., B.M.K.B., N.A.T.) and Department of Neurosurgery (B.S.), Massachusetts General Hospital, Boston, MA 02114, and Harvard Medical School (F.G.A., B.S., A.T.F., L.B.N., K.K.M., A.K., B.M.K.B., N.A.T.), Boston, MA 02115.
authors.forename: Brooke
authors.initials: B
authors.lastname: Swearingen
authors.affiliation: Neuroendocrine Unit (F.G.A., A.T.F., L.B.N., K.K.M., A.K., B.M.K.B., N.A.T.) and Department of Neurosurgery (B.S.), Massachusetts General Hospital, Boston, MA 02114, and Harvard Medical School (F.G.A., B.S., A.T.F., L.B.N., K.K.M., A.K., B.M.K.B., N.A.T.), Boston, MA 02115.
authors.forename: Alexander T
authors.initials: AT
authors.lastname: Faje
authors.affiliation: Neuroendocrine Unit (F.G.A., A.T.F., L.B.N., K.K.M., A.K., B.M.K.B., N.A.T.) and Department of Neurosurgery (B.S.), Massachusetts General Hospital, Boston, MA 02114, and Harvard Medical School (F.G.A., B.S., A.T.F., L.B.N., K.K.M., A.K., B.M.K.B., N.A.T.), Boston, MA 02115.
authors.forename: Lisa B
authors.initials: LB
authors.lastname: Nachtigall
authors.affiliation: Neuroendocrine Unit (F.G.A., A.T.F., L.B.N., K.K.M., A.K., B.M.K.B., N.A.T.) and Department of Neurosurgery (B.S.), Massachusetts General Hospital, Boston, MA 02114, and Harvard Medical School (F.G.A., B.S., A.T.F., L.B.N., K.K.M., A.K., B.M.K.B., N.A.T.), Boston, MA 02115.
authors.forename: Karen K
authors.initials: KK
authors.lastname: Miller
authors.affiliation: Neuroendocrine Unit (F.G.A., A.T.F., L.B.N., K.K.M., A.K., B.M.K.B., N.A.T.) and Department of Neurosurgery (B.S.), Massachusetts General Hospital, Boston, MA 02114, and Harvard Medical School (F.G.A., B.S., A.T.F., L.B.N., K.K.M., A.K., B.M.K.B., N.A.T.), Boston, MA 02115.
authors.forename: Anne
authors.initials: A
authors.lastname: Klibanski
authors.affiliation: Neuroendocrine Unit (F.G.A., A.T.F., L.B.N., K.K.M., A.K., B.M.K.B., N.A.T.) and Department of Neurosurgery (B.S.), Massachusetts General Hospital, Boston, MA 02114, and Harvard Medical School (F.G.A., B.S., A.T.F., L.B.N., K.K.M., A.K., B.M.K.B., N.A.T.), Boston, MA 02115.
authors.forename: Beverly M K
authors.initials: BM
authors.lastname: Biller
authors.affiliation: Neuroendocrine Unit (F.G.A., A.T.F., L.B.N., K.K.M., A.K., B.M.K.B., N.A.T.) and Department of Neurosurgery (B.S.), Massachusetts General Hospital, Boston, MA 02114, and Harvard Medical School (F.G.A., B.S., A.T.F., L.B.N., K.K.M., A.K., B.M.K.B., N.A.T.), Boston, MA 02115.
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Tritos
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002940:Circadian Rhythm; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006854:Hydrocortisone / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D047748:Pituitary ACTH Hypersecretion / Q000175:diagnosis* / Q000601:surgery*; D011184:Postoperative Period; D012008:Recurrence; D012074:Remission Induction; D012189:Retrospective Studies; D012463:Saliva / Q000737:chemistry*; D012680:Sensitivity and Specificity; D055815:Young Adult
chemical_list: D006854:Hydrocortisone