TY - JOUR
T1 - Diagnostic Pitfalls in Cushing Disease
T2 - Surgical Remission Rates, Test Thresholds, and Lessons Learned in 105 Patients
AU - Mallari, Regin Jay
AU - Thakur, Jai Deep
AU - Barkhoudarian, Garni
AU - Eisenberg, Amy
AU - Rodriguez, Amanda
AU - Rettinger, Sarah
AU - Cohan, Pejman
AU - Nieman, Lynnette
AU - Kelly, Daniel F.
N1 - Publisher Copyright:
© 2021 The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.
PY - 2022/1/1
Y1 - 2022/1/1
N2 - Context: Confirming a diagnosis of Cushing disease (CD) remains challenging, yet is critically important before recommending transsphenoidal surgery for adenoma resection. Objective: To describe predictive performance of preoperative biochemical and imaging data relative to post-operative remission and clinical characteristics in patients with presumed CD. Design, Setting, Patients, Interventions: Patients (n=105; 86% female) who underwent surgery from 2007 through 2020 were classified into 3 groups: group A (n=84) pathology-proven ACTH adenoma; group B (n=6) pathology-unproven but with postoperative hypocortisolemia consistent with CD; and group C (n=15) pathology-unproven, without postoperative hypocortisolemia. Group A + B were combined as confirmed CD and group C as unconfirmed CD. Main outcomes: Group A + B was compared with group C regarding predictive performance of preoperative 24-hour urinary free cortisol (UFC), late night salivary cortisol (LNSC), 1-mg dexamethasone suppression test (DST), plasma ACTH, and pituitary magnetic resonance imaging (MRI). Results: All groups had a similar clinical phenotype. Compared with group C, group A + B had higher mean UFC (P<0.001), LNSC (P=0.003), DST (P=0.06), and ACTH (P=0.03) and larger MRI-defined lesions (P<0.001). The highest accuracy thresholds were: UFC 72 μg/24 hours; LNSC 0.122 μg/dL, DST 2.70 μg/dL, and ACTH 39.1 pg/mL. Early (3-month) biochemical remission was achieved in 76/105 (72%) patients: 76/90(84%) and 0/15(0%) of group A + B vs group C, respectively, P<0.0001. In group A + B, nonremission was strongly associated with adenoma cavernous sinus invasion. Conclusions: Use of strict biochemical thresholds may help avoid offering transsphenoidal surgery to presumed CD patients with equivocal data and improve surgical remission rates. Patients with Cushingoid phenotype but equivocal biochemical data warrant additional rigorous testing.
AB - Context: Confirming a diagnosis of Cushing disease (CD) remains challenging, yet is critically important before recommending transsphenoidal surgery for adenoma resection. Objective: To describe predictive performance of preoperative biochemical and imaging data relative to post-operative remission and clinical characteristics in patients with presumed CD. Design, Setting, Patients, Interventions: Patients (n=105; 86% female) who underwent surgery from 2007 through 2020 were classified into 3 groups: group A (n=84) pathology-proven ACTH adenoma; group B (n=6) pathology-unproven but with postoperative hypocortisolemia consistent with CD; and group C (n=15) pathology-unproven, without postoperative hypocortisolemia. Group A + B were combined as confirmed CD and group C as unconfirmed CD. Main outcomes: Group A + B was compared with group C regarding predictive performance of preoperative 24-hour urinary free cortisol (UFC), late night salivary cortisol (LNSC), 1-mg dexamethasone suppression test (DST), plasma ACTH, and pituitary magnetic resonance imaging (MRI). Results: All groups had a similar clinical phenotype. Compared with group C, group A + B had higher mean UFC (P<0.001), LNSC (P=0.003), DST (P=0.06), and ACTH (P=0.03) and larger MRI-defined lesions (P<0.001). The highest accuracy thresholds were: UFC 72 μg/24 hours; LNSC 0.122 μg/dL, DST 2.70 μg/dL, and ACTH 39.1 pg/mL. Early (3-month) biochemical remission was achieved in 76/105 (72%) patients: 76/90(84%) and 0/15(0%) of group A + B vs group C, respectively, P<0.0001. In group A + B, nonremission was strongly associated with adenoma cavernous sinus invasion. Conclusions: Use of strict biochemical thresholds may help avoid offering transsphenoidal surgery to presumed CD patients with equivocal data and improve surgical remission rates. Patients with Cushingoid phenotype but equivocal biochemical data warrant additional rigorous testing.
KW - 24-hour urinary free cortisol
KW - ACTH
KW - Cushing's disease
KW - pituitary adenoma
KW - salivary cortisol
KW - transsphenoidal surgery
UR - http://www.scopus.com/inward/record.url?scp=85122839592&partnerID=8YFLogxK
U2 - 10.1210/clinem/dgab659
DO - 10.1210/clinem/dgab659
M3 - Article
C2 - 34478542
AN - SCOPUS:85122839592
SN - 0021-972X
VL - 107
SP - 205
EP - 218
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 1
ER -