Revisiting Cushing Syndrome, Milder Forms Are Now a Common Occurrence: A Single-Center Cohort of 76 Subjects

Objective Guidelines recommend initiating testing for Cushing's syndrome (CS) on the basis of a "strong clinical suspicion". Our experience suggests classical stigmata are absent in the majority of patients with CS diagnosed in recent years. We aimed to confirm this premise by revisiting the clinical features of this syndrome in a modern series of patients from one center. Methods Computerized records of subjects with CS diagnosed at Tel Aviv-Sourasky Medical Center between 2000-2018 were reviewed. A Cushing's inventory score (CIS), including all clinical components of the syndrome, was computed for each subject. Data were compared between the subtypes, and evaluated in light of those in the literature. Results Of the 76 subjects with CS (60 women/16 men), 49 had Cushing's disease (64.5%), 16 had an adrenal adenoma (21.1%), 7 an adrenocortical carcinoma (9.2%), and 4 had ectopic ACTH secretion (5.3%). In only 20.3% a clinical suspicion of CS led to testing. Catabolic signs of CS were present in less than 30% of cases. The most common symptom was weight gain (77.6%), and the most common comorbidity was hypertension (61.8%). There were no differences in CIS between the subtypes. Signs, symptoms, and comorbidities were all significantly less common than in the classical syndrome. Conclusions - Modern CS presents with subtler features than in the past. Initiating a testing cascade solely on the basis of a strong clinical suspicion may lead to underdiagnosis of milder cases. A concerted effort to devise cost-efficient testing for CS in the current era is needed.