Hypertension and Cushing's syndrome: hunt for the red flag

Introduction The prevalence of secondary hypertension is reported to be 5-15% of people with hypertension. Causes of secondary hypertension include Cushing's syndrome (CS), a rare but serious clinical condition characterized by chronic endogenous hypercortisolism associated with increased morbidity and mortality, especially for cardiovascular complications. The challenge for the clinician is thus to identify the phenotype of hypertensive patients who should be screened for endogenous hypercortisolism. Methods This study was performed according to the PRISMA statement. The search was last updated in June 2023, and only English language studies were considered. Titles and abstracts have been screened for articles selection, identifying only those that dealt with prevalence of Cushing's syndrome in hypertensive patients. Finally, eight papers were included in the review. Data regarding year of publication, populations' characteristics, inclusion criteria, screening test and cut-off used, and CS prevalence have been extracted. Results: The study search identified eight studies, from 1977 to 2020, including a total number of 11,504 patients, ranging from 80 to 4429 patients for each study. The prevalence of CS reported was variable among the studies, ranging from 0 to 7.7%, having Cushing's disease (CD) a prevalence range of 0-1.2%. The highest prevalence has been found in selected populations of hypertensive patients younger than 40 years (6.2%) or harbouring an adrenal lesion (7.7%). The most used screening test was 1 mg overnight dexamethasone suppression test (1 mg DST), with different cut-off. Conclusion The most fitting CS profile encompasses younger age (i.e., < 40 years old), rapidly evolving hypertension and the presence of adrenal adenomas, along with subjects with pituitary lesions, who should still be prioritized in the diagnostic pathway. Overall, in the case of hypertensive patients presenting a clinical picture highly suggestive of CS, it is advisable to perform one of the available screening tests (UFC, 1 mg DST, LNSC). LNSC is likely the most discriminatory test and may be preferred, depending on its availability. Conversely, for hypertensive patients with an adrenal incidentaloma, the 1 mg DST is recommended as the screening test to exclude CS.