The Modern Presentation, Etiology, and Rate of Occurrence of Cushing Syndrome Differs when Compared to Prior Population-Based Studies

TL;DR

This study finds that adrenal Cushing Syndrome is more common than previously thought and presents differently than Cushing disease in a Wisconsin population.

Contribution

The study reports a higher estimated incidence of endogenous Cushing Syndrome in Wisconsin compared to prior European population studies.

Findings

Adrenal Cushing Syndrome was more common than Cushing disease in the study cohort.

The estimated incidence of endogenous Cushing Syndrome in Wisconsin is 11.1 cases/million population/year.

Adrenal CS cases showed milder cortisol excess compared to Cushing disease and ectopic ACTH syndrome.

Abstract

Endogenous Cushing Syndrome (CS) is considered a rare disorder, with European population studies estimating an incidence of 1.5-3.2 cases/million population/year and Cushing disease (CD) being recognized as the most common etiology. The purpose of this study is to characterize the etiologies of endogenous CS, CS severity, and case frequency of CS at a single institution.

Between May 2017 and December 2022, clinic records from a single tertiary care medical center were reviewed to identify Wisconsin residents who were newly diagnosed and treated for CS. We collected information on the etiology, biochemical data, and evidence of physical features of CS.

A total of 185 patients diagnosed with and treated for endogenous CS in our state. Of these, 111 (60%) had adrenal CS, 68 (36.8%) had CD, and 6 (3.2%) had ectopic ACTH syndrome. Patients with adrenal CS had less severe hypercortisolism compared to CD and ectopic ACTH syndrome and a lower frequency of Cushingoid appearance at diagnosis. The case frequency within our institution’s state was 7.2 cases/million population/year (total population). Adjusting for institutional state-wide market share, we estimate a more accurate state-wide case frequency of CS to be 11.1 cases/million population/year.

Adrenal CS was more common than CD in our cohort and often presented with milder cortisol excess that still required treatment. The relative case frequency of endogenous CS in Wisconsin may approach 11 case/million population/year based on this single-institutional data, but further population-based studies are needed to estimate the incidence of endogenous CS.

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