Cushing Syndrome May Be More Common in the United States Than Previously Estimated, Suggests Single-Institution Study

Core Concepts

The prevalence of Cushing syndrome in the United States may be significantly higher than current estimates, with adrenal Cushing syndrome being more common than pituitary Cushing disease, and many cases presenting without classic physical features.

Abstract

The study, conducted at the University of Wisconsin, Milwaukee, found that the incidence of Cushing syndrome in Wisconsin is at least 7.2 cases per million patient-years, which is considerably higher than the 1-3 cases per million patient-years estimated in previous European studies.
The researchers found that adrenal Cushing syndrome was more common than pituitary ACTH-secreting tumors (Cushing disease), accounting for 60% of cases. Additionally, fewer than half of individuals with adrenal Cushing syndrome had the classic physical features of hypercortisolism, such as weight gain, round face, excessive hair growth, and stretch marks.
The study authors suggest that Cushing syndrome cases are being missed, potentially due to the obesity and diabetes epidemics, which can make some clinical features of cortisol excess more common and less notable. As a result, providers may not think to screen for Cushing syndrome, leading to delayed diagnosis and increased risk of complications from uncontrolled hypercortisolism.
The session moderator, Dr. Sharon L. Wardlaw, suggested that the Wisconsin group may have a lower threshold for diagnosing the milder cortisol elevation seen with adrenal Cushing syndrome, or that it is being underdiagnosed in other places. However, she emphasized that even milder cases of hypercortisolism can have long-term damaging effects and should be detected and treated.
The study authors noted that the data from the Wisconsin Hospital Association indicate that the University of Wisconsin's Milwaukee facility treated just about half of the patients in the state who were discharged from the hospital with a Cushing syndrome diagnosis during 2019-2023. This suggests that the actual or approximate incidence of Cushing syndrome in Wisconsin may be as high as 14-15 cases per million per year, rather than the 7.2 cases reported in the study.

Stats

"The incidence of CS in the state works out to 7.2 cases per million population per year."
"Data from the Wisconsin Hospital Association show that the University of Wisconsin's Milwaukee facility treated just about half of patients in the state who are discharged from the hospital with a diagnosis of CS during 2019-2023. So...that means that an actual or approximate incidence of 14-15 cases per million per year rather than the 7.2 cases that we produce."
"Etiologies were 60% adrenal (111 patients), 36.8% pituitary (68 patients), and 3.2% ectopic (6 patients)."
"Classic physical features of CS were present in 91% of people with pituitary CS and 100% of those ectopic CS but just 44% of individuals with adrenal CS."

Quotes

"Cases are absolutely being missed.... Clinicians should realize that cortisol excess is not rare. It may not be common, but it needs to be considered in patients with any constellation of features that are seen in cortisol excess."
"If you screen for Cushing with a dexamethasone suppression test...[i]f you have autonomous secretion by the adrenal, you don't suppress as much.... When you measure 24-hour urinary cortisol, it may be normal. So you're in this in-between [state].... Maybe in Wisconsin they're diagnosing it more. Or, maybe it's just being underdiagnosed in other places."

Key Insights Distilled From

Is Cushing Syndrome More Common in the US Than We Think?

by Miriam E. Tu... at www.medscape.com 06-07-2024

https://www.medscape.com/viewarticle/cushing-syndrome-more-common-us-than-we-think-2024a1000ar4

Deeper Inquiries

What factors, beyond the obesity and diabetes epidemics, could contribute to the underdiagnosis of Cushing syndrome in the United States?

In addition to the obesity and diabetes epidemics, several other factors could contribute to the underdiagnosis of Cushing syndrome in the United States. One significant factor is the lack of awareness among healthcare providers about the diverse clinical presentations of the condition. Since Cushing syndrome can manifest with a wide range of symptoms beyond the classic physical features like weight gain and round face, clinicians may not always consider it in their differential diagnosis. Moreover, the nonspecific nature of some symptoms, such as fatigue, muscle weakness, and mood changes, can overlap with other common conditions, leading to misdiagnosis or delayed diagnosis of Cushing syndrome. Furthermore, the complexity of the diagnostic process, which often involves multiple biochemical tests and imaging studies, can pose challenges and may result in underutilization of these diagnostic tools in clinical practice.

How can healthcare providers be better equipped to recognize and diagnose milder cases of Cushing syndrome, which may present without the classic physical features?

Healthcare providers can be better equipped to recognize and diagnose milder cases of Cushing syndrome by increasing their awareness of the condition and its varied presentations. Continuous medical education and training programs focusing on the diverse clinical manifestations of Cushing syndrome, including the milder forms, can help clinicians develop a high index of suspicion for the condition. Implementing screening protocols for at-risk populations, such as individuals with uncontrolled diabetes, hypertension, or unexplained osteoporosis, can aid in the early detection of milder cases. Additionally, utilizing a multidisciplinary approach involving endocrinologists, primary care physicians, and other specialists can facilitate comprehensive evaluation and timely diagnosis of Cushing syndrome, even in the absence of classic physical features.

What are the potential long-term health consequences of undiagnosed and untreated mild hypercortisolism, and how can early detection and treatment improve patient outcomes?

Undiagnosed and untreated mild hypercortisolism, a hallmark of Cushing syndrome, can have significant long-term health consequences on patients. Chronic exposure to excess cortisol levels can lead to various complications, including osteoporosis, muscle weakness, glucose intolerance, hypertension, cardiovascular disease, and frailty. Moreover, prolonged hypercortisolism can adversely affect metabolic processes, immune function, and mental health, contributing to a reduced quality of life and increased morbidity. Early detection and treatment of mild hypercortisolism are crucial in preventing the progression of these complications and improving patient outcomes. Timely intervention, such as surgical removal of adrenal or pituitary tumors causing cortisol excess, pharmacological management, or radiation therapy for ectopic ACTH-secreting tumors, can help normalize cortisol levels, alleviate symptoms, and mitigate the risk of long-term sequelae associated with untreated Cushing syndrome. Regular monitoring, lifestyle modifications, and ongoing medical management are essential components of the comprehensive care plan for individuals with Cushing syndrome to optimize their health and well-being.