Exploring Reasons for the Underdiagnosis of Hypercortisolism
Panelists discuss how hypercortisolism presents with both overt symptoms like central obesity, muscle wasting, easy bruising, purple striae, moon face, and buffalo hump, as well as nonspecific features including weight gain, resistant hyperglycemia, severe hypertension, dyslipidemia, osteoporosis, and psychiatric disorders, explaining that these overlapping symptoms with common chronic diseases like diabetes and hypertension often mask the underlying condition, leading to underdiagnosis as clinicians focus on adding more medications rather than investigating potential underlying causes, while the disease's perceived rarity in medical education further contributes to missed diagnoses despite hypercortisolism being more prevalent than previously thought.
This video segment explores the signs and symptoms of hypercortisolism and explains why the condition is frequently underdiagnosed. The discussion distinguishes between overt Cushing syndrome symptoms, which include central obesity, muscle wasting, easy bruising, purple striae wider than one centimeter, moon face, buffalo hump, and thin skin, and more nonspecific features commonly seen in the general population. These nonspecific symptoms include weight gain, resistant hyperglycemia, diabetes, severe hypertension, dyslipidemia, osteoporosis, and psychiatric disorders—collectively resembling metabolic syndrome.
The pathophysiology of hypercortisolism involves multiple mechanisms that contribute to disease progression. High cortisol levels promote insulin resistance and stimulate hepatic gluconeogenesis, leading to increased sugar production. The condition also impairs pancreatic beta cell function and incretin effects. Additionally, an enzyme called 11-beta HSD1 becomes overexpressed in adipose tissue, converting inactive cortisone to active cortisol, creating a cycle that worsens hyperglycemia. This enzyme's activity is enhanced by chronic stress, creating a psychological-physiological link. The condition significantly increases cardiovascular mortality risk, particularly in patients with type 2 diabetes, with mortality rates potentially increasing threefold.
Hypercortisolism is frequently underdiagnosed due to overlapping symptoms with common chronic conditions like diabetes and hypertension. Clinicians often focus on escalating medications rather than investigating underlying causes when patients present with resistant hyperglycemia or difficult-to-control blood pressure. The condition is more prevalent than previously thought, but health care providers are taught that Cushing syndrome is rare, leading to missed diagnoses. Patients may be incorrectly labeled as non-adherent when their conditions remain poorly controlled despite multiple medications. The key to improving diagnosis is for clinicians to pause and consider whether persistent, treatment-resistant conditions might indicate an underlying hypercortisolism rather than simply adding more medications.
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