What are the signs and symptoms of hypercortisolism?

Hypercortisolism can be difficult to diagnose because its signs and symptoms are common and nonspecific. It can manifest as a constellation of diseases and complications.1,2
molecule constellation
patient picturesPatients in the above photos were diagnosed with hypercortisolism/Cushing syndrome. Some photographs from: Cushing H. Clinical manifestations of disordered function. In: The Pituitary Body and Its Disorders: Clinical States Produced by Disorders of the Hypophysis Cerebri. Philadelphia, PA: JB Lippincott Company; 1912. All other photographs used with permission.
patient picturesPatients in the above photos were diagnosed with hypercortisolism/Cushing syndrome. Photographs from: Cushing H. Clinical manifestations of disordered function. In: The Pituitary Body and Its Disorders: Clinical States Produced by Disorders of the Hypophysis Cerebri. Philadelphia, PA: JB Lippincott Company; 1912.

Understanding the spectrum of hypercortisolism

Range of biochemical and clinical features along the disease continuum

Hypercortisolism, also referred to as Cushing syndrome, occurs when the body is exposed to high levels of the hormone cortisol for a long period of time.1

Hypercortisolism manifests as a spectrum of diseases and complications, and tends to be progressive.1

Less Severe Hypercortisolism

Severe Hypercortisolism

Biochemical Evaluation

Less Severe Hypercortisolism

  • Biochemically less severe based on cortisol secretion patterns2
  • Referred to as subclinical Cushing syndrome, subclinical hypercortisolism, mild Cushing syndrome, mild autonomous cortisol excess, and mild hypercortisolism
  • Biochemical evidence of autonomous cortisol secretion above diagnostic threshold criteria2

Severe Hypercortisolism

  • Biochemically severe based on cortisol secretion patterns2
  • Referred to as classically described overt Cushing syndrome, Cushing Disease, and overt hypercortisolism
  • Significantly elevated cortisol levels above diagnostic threshold criteria2

Clinical Presentation

Less Severe Hypercortisolism

  • Phenotypic physical features associated with classically described overt Cushing syndrome may not be present (eg, moon face, buffalo hump, striae); however, patients experience multiple progressive metabolic derangements and other features of cortisol excess3,4,5

Severe Hypercortisolism

  • Historically defined by the presence of phenotypic physical features considered highly specific to the disorder (eg, moon face, buffalo hump, striae)6

Cause

Less Severe Hypercortisolism

  • More commonly caused by an ACTH-independent source (adrenal adenoma or hyperplasia), generally leading to a comparatively more gradual onset, progression, and worsening of signs/symptoms2

Severe Hypercortisolism

  • More commonly caused by an ACTH-dependent source, generally leading to a comparatively more rapid onset, progression, and worsening of signs/symptoms2

Clinical presentation of hypercortisolism is complex

  • Although hypercortisolism is clinically unmistakable when full blown, the spectrum of clinical presentation is broad, and the diagnosis can be challenging in less severe cases.1
  • Few, if any, features of hypercortisolism are unique, but some are more discriminatory than others, including reddish purple striae, plethora, proximal muscle weakness, bruising with no obvious trauma, and unexplained osteoporosis.1
  • More often patients have a number of features that are caused by cortisol excess, but those symptoms (eg, hypertension, glucose intolerance, obesity) may also be caused by other disease processes that are common in the general population. As a result, hypercortisolism may be challenging to diagnose.1

Patient Story

pat's headshot

“My doctors kept chiding me to lose weight and exercise. I couldn’t convince them that I WAS trying to eat healthy and exercise...”

Hypercortisolism causes multisystemic dysfunction

The unusual features or comorbidities associated with hypercortisolism may be hidden in some patients.1,7,8

constellation of symptoms
constellation of symptoms

Discover who should be screened for hypercortisolism

Hypercortisolism-related physical impairments include insulin resistance, hypertension, and dysfunctional bone metabolism that may lead to osteoporosis and bone fracture.2,7,9,10

Even when the clinical signs of classically described overt Cushing syndrome are not present, patients with adrenal adenomas and less severe hypercortisolism showed an increased risk of cardiovascular events and mortality.4

Hypercortisolism tends to progress and severe hypercortisolism is probably associated with a worse outcome. It is likely that early recognition and treatment would reduce the risk of residual morbidity.1

Learn more about who should be screened for hypercortisolism

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Clinical Consequences