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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

Evidence of autonomous cortisol secretion above diagnostic threshold criteria; however, secretion patterns are considered biochemically less severe2

Referred to as subclinical Cushing syndrome, subclinical hypercortisolism, mild Cushing syndrome, mild autonomous cortisol excess, and mild hypercortisolism

Severe Hypercortisolism

Significantly elevated autonomous cortisol secretion above diagnostic threshold criteria; secretion patterns are considered biochemically severe2

Referred to as classically described overt Cushing syndrome, Cushing syndrome, Cushing disease, and overt hypercortisolism

Clinical Presentation

Less Severe Hypercortisolism

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

Severe Hypercortisolism

Historically defined by the presence of phenotypic physical features considered highly specific to the disorder (eg, moon facies, dorsocervical fat pad/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/symptoms2,7

Severe Hypercortisolism

More commonly caused by an ACTH-dependent source, generally leading to a comparatively more rapid onset, progression, and worsening of signs/symptoms2,7

ACTH=adrenocorticotropic hormone.

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

No single sign or symptom is pathognomonic of hypercortisolism2,7,9

The unusual features or comorbidities associated with hypercortisolism may be hidden in some patients. When present, features may include (in no particular order)1,7,8:

  • Muscle weakness/Atrophy
  • Osteoporosis/Vertebral fracture
  • Dermatologic manifestations
  • Gonadal dysfunction/Menstrual irregularity
  • Clotting/Thrombosis
  • Diabetes mellitus/Insulin resistance
  • Obesity
  • Hypertension/Dyslipidemia
  • Recurrent infections
  • Insomnia/Concentration difficulties/Psychiatric or mood disturbances

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 clinical signs of classically described overt Cushing syndrome are not present, patients with adrenal adenomas and less severe hypercortisolism have an increased risk of CV events and mortality.11

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
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