Skip to main content

Saturn Medic

Clinical Subject Page

Cushing Syndrome

Cushing Syndrome is a clinical disorder caused by prolonged exposure to excessive glucocorticoids, either from exogenous corticosteroid therapy or endogenous overproduction of cortisol

Also called

Hypercortisolism

ICD-10

E24.9

Specialty

Endocrine

Onset

Chronic

Reviewed

August 2026

On This Page

Overview

    • Cushing Syndrome results from prolonged exposure to excessive cortisol.
    • The most common overall cause is exogenous glucocorticoid therapy.

    -Endogenous Cushing Syndrome may be:

     

    -ACTH-dependent

    • Pituitary ACTH-secreting adenoma — Cushing Disease
    • Ectopic ACTH secretion

    -ACTH-independent

    • Adrenal cortisol-producing adenoma
    • Adrenal carcinoma
    • Bilateral adrenal disorders 

Etiology & Risk Factors

-Etiology

–Exogenous Cushing Syndrome:

The most common cause overall is prolonged use of glucocorticoids, such as:

  • Prednisolone
  • Dexamethasone
  • Hydrocortisone

–Endogenous Cushing Syndrome:

ACTH-dependent

  • Pituitary ACTH-secreting adenoma — Cushing Disease
  • Ectopic ACTH secretion, commonly from neuroendocrine tumors such as small-cell lung cancer
  • Rarely ectopic corticotropin-releasing hormone (CRH) secretion

ACTH-independent

  • Adrenal cortisol-producing adenoma
  • Adrenal carcinoma

 

-Risk Factors:

  • Long-term glucocorticoid therapy
  • Pituitary adenoma
  • Adrenal tumors
  • Ectopic ACTH-producing tumors
  • Certain inherited endocrine tumor syndromes

Pathophysiology

Excess glucocorticoid exposure → prolonged cortisol action → increased gluconeogenesis + insulin resistance + protein catabolism + altered fat distribution + mineralocorticoid effects → central obesity + hyperglycemia + proximal muscle weakness + thin skin/easy bruising + hypertension + other systemic manifestations

 

For endogenous disease:

Pituitary ACTH adenoma → increased ACTH → bilateral adrenal cortisol production → hypercortisolism → Cushing Disease

Clinical Presentation

-Symptoms:

  • Weight gain
  • Fatigue
  • Muscle weakness
  • Easy bruising
  • Mood changes
  • Depression
  • Anxiety
  • Irritability
  • Difficulty concentrating
  • Headache
  • Menstrual irregularities
  • Reduced libido

-Signs:

  • Central obesity
  • Rounded “moon face”
  • Facial plethora
  • Dorsocervical fat accumulation (buffalo hump)
  • Thin skin
  • Easy bruising
  • Proximal muscle weakness
  • Acne
  • Hirsutism

History Taking

-Ask about:

  • Weight gain and distribution of weight
  • Changes in facial appearance
  • Easy bruising
  • Skin changes
  • Purple abdominal striae
  • Muscle weakness
  • Difficulty climbing stairs or rising from a chair
  • Hypertension
  • Menstrual irregularities
  • Reduced libido
  • Mood changes
  • Depression or anxiety

Physical Examination

-General Examination

  • Body mass index
  • Waist circumference
  • Blood pressure
  • Heart rate
  • Weight distribution
  • Facial appearance

 

-Look for:

  • Central obesity
  • Moon facies
  • Facial plethora
  • Dorsocervical fat pad
  • Thin skin
  • Easy bruising

 

-System-Specific Examination:

–Skin:

  • Wide violaceous striae
  • Thin skin
  • Easy bruising
  • Acne
  • Poor wound healing
  • Hyperpigmentation in some ACTH-dependent cases

 

–Musculoskeletal:

  • Proximal muscle weakness
  • Muscle wasting

 

–Endocrine:

  • Features of diabetes
  • Hirsutism
  • Menstrual abnormalities
  • Reduced sexual function

Investigations

-Biochemistry / Specific Tests

-Recommended screening tests include:

  • 24-hour urinary free cortisol
  • Late-night salivary cortisol

 

– 1 mg overnight dexamethasone suppression test

  • Usually, abnormal results should be confirmed with an appropriate additional test unless the clinical and biochemical picture is unequivocal.

 

-Additional laboratory tests

  • Serum electrolytes
  • Glucose
  • HbA1c
  • Lipid profile
  • Renal function
  • Liver function when indicated
  • Bone mineral assessment when appropriate
  • ACTH

 

-Imaging

Imaging is performed after biochemical confirmation and after determining whether the condition is ACTH-dependent or ACTH-independent.

Possible investigations include:

  • Pituitary MRI
  • Adrenal CT or MRI
  • CT/MRI of the chest or abdomen when ectopic ACTH secretion is suspected

 

-Special / Confirmatory Tests

High-Dose Dexamethasone Suppression Test

May help distinguish pituitary from ectopic ACTH production in selected cases, but it is not the preferred standalone test.

Diagnosis

1. Confirm endogenous hypercortisolism

Use one or more appropriate tests:

  • 24-hour urinary free cortisol
  • Late-night salivary cortisol
  • 1-mg overnight dexamethasone suppression test

2. Determine the cause

Measure ACTH:

-Low ACTH → ACTH-independent → investigate adrenal source

-Normal/high ACTH → ACTH-dependent → distinguish pituitary Cushing Disease from ectopic ACTH secretion

Home / Home / Clinical Cases / Endocrine System Clinical Cases / Cushing Syndrome
Related Topics

Management

1. Definitive Treatment

Treatment depends on the cause.

-Cushing Disease

  • Transsphenoidal resection of the pituitary adenoma is generally first-line treatment.

 

-Adrenal Cushing Syndrome

  • Surgical removal of the cortisol-producing adrenal tumor is generally definitive.

 

-Ectopic ACTH Syndrome

  • Identify and treat the underlying ACTH-producing tumor.

 

-Exogenous Cushing Syndrome

  • Carefully reduce glucocorticoid exposure when medically appropriate.
  • Tapering should be individualized to avoid adrenal insufficiency.

 

2. Medical Treatment

Medical therapy may be used:

  • When surgery is delayed
  • When surgery is contraindicated
  • For persistent or recurrent disease
  • As a bridge to definitive treatment

Important medications include:

-Steroidogenesis inhibitors

  • Ketoconazole
  • Metyrapone
  • Osilodrostat

These reduce cortisol synthesis.

-Glucocorticoid receptor antagonist

  • Mifepristone

Blocks cortisol action and may be useful in selected patients, particularly those with hyperglycemia.

 

3. Supportive Management

  • Control hypertension
  • Treat diabetes or hyperglycemia
  • Prevent and treat infections
  • Assess cardiovascular risk

Complications

  • Hypertension
  • Diabetes mellitus
  • Cardiovascular disease
  • Osteoporosis
  • Pathological fractures
  • Proximal muscle weakness
  • Increased infection risk
  • Venous thromboembolism
  • Psychiatric disorders
  • Menstrual irregularities
  • Infertility
  • Erectile dysfunction

Prognosis

-Prognosis depends on:

  • Cause of Cushing Syndrome
  • Duration and severity of hypercortisolism
  • Tumor size and invasiveness
  • Success of definitive treatment
  • Presence of cardiovascular and metabolic complications
  • Recurrence

Successful treatment can significantly improve metabolic, cardiovascular, and musculoskeletal abnormalities, although some complications may persist if disease was longstanding.

Key Points / Clinical Pearls

  • Cushing Syndrome is caused by prolonged exposure to excessive cortisol.
  • The most common overall cause is exogenous glucocorticoid therapy.
  • Endogenous Cushing Syndrome can be ACTH-dependent or ACTH-independent.
  • Cushing Disease specifically means pituitary ACTH excess from a corticotroph adenoma.
  • Typical features include central obesity, moon facies, facial plethora, hypertension, and proximal muscle weakness.
  • Wide violaceous striae and easy bruising are important clinical clues.
  • Children may present with weight gain and reduced linear growth.
  • Initial biochemical testing includes 24-hour urinary free cortisol, late-night salivary cortisol, or a 1-mg overnight dexamethasone suppression test.
  • Once endogenous hypercortisolism is confirmed, ACTH determines the next diagnostic pathway.
  • Low ACTH suggests an adrenal/ACTH-independent source.
  • Normal or high ACTH suggests pituitary or ectopic ACTH-dependent disease.
  • Nieman LK, Biller BMK, Findling JW, et al. The Diagnosis of Cushing's Syndrome: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2008;93(5):1526-1540. Journal of Clinical Endocrinology & Metabolism .
  • Nieman LK, Biller BMK, Findling JW, et al. Treatment of Cushing's Syndrome: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2015;100(8):2807-2831. Journal of Clinical Endocrinology & Metabolism .
  • Lacroix A, Feelders RA, Stratakis CA, Nieman LK. Cushing's syndrome. Lancet. 2015;386(9996):913-927. The Lancet .
  • Fleseriu M, Auchus R, Bancos I, et al. Consensus on Diagnosis and Management of Cushing's Disease: A Guideline Update. Lancet Diabetes Endocrinol. 2021;9(12):847-875. The Lancet Diabetes & Endocrinology .
  • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Cushing's Syndrome . National Institutes of Health.