Coupon Accepted Successfully!


Cushing’s Syndrome



The adrenal cortex produces steroids:

  1. Glucocorticoids (eg cortisol)             
  2. Mineralocorticoids                
  3. Androgens

Cushing's syndrome:

  1. This is chronic glucocorticoid excess.  
  2. The commonest cause is exogenous steroid treatment.
  3. Endogenous causes are much rarer   
  4. 85% are due to ACTH, of these a pituitary adenoma (Cushing's disease) is the commonest cause. 

Causes of Cushing Syndrome

  1. ACTH-dependent causes: ( ACTH)
    1. Cushing's disease Bilateral adrenal hyperplasia due to an ACTH secreting pituitary adenoma
    2. Ectopic ACTH production Especially small cell lung cancer and carcinoid tumors Q), Pancrease Ca, bronchial adenoma.
  2. ACTH-independent causes: (ACTH due to -ve feedback).
    1. Iatrogenic Pharmacological doses of steroids (most common cause of cushing).
    2. Adrenal adenoma or carcinoma may be associated with abdominal pain and virilization in women
    3. Adrenal nodular hyperplasia 

The most common histopathologic classification of adrenocortial co is the Weiss score.


Summary of Causes (Ref. Hari. 18th ed., Pg- 2945)

Cause Serum ACTH Diagnosis   Rx
Iatrogenic Reduce History Reduce dose
Pituitary adenoma Raise CT (Head)  Surgery
Ectopic ACTH secreting tumor Raise CT (Chest) Surgery
Adrenal adenoma / Ca     Reduce CT abdomen Surgery


Extra Edge:

  1. Adrenal adenoma has size less than 6cm and adrenal carcinoma has size more than 6 cm.
  2. Loss of diurnal variation of steroid hormones in the body is the first feature of Cushing syndrome.

Features of Cushing’s syndrome

  1. Symptoms due to excess of glucocorticoid
    1. The loss of proteins from the muscle in particular causes severe weakness of proximal muscles (Proximal myopathy)
    2. The protein collagen fibres in the subcutaneous tissue are diminished so that the subcutaneous tissue tear easily resulting in development of large purplish striae where they have torn apart.
    3. Elevated blood glucose concentration. Insulin resistance can occur
    4. Mobilization of fat from the lower part of the body with concomitant extra deposition of fat in the thoracic and upper abdominal regions (Centripetal obesity) giving rise to a buffalo torso. The excess secretion of steroid also leads to an edematous appearance of the face. ("moon facies"). 
  2. Symptoms due to excess of mineralocorticoid
    1. Salt and water retention leads to sustained hypertension.
    2. Significant K+ depletion (Hypokalemia) 

Note: Episodic hypertension occurs in pheochromocytoma

  1. Symptoms due to excess of androgen
    1. Hirsutism
    2. Facial acne
    3. Oligomenorrhea
    4. Amenorrhea
  2. Other Symptoms
    1. Psychosis, insomnia, euphoria
    2. Osteoporosis



Investigation of Suspected Cushing’s syndrome­

  1. The diagnosis of Cushing's syndrome depends on the demonstration of increased cortisol production and failure to suppress cortisol secretion normally when dexamethasone is administered.
  2. Once the diagnosis is established, further testing is designed to determine the etiology.
  3. Confirm the diagnosis (a raised cortisol) & then localize the source on the basis of laboratory testing. (Ref. Hari. 18th ed, .Fig, 342.9, Pg- 2947)

Recent advances: New algorithm for diagnosis of Cushing syndrome.

: The diagnosis of Cushing’s syndrome depends on the demonstration of increased cortisol production and failure to suppress.

  1. Increase 24h urinary free cortisol
  2. Dexamethasone (DM) suppression test
    1. Low dose DM suppression test is done to differentiate between Cushing syndrome and simple obesity. 
    2. High dose suppression test is done to differentiate between Cushing syndrome due to pituitary adenoma and ectopic secretion of ACTH

Table - Treatment Modalities for Patients with Adrenal Hyperplasia Secondary to Pituitary ACTH Hypersecretion (Ref. Hari. 18th ed., Pg - 2948)

  1. Treatments to reduce pituitary ACTH production
    1. Transsphenoidal resection of microadenoma
    2. Radiation therapy
  2. Treatments to reduce or eliminate adrenocortical cortisol secretion
    1. Bilateral adrenalectomy
    2. Medical adrenalectomy:- i.e. Drugs used to reduce steroid synthesis. 
      1. Metyrapone
      2. Mitotane
      3. Aminoglutethimide
      4. Ketoconazole  
      5. Mifepristone
      6. Trilostane
      7. Cyproheptadine
      8. Etomidate.


Extra Edge:
  1. Mifepristone is a synthetic steroid compound. It is a progesterone receptor antagonist used as an abortifacient in the first months of pregnancy, and in smaller doses as an emergency contraceptive. Mifepristone is also a powerful glucocorticoid receptor antagonist, is used in refractory Cushing's Syndrome (due to ectopic/neoplastic ACTH/Cortisol secretion).
  2. Recent Advances: Mifepristone  have been approved for the control of hyperglycemia in adults with endogenous Cushing’s syndrome.

Pseudo Cushing’s syndrome

  1. Some patient resemble like Cushing’s syndrome (Pseudo Cushing syndrome).
  2. These are patient with obesity, chronic alcoholism, depression and acute illness of any type.


  1. Many incidental masses (so called incidentalomas) are discovered during radiographic testing for another condition, rather than testing performed because of suspected adrenal disorder.
  2. Many of them turn out to be adrenocortical adenoma. Especially in the patient above the age of 30 yrs. 
Nelson Syndrome:
  1. It is the rapid enlargement of a pituitary adenoma that occurs after the removal of both adrenal glands.
  2. Most aggressive growing pituitary tumor.
  3. Removal of both adrenals eliminates production of cortisol, and the lack of cortisol ‘s negative feedback can allow any preexisting pituitary adenoma to grow unchecked.
  4. Continued growth can cause mass effects due to physical compression of brain tissue, along with increased production of  ACTH and  MSH.
  5. Very high serum ACTH (> 100 micro gram/ml) causing hyperpigmentation and due to mass effect causes headache. It can invade cavernous sinus. 
  6. Treatment of Nelson Syndrome: Pituitary surgery is performed in some cases. The risk can also be minimized by pituitary irradiation.

Test Your Skills Now!
Take a Quiz now
Reviewer Name