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Cushing's Syndrome


What is Cushing's syndrome?
Cushing's syndrome is the result of the excessive production of corticosteroids by the adrenal glands. An overproduction of corticotropin (ACTH) - the hormone that controls the adrenal gland - by the pituitary gland, which stimulates the adrenal glands to produce corticosteroids, may be one cause. It is called Cushing's disease and the result of ACTH-secreting pituitary adenoma. Alt. In addition, certain lung cancers and other tumors outside the pituitary gland may produce corticotropins. Other causes include benign or cancerous tumors on the adrenal glands.

What are the symptoms of Cushing's syndrome?

Cushing’s disease or syndrome is often associated with significant morbidities, such as diabetes mellitus, cardiovascular disease, osteoporosis, reduced quality of life, and increased mortality.

The following are the most common symptoms. However, each individual may experience symptoms differently. Symptoms may include:

  • upper body obesity
  • round face
  • increased fat around neck
  • thinning arms and legs
  • fragile and thin skin
  • stretch marks on abdomen, thighs, buttocks, arms, and breasts
  • bone and muscle weakness
  • severe fatigue
  • high blood pressure
  • high blood sugar
  • irritability and anxiety
  • excess hair growth in women
  • irregular or stopped menstrual cycles in women
  • reduced sex drive and fertility in men

How is Cushing's syndrome diagnosed?

In addition to a complete medical history and medical examination, diagnostic procedures for Cushing's syndrome may include:

For the initial testing for Cushing’s syndrome, Endocrine Society guideline has recommend one of the following tests based on its suitability for a given patient:
1. Urine free cortisol (UFC; at least two measurements)
2. Late-night salivary cortisol (two measurements)
3. 1-mg overnight dexamethasone suppression test (DST)
4. Longer low-dose DST (2 mg/d for 48 h)

Figure 1. Appearance of the patient with Cushing’s syndrome

Figure 2.

Additional testing may include:

  • 24-hour urinary test to measure for corticosteroid hormones
  • blood test for ACTH level
  • dexamethasone suppression test - to differentiate whether the excess production of corticotropins are from the pituitary gland, brain (pituitary) tumor, or tumors elsewhere
  • corticotropin-releasing hormone (CRH) stimulation test - to differentiate whether the cause is a pituitary tumor or an adrenal tumor
  • computed tomography (CT scan) - a non-invasive procedure that takes cross-sectional images of the abdomen and brain or other internal organs;
  • magnetic resonance imaging (MRI) - a non-invasive procedure that produces two-dimensional views of an internal organ or structure, especially the adrenal gland and brain

For more detailed information the Endocrine Society has developed clinical guideline for diagnosis of Cushing's Syndrome "The Diagnosis of Cushing's Syndrome"

(First published in the Journal of Clinical Endocrinology & Metabolism, May 2008, 93(5):1526–1540)

Treatment for Cushing's syndrome:

Transsphenoidal adenomectomy (surgical removal of pituitary tumor) is generally considered the first-line treatment for patients with Cushing’s disease. Treatment for Cushing's syndrome depends on its cause and is mostly surgical. Surgery is indicated to remove adrenal gland(s) with tumor(s). Other treatment may include radiation, chemotherapy, and use of certain hormone-inhibiting drugs

New Options in the Medical Management of Cushing's Disease:

Management of persistent Cushing's Disease is challenging. Radiotherapy is frequently employed as a second-line treatment option. Adrenocortical steroidogenesis inhibitors (ketoconazole, metyrapone) and the dopamine-receptor agonist cabergoline have been used in clinical practice. New group of medications, called the glucocorticoid receptor antagonist mifepristone (Korlym™) and the somatostatin-receptor ligand pasireotide (Signifor®), may be a more attractive option for most patients due to its action at the underlying tumor and the ability to monitor biochemical responses. However, mifepristone may be more appropriate when it is necessary to avoid or minimize risk for hyperglycemia-related complications. (P. Cohan. Pasireotide and Mifepristone in Cushing’s Disease, Endocr Pract. 2014;20(No. 1)