Cushing disease

Clinic

• Cushing's disease is one cause of Cushing's syndrome
• It is characterized by increased secretion of ACTH from the anterior pituitary (secondary hypercortisolism).
• Pituitary adenoma or Excess production of hypothalamus CRH (tertiary hypercortisolism) stimulates the synthesis of cortisol by adrenal glands.
• Pituitary adenomas are responsible for 80% of endogenous Cushing's syndrome.
• The equine version of this disease is Pituitary pars intermedia dysfunction.
• This should not be confused with ectopic Cushing syndrome or exogenous steroid use.

Signs / Symptoms

• In children, the two main symptoms are obesity and decreased linear growth.
• The most common symptoms seen in male patients are purple striae, muscle atrophy, osteoporosis, and kidney stones.

Common

• Weight gain / Buffalo Hump /Moon face Extra fat around neck
• High blood pressure
• Poor short-term memory /concentration
• Irritability / Fatigue
• Hirsutism
• Impaired immunological function
• Red, ruddy face
• Red stretch marks
• Irregular menstruation

Less common

The less-common signs and symptoms of Cushing's disease include the following:

• insomnia
• recurrent infection
• thin skin and stretch marks
• easy bruising
• weak bones
• acne
• balding (women)
• depression
• hip and shoulder weakness
• swelling of feet/legs
• diabetes mellitus
• erectile dysfunction

Causes

Too much cortisol causes Cushing syndrome, including:

• Use of glucocorticoid medications
• Pituitary tumors
• Adrenal cortical tumors
• Lung, pancreas, thyroid and thymus tumors.
• Ectopic ACTH syndrome happens when tumors that develop outside of the pituitary gland produce ACTH. These types of tumors are typically malignant. The most common type is small cell lung cancer.

Pseudo Cushing's syndrome

• Also known as non-neoplastic hypercortisolism
• It is a medical condition in which patients display Signs/ Symptoms and abnormal cortisol levels seen in Cushing's syndrome.
• However, pseudo-Cushing's syndrome is not caused by a problem with the hypothalamic-pituitary-adrenal axis as Cushing's is
• It is mainly an idiopathic condition
• A cushingoid appearance is sometimes linked to excessive alcohol consumption.
• Elevated levels of total cortisol can also be due to estrogen found in oral contraceptive pills that contain a mixture of estrogen and progesterone.
• Estrogen can cause an increase of cortisol-binding globulin and thereby cause the total cortisol level to be elevated.

Diagnosis

• Levels of cortisol and ACTH both elevated
• 24-hour urinary cortisol levels elevated
• Dexamethasone suppression test
• Late night salivary cortisol (LNSC)
• Loss of diurnal variation in cortisol levels (seen only in true Cushing's Syndrome)
• High mean corpuscular volume and gamma-glutamyl transferase may be clues to alcoholism

Differential diagnosis

• Alternative causes of Cushing's should be excluded with imaging of lungs, adrenal glands, and pituitary gland; these often appear normal in Cushing's
• In the alcoholic patient with pseudo-Cushing's, admission to hospital (and avoidance of alcohol) will result in normal midnight cortisol levels within five days, excluding Cushing's
• Another cause for Cushing's syndrome is adrenocortical carcinoma. This is a rare form of cancer with an incidence of 1-2 per million people annually. About 60% of these cancers produce hormones, with cortisol being the most frequent. Most patients present in an advanced disease state and the outcome is dismal.
• PCOS may have similar symptoms
• CFS