Cushing’s Syndrome/Disease – Causes, Symptoms, Diagnosis and Treatments

Cushing’s Syndrome/Disease | American Association of Neurological Surgeons

Cushing ‘s syndrome is a disorder caused by the body ’ s exposure to an surfeit of the hormone hydrocortisone. Cortisol affects all tissues and organs in the soundbox. These effects together are known as Cushing ‘s syndrome .
Cushing ’ mho syndrome can be caused by overuse of hydrocortisone medicine, as seen in the treatment of chronic asthma or rheumatoid arthritis ( iatrogenic Cushing ’ s syndrome ), overindulgence output of hydrocortisone from a tumor in the adrenal gland gland or elsewhere in the body ( ectopic Cushing ’ s syndrome ) or a tumor of the pituitary gland secreting adrenocorticotropic hormone ( ACTH ) which stimulates the over-production of hydrocortisone from the adrenal gland ( Cushing ’ sulfur disease ) .
Cortisol is a normal hormone produced in the extinct assign of the adrenal gland glands. When functioning correctly, hydrocortisone helps the body respond to tension and variety. It mobilizes nutrients, modifies the body ‘s reaction to excitement, stimulates the liver to raise blood boodle and helps control the measure of water in the torso. Cortisol production is regulated by the ACTH produced in the pituitary gland .

Prevalence of Cushing’s Syndrome

  • An estimated 10-15 per million people are affected every year.
  • Pituitary adenomas (Cushing’s disease) account for more than 70 percent of cases in adults and about 60-70 percent of cases in children and adolescents.
  • Cushing’s syndrome most commonly affects adults ages 20-50 and is more prevalent in females, accounting for about 70 percent of all cases.

Underlying Causes

Pituitary Adenomas — Cushing’s Disease

pituitary adenomas are benign tumors of the pituitary gland that secrete increase amounts of ACTH causing excessive hydrocortisone production. Most patients have a single adenoma. First described in 1912 by neurosurgeon Harvey Cushing, MD, in his book The Pituitary Body and Its Disorders, Cushing ’ second disease is the most common lawsuit of ad-lib Cushing ’ s syndrome, accounting for 60-70 percentage of all cases .

Ectopic ACTH Syndrome

Some benign or malignant ( cancerous ) tumors that rise outside the pituitary gland can produce ACTH. This condition is known as ectopic ACTH syndrome. Lung tumors ( malignant adenoma or carcinoids ) cause more than 50 percentage of these cases. early less park types of tumors that can produce ACTH are thymomas, pancreatic isle cell tumors and medullary carcinoma of the thyroid gland .

Adrenal Tumors

An abnormality of the adrenal glands, such as an adrenal tumor, may cause Cushing ‘s syndrome. Most of these cases involve non-cancerous tumors called adrenal adenoma, which release surfeit hydrocortisone into the lineage .
Adrenocortical carcinoma, or adrenal cancers, are the least common cause of Cushing ‘s syndrome. Cancer cells secrete excess levels of several adrenal cortical hormones including hydrocortisone and adrenal androgens. Adrenocortical carcinoma much cause very senior high school hormone levels and a rapid onset of symptoms .

Familial Cushing’s Syndrome

Most cases of Cushing ‘s syndrome are not genetic. however, some individuals may develop Cushing ‘s syndrome due to an inherit tendency to develop tumors of one or more endocrine glands. In primary pigmented micronodular adrenal disease, children or young adults develop small cortisol-producing tumors of the adrenal glands. In multiple endocrine neoplasia type I ( MEN I ), hormone-secreting tumors of the parathyroid gland glands, pancreas and pituitary gland can occur. Cushing ‘s syndrome in MEN I may be due to a pituitary, ectopic or adrenal tumor .

Signs and Symptoms Associated with Cushing’s Syndrome/Disease:

  • Weight gain in face (moon face)
  • Weight gain above the collar bone (supraclavicular fat pad)
  • Weight gain on the back of neck (buffalo hump)
  • Skin changes with easy bruising in the extremities and development of purplish stretch marks (striae) particularly over the abdomen or axillary region
  • Red, round face (plethora)
  • Central obesity with weight gain centered over the chest and abdomen with thin arms and legs
  • Excessive hair growth (hirsutism) on face, neck, chest, abdomen and thighs
  • Female balding
  • Generalized weakness and fatigue
  • Blurry vision
  • Vertigo
  • Muscle weakness
  • Menstrual disorders in women (amenorrhea)
  • Decreased fertility and/or sex drive (libido)
  • Hypertension
  • Poor wound healing
  • Diabetes mellitus
  • Severe depression
  • Extreme mood swings

Diagnosis

The diagnosis of Cushing ‘s syndrome is based on clinical suspicion combined with a review of the patient ’ s medical history, physical examination and testing ground tests to help determine the being of excessive levels of hydrocortisone. A patient suspected of having Cushing ’ s syndrome must initially have an appearance indicative of excess hydrocortisone production combined with an raise 24-hour urinary body waste of hydrocortisone. In assessing the physical features of Cushing ’ s syndrome, it can much be beneficial to compare old and holocene photograph to reveal the classic changes in facial and body appearance associated with this perturb .
The following tests can help determine if there are excessive levels of cortisol being produced:

  • The 24-hour urinary cortisol test measures the amount of cortisol being produced within the urine over the course of an entire day. Levels higher than 50-100 micrograms per day in an adult suggest the presence of Cushing’s syndrome. Although the majority of patients with Cushing’s syndrome have elevated levels of cortisol, it is becoming increasingly evident that many patients with a mild case of Cushing’s syndrome may also have normal levels of cortisol resulting in several 24-hour urine collections to confirm a diagnosis.
  • The low-dose dexamethasone suppression test measures the response of the adrenal glands to ACTH and has been widely utilized for four decades. It involves taking a small dose of a cortisol-like drug, dexamethasone (1 mg), at 11 p.m., then having blood drawn to screen for cortisol the following morning. In patients without Cushing’s syndrome, the morning level of cortisol is typically very low, indicating that ACTH secretion was suppressed by the evening dose of dexamethasone. In patients with Cushing’s syndrome, the morning cortisol level will be high. It is evident that normal patients will suppress their cortisol to a very low level (1.8 mg/dl), whereas those suffering from Cushing’s syndrome will not. Using this strict criterion, this test should provide an estimated 95-97 percent diagnostic accuracy rate. However, some patients with a mild case of Cushing’s syndrome can suppress their cortisol to low levels making it difficult to fully diagnose utilizing this test.
  • The late-night salivary cortisol test is a relatively new test that checks for elevated levels of cortisol in the saliva between 11 p.m. and midnight. Cortisol secretion is usually very low late at night, but in patients with Cushing’s syndrome, the level will always be elevated during this time. Collection of saliva requires special sampling tubes; however, this is an easy test for patients to perform and can be done multiple times. Normal levels of late-night salivary cortisol virtually exclude the diagnosis of Cushing’s syndrome. When administered correctly, this test should provide an estimated 93-100 percent diagnostic accuracy rate.

After a definitive diagnosis has been made, the source must then be determined. The first step in distinguishing the underlie campaign is the measurement of ACTH. Patients with ACTH-secreting tumors will either have a normal or raised level of ACTH. In contrast, patients with an excess of adrenal hydrocortisone will have a subnormal level. Performing a high-dose dexamethasone suppression test may be helpful in this situation. This test, similar to the low-dose dexamethasone suppression test, involves taking a high dose of dexamethasone ( 8 milligram ) at 11 post meridiem then having blood draw to filmdom for the presence of hydrocortisone the following morning. In normal patients, the good morning tied of hydrocortisone will again be very first gear. Patients with pituitary tumors will besides suppress their serum hydrocortisone level, but those with adrenal tumors will maintain a senior high school horizontal surface of hydrocortisone production. A senior high school grade of hydrocortisone points to a non-pituitary beginning .
Despite the tests described above, distinguishing a pituitary from a non-pituitary ACTH-secreting tumor can be diagnostically challenging. The majority of patients with ACTH-secreting tumors have a pituitary wound that is much identical small.

The following tests are recommended:

  • Magnetic Resonance Imaging (MRI) of the pituitary gland with gadolinium enhancement is a recommended approach. When an obvious pituitary tumor (>5 mm) is identified with an MRI, further diagnostic evaluation may not be needed depending on the clinical presentation. However, about 50 percent of patients will have a “normal” MRI of the pituitary, with 10 percent having incidental tumors unrelated to ACTH production. In such cases, the MRI will not provide a definitive diagnosis and additional tests will be required.

  • Petrosal sinus sampling is a test used to distinguish the source of ACTH secretion and should only be performed after the diagnosis of Cushing’s syndrome has been confirmed. ACTH and other pituitary hormones produced in the pituitary gland enter the blood stream by drainage through veins called the inferior petrosal sinuses. To perform this procedure, a catheter is placed in both veins at the same time and blood is sampled for ACTH before and after the administration of the corticotropin-releasing hormone (CRH) and at two, five and 10 minute intervals. This invasive technique should be performed at a medical center by a medical professional with extensive experience in this procedure. When administered correctly, this test should provide an estimated 95-98 percent diagnostic accuracy rate.

Treatment of Cushing’s Syndrome

treatment of Cushing ’ s syndrome depends on the underlie induce of excess cortisol but may possibly include operating room, radiation, chemotherapy or the use of cortisol-inhibiting drugs. If the cause is iatrogenic, from long-run use of glucocorticoid hormones to treat another disorder, the doctor will gradually reduce the venereal disease of the outwardly administered steroid to the lowest dose adequate for manipulate of that disorder. Once control is established, the drug of glucocorticoid hormones may be given on alternate days to lessen side effects for the patient .

Treatment of Cushing’s Disease

Microsurgical resection of an ACTH-secreting pituitary adenoma is the optimum treatment for Cushing ’ second disease with bring around rates of 80-90 percentage if a tumor is found. Surgery is most often done through a transnasal transsphenoidal approach, which will not leave a visible scar. This type of surgery may be performed, per the surgeon ’ randomness preference, using either a minimally invasive operating microscope or with the consumption of an endoscope. overtone removal of the pituitary gland ( subtotal hypophysectomy ) may be used in patients without distinctly identifiable adenoma.

In patients to whom a remission is not obtained after surgery, the use of various medications that can inhibit cortisol production may be used, such as:

  • Ketoconazole (Nizoral)
  • Mitotane (Lysodren)
  • Metyrapone (Metopirone)
  • Mifepristone (Korlym)

These agents are not arsenic effective as operation and are considered a second–line path of discussion. In some patients who are particularly tolerant to all forms of therapy, removal of the adrenal gland glands bilaterally ( bilateral adrenalectomy ) may be considered .
Post-surgery, with successful tumor removal, the production of ACTH drops below normal. This decrease is natural and temp, and patients are prescribed a synthetic form of hydrocortisone such as hydrocortisone or prednisone to compensate this change. Most patients can discontinue refilling therapy within six to 12 months, but others may require the use of oral steroids for several years to, possibly, their life. Patients who need adrenal surgery may besides require steroid hormone substitute therapy .
One extra treatment option in patients who have failed surgical procedures or are besides senior high school risk medically to bring to operation is radiation therapy. Radiation therapy, which is administered over a six-week period to the pituitary gland, has yielded improvement in 40-50 percentage of adults and up to 85 percentage of children.

Stereotactic radiosurgery has besides been found to be an effective treatment for patients with ACTH-secreting pituitary adenoma. A late study demonstrated endocrine absolution in 54 percentage of patients and tumor-growth control in 96 percentage. however, ongoing observation is required to monitor for tumor emergence, disease recurrence, the development of new hormone deficiencies and damage to the eye pathways and brain.

Cushing’s Syndrome/Disease Resources

  • Cushing’s Help and Support
  • Cushing’s Support & Research Foundation
  • National Endocrine and Metabolic Diseases Information Service
  • Pituitary Network Association

The AANS does not endorse any treatments, procedures, products or physicians referenced in these affected role fact sheets. This information is provided as an educational service and is not intended to serve as aesculapian advice. Anyone seeking specific neurosurgical advice or aid should consult his or her neurosurgeon, or locate one in your area through the AANS ’ Find a Board-certified Neurosurgeon ” on-line creature .

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