Cushing’s Syndrome

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Prolonged, extensive and inapt exposure to extreme glucocorticoids gives rise to Cushing’s syndrome. These glucocorticoids include topical as well as inhaled ones. This syndrome is a hormone problem, which is also called hypercortisolism additionally happens when the body is making a great deal of cortisol. If left untreated, this syndrome will result to a considerable rate of morbidity and mortality. When its signs and symptoms are florid, its diagnosis is uncomplicated. Incidence of Cushing’s syndrome is dependent on the population being studied. Prevalence of this syndrome ranges from 0. 7 to 2. 4 million population per year (Newell-Price et al, 2006).

It is suggested by new data available that this syndrome is more common than it was formerly thought. There is a reported incidence of Cushing’s syndrome being 2% and 5% of those patients screened with type 2 diabetes; particularly those who had poor blood glucose control and had hypertension. These studies proved the diagnosis of Cushing’s syndrome not based on its clinical manifestation but based on its patient’s metabolic control improvement after the intervention of clinical measures for Cushing’s syndrome.

Roughly 1 in 500,000 and a projected 10 to 15 of every million people are affected with Cushing’s syndrome each year. Cortisol is a hormone that has a number of essential functions. It sustains the body when it is faced with physical stress. It is also the hormone responsible for preserving the blood pressure within normal limits when there is blood loss due to accidents. The body makes more cortisol during stress brought about by physical illness as well as psychological problems. This hormone is also vital in the body’s metabolism (Health Source, 2008).

The brain and pituitary gland are in charge as to how much cortisol the body makes. This hormone is particularly produced in the adrenal glands. These glands are the two small glands located on top of each kidney. Too much body’s production of cortisol may be a consequence of having a tumor (benign or malignant) in any of the glands. Widespread and frequent tumors are pituitary adenoma and adrenal adenoma. In some instances, tumors from other parts of the body may also cause an increase in the amount of cortisol that the body produced.

Oftentimes, these tumors are in the lungs, thyroid and pancreas. Although this syndrome may be brought about by the body’s increase production of it due to tumors, most incidence of this syndrome is due to an increased, extreme and lengthy consumption of cortisone medications. Cortisol has a natural anti-inflammatory function. Physicians prescribed cortisol to treat and manage diseases where inflammation is the major dilemma. These diseases include asthma, rheumatoid arthritis as well as lupus. A familiar example of a cortisol medication is prednisone.

These medications as a group are well known as corticosteroids, glucocorticoids, or steroids (Health Source, 2008). This medication is also utilized in preventing the rejection of transplanted organs. In cases like this, this medication may then be taken all throughout the particular patient’s lifetime. Signs and Symptoms of Cushing’s syndrome Being vigilant of the early signs and symptoms of Cushing’s syndrome is very important for its early detection, diagnosis and management. Recognizing its early mental manifestations and demonstrations will avert frustrations and spare patients a number of morbidity.

When typical physical signs of Cushing’s arise, patients are already suffering enormously. The following early signs of Cushing’s syndrome are as follows: being depressed, irritable (Cushing’s patients illustrates themselves as having a “short fuse”), experiences insomnia, decreased / loss of libido, complains of memory problem especially impaired short-term memory and failure to focus attention and maintain their usual concentration (Kubetin, 2000). Symptoms of Cushing’s syndrome include the presentation of a moon facie.

An increased of fat in the abdomen, trunk area and upper back also persists causing a buffalo hump look. The most distinguished physical manifestation of Cushing’s syndrome from that of obesity is the presentation of protein wasting-presence of thin skin. Patients may show skin bruising as their skin easily gets bruised. Stretch marks may be common in the abdomen, breasts and thighs. Women may experience an increased body hair and may have an irregular and even cessation of menstrual periods. Also, excess cortisol inclines to an elevated blood pressure. With this, patients may also experience high blood pressure.

Increased incidence of occult Cushing’s syndrome is found in overweight and in patients with type 2 diabetes (Fonseca, 2004). Since an increased in cortisol can cause type 2 diabetes (non-insulin dependent); symptoms of diabetes like increased and frequency of urination, tiredness and exhaustion and blurred vision may also be manifested (Chiodini et al, 2007). Purple striae, osteoporosis, muscle atrophy and kidney stones are more numerous and common in men. Male and female patients presented the same gonadal dysfunction. Decreased bone-mineral density was revealed as one of the side effects of glucocorticoid use.

Bone loss is worse in primary adrenal Cushing’s syndrome compared to the pituitary-dependent Cushing’s syndrome (Newell-Price et al, 2006). Moreover, Cushing’s syndrome attributed from production of adrenocorticotrophic hormone (ACTH) from solid tumors also causes life-threatening hypercortisolemia. These tumors may be bronchial carcinoids, lung squamous cell carcinoma or even carcinoid from the duodenum. All these tumors presented ectopic adrenocorticotropic hormone producing cortisol leading to excess cortisol in the body(Uecker & Janzow, 2005). Diagnosis of Cushing’s syndrome

Physicians (health care providers) will do a complete and thorough physical examination and history when obvious signs and symptoms of Cushing’s syndrome is presented by the patient. Signs and symptoms like: an increased blood pressure, thin skin bruises, buffalo hump look (fat in trunk and abdomen and thinning of arms and legs) and moon facie will be given a significant account. Patient will be assessed for any usage/treatment of steroid medications. There is an uncomplicated diagnosis once the patient presented the features and manifestations stated above and steroid management and therapy is being used.

If the patient is not taking any cortisol/steroid medications at all, the following tests may be crucial and necessary: skull X-ray, MRI, CT scan, 24-hr urine cortisol test, dexamethasone suppression test and midnight cortisol assessment or late-night salivary cortisol(Health Source 2008). Biochemical verification of the hypercortisolaemic state must be recognized prior to any effort of obtaining differential diagnosis. This is done to prevent any misdiagnosis leading to unsuitable treatment and poor management (Newell-Price et al, 2006).

No single test is perfect for the diagnosis of Cushing’s syndrome. Since each test has different sensitivities, the use of several tests is beneficial. The skull X-ray, MRI and CT scan are ordered to rule out tumors in the pituitary and other parts of the body. 24-hour urine cortisol test is done to verify if the body is making excessive amounts of cortisol. The binding proteins are saturated by excess circulating cortisol whereby it is then sent out in the urine as free cortisol. This is a straightforward evaluation of circulating free cortisol. This circulating free cortisol is biologically effective.

Results showing 4x greater than its upper limit of its normal value is indicative of Cushing’s syndrome. The dexamethasone suppression test is done to prove and confirm the extra cortisol produced by the body is from the pituitary tumor or a tumor existing from other part of the body. There are two tests that are commonly used: the 48-hr or the overnight dexamethasone suppression test. For the 48-h suppression test, 0. 5mg dexamethasone is given every six hours x 4 times. Serum cortisol measurement is obtained during the first and last administration of dexamethasone.

For the overnight dexamethasone test, 1mg is administered at midnight and the serum cortisol measurement is obtained the following morning. To rule out Cushing’s syndrome, the concentration of serum cortisol should not exceed 50nmol in either of the two tests mentioned above. Studies revealed that this test sometimes gives false-positive results. It is important to repeat this test as well as include other investigations if medical doubts remain high. Individuals with Cushing’s syndrome have no normal cortisol circadian rhythm. Midnight plasma cortisol concentration not exceeding 50 nmol/L rules out Cushing’s syndrome.

In addition, salivary cortisol signifies the amount of free circulating cortisol. This screening is greatly appropriate due to its effortless collection of sample. Saliva is also stable in room temperature thus making it more suitable screening method. This test had been proven to be a good screening method based on its non-invasiveness and diagnostic performance (Cardoso et al, 2009). Once a diagnosis is established, apt initiation of medication therapy should then be made. The treatment and management of Cushing’s syndrome is dependent on the amount of extra cortisol in the body.

Treatment of Cushing’s syndrome If the cause of the extra cortisol in the body is just due to the administration of cortisol medications, the physician may just lower the dosage of cortisol taken. In other cases, physicians may change the frequency of treatment. Every day dose may then be changed to every other day. If the body itself is making the excess cortisol, treatment includes medical therapy to lower cortisol and may also require surgery, chemotherapy and radiation to remove and treat the tumor. Medications like Metyrapone, Ketoconazole and Mitotane are prescribed to lower cortisol .

The mechanism of action of these medications directly inhibits the synthesis and secretion of cortisol in the adrenal glands. These drugs may not be as efficient for long-term management of the syndrome. These medications are prescribed primarily as a preparation prior to the upcoming surgical procedure or as an adjunctive management post surgery (Newell-Price et al, 2006). Transsphenoidal surgery is done to remove the tumor from the pituitary gland without harming the pituitary function. Its results showed 60% to 80% of initial remission rate.

If the disease persists, urgent reoperation is conducted. Ongoing requirement of alternative therapies are needed, as this procedure does not promise possible recurrences. Pituitary radiotherapy may then be required for persistent hypercortisolism after transsphenoidal surgery. The existing treatment of choice for Cushing’s syndrome is laparoscopic surgery for unilateral adrenal adenomas. The prognosis of this procedure is good, however, the results are uniformly unfortunate for patients with adrenocortical carcinomas. Adrenocortical carcinomas occasionally present metastases.

Patients are also given a five-year survival duration. In addition, total bilateral removal of the adrenal glands produces rapid and great results in decreasing the clinical manifestations of patients. However, patients requiring a unilateral removal of the adrenal glands have the most excellent recorded results (Poulin et al, 2003). The need for a lifetime therapy of corticosteroids and glucocorticoids will be needed after the removal of both adrenal glands. Laparoscopic adrenal procedures give low morbidity that’s why this is considered as the main treatment for patients with Cushing’s syndrome.

Some clinicians promote pituitary radiotherapy together with adrenalectomy to decrease the risk of Cushing’s syndrome. Prevention of Cushing’s syndrome It is really important to seek medical attention right away if one is taking steroid medications and are showing signs and symptoms of Cushing’s syndrome. Blood pressure as well as blood sugar levels should also be checked regularly. Individuals should be knowledgeable in terms of the medications they are taking and its side effects. The use of non-steroidal medications in managing inflammatory diseases should be given priority first prior to the use of steroids.

References Cardoso, E. M. L. , Aggreger, A. L. , Tumilasci, O. , R. & Contreras, L. N. (2009). Diagnostic value of salivary cortisol in Cushing’s syndrome. Endocrinology 70. 4, p516. Chiodini, I. , Adda, G. , Scillitani, A. & Coletti, F. (2007). Cortisol secretion in patients with type 2 diabetes: relationship with chronic complications. Diabetes Care, 30, 83. Fonseca, V. , (2004). Occult Cushing’s syndrome. Diabetes Care, 27:5, 1253. Health Source – Consumer edition. (1 January 2008). Cushing’s syndrome. Kubetin, S. K. (2000). Early signs of Cushing’s.

OB GYN News. International Medical News Group. Newell-Price, J. , Bertagna, X. , Grossman, A. & Nieman, L. K. (2006). Cushing’s syndrome. The Lancet, 367, 1605. Poulin, E. C. , Schlachta, C. M. , Burpee, S. E. , Pace, K. T. & Mamazza, J. (2003). Laparoscopic adrenalectomy: pathologic features determine outcome. Canadian Journal of Surgery, 46, 340-345. Uecker, J. M. & Janzow, M. T. (2005). A case of Cushing syndrome secondary to ectopic adrenocorticotropic hormone producing carcinoid of duodenum. The American Surgeon, 71, 445-446.

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