Exogenous Cushing�s Syndrome
As its name implies, the source of increased corticoids in the advent of exogenous syndrome is externally administered steroids. �Excess exogenous corticosteroid can result from steroid treatment for asthma and inflammatory processes, such as polymyositis, connective tissue disorders, and rheumatoid arthritis.� (Lim) Cushing�s syndrome secondary to administration of corticosteroids is the most common of all types of Cushing�s. (Adler; DeGroot 1747)
Following administration of corticosteroids, the feedback loop of the HPA axis is inactivated at the hypothalamus level and the hypothalamus stops releasing CRH, as the pituitary stops releasing ACTH. The adrenals therefore drop their output of glucocorticoids, but the glucocorticoids are still being administered to the body, tossing the HPA axis into a shift towards inactivity. Sudden withdrawal from or cessation of corticosteroid therapy in this case after about 30 days will result in a period of reduction or absence of glucocorticoids from systemic circulation. The result may be mild occurrence similar to Addison�s, or may result in a full-blown adrenal crisis.
The less common of endogenous Cushing�s syndrome is known as Cushing�s disease, proper. The categorization of �disease� implies that the source of the ACTH excess is an adenoma on the Pituitary gland. (Merck 107; Ferris 244) The increased mass of the pituitary may contain cells that are specialized in the production of ACTH. In spite of feedback from the negative loop of the HPA axis, the cells continue to secrete ACTH, causing continual stimulation of the adrenal cortex to release glucocorticoids and mineralocorticoids into the bloodstream, with any combination of the effects discussed in the first part of this paper.
Non-pituitary growths that secrete ACTH may be located in the lungs, bronchi, or other tissue differentiated from the same stem cells which differentiate into pituitary ACTH secreting cells. Regardless of their location, they continue to secrete ACTH, apart from the influence of the HPA axis and its feedback loop. The result is a chronic, long-term elevation of systemic levels of glucocorticoids, as the adrenal cortex continues to be stimulated by the presence of the ACTH to produce and release stores of cortisol. As one might imagine, the adrenal glands are typically found by MRI to be hypertrophied, due to their prolonged duration of stimulation and increased workload. (DeGroot 1746)
In the final type of endogenous Cushing�s, the adrenal glands themselves may have actively-secreting tumors, which cause the overproduction of mineralocorticoids and glucocorticoids. In this instance, the adrenals produce cortisol independent of stimulation by ACTH from the pituitary gland. The negative feedback cycle again is bypassed in this setting, (DeGroot 1746) but the ultimate outcome is the same with regard to increased systemic levels of cortisol.
Diagnostic tools for the differentiation of Cushing�s syndrome include magnetic resonance imaging of the pituitary, lower respiratory tract, and adrenal glands. This is an expensive process, however. Therefore, initial evaluation will include less costly approaches. Of considerable diagnostic value is evaluation of fluctuations in urinary cortisol levels during a 24 hour period to compare levels against normal diurnal variation levels in the healthy mean. If deviations from normal are detected, then the physician may choose to proceed with a dexamethasone suppression test. (DeGroot 1645; Ferris 245) As indicated above, dexamethasone will suppress activity of ACTH-secreting pituitary tissue, thus inducing a lowering of cortisol levels by manipulation of the HPA axis. In the event that the increased cortisol is occurring secondary to an adrenal growth, the dexamthasone suppression test will have no effect on increased levels of cortisol.
Treatment and Cure
Diagnosis of Cushing�s syndrome may be missed for months or years, unless the patient is presenting with multiple obvious signs and symptoms of the disorder. Unfortunately, this gives any malignant growths a period during which to grow and possibly metastasize. This could be the case if the patient�s presenting complaint suggests idiopathic conditions such as Type II Diabetes Mellitus, hypertension, or renal insufficiency, any of which may occur for reasons other than Cushing�s syndrome, per se. A strong indication to the medical professional as to an etiology of primary hypercortisolism would naturally be a pharmacological regimen of corticosteroids for any of a range of other medical conditions. In these cases, the clinical clues lend themselves to an earlier intervention and correction. However, in the case of endogenous Cushing�s, the cause of hypercortisolism may go undetected until such time as the symptoms begin to interfere with the patient�s quality of life. At that point, tissue and organ damage may be more widespread, as the cause of the condition continues to inflict damage to the organism.
The definitive treatment of Cushing�s syndrome is dependent on the root cause of hypercortisolism. The treatment of exogenous Cushing�s syndrome will include discontinued glucocorticoid ingestion. �A weaning schedule should be followed�for the patient in whom (steroid therapy) cannot be discontinued, a change in dose or schedule may ameliorate symptoms.� (DeGroot 1762). If the cause of increased serum cortisol is a pituitary adenoma, then treatment is aimed at removal of the malignancy through trans-sphenoidal surgical resection of the pituitary tumor. (Adler) If the cause is an ectopic, non-pituitary, ACTH-secreting adenoma, then cure is aimed at removal of the tumor in combination with radiation and/or chemotherapy (Adler), which will come with its own set of symptoms and side effects.