Page 47 Complete Your CE Test Online - Click Here Incidence and etiology Cushing’s syndrome is 10 times more common in women than in men and is most often diagnosed in persons between the ages of 25 and 40. It affects 13 out of every one million people[5,6] . Cushing’s syndrome can be categorized as three types[11] : ● ● Primary: Primary Cushing’s syndrome is due to disease of the adrenal cortex. ● ● Secondary: Secondary Cushing’s syndrome is caused by hyperfunction of cells that secrete corticotropin in the anterior pituitary gland. ● ● Tertiary: Tertiary Cushing’s syndrome is due to dysfunction or injury of the hypothalamus. The majority of cases of Cushing’s syndrome (70%) are caused by excess production of corticotropin. This leads to hyperplasia (excessive cell proliferation) of the adrenal cortex[5,11] . Causes of corticotropin overproduction include[5,11,28] : ● ● Pituitary hypersecretion (Cushing’s disease) usually due to pituitary adenomas. ● ● A corticotropin-producing tumor located in another organ especially a cancerous tumor of the pancreas or bronchus. This is sometimes referred to as ectopic ACTH syndrome. ● ● Administration of synthetic glucocorticoids including glucocorticoid steroid hormones such as prednisone, which may be taken for asthma, rheumatoid arthritis, and other inflammatory diseases. The remaining 30% of patients are affected by Cushing’s syndrome that is caused by cortisol-secreting adrenal tumors that are usually benign. However, in infants, the usual cause is adrenal cancer[5,11] . Etiology alert! Rarely, Cushing’s syndrome may be due to an inherited tendency to develop tumors of one or more of the endocrine glands [28] . Complications There are a number of complications associated with Cushing’s syndrome. These complications are related to pathological effects of the disorder[5,6,11] : ● ● Lipidosis, a disorder of fat metabolism, may occur. ● ● Increased gastric secretion, pepsin production, and decreased amounts of gastric mucous can lead to the development of peptic ulcers. ● ● Increased hepatic gluconeogenesis and insulin resistance may lead to impaired glucose tolerance. ● ● Increased calcium resorption from bone can cause osteoporosis and pathological fractures. ● ● Decreased lymphocyte production, hyperglycemia, and inhibited antibody formation can lead to frequent infections and/or slow healing of wounds. ● ● Sodium and water retention contribute to the development of hypertension, which is quite common in persons with Cushing’s syndrome. Ischemic heart disease and heart failure may develop. ● ● Increased adrenal androgen production can cause menstrual problems and disturbances in sexual function. ● ● A decreased ability to cope with physical or psychological stress can lead to mental health disturbances that can range in severity from mood swings to psychosis. Signs and symptoms Cushing’s syndrome can have adverse effects on multiple body systems. Effects are directly related to the adrenocortical hormone involved[5] . Differentiation between Cushing’s syndrome and cushingoid syndrome! Differentiating between Cushing’s syndrome and cushingoid syndrome can be challenging. Chronic depression, alcoholism, and long-term treatment with corticosteroids can combine to produce cushingoid syndrome, an adverse consequence characterized by fat deposits between the shoulders and around the waist and many systemic abnormalities. Cushing’s syndrome has similar signs, but can be differentiated from cushingoid syndrome by the additional presence of hypertension, renal problems, hyperglycemia, muscle weakness, tissue wasting, and frequently changing emotional states (emotional lability)[5] . Signs and symptoms of Cushing’s syndrome can be grouped according the body system affected. ● ● Cardiovascular system: Sodium and water retention leads to hypertension, left ventricular hypertrophy, expanded blood volume, edema, weight gain, fatigue, capillary weakness stemming from protein loss, bleeding, petechiae, and ecchymosis [5,6] . ● ● Endocrine and metabolic systems: Diabetes mellitus, decreased glucose tolerance, fasting hyperglycemia, and glycosuria[5] . ● ● Gastrointestinal system: Increased gastric secretion, pepsin production, and decreased gastric mucous can cause peptic ulcer [5,11] . ● ● Immune system: Excessive levels of adrenocortical hormones can cause decreased lymphocyte production and suppressed antibody formation. This increases the likelihood of infection, slows the wound healing process, and decreases the body’s ability to withstand stress[5,6] . Cushing’s syndrome alert! Immune system suppression can mask infection, even severe infections[5] . It is important for HCPs to recognize, and to teach patients and families to recognize, even the slightest signs of infection. ● ● Integumentary system: Characteristic fat pads form above the clavicles, over the upper back (buffalo hump) on the face (moon face), and around the trunk. Arms and legs are slender because of muscle wasting. Acne and hirsutism (male patterned hair growth) are evident in females. Purplish striae are evident on the skin. The skin is thin and fragile, and scalp hair thins[5,6,11] . ● ● Musculoskeletal system: Muscle weakness because of low potassium levels is evident. Loss of muscle mass may occur. Decreased bone mineral often leads to pathologic fractures and, in children, skeletal growth retardation[5,6,11] . ● ● Renal/urologic system: Sodium and fluid retention occurs. There is increased excretion of potassium, inhibited antidiuretic hormone secretion, and formation of ureteral calculi[5] . ● ● Reproductive system: Increased androgen leads to hypertrophy of the clitoris and amenorrhea or oligomenorrhea in women. Sexual dysfunction and loss of libido may also occur[5,6] . Diagnosis Diagnosis depends on the patient’s clinical presentation and the results of various diagnostic tests. The first step in the diagnostic process is the review of signs and symptoms, especially notable being the characteristic moon face, buffalo hump, muscle weakness, and purple striae[5] . A clinical picture that suggests Cushing’s syndrome requires determination of plasma steroid levels. Plasma cortisol levels should be obtained in the morning since levels are higher in the morning and decrease gradually throughout the day. In the presence of Cushing’s syndrome cortisol levels do not fluctuate. They remain consistently elevated throughout the day. Analysis of a 24-hour urinary cortisol collection provides evidence of consistently elevated cortisol levels [5,11] . If morning plasma cortisol levels are elevated, and 24-hour urinary cortisol collection show consistent elevation, Cushing’s syndrome is considered to be likely and should be confirmed by additional testing [5,11] . Test results indicative of Cushing’s syndrome include[6,11] : ● ● Significantly elevated plasma cortisol levels. ● ● Increased blood glucose levels. ● ● Glucose intolerance. ● ● Reduced eosinophils. ● ● Hypokalemia. ● ● Elevated urinary 17-hydroxycorticoids and 17-ketogenic steroids.