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Original Editors - Jessica Stevenson from Bellarmine University's Pathophysiology of Complex Patient Problems project. Cushing’s syndrome is a general term for increased secretion of cortisol by the adrenal cortex. Females are eight times more likely than males to develop hypercortisolism from a pituitary tumor and three times more likely to develop a cortisol-secreting adrenal tumor: However, hormone-producing lung tumors that cause hypercortisolism are more common in males. Non-iatrogenic Cushing’s syndrome occurs mainly in women, with an average age of onset of 20 to 40 years, although it can be seen in people up to age 60 years. Clinical manifestations include “moon” face (very round), buffalo hump (truncal obesity with prominent supraclavicular and dorsal cervical fat pads) [4], protuberant abdomen with accumulation of fatty tissue and stretch marks with purple striae, muscle wasting and weakness, thin extremities, decreased bone density (especially spine), kyphosis and back pain (secondary to bone loss), easy bruising and poor wound healing due to thin and atrophic skin [4], acne, psychiatric or emotional disturbances, impaired reproductive function (decreased libido and changes in menstrual cycle, and diabetes mellitus.
Cushing’s syndrome involves the HPA axis causing excess cortisol release from the adrenal glands. Initially, the patient’s general condition should be supported by high protein intake and appropriate administration of vitamin K. If the results of these tests are indeterminate, the patient is hospitalized for measurement of serum cortisol at midnight, which is more likely to be conclusive. Pituitary imaging is done if ACTH levels and provocative tests suggest a pituitary cause; gadolinium-enhanced MRI is most accurate, but some microadenomas are visible on CT.
X-rays or DEXA scans may be needed to assess for fractures or to rule out osteopenia or osteoporosis, respectively. In children with Cushing’s disease, pituitary tumors are very small and usually cannot be detected with MRI. ACTH-dependent Cushing’s syndrome may result from hypersecretion of ACTH by the pituitary gland, secretion of ACTH by a nonpituitary tumor, such as small cell carcinoma of the lung or a carcinoid tumor (ectopic ACTH syndrome), or administration of exogenous ACTH. ACTH-independent Cushing’s syndrome usually results from therapeutic administration of corticosteroids or from adrenal adenomas or carcinomas. Pseudo-Cushing’s syndrome occurs when conditions such as depression, alcoholism, estrogen therapy, or eating disorders cause changes similar to those of Cushing’s syndrome. Treatment to restore hormone balance and reverse Cushing’s syndrome or disease may require radiation, drug therapy, or surgery, depending on underlying cause (e.g.
Pituitary tumors that produce excessive ACTH are removed surgical or extirpated with radiation.
Bilateral adrenalectomy is reserved for patients with pituitary hyperadrenocorticism who do not respond to both pituitary exploration (with possible adenomectomy) and irradiation. Therapists are more likely to treat people who have developed medication-induced Cushing’s syndrome. Because cortisol suppresses the inflammatory response of the body, it can mask early signs of infection.
Differential diagnoses for Cushing’s syndrome are obesity, diabetes, polycystic ovarian syndrome, other metabolic and endocrine problems. Differentiation of Cushing syndrome from pseudo–Cushing syndrome can sometimes be a challenge.
In patients who chronically abuse alcohol, clinical and biochemical findings suggestive of Cushing syndrome are often encountered.
Patients with depression often have perturbation of the HPA axis, with abnormal cortisol hypersecretion. Learn about the shoulder in this month's Physiopedia Plus learn topic with 5 chapters from textbooks such as Magee's Orthopedic Physical Assessment, 2014 & Donatelli's Physical therapy of the shoulder 2012.
The American College of Chest Physicians offers this lesson as a review of a previously offered self-study program. Part 2: Recommendations for Hypertension Treatment 2012 Canadian Hypertension Education Program Recommendations. 2012 Canadian Hypertension Education Program (CHEP) A red flag has been posted where recommendations were updated for 2012.

Key CHEP Messages for the Management of Hypertension 1.Assess blood pressure at all appropriate visits. 2012 Canadian Hypertension Education Program (CHEP) Important messages from past recommendations High dietary sodium is estimated to increase blood pressure in the Canadian population to the extent that 1,000,000 Canadians meet the diagnostic criteria for hypertension who would otherwise have normal blood pressure Most of the sodium in Canadian diets comes from processed foods and restaurants. Lifestyle Recommendations for Hypertension: Weight Loss Height, weight, and waist circumference (WC) should be measured and body mass index (BMI) calculated for all adults. Lifestyle Recommendations for Hypertension: Stress Management Hypertensive patients in whom stress appears to be an important issue Individualized cognitive behavioural interventions are more likely to be effective when relaxation techniques are employed.
Epidemiologic impact on mortality of blood pressure reduction in the population Reduction in SBP (mmHg) % Reduction in Mortality StrokeCHDTotal 2-6-4-3 3-8-5-4 5-14-9-7 Adapted from Whelton, PK et al. In women, masculinizing effects such as hypertrichosis, breast atrophy, voice changes, and other signs of virilism are noted.
When the normal function of the glucocorticoids becomes exaggerated, a wide range of physiologic responses can be triggered.
These tests may be conducted to obtain a baseline measurement of bone density or they may be obtained in response to an individual’s report of musculoskeletal symptoms such as bone pain or backache. Rare causes include primary pigmented nodular adrenal dysplasia (usually in adolescents) and macronodular dysplasia (in older patients).
Cortisol has a key role in glucose metabolism and a lesser part in protein, carbohydrate, and fat metabolism.
If these medications are stopped suddenly rather than reduced gradually, the atrophied adrenal gland will not be able to provide the cortisol necessary for physiologic needs. If no tumor is demonstrated on imaging but a pituitary source is likely, total hypophysectomy may be attempted, particularly in older patients. Patients must receive cortisol during the surgical and postoperative periods because their nontumorous adrenal cortex will be atrophic and suppressed.
This condition occurs after these individuals have received a large dose of cortisol (also known as hydrocortisone) or cortisol derivitives. Any unexplained fever without other symptoms should be a warning to the physical therapist of the need for medical follow-up.
To maintain muscle and bone mass, weight-bearing exercises such as push-ups, sit-ups, or lifting weights are helpful.
A pseudo-Cushing state is defined as having some of the clinical features and biochemical evidence of Cushing syndrome. Discontinuation of alcohol causes disappearance of these abnormalities, and, therefore, this syndrome is often specifically referred to as alcohol-induced pseudo-Cushing syndrome.
Physiopedia is not a substitute for professional advice or expert medical services from a qualified healthcare provider. 2.Maintaining a healthy lifestyle and weight lowers blood pressure and prevents hypertension. Considerations Regarding the Choice of First-Line Therapy Use caution in initiating therapy with 2 drugs in whom adverse events are more likely (e.g. A more specific but equally sensitive test is to give dexamethasone 0.5 mg po q 6 h for 2 days (low dose).
Patients with Cushing’s syndrome occasionally have a normal morning cortisol level but lack normal diurnal decline in cortisol production, such that midnight plasma cortisol levels are above normal and the total 24-hr cortisol production is elevated. If ACTH is detectable (ACTH-dependent Cushing’s syndrome), provocative tests help differentiate Cushing’s disease from ectopic ACTH syndrome, which is rarer. Cortisol also helps maintain blood pressure and cardiovascular function while reducing the body’s inflammatory responses. Marked weakness of the quadriceps muscle often prevents affected people from rising out of a chair unassisted.
A life-threatening situation known as acute adrenal insufficiency can develop, requiring emergency cortisol replacement.

For individuals with muscle wasting or at risk for muscle atrophy, a high-protein diet may be prescribed. Younger patients usually receive supervoltage irradiation of the pituitary, delivering 45 Gy. Exogenous steroids are administered for a number of inflammatory and other disorders such as asthma or rheumatoid arthritis.
However, resolution of the primary condition results in disappearance of the cushingoid features and biochemical abnormalities. Because excess glucocorticoids can lead to emotional liability and depression, distinguishing between depression and mild Cushing syndrome is often a diagnostic challenge. Promote: smoking cessation, healthy diet reducing dietary sodium and increased physical activity. Health care professionals need to be aware of this important care gap and recommend pharmacotherapy. Measures of cortisol production may be unreliable, and severe hypercholesterolemia may develop. A patient with suspected Cushing’s syndrome with grossly elevated UFC (> 4 times the upper limit of normal) almost certainly has Cushing’s syndrome. In general, a clear failure to suppress levels in response to low-dose dexamethasone establishes the diagnosis. Alternatively, salivary cortisol samples may be collected and stored in the refrigerator at home. In response to high-dose dexamethasone (2 mg po q 6 h for 48 h), the 9 AM serum cortisol falls by > 50% in most patients with Cushing’s disease but infrequently in those with ectopic ACTH syndrome. Overproduction of cortisol causes liberation of amino acids from muscle tissue with resultant weakning of protein structures (specifically muscle and elastic tissue).
ACE inhibitors, renin inhibitors and ARBs are contraindicated in pregnancy and caution is required in prescribing to women of child bearing potential. Plasma cortisol may be spuriously elevated in patients with congenital increases of corticosteroid-binding globulinor in those receiving estrogen therapy, but diurnal variation is normal in these patients. However, in children, irradiation may reduce secretion of growth hormone and occasionally cause precocious puberty. Beta blockers are not recommended as first line therapy for patients age 60 and over without another compelling indication.
In special centers, heavy particle beam irradiation, providing about 100 Gy, is often successful, as is a single focused beam of radiation therapy given as a single dose-radiosurgery.
Diuretic-induced hypokalemia should be avoided through the use of potassium sparing agents if required. Response to irradiation occasionally requires several years, but response is more rapid in children. The use of dual therapy with an ACE inhibitor and an ARB should only be considered in selected and closely monitored people with advanced heart failure or proteinuric nephropathy. Sometimes ACTH-secreting tumors respond to long-acting somatostatin analogs, although administration for > 2 years requires close follow-up, because mild gastritis, gall stones, cholangitis, and malabsorption may develop. ACE-inhibitors are not recommended (as monotherapy) for black patients without another compelling indication.

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