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Cushing's Disease

Cushing's Syndrome

Cushing's disease is caused by prolonged exposure to inappropriately high levels of the hormone cortisol due to increased secretion of adrenocorticotropic hormone. Common symptoms include weight gain, skin changes, hyperhidrosis, infertility, hirsutism, amenorrhea, muscle weakness and psychological problems.

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Presentation

The following signs and symptoms are common:

Easy Bruising
  • Signs and symptoms of Cushing’s syndrome COMMON FEATURES LESS COMMON FEATURES Weight gain Insomnia Hypertension Recurrent infection Poor short-term memory Thin skin and stretch marks Irritability Easy bruising Excess hair growth (women) Depression Red[pituitarysociety.org]
  • Too much cortisol can lead to Cushing’s syndrome, causing symptoms including: Weight gain in the neck, face and upper body Flushing in the face Easy bruising Purple stretch marks on the stomach Diabetes High blood pressure Osteoporosis Excess facial hair[froedtert.com]
  • Excessive cortisol production causes: Weight gain, particularly in the abdomen and neck Loss of muscle Depression Sleep disturbance Memory loss Difficulty concentrating Loss of sexual function Infertility Loss of menstrual periods Thin skin, easy bruising[neurosciences.uvahealth.com]
  • Skin changes occur and include easy bruising, stretch marks and acne. Women can develop thicker facial and body hair, while men can have decreased fertility and libido.[livestrong.com]
  • bruising, excess body and facial hair, interrupted menstrual cycle, and purple stretch marks (striae) on the abdomen, breasts, and thighs.[novartis.com]
Weakness
  • Additional problems such as muscle weakness arise because of loss of protein in body tissues. Table 1.[pituitarysociety.org]
  • Common symptoms include weight gain, skin changes, hyperhidrosis, infertility, hirsutism, amenorrhea, muscle weakness and psychological problems.[symptoma.com]
  • In contrast, non-mutated aggressive tumors such as CCA may respond better to the alkylating agent temozolomide because of their significantly weak expression of MGMT.[ncbi.nlm.nih.gov]
  • Some symptoms are Upper body obesity Thin arms and legs Severe fatigue and muscle weakness High blood pressure High blood sugar Easy bruising Lab tests can show if you have it and find the cause.[fpnotebook.com]
Weight Gain
  • Common clinical signs and symptoms include weight gain, hypertension, and osteoporosis. Effective treatment of Cushing's disease can normalize biochemical levels, reverse comorbidities, and improve overall survival and quality of life.[ncbi.nlm.nih.gov]
  • The most common symptoms in adults are weight gain (especially in the trunk, and often not accompanied by weight gain in the arms and legs), high blood pressure (hypertension), and changes in memory, mood and concentration.[pituitarysociety.org]
  • The findings in this patient demonstrate that decreased growth rate despite rapid weight gain in children can be early sign of Cushing's disease and emphasize the importance of monitoring of growth in obese children.[ncbi.nlm.nih.gov]
  • All three exhibited the typical symptoms and signs of weight gain and growth retardation. Tw o also demonstrated personality changes, hypertension and hypokalemia, the last of these being rarely reported in patients with Cushing's disease.[ncbi.nlm.nih.gov]
  • Weight Gain Rapid weight gain and obesity is one of the most common symptoms of Cushing’s syndrome, and the location of the gain is specific. The trunk of the body—the torso—is where the weight gain occurs, leaving the arms and legs alone.[activebeat.com]
Fatigue
  • Some symptoms are Upper body obesity Thin arms and legs Severe fatigue and muscle weakness High blood pressure High blood sugar Easy bruising Lab tests can show if you have it and find the cause.[fpnotebook.com]
  • Read Next: 3 Steps to Heal Adrenal Fatigue[draxe.com]
  • Weight gain Insomnia Hypertension Recurrent infection Poor short-term memory Thin skin and stretch marks Irritability Easy bruising Excess hair growth (women) Depression Red, ruddy face Weak bones Extra fat around neck Acne Round face Balding (women) Fatigue[pituitarysociety.org]
Buffalo Hump
  • In addition to the typical clinical symptoms such as moon face,buffalo hump,and central obesity,the CD patients may also experience mental disorders and cognitive dysfunction.[ncbi.nlm.nih.gov]
  • One of the main signs is weight gain and more body fat, such as: increased fat on your chest and tummy, but slim arms and legs a build-up of fat on the back of your neck and shoulders – known as a "buffalo hump" a red, puffy, rounded face Other symptoms[nhs.uk]
  • Excess levels of cortisol can lead to severe physical and physiological changes in the body, including uncontrollable weight gain, central obesity (abdomen that sticks out with thin arms and legs), a round, red full face, buffalo hump (collection of fat[novartis.com]
Infertility
  • Common symptoms include weight gain, skin changes, hyperhidrosis, infertility, hirsutism, amenorrhea, muscle weakness and psychological problems.[symptoma.com]
  • […] symptoms including: Weight gain in the neck, face and upper body Flushing in the face Easy bruising Purple stretch marks on the stomach Diabetes High blood pressure Osteoporosis Excess facial hair and fewer menstrual periods in women Muscle weakness Infertility[froedtert.com]
  • Excessive cortisol production causes: Weight gain, particularly in the abdomen and neck Loss of muscle Depression Sleep disturbance Memory loss Difficulty concentrating Loss of sexual function Infertility Loss of menstrual periods Thin skin, easy bruising[neurosciences.uvahealth.com]
  • There are discussions of the signs and symptoms and the most common co-morbidities, such as diabetes mellitus, hypertension, osteoporosis, amenorrhea, and infertility.[elsevier.com]
  • Hyperprolactinemia causes milk discharge from the breast (galactorrhea), menstrual irregularities (oligomenorrhea or amenorrhea) and infertility in women and impotence in men.[emoryhealthcare.org]
Polydipsia
  • Although she had the typical clinical manifestations of Cushing’s syndrome including obesity, facial plethora, menstrual disorder, hypertension, and polydipsia/polyuria, and typical laboratory findings, including hypokalemia and hyperlipemia, at the age[academic.oup.com]
  • Affected dogs show polyuria, polydipsia, polyphagia, muscle weakness and atrophy, pendulous abdomen, hair loss and an increased susceptibility to infection, particularly of the skin and urinary tract.[medical-dictionary.thefreedictionary.com]
Hypertension
  • This is a longitudinal study performed in 10 patients with active CD matched with 10 hypertensive and 10 healthy controls. All subjects had MR after CD diagnosis and 6 months after cortisol normalization.[ncbi.nlm.nih.gov]
  • We describe here the case of a 12-year old girl with CD who developed benign intracranial hypertension during treatment with ketoconazole.[ncbi.nlm.nih.gov]
  • Common clinical signs and symptoms include weight gain, hypertension, and osteoporosis. Effective treatment of Cushing's disease can normalize biochemical levels, reverse comorbidities, and improve overall survival and quality of life.[ncbi.nlm.nih.gov]
  • A 40-year-old woman with Cushing's disease presented with hypertensive cerebral hemorrhage.[ncbi.nlm.nih.gov]
  • In this article, hormonal evaluation in a middle-aged woman with diabetes, hypertension and incidentally discovered unilateral adrenal myelolipoma revealed underlying subclinical Cushing's disease.[ncbi.nlm.nih.gov]
Hirsutism
  • The clinical signs suggesting Cushing's disease, such as obesity, moon face, hirsutism, and facial plethora are already present on presentation.[ncbi.nlm.nih.gov]
  • Common symptoms include weight gain, skin changes, hyperhidrosis, infertility, hirsutism, amenorrhea, muscle weakness and psychological problems.[symptoma.com]
  • An 8-year-old prepubertal boy presented with rapid weight gain accompanied by a decreasing growth velocity and hirsutism. Thyroid function tests and growth factor levels were normal, thus excluding hypothyroidism and growth hormone deficiency.[ncbi.nlm.nih.gov]
  • A 38-year-old female presented with unexplained weight gain, hirsutism, amenorrhea, asthenia, recurrent cutaneous micotic infections and alopecia.[ncbi.nlm.nih.gov]
  • New or worsening hirsutism (n 2) and/or acne (n 3) were reported among four female patients, all of whom had increased testosterone levels. Osilodrostat treatment reduced UFC in all patients; 78.9% (n/N 15/19) had normal UFC at week 22.[ncbi.nlm.nih.gov]
Thin Skin
  • Signs and symptoms of Cushing’s syndrome COMMON FEATURES LESS COMMON FEATURES Weight gain Insomnia Hypertension Recurrent infection Poor short-term memory Thin skin and stretch marks Irritability Easy bruising Excess hair growth (women) Depression Red[pituitarysociety.org]
  • Symptoms may include upper body obesity, round face, and thin skin. Treatment depends on the cause. It may include surgery, radiation, chemotherapy, or medicines.[swedish.org]
  • Excessive cortisol production causes: Weight gain, particularly in the abdomen and neck Loss of muscle Depression Sleep disturbance Memory loss Difficulty concentrating Loss of sexual function Infertility Loss of menstrual periods Thin skin, easy bruising[neurosciences.uvahealth.com]
  • Symptoms may include: Upper body obesity Round face Increased fat around neck Thinning arms and legs Fragile and thin skin Stretch marks on abdomen, thighs, buttocks, arms, and breasts Bone and muscle weakness Severe fatigue High blood pressure High blood[hopkinsmedicine.org]
Hyperpigmentation
  • The disease manifests with signs of CS (truncal and facial obesity and signs of hypercatabolism) as well as skin hyperpigmentation and/or neurological complications in some cases of corticotroph macro-adenoma.[orpha.net]
  • Hyperpigmentation of the skin may occur due to the fact that circulating ACTH has some melanocyte stimulating hormone (MSH) like activity.[symptoma.com]
  • Nelson syndrome Nelson syndrome occurs when the pituitary gland continues to expand after bilateral adrenalectomy, causing a marked increase in the secretion of ACTH and its precursors, resulting in severe hyperpigmentation.[merckmanuals.com]
  • Enlarging corticotroph tumor can manifest clinically with compressive symptoms such as headache, vision change, ocular palsy and hyperpigmentation due to very high ACTH concentrations.[emedicine.medscape.com]
Flushing
  • Too much cortisol can lead to Cushing’s syndrome, causing symptoms including: Weight gain in the neck, face and upper body Flushing in the face Easy bruising Purple stretch marks on the stomach Diabetes High blood pressure Osteoporosis Excess facial hair[froedtert.com]
  • The signs and symptoms are weight gain (particularly around the midriff), puffiness of the face with a characteristic ‘flushed’ appearance, reduction in sex drive, irregular periods, thinning and bruising of the skin, stretch marks (particularly in the[yourhormones.info]
Osteoporosis
  • This case illustrates the need to consider secondary causes of osteoporosis in a young man with bone fractures, namely Cushing's syndrome.[ncbi.nlm.nih.gov]
  • Secondary osteoporosis is a frequently underestimated bone disorder. It is a secondary cause of bone loss that affects more than half of men and premenopausal and perimenopausal women, and about one-fitfth of postmenopausal women.[ncbi.nlm.nih.gov]
  • Common clinical signs and symptoms include weight gain, hypertension, and osteoporosis. Effective treatment of Cushing's disease can normalize biochemical levels, reverse comorbidities, and improve overall survival and quality of life.[ncbi.nlm.nih.gov]
  • A 42-year old man is reported who presented with bone fracture and osteoporosis and diagnosed with Cushing's disease. Six months after surgical treatment of his pituitary adenoma, he developed progressive multiple sclerosis.[ncbi.nlm.nih.gov]
  • Endogenous hypercortisolism is associated with an increased risk of cardiovascular and metabolic manifestations, as well as respiratory disorders, psychiatric complications, osteoporosis and infections, leading to high rates of morbidity and mortality[ncbi.nlm.nih.gov]
Muscle Weakness
  • Some symptoms are Upper body obesity Thin arms and legs Severe fatigue and muscle weakness High blood pressure High blood sugar Easy bruising Lab tests can show if you have it and find the cause.[fpnotebook.com]
  • Other symptoms include muscle weakness and fatigue and changing mental status with easy irritability and poorly controlled emotions.[livestrong.com]
  • Common symptoms include weight gain, skin changes, hyperhidrosis, infertility, hirsutism, amenorrhea, muscle weakness and psychological problems.[symptoma.com]
  • Additional problems such as muscle weakness arise because of loss of protein in body tissues. Table 1.[pituitarysociety.org]
Proximal Muscle Weakness
  • The following signs and symptoms are common: Weight gain Skin changes Hirsutism Menstrual disorders Progressive proximal muscle weakness Infertility Impotence Moodiness, irritability, or depression New-onset or worsening of hypertension and diabetes mellitus[symptoma.com]
  • Other common clinical features include hirsutism, acne, striae, plethora, fatigue, psychological disturbances, hypertension, and proximal muscle weakness.[clinicaladvisor.com]
  • Individuals often experience proximal muscle weakness, easy bruising, weight gain, hirsutism , and, in children, growth retardation . Hypertension , osteopenia, diabetes mellitus, and impaired immune function may also occur.[emedicine.medscape.com]
Back Pain
  • ., patients with multiple sclerosis or lower back pain), our results indicate that psychosocial impairment in CD is significantly influenced by how the patient deals with the illness.[ncbi.nlm.nih.gov]
  • High doses of injectable steroids for treatment of back pain can also cause this syndrome.[healthline.com]
  • It's also possible to develop Cushing syndrome from injectable corticosteroids — for example, repeated injections for joint pain, bursitis and back pain.[mayoclinic.org]
  • However, she did not have muscular weakness, back pain, striae cutis, acne, or bruising. Her blood pressure was 200/110 mm Hg.[academic.oup.com]
Muscular Atrophy
  • Hirsutism, plethora facial, muscular weakness and muscular atrophy were more frequent in the MIC patients. Nephrolithiasis, osteopenia, hyperprolactinaemia and galactorrhoea were more prevalent in MAC patients.[ncbi.nlm.nih.gov]
  • atrophy; edema; hypokalemia; and some degree of emotional change.[medical-dictionary.thefreedictionary.com]
Psychiatric Manifestation
  • View Article PubMed Google Scholar Jeffcoate WJ, Silverstone JT, Edwards CR, Besser GM: Psychiatric manifestations of Cushing's syndrome: response to lowering of plasma cortisol. Q J Med. 1979, 48: 465-472.[ojrd.biomedcentral.com]
Irritability
  • Patients also display psychiatric effects including irritability, psychosis or depression. Increased susceptibility to infections and poor wound healing are common.[symptoma.com]
  • Signs and symptoms of Cushing’s syndrome COMMON FEATURES LESS COMMON FEATURES Weight gain Insomnia Hypertension Recurrent infection Poor short-term memory Thin skin and stretch marks Irritability Easy bruising Excess hair growth (women) Depression Red[pituitarysociety.org]
  • […] include: Upper body obesity Round face Increased fat around neck Thinning arms and legs Fragile and thin skin Stretch marks on abdomen, thighs, buttocks, arms, and breasts Bone and muscle weakness Severe fatigue High blood pressure High blood sugar Irritability[hopkinsmedicine.org]
  • Other symptoms include muscle weakness and fatigue and changing mental status with easy irritability and poorly controlled emotions.[livestrong.com]
Asthenia
  • A 38-year-old female presented with unexplained weight gain, hirsutism, amenorrhea, asthenia, recurrent cutaneous micotic infections and alopecia.[ncbi.nlm.nih.gov]
  • The most common AEs observed during osilodrostat treatment were nausea, diarrhea, asthenia, and adrenal insufficiency (n 6 for each).[ncbi.nlm.nih.gov]
  • Main side effects are digestive (nausea, vomiting, diarrhea), neurologic (sleepiness, asthenia) and metabolic (hypercholesterolemia).[ojrd.biomedcentral.com]
Excitement
  • The pathogenesis of Cushing's disease is poorly understood; two recent reports identifying somatic mutations in USP8 in pituitary corticotroph tumors provide exciting advances in this field.[nature.com]
  • Cortisol is an essential hormone for many body functions, including maintaining normal electrical excitation of the heart, blood glucose level, nerve cell conduction, and adequate circulatory volume, and for metabolizing proteins, fats, and carbohydrates[medical-dictionary.thefreedictionary.com]
Amenorrhea
  • A 38-year-old woman was admitted to our hospital because of amenorrhea, multiple bone fractures, and a Cushingoid appearance.[ncbi.nlm.nih.gov]
  • Common chief complaints include increased facial hair, weight gain, amenorrhea, changes in the face, neck, and abdomen, with muscle wasting of the lower extremities.[ncbi.nlm.nih.gov]
  • A 38-year-old female presented with unexplained weight gain, hirsutism, amenorrhea, asthenia, recurrent cutaneous micotic infections and alopecia.[ncbi.nlm.nih.gov]
  • It is characterized by upper body OBESITY; OSTEOPOROSIS; HYPERTENSION; DIABETES MELLITUS; HIRSUTISM; AMENORRHEA; and excess body fluid.[fpnotebook.com]
Polyuria
  • Nine days postpartum, the patient was still unable to move in her bed, complained of strong thirst, and had hypotonic polyuria (8,900 mL/day). At that time, endocrinological consultation was made. Her body weight decreased to 66 kg.[academic.oup.com]
  • Affected dogs show polyuria, polydipsia, polyphagia, muscle weakness and atrophy, pendulous abdomen, hair loss and an increased susceptibility to infection, particularly of the skin and urinary tract.[medical-dictionary.thefreedictionary.com]
Sexual Dysfunction
  • dysfunction (amenorrhea in females and erectile dysfunction in males) and could explain Minnie's symptoms.[en.wikipedia.org]
Oligomenorrhea
  • Hyperprolactinemia causes milk discharge from the breast (galactorrhea), menstrual irregularities (oligomenorrhea or amenorrhea) and infertility in women and impotence in men.[emoryhealthcare.org]

Workup

Workup for a suspected case of Cushing's disease is done to confirm or exclude the diagnosis of Cushing syndrome and to differentiate ACTH-independent disease from ACTH-dependent disease followed by imaging of pituitary or adrenal to localize the anatomic source [5] [6].

Urinary free cortisol

Urinary free cortisol (UFC) in a 24-hour urine specimen is the most sensitive screening test for the diagnosis of Cushing syndrome and can be done on an outpatient basis. UFC levels are almost never normal in Cushing syndrome. If the UFC is more than three times the upper limit of normal, the patient is presumed to have Cushing syndrome. However, if the results are equivocal, the patient may either be retested later or subjected to further tests [7] [8].

Overnight dexamethasone suppression test

1 mg dexamethasone is administered at 11 p.m. and plasma cortisol is measured at 8 a.m. In normal individuals dexamethasone suppresses the early morning surge of cortisol while in Cushing syndrome cortisol levels remain high. If both of the above tests are normal, Cushing syndrome is unlikely and is excluded. The above two tests may be falsely positive in conditions causing pseudo-Cushing syndrome such as obesity, acute or chronic illness, alcoholism, depression, drugs and high estrogen states.

Low dose dexamethasone suppression test

0.5 mg dexamethasone is administered every 06 hourly for 48 hours. Plasma cortisol and urinary free cortisol samples are obtained. This test distinguishes between pseudo-Cushing syndrome and Cushing syndrome.

High dose dexamethasone suppression test and ACTH levels

These tests help to localize the cause of Cushing syndrome. ACTH levels are non-detectable in adrenal tumors but high in cases of ectopic or pituitary tumors. Ectopic production of ACTH shows no suppression with high dose dexamethasone suppression test while in Cushing's disease decrease in more than 50% in urinary free cortisol is suggestive of an anterior pituitary adenoma.

Imaging

The above mentioned biochemical tests are followed by imaging studies. MRI pituitary is done if pituitary adenoma is suspected. CT scan chest and abdomen are done if ectopic ACTH production is suspected to localize the tumor. Inferior petrosal sinus sampling (IPSS) can be performed by experienced interventional radiologist to differentiate pituitary oversecretion of ACTH from ectopic ACTH production in difficult cases.

Nephrolithiasis
  • Nephrolithiasis, osteopenia, hyperprolactinaemia and galactorrhoea were more prevalent in MAC patients.[ncbi.nlm.nih.gov]
  • Adequate prophylaxis with anticoagulants can reverse the prothrombotic state and greatly reduce the risk of postoperative thromboembolic events (49) Vascular morbidity (10%) (49) VTE (incidence 2.5–3.1 per 1000 persons per year) (57) Kidney disease Nephrolithiasis[eje.bioscientifica.com]
Cortisol Increased
  • In the corticotropin-releasing hormone (CRH) test, ACTH and cortisol increased only by 28%. Repeated magnetic resonance imaging (MRI) finally revealed a microadenoma in the anterior pituitary, thus establishng the diagnosis of Cushing's disease.[ncbi.nlm.nih.gov]
  • CRH test (100 μg intra-venously): more than 50% ACTH and 20% cortisol increase is in favor of Cushing’s disease. Sensitivity and specificity are close to 90% [ 34 ].[ojrd.biomedcentral.com]
Hemoglobin Increased
  • Blood count may show increased hemoglobin, increased neutrophils and decreased lymphocytes or eosinophils.[ojrd.biomedcentral.com]
Hypertriglyceridemia
  • In some study populations, the prevalence of hypertriglyceridemia was lower than in BMI-matched controls (12) .[eje.bioscientifica.com]
Potassium Decreased
  • As the level of potassium decreased, the chances of abnormal heart rhythms increase. These can be as mild as skipped beats or as serious as ventricular fibrillation, an abnormal rhythm that can be fatal. Lose Weight. Feel Great![livestrong.com]

Treatment

Treatment modalities are aimed at normalizing the cortisol levels and prevent the deleterious effects of hypercortisolism. Treatment options include surgical options and pharmacotherapy. In Cushing's disease the procedure of choice is transsphenoidal surgery to remove the pituitary adenoma. Pituitary irradiation is done in unsuccessful cases. Medical therapy is employed for the treatment of Cushing's disease when surgery is contraindicated or for control of hypercortisolism in patients waiting or surgery or reappearance of symptoms after surgery.

Various drugs used to treat Cushing's disease [9] are:

  • Adrenal enzyme inhibitors: Aminoglutethimide, metyrapone, ketoconazole, fluconazole, etomidate and trilostane inhibit the enzymes involved in steroidogenesis. Ketoconazole is started and if hypercortisolism is not controlled, metyrapone is added.
  • Adrenocorticolytic drugs: Mitotane is used for the treatment of adrenal carcinoma. It is also used in cases of Cushing's disease during or after pituitary irradiation.
  • Drugs that target pituitary and reduce ACTH levels: These include cabergoline (a dopamine agonist) and pasireotide (a somatostatin analog).

Prognosis

If Cushing's disease remains untreated it may be fatal. Most deaths are due to cardiovascular and thromboembolic complications like myocardial infarction, pulmonary edema, hypertensive crisis and deep venous thrombosis. There is an increased incidence of opportunistic bacterial and fungal infections in such patients. With the development of surgical options and medical therapy, the prognosis improved, but advanced disease and unresectable tumors at the time of diagnosis may be present.

Etiology

In Cushing's disease pituitary hypersecretion of ACTH occurs. In 90% of cases this is caused by a microadenoma while in other cases it is caused by a macroadenoma (tumors more than 1 cm in size). Rarely Cushing's disease is diagnosed as a part of multiple endocrine neoplasia type 1 (MEN 1).

Ectopic ACTH secretion occurs from small cell carcinoma of the lung [1], carcinoid tumors, medullary carcinoma of the thyroid and pheochromocytoma. Overproduction of ACTH and iatrogenic administration of ACTH are rare causes of ACTH-dependent Cushing syndrome.

Epidemiology

Cushing's disease is a rare condition, seen more frequently in women. It most often occurs between the second and fourth decade of life.

Sex distribution
Age distribution

Pathophysiology

Glucocorticoid excess has deleterious effects on all systems on the body. There is redistribution of body fat manifesting in the form of moon facies, buffalo hump and central obesity. Abdominal striae and skin bruising result from atrophy of the skin and connective tissue. An increased incidence of osteoporosis, fractures in adults and growth retardation in children was reported. Steroid induced proximal myopathy leads to lethargy and poor mobility of patients. Hypertension, edema and hypokalemia result due to the increased mineralocorticoid effect of steroids [2].

Glucose intolerance or diabetes mellitus follows due to the antiinsulin effects of cortisol. Glucose intolerance occurs due to increased gluconeogenesis and glycogenesis by cortisol and may lead to overt diabetes mellitus which is present in 10-15% patients with Cushing syndrome [3]. Gonadal dysfunction causes hirsutism, acne, amenorrhea and infertility in women while decreased libido, loss of body hair, small testes and impotence occur in men. Patients also display psychiatric effects including irritability, psychosis or depression. Increased susceptibility to infections and poor wound healing are common [4]. Hyperpigmentation of the skin may occur due to the fact that circulating ACTH has some melanocyte stimulating hormone (MSH) like activity. Patients with ACTH-producing tumors may present with headaches, visual disturbances and other endocrine disorders.

Prevention

There are no guidelines for prevention of Cushing' disease.

Summary

Cushing syndrome refers to the constellation of clinical features that result from chronic exposure to excess glucocorticoids. The high levels of glucocorticoids can come from exogenous (iatrogenic) or endogenous sources. Endogenous causes can be overproduction of cortisol by an adrenal tumor or increased adrenocorticotropic hormone (ACTH) production due to a pituitary tumor - a condition referred to as Cushing's disease.

Cushing's disease presents with a wide variety of signs and symptoms none of which are specific to this disorder. Laboratory investigations and imaging techniques are used to establish the diagnosis of Cushing's disease and localize the lesion. Treatment aims at normalizing the cortisol levels and includes pharmacotherapy and surgical options to remove the tumor.

Patient Information

Cushing's disease is caused by high levels of a hormone called cortisol in human body. Cortisol is produced by a small organ present on top of each kidney called adrenal gland and is required for normal functioning of human body. Cortisol is made in the adrenal glands as a result of a signal passed from a small organ present near brain called pituitary. Cushing's disease is caused by an abnormal growth in the pituitary. People with Cushing's disease may have one or more of these symptoms: Weight gain especially around neck and waist, easy bruising and poor wound healing of the skin, increased blood sugar levels, high blood pressure, feeling too weak to get up from sitting position and perform day to day activities, stretch marks on the abdomens that are purple colored, mood changes and irregularities in the monthly menstrual cycles. The disorder is diagnosed by blood tests, CT scan and MRI scans. Cushing's disease is treated by surgery and medicines. Surgery removes the abnormal growth in the pituitary. Medicines can be used to normalize the levels of cortisol to control the symptoms caused by an increased amount of cortisol.

References

Article

  1. Govindan R, Page N, Morgensztern D, et al. Changing epidemiology of small-cell lung cancer in the United States over the last 30 years: analysis of the surveillance, epidemiologic, and end results database. J Clin Oncol 2006; 24:4539.
  2. Pareira AM, Delgadov V, Romijn JA, et al. Cardiac dysfunction is reversed upon successful treatment of Cushing’s syndrome. Eur J Endocrinol. Feb 2010; 162(2):331-40.
  3. Yanovski JA, Cutler GB Jr. Glucocorticoid action and the clinical features of Cushing’s syndrome. Endocrinol Metab Clin North Am. Sep 1994; 23(3):487-509.
  4. Raff H, Findling JW. A physiologic approach to diagnosis of the Cushing syndrome. Ann Intern Med. Jun 17 2003:138(12):980-91.
  5. Elamin MB, Murad MH, Multan R, et al. Accuracy of diagnostic tests for Cushing’s syndrome: A systematic review and metaanalyses. J Clin Endocrinol Metab 2008; 93:1553.
  6. Arnaldi G, Angeli A, Atkinson AB, et al. Diagnosis and complications of Cushing’s syndrome: a consensus statement. J Clin Endocrinol Metab 2003; 88:5593.
  7. Kidambi S, Raff H, Findling JW. Limitations of nocturnal salivary cortisol and urine free cortisol in the diagnosis of Cushing syndrome. Eur J Endocrinol. Dec 2007; 157(6):725-31.
  8. Flack MR, Oldfield EH, Cutler GB Jr, et al. Urine free cortisol in the high-dose dexamethasone suppression test for the differential diagnosis of the Cushing syndrome. Ann Internal Med. Feb 1 1992; 116(3):211-7.
  9. Kamenický P, Droumaguet C, Salenave S, et al. Mitotane, metyrapone, and ketoconazole combination therapy as an alternative to rescue adrenalectomy for severe ACTH-dependent Cushing's syndrome. J Clin Endocrinol Metab 2011; 96:2796.

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Last updated: 2018-06-22 08:18