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
• Immune suppression
• Osteoporosis
• Growth retardation

• 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]

  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]

  Each individual beam is too weak to damage healthy tissue, but at the point where the beams converge they deliver a dose of radiation that is lethal to the tumor. [barrowneuro.org]

• Weight Gain

  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]

  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]

• Fatigue

  Prognosis Untreated Cushing's disease can lead to severe complications such as excessive fatigue, intolerable headaches, nausea and vomiting, pathological bone fractures, diabetes, hypertension, and premature death. [skullbaseinstitute.com]

  Difficulty in walking involving joint site unspecified 728.2 Muscular wasting and disuse atrophy, not elsewhere classified 728.89 Other disorders of muscle, ligament, and fascia 729.9 Other and unspecified disorders of soft tissue 780.7 Malaise and fatigue [accessphysiotherapy.mhmedical.com]

  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]

  Overproduction of cortisol can result in Cushing syndrome, with signs and symptoms such as weight gain, skin changes and fatigue. Cushing syndrome is rare but can cause significant long-term health problems. [youtube.com]

• Buffalo Hump

  She did not have a Cushingoid appearance, such as a moon-face, buffalo hump, purple striae or central obesity. The laboratory data revealed a serum GH level of 4.6 ng/mL and serum insulin-like growth factor-1 level of 811 ng/mL. [ncbi.nlm.nih.gov]

  [Photographer: Renea's family] September 2001 Libby's 3rd birthday party.....full-blown Cushing's....moon face, acne, buffalo hump, facial flushing, sweating all the time..... [cushings-help.com]

  Symptoms and signs of Cushings syndrome and disease may include: Change in body habitus: weight gain in face (moon face), above the collar bone (supraclavicular) and on back of neck (buffalo hump) Skin changes with easy bruising, purplish stretch marks [pituitary.org]

  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 [novartisoncology.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 [uvahealth.com]

• Easy Bruising

  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]

  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]

  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 [uvahealth.com]

  The clinical features which best discriminate Cushing’s syndrome from those without this disorder include muscle weakness, easy bruising, thin skin and wide purple stretch marks. [web.archive.org]

• Abdominal Pain

  Post-operative relative adrenal insufficiency is often accompanied by lightheadedness, dizziness, nausea, vomiting, abdominal pain, fatigue and weight loss. [csrf.net]

  Moghadam, Acute abdominal pain in a man with Cushing syndrome, Acta Clinica Belgica, 70, 5, (372), (2015). Michael S. Broder, Maureen P. Neary, Eunice Chang, Dasha Cherepanov, Gordon H. Sun and William H. [doi.org]

• Polydipsia

  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]

  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]

• Hypertension

  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]

• Tachycardia

  Thin extremities (80%)1 Atrophy of skin and dermal connective tissue (70%)1 Easy bruising (50%)1 Muscle wasting and weakness (70%)1 Weight gain; increased body fat in trunk and thoracic back (80%)1 Pallor Flushed face Chest pain Fatigue Rapid breathing Tachycardia [accessphysiotherapy.mhmedical.com]

• 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]

  If osteoporosis is present, this may require further medication to improve the strength of the bones. [yourhormones.info]

• 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]

  weakness Infertility Depression Significant problems with memory and thinking Causes of Cushing’s Syndrome The most common cause of Cushing’s syndrome is cortisol-like steroid medications, such as prednisone. [froedtert.com]

• Back Pain

  CONCLUSION: Similar to several studies in non-pituitary patient cohorts (e.g., 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 [ncbi.nlm.nih.gov]

  It's also possible to develop Cushing syndrome from injectable corticosteroids — for example, repeated injections for joint pain, bursitis and back pain. [mayoclinic.org]

  High doses of injectable steroids for treatment of back pain can also cause this syndrome. [healthline.com]

  Leakage of urine Incomplete emptying of the bladder Constipation Needing to push organs back up into the vagina to empty the bladder or have a bowel movement Pain during sex Problems putting in tampons or vaginal applicators Pelvic pressure that gets [urmc.rochester.edu]

• Proximal Muscle Weakness

  Muscle weakness. In particular a proximal muscle weakness. The proximal muscles are the ones in your arms and legs nearest to the body. So, the muscles around the thigh, pelvis, shoulders and upper arms are the proximal muscles. [patient.info]

  Gowers' sign Gowers' sign Differential diagnosis Duchenne muscular dystrophy Gowers' sign is a medical sign that indicates weakness of the proximal muscles, namely those of the lower limb. [en.wikipedia.org]

  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]

• Muscular Atrophy

  RESULTS: 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]

  See also[edit] Spinal muscular atrophy References[edit] ^ synd/1228 at Who Named It? ^ W. R. Gowers. A manual of the nervous system. [en.wikipedia.org]

  atrophy; edema; hypokalemia; and some degree of emotional change. [medical-dictionary.thefreedictionary.com]

• Hirsutism

  Common symptoms include weight gain, skin changes, hyperhidrosis, infertility, hirsutism, amenorrhea, muscle weakness and psychological problems. [symptoma.com]

  A 38-year-old female presented with unexplained weight gain, hirsutism, amenorrhea, asthenia, recurrent cutaneous micotic infections and alopecia. [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]

  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 [uvahealth.com]

  The clinical features which best discriminate Cushing’s syndrome from those without this disorder include muscle weakness, easy bruising, thin skin and wide purple stretch marks. [web.archive.org]

  A doctor may suspect Cushing syndrome if a person has the telltale signs, such as a rounded face, a pad of fatty tissue between the shoulders, thin skin with bruises and stretch marks, and poor growth. [kidshealth.org]

  Memory loss was due to job stress and thin skin and easy bruising were due to sun exposure. After foot and back fractures at age 47, I was finally diagnosed. [csrf.net]

• 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]

  Muscle wasting and weakness (70%)1 Weight gain; increased body fat in trunk and thoracic back (80%)1 Pallor Flushed face Chest pain Fatigue Rapid breathing Tachycardia Palpitations Hypertension Skin changes, striae on the abdomen and chest Darkening/hyperpigmentation [accessphysiotherapy.mhmedical.com]

  Hyperpigmentation of the skin may occur due to the fact that circulating ACTH has some melanocyte stimulating hormone (MSH) like activity. [symptoma.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]

  [Photographer: Renea's family] September 2001 Libby's 3rd birthday party.....full-blown Cushing's....moon face, acne, buffalo hump, facial flushing, sweating all the time..... [cushings-help.com]

  Round face; moon face (80%)1 Thick neck (80%)1 Thin extremities (80%)1 Atrophy of skin and dermal connective tissue (70%)1 Easy bruising (50%)1 Muscle wasting and weakness (70%)1 Weight gain; increased body fat in trunk and thoracic back (80%)1 Pallor Flushed [accessphysiotherapy.mhmedical.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]

• Sweating

  [Photographer: Renea's family] September 2001 Libby's 3rd birthday party.....full-blown Cushing's....moon face, acne, buffalo hump, facial flushing, sweating all the time..... [cushings-help.com]

  […] fat in trunk and thoracic back (80%)1 Pallor Flushed face Chest pain Fatigue Rapid breathing Tachycardia Palpitations Hypertension Skin changes, striae on the abdomen and chest Darkening/hyperpigmentation of skin Stretch marks Acne Excessive thirst Sweating [accessphysiotherapy.mhmedical.com]

  The most common symptoms of GH excess are enlargement of the hands, feet and face and excessive sweating. Patients may also experience headaches, irregular periods (in women), impotence (in men) and peripheral vision loss. [emoryhealthcare.org]

  […] using Korlym and call your doctor at once if you have: nausea, unusual weakness, tired feeling; abnormal vaginal bleeding; a light-headed feeling, like you might pass out; new or worsening medical problems; low blood sugar - headache, hunger, weakness, sweating [drugs.com]

  About 50 percent of affected individuals produce excessive amounts of thyroid hormone (hyperthyroidism), resulting in a fast heart rate, high blood pressure, weight loss, tremors, sweating, and other symptoms. [ghr.nlm.nih.gov]

• Mood Swings

  May 1993 Senior photo...as I believe my Cushing's was starting....the hump was slowly starting to appear and I had terrible depression/mood swings[Photographer: Renea's family] September 1996 I had spent the summer working outdoors....I felt at my best [cushings-help.com]

  swings DIAGNOSIS Comparison of old and recent photographs will often demonstrate the marked changes in facial appearance and body habitus of patients who develop Cushing's syndrome or Cushing's disease. [pituitary.org]

  For example, you may put on some weight, have mood swings and just not feel right. However, it is difficult to say why. You may even be treated for depression or obesity before the cause of your symptoms becomes clear. [patient.info]

  (Things like: fatigue, muscle weakness, abdominal and facial weight gain, depression, mood swings.) Drugs can help with these ongoing symptoms. [urologyhealth.org]

  swings Cushing's syndrome can also cause high blood pressure, which can be serious if not treated. [nhs.uk]

• Psychiatric Manifestation

  W. et al., Psychiatric manifestations of Cushings syndrome: response to lowering of plasma cortisol,, QJ Med, 1979; 191:465-72 (8.) Cohen, S. I., Cushing's syndrome: A psychiatric study of 29 patients, Br J Psychiat, 1980; 136:120-4 (9.) [go.galegroup.com]

  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. 5. Newell-Price J, Bertagna X, Grossman AB, Nieman LK: Cushing's syndrome. [ojrd.biomedcentral.com]

  (escape may occur) Nausea, vomiting, orthostasis, headache, vivid dreams, psychiatric manifestations Effective in doses that are generally higher than those used in hyperprolactinaemia Pasireotide Centrally acting 0.3‐0.9 mg sc bid 21%a aBased on normalization [onlinelibrary.wiley.com]

  Depressed mood and other psychiatric manifestations of Cushing's syndrome: relationship to hormone levels. Psychosom Med. (1981) 43:3–18. doi: 10.1097/00006842-198102000-00002 PubMed Abstract | CrossRef Full Text | Google Scholar 71. [frontiersin.org]

• Loss of Libido

  Lack of sex drive (loss of libido). Periods may become irregular, or stop, in women. 'Thinning' of the bones (osteoporosis). You may fracture a bone more easily than usual. 'Water retention' (oedema) around the ankles. Excess thirst. [patient.info]

  Men (and women) with this disorder may experience a decrease in fertility and a diminished or absent sex drive (loss of libido). [rarediseases.org]

• Headache

  However, clinical symptoms like headaches, visual field impairment, and finally hearing loss started to progress from the eighth cycle. [ncbi.nlm.nih.gov]

  Patients may also experience headaches, irregular periods (in women), impotence (in men) and peripheral vision loss. [emoryhealthcare.org]

• 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]

  Easy bruising Hirsutism in women (excessive hair on face, abdomen, and legs) Irregular menstrual periods in women; sexual difficulties in men Severe fatigue, weak muscles, and easy fractures of bones High blood pressure Diabetes Infections Anxiety, irritability [jamanetwork.com]

  […] 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]

• Asthenia

  A 38-year-old female presented with unexplained weight gain, hirsutism, amenorrhea, asthenia, recurrent cutaneous micotic infections and alopecia. [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]

  “I got really excited and2016. patients with them. [studyres.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]

• Difficulty Concentrating

  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 [uvahealth.com]

• Amenorrhea

  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]

  It is characterized by upper body OBESITY; OSTEOPOROSIS; HYPERTENSION; DIABETES MELLITUS; HIRSUTISM; AMENORRHEA; and excess body fluid. [fpnotebook.com]

• Sexual Dysfunction

  dysfunction (amenorrhea in females and erectile dysfunction in males) and could explain Minnie's symptoms.[3] Experimental evidence and case reports by Cushing led to his publication in 1932 on pituitary basophilism as the cause of Cushing's disease. [en.wikipedia.org]

  Sexual dysfunction One study reported an 18% rate of dyspareunia resulting in deteriorated sexual function after anterior colporrhaphy concomitant with posterior colpoperineorrhaphy. [22] A study from Taiwan suggested that transvaginal mesh repair, though [emedicine.medscape.com]

  dysfunction, feeling crummy, cognitive changes, neg. effects on self-confidence, confused in large crowds/noisy places, felt like I was on psychotropic drugs and slipping between dimensions, being cyclical, worry about residual effects on my brain, foggy [hindawi.com]

  A study in a sample of 29 sexually-active women with active CS (89.7% with CD) showed that female sexual dysfunction was present in 88.9% of the patients. Scores of the Female Sexual Function Index (FSFI) were lower than in healthy controls. [frontiersin.org]

• Irregular Menstruation

  Women with Cushing disease may experience irregular menstruation and have excessive hair growth (hirsutism) on their face, abdomen, and legs. Men with Cushing disease may have erectile dysfunction. [ghr.nlm.nih.gov]

  menstruation[7] Less common[edit] The less-common signs and symptoms of Cushing's disease include the following: insomnia recurrent infection thin skin and stretch marks[8] easy bruising weak bones acne balding (women) depression hip and shoulder weakness [en.wikipedia.org]

• 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]

• 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 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]

• Hyperglycemia

  Hyperglycemia-related AEs occurred in 40.0 % of patients with acromegaly treated with pasireotide SC, and 10.0 % discontinued treatment because of hyperglycemia. [ncbi.nlm.nih.gov]

  Overall, 118 of 162 patients (73%) had a hyperglycemia-related adverse event; 6% of patients discontinued treatment because of a hyperglycemia-related adverse event. [nejm.org]

  Avogaro, Italian Society for the Study of Diabetes (SID)/Italian Endocrinological Society (SIE) guidelines on the treatment of hyperglycemia in Cushing’s syndrome and acromegaly, Journal of Endocrinological Investigation, 10.1007/s40618-015-0404-6, 39 [doi.org]

• ACTH Increased

  However, ACTH increase after h-CRH was significantly higher after delivery than during gestation (p < 0.003), while ACTH responses to DDAVP were similar. [ncbi.nlm.nih.gov]

  The plasma ACTH levels of inferior petrosal sinus on the ipsilateral side to the tumor were significantly increased in four cases out of seven(57.1%) compared to those of contralateral side hut renaming one case showed significant ACTH increase on CRE [ir.ymlib.yonsei.ac.kr]

  If the level of ACTH increases in the bloodstream, the adrenal glands make more cortisol. However, cortisol has what is known as a negative feedback effect on the pituitary gland. [patient.info]

• Cortisol Increased

  Cushing's syndrome was confirmed by elevated 24-h urinary free cortisol levels, increased diurnal cortisol levels, and a lack of cortisol suppression in the low-dose dexamethasone suppression test. [ncbi.nlm.nih.gov]

  Blood count may show increased hemoglobin, increased neutrophils and decreased lymphocytes or eosinophils. [ojrd.biomedcentral.com]

• Cortisol Increased

  Cushing's syndrome was confirmed by elevated 24-h urinary free cortisol levels, increased diurnal cortisol levels, and a lack of cortisol suppression in the low-dose dexamethasone suppression test. [ncbi.nlm.nih.gov]

  Blood count may show increased hemoglobin, increased neutrophils and decreased lymphocytes or eosinophils. [ojrd.biomedcentral.com]

• ACTH Decreased

  When the cortisol level is high, production of CRH and ACTH decrease. [labtestsonline.org]

  After the tumor was resected, the plasma concentrations of cortisol and ACTH decreased, but they were high over the next 24 hours and responded strongly to CRH administration. [academic.oup.com]

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).

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.

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.

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

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.

There are no guidelines for prevention of Cushing' disease.

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.

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.

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.