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Iatrogenic Cushing's Disease

Iatrogenic Cushing's Syndrome

Iatrogenic Cushing's disease (iatrogenic Cushing's syndrome) is the most common cause of cushingoid symptoms. Glucocorticoids, not only those given by oral and parenteral routes, but also those administered topically, or as drops or inhalants, can lead to the development of the condition. The progress of the disease may sometimes be facilitated by interactions with other drugs that prolong glucocorticoid action. Taking steroids suppresses endogenous glucocorticoid production, putting patients at risk of developing an adrenal crisis if the medication is discontinued suddenly.


Presentation

The set of symptoms accompanying abnormally high levels of plasma glucocorticoids – whether of endogenous or exogenous origin - is called Cushing’s syndrome. Endogenous Cushing’s syndrome can be adrenocorticotropic hormone (ACTH) dependent or independent. In ACTH-dependent condition, ACTH levels are high, whereas, in ACTH-independent cases, which often derive from adrenal neoplasms, ACTH levels are low because of the feedback effect of the glucocorticoids on the pituitary gland. Cushing’s syndrome caused by exogenously administered glucocorticoids is called iatrogenic Cushing's disease or iatrogenic Cushing's syndrome. It occurs more frequently than the endogenous condition due to the extensive use of glucocorticoids for their anti-inflammatory and immunosuppressive effects.

The severity of the Cushing’s syndrome symptoms in patients on glucocorticoids will depend on the dosage, the length of treatment, and the variant of glucocorticoid compound used. Many different versions of glucocorticoids have been synthesized with the aim of optimizing their effects, and these compounds may differ in many respects; for example, by their rate of absorption, metabolism, water solubility, and affinity for glucocorticoid and mineralocorticoid receptors. Drug interactions also have an important role in the development of the condition. Prominent examples are drugs that inactivate cytochrome P450 enzymes, interfering with the breakdown of glucocorticoids, and thereby enhancing their activities. Ritonavir, a protease inhibitor and a component of combination antiretroviral therapy, is a powerful inhibitor of cytochrome P450. Its use, together with fluticasone has led to exogenous Cushing’s disease, with complications of osteoporosis and diabetes [1]. Together with oral budesonide, it resulted in weakness, muscle wasting, and other characteristic symptoms in a hepatitis sufferer [2]. Inhaled fluticasone propionate taken together with antidepressants was reported to result in the rapid development of symptoms of Cushing’s syndrome [3].

The increased prevalence of obesity can make it difficult to identify a patient with true Cushing’s syndrome [4], but there are several characteristic features of the condition that together allow it to be diagnosed (apart from laboratory tests that verify the condition). These effects include redistribution of fat resulting in moon face and centripetal obesity, glucocorticoid acne, buffalo hump, thinning of the skin, and purple striae. Patients also notice a weakening of muscles, diabetes, hypertension, increased infections, problems with wound healing, osteopenia, osteoporosis [5], and psychological problems. Women may experience hormonal problems leading to amenorrhea and infertility. Men may also be affected with infertility and loss of libido. Diabetes and peptic ulceration may also cause symptoms. Children’s growth is retarded, but otherwise, their symptoms are somewhat different and less striking than those of adults [6].

Easy Bruising
  • 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]
  • He had plethoric face, prominent neck hump, pink striae, easy bruising, and vellous hypertrichosis [Figure 1] . There was erythroderma studded with small pustules.[e-ijd.org]
  • In 2013 she started gaining weight, noticed easy bruising of her forearms, and developed muscle cramps, lightheadedness, and fatigue.[acgcasereports.gi.org]
  • Use of ICS are associated with increased risk of pneumonia, tuberculosis, easy bruising, osteoporosis, diabetes, oro-pharyngeal candidiasis, hoarseness of voice and even iatrogenic CS in patients with COPD, where the risk-benefit ratio has to be considered[benthamopen.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]
Weight Gain
  • gain and energy level.[pediatrics.aappublications.org]
  • He also complained of progressive weight gain, body ache, and generalized weakness.[e-ijd.org]
  • Weight gain in face ( moon face ) Weight gain above the collar bone (supraclavicular fat pad) Weight gain on the back of neck ( buffalo hump ) Skin changes with easy bruising in the extremities and development of purplish stretch marks ( striae ) particularly[aans.org]
  • 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]
  • After six weeks of intensive corticosteroid ophthalmic therapy, the patient was noted to have developed stigmata of adrenal suppression including weight gain; rapid development of striae over trunk, back, legs and arms; fat deposition in both cheeks and[omicsonline.org]
Buffalo Hump
  • These effects include redistribution of fat resulting in moon face and centripetal obesity, glucocorticoid acne, buffalo hump, thinning of the skin, and purple striae.[symptoma.com]
  • The authors note that the patient was referred to the pediatric department with stunted growth, truncal obesity, purple skin striate, buffalo hump, and moon face six months after initiation of topical ocular GC treatment.[medicalxpress.com]
  • She had a body mass index of 33 kg/m 2 , several small ecchymoses on her forearms, and a suggestion of a “buffalo hump.” Physical examination was otherwise unremarkable.[acgcasereports.gi.org]
  • 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]
  • Indeed, many people prescribed glucocorticoids do not just gain weight, they also present with localised hypertrophy of adipose tissue including the typical “moon face,” double chin, “buffalo hump,” “bull neck,” or “pendulum” abdomen.[bmj.com]
Supraclavicular Fat Pads
  • Weight gain in face ( moon face ) Weight gain above the collar bone (supraclavicular fat pad) Weight gain on the back of neck ( buffalo hump ) Skin changes with easy bruising in the extremities and development of purplish stretch marks ( striae ) particularly[aans.org]
  • Common: centripetal obesity with dorsocervical and supraclavicular fat pads, facial plethora and "moon face," fatigue, hyperglycemia, hypertension, mood lability, easy bruisability and skin atrophy, oligo/amenorrhea, hirsutism/acne (ACTH-dependent) More[hopkinsguides.com]
  • Individuals with Cushing syndrome can develop moon facies, facial plethora, supraclavicular fat pads, buffalo hump, truncal obesity, and purple striae, as shown in the image below. Physical findings in Cushing syndrome.[emedicine.medscape.com]
  • Physical Obesity Patients may have increased adipose tissue in the face (moon facies), upper back at the base of neck (buffalo hump), and above the clavicles (supraclavicular fat pads).[emedicine.medscape.com]
  • See also Addison's disease, Cushing's disease, Nelson's syndrome . observations Characteristically the patient with Cushing's syndrome has a decreased glucose tolerance; central obesity; round "moon" face; supraclavicular fat pads; an overhanging, striae-covered[medical-dictionary.thefreedictionary.com]
Cushingoid Facies
  • facies and poor growth.[pediatrics.aappublications.org]
  • Clinical features reported includes 'Cushingoid facies' or 'moon face', dorso-cervical fat pad (also known as 'buffalo hump'), central obesity and weight gain, facial hirsutism, striae and easy bruising, most of them were common symptoms associated with[benthamopen.com]
Hypertension
  • Patients also notice a weakening of muscles, diabetes, hypertension, increased infections, problems with wound healing, osteopenia, osteoporosis, and psychological problems.[symptoma.com]
  • The adverse metabolic features associated with glucocorticoid use include obesity, skeletal muscle myopathy, hypertension, insulin resistance and diabetes and are collectively termed 'iatrogenic Cushing's syndrome'.[clinicaltrials.gov]
  • Hypertension is seen in up to 75% of cases.[benthamopen.com]
  • It is characterized by upper body OBESITY; OSTEOPOROSIS; HYPERTENSION; DIABETES MELLITUS; HIRSUTISM; AMENORRHEA; and excess body fluid.[fpnotebook.com]
  • Her hypertension was controlled by medication with nifedipine (20 mg), spironolactone (50 mg) and candesartan (8 mg).[nature.com]
Muscle Weakness
  • Potty belly due to muscle weakness, fat redistribution and water retention. Muscle weakness leads to instability in standing and walking. Significant coat problems and hair loss. Hair is unable to grow back until the dose is lowered.[secondchanceaihadogs.com]
  • He had significant proximal muscle weakness of lower limbs with preservation of deep tendon reflexes. On investigation, testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were low [Table 1] . Serum cortisol ( [Table 1] .[e-ijd.org]
  • 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]
  • weakness and wasting, back pain , osteopenia and osteoporosis , depression and other psychological symptoms, hypertension , and menstrual disturbances ( oligomenorrhea and amenorrhea ) in women.[britannica.com]
Muscular Atrophy
  • atrophy Spinal stenosis Spinocerebellar ataxia Spleen Splenic rupture Splenomegaly Spondylolisthesis Sports injuries Staphylococcal diseases Staphylococcal scalded skin syndrome Statins Statistical analysis of data Stevens-Johnson syndrome Stiff person[amboss.com]
  • atrophy; edema; hypokalemia; and some degree of emotional change.[medical-dictionary.thefreedictionary.com]
Thin Skin
  • Dry, flaking, and thinning skin, risk of staph infections, difficulty with wound healing, darkening and blackening of skin. Risk of developing iatrogenic diabetes. Increased susceptibility to infections.[secondchanceaihadogs.com]
  • 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]
  • Signs and symptoms include a round face, upper body obesity, fragile and thin skin, purple stretch marks in the skin, fatigue, muscle weakness, hypertension, diabetes mellitus, hypertrichosis and amenorrhea in women, impotence in men, and osteoporosis[fpnotebook.com]
  • skin with easy bruising Muscle and bone changes include: Backache, which occurs with routine activities Bone pain or tenderness Collection of fat between the shoulders and above the collar bone Rib and spine fractures caused by thinning of the bones[medlineplus.gov]
Purpura
  • Purpura Schönlein-Henoch (HSP) Purpura anularis teleangiectoides Purpura durch Gerinnungsstörungen Purpura durch vaskuläre Störungen Purpura fulminans Purpura lichenoides pigmentosa Purpura pigmentosa progressiva Pusteln, follikuläre Pusteln, nichtfollikuläre[wikiderm.de]
  • […] amniotic sac Thigh, knee, and popliteal fossa Thin basement membrane nephropathy Thoracic aortic aneurysm Thoracic cavity Thoracic outlet syndrome Thromboangiitis obliterans Thrombocytopenia Thrombosed external hemorrhoid Thrombotic thrombocytopenic purpura[amboss.com]
  • Patients may have telangiectasias and purpura. Cutaneous atrophy with exposure of subcutaneous vasculature tissue and tenting of skin may be evident. Glucocorticoid excess may cause increased lanugo facial hair.[emedicine.medscape.com]
Striae Distensae
  • Stewart-Treves-Syndrom Still, Morbus Stomatitis Plaut-Vincenti Stomatitis angularis Stomatitis aphthosa Stomatitis electro-galvanica Stomatitis epidemica Stomatitis gangraenosa Strahlendermatitis Streptokokken Streptokokkengangrän Streptokokkensepsis Striae[wikiderm.de]
Delayed Wound Healing
  • Other possible signs include poor skin and hair condition, muscle atrophy, increased abdominal fat, enlarged liver, chronic or recurrent infections (especially skin or urinary), delayed wound healing, excessive panting, sodium retention (which can cause[hallettvet.com]
Facial Redness
  • The most common symptoms and signs of excess levels of cortisol in the body are obesity, facial plethora (facial redness), violaceous abdominal striae (purple or bluish stripes on the abdomen), thinning of the skin that leads to spontaneous bruising,[britannica.com]
Psychiatric Manifestation
  • manifestations such as depression and psychosis (Newell-Price et al. 2006 ).[springerplus.springeropen.com]
  • 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]
Emotional Lability
  • Psychological problems such as depression, cognitive dysfunction, and emotional lability may develop.[emedicine.medscape.com]
  • Common psychiatric abnormalities include agitated depression, lethargy, paranoia, overt psychosis, insomnia, emotional lability, irritability, anxiety and panic attacks [ 65 Kelly WF. Psychiatric aspects of Cushing's syndrome.[benthamopen.com]
Irritability
  • […] hyperbilirubinemia Innate immune system Insertional tendinopathy Insulin Insulinoma Interactive images Internal hernia Interstitial lung disease Intestinal ischemia Intracerebral hemorrhage Intravenous anaesthetics Intussusception Iron deficiency anemia Irritable[amboss.com]
  • Gastrointestinal (GI) irritation may lead to peptic ulcers, and both insulin resistance and glucose intolerance can cause hyperglycemia. Causes The causes are divided into three categories: iatrogenic, primary, and secondary.[medical-dictionary.thefreedictionary.com]
  • Common psychiatric abnormalities include agitated depression, lethargy, paranoia, overt psychosis, insomnia, emotional lability, irritability, anxiety and panic attacks [ 65 Kelly WF. Psychiatric aspects of Cushing's syndrome.[benthamopen.com]
  • […] immune defense mechanisms with increased rate of infections Gonadal dysfunction and hyperandrogenism: hirsutism (more frequently on the face), menstrual irregularity (oligoamenorrhea, amenorrhea) Mild to severe psychic disturbances(anxiety, depression, irritability[ojrd.biomedcentral.com]
Excitement
  • 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
  • Women may experience hormonal problems leading to amenorrhea and infertility. Men may also be affected with infertility and loss of libido. Diabetes and peptic ulceration may also cause symptoms.[symptoma.com]
  • It is characterized by upper body OBESITY; OSTEOPOROSIS; HYPERTENSION; DIABETES MELLITUS; HIRSUTISM; AMENORRHEA; and excess body fluid.[fpnotebook.com]
  • […] the abdomen), thinning of the skin that leads to spontaneous bruising, muscle weakness and wasting, back pain , osteopenia and osteoporosis , depression and other psychological symptoms, hypertension , and menstrual disturbances ( oligomenorrhea and amenorrhea[britannica.com]
  • […] centered over the chest and abdomen with thin arms and legs Excessive hair growth (hirsutism) on face, neck, chest, abdomen and thighs Female balding Generalized weakness and fatigue Blurry vision Vertigo Muscle weakness Menstrual disorders in women ( amenorrhea[aans.org]
  • Common: centripetal obesity with dorsocervical and supraclavicular fat pads, facial plethora and "moon face," fatigue, hyperglycemia, hypertension, mood lability, easy bruisability and skin atrophy, oligo/amenorrhea, hirsutism/acne (ACTH-dependent) More[hopkinsguides.com]
Oligomenorrhea
  • […] bluish stripes on the abdomen), thinning of the skin that leads to spontaneous bruising, muscle weakness and wasting, back pain , osteopenia and osteoporosis , depression and other psychological symptoms, hypertension , and menstrual disturbances ( oligomenorrhea[britannica.com]
  • […] increase in intraocular pressure, benign intracranial hypertension, cataracts, osteoporosis, aseptic necrosis of the femoral head, and pancreatitis, are more common in iatrogenic than endogenous CS, whereas features like hypertension, hirsutism, and oligomenorrhea[benthamopen.com]
Polyuria
  • […] oligo/amenorrhea, hirsutism/acne (ACTH-dependent) More specific: broad ( 1cm) purple striae, proximal muscle weakness Other: increased risk of infection, increased cardiovascular risk, thromboembolism, bone loss, fractures, kidney stones, polydipsia, polyuria[hopkinsguides.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]

Workup

Before any other examination, a suspicion of Cushing’s disease should prompt a thorough review of all medications, including different forms of the administered glucocorticoids, to exclude or verify the possibility of the condition’s iatrogenic origin. Apart from glucocorticoids, other compounds, like megestrol acetate with progesterone activity, also have glucocorticoid-like effects [7]. Herbal products have also been reported to contain glucocorticoids [8].

Laboratory workup shows signs of adrenal suppression (early morning cortisol and ACTH levels being low [1] [2] [3]), owing to low ACTH output caused by the exogenous glucocorticoids. However, it should be remembered that hydrocortisone increases cortisol levels [9]. Dehydroepiandrosterone sulfate levels are also low. ACTH stimulation tests are also below normal [1] [3]. Tests for 24-h urinary cortisol tend to be normal, at the lower values of the normal range [2] [3]. Patients are often hypokalemic, and blood glucose may be high [3]. Bone mineral density measurement will determine the level of osteopenia or osteoporosis.

Nephrolithiasis
  • […] fungoides Myelodysplastic syndromes Myelopathy Myeloproliferative neoplasms Myocarditis Myotonic syndromes Narcolepsy Nasal papilloma Necrotizing enterocolitis Neonatal jaundice Neonatal respiratory distress syndrome Neoplastic meningitis Nephritic syndrome Nephrolithiasis[amboss.com]
  • Typical features include weight gain, central obesity, dorsocervical hump, moon face, facial plethora, thin skin, easy bruising, abdominal striae, hirsutism, proximal myopathy, osteopenia, glucose intolerance, hypertension, nephrolithiasis and psychiatric[springerplus.springeropen.com]

Treatment

  • She arrived at the ophthalmology department with a complaint of painful eyes, and was diagnosed with bilateral iridocyclitis and started on betamethasone sodium phosphate eye drop treatment .[medicalxpress.com]
  • A treatment attempt with standard-dose mesalamine was unsuccessful, but treatment with budesonide restored her digestive health. She was maintained on 9 mg daily, but efforts to lower the dose were unsuccessful.[acgcasereports.gi.org]
  • On hospital discharge, otolaryngology felt that the patient should continue with dexamethasone treatment because of continued respiratory distress and improvement of the patient's respiratory status on treatment.[pediatrics.aappublications.org]
  • Discussion: Inhaled steroids in the treatment of asthma or COPD do not usually lead to relevant systemic adverse events.[thieme-connect.com]
  • Moreover, we searched the drug treatment files for relevant prescriptions.[bmj.com]

Prognosis

  • However, surgery helps the patient for a while only when the tumour is malignant and the long term prognosis is poorer than that of benign tumours. (iii) Pituitary gland tumour - This is the cause of 85% of cushingoid cases.[highstreeteppingvetclinic.com]
  • It is wise therefore to give slightly suboptimal replacement therapy ( Adrenal carcinomas have a very poor prognosis and most patients are dead within 2 years.[emedmd.com]
  • Prognosis Prognosis depends on the source of the problem. When pituitary adenomas are identified as the source of increased ACTH leading to cortisol excess, about 80% of patients are cured by surgery.[medical-dictionary.thefreedictionary.com]
  • Untreated Cushing associated with high risk of mortality, poor prognosis seen in ectopic ACTH syndrome and adrenocortical carcinoma Basis for recommendation Nieman LK et al: The diagnosis of Cushing's syndrome: an Endocrine Society Clinical Practice Guideline[hopkinsguides.com]
  • Prognosis depends on the underlying cause and ability to control the cortisol excess.[physio-pedia.com]

Etiology

  • Use Additional Use Additional Help Certain conditions have both an underlying etiology and multiple body system manifestations due to the underlying etiology.[icd10data.com]
  • It has been commonly described with oral and topical steroid use, but scarce reports have documented intranasal steroid usage as the etiology in infancy.[pediatrics.aappublications.org]
  • Steps necessary for the etiological diagnosis of ACTH dependent Cusging’s syndrome are summarized in Figure 2 . Figure 2 Steps necessary for the etiological diagnosis of ACTH-dependent Cushing’s syndrome.[ojrd.biomedcentral.com]
  • May have non-specific manifestations of Cushing and mildly elevated cortisol (1-3 times upper limit of normal) which revert to normal with treatment of underlying etiology.[hopkinsguides.com]

Epidemiology

  • J Clin Endocrinol Metab 85:637, 2000 [PMID:10690869] Etxabe J, Vazquez JA: Morbidity and mortality in Cushing's disease: an epidemiological approach.[hopkinsguides.com]
  • […] cohort study Research BMJ 2012 ; 345 doi: (Published 30 July 2012) Cite this as: BMJ 2012;345:e4928 Laurence Fardet , associate professor and senior consultant in internal medicine 1 2 3 4 , Irene Petersen , principal research associate in statistics and epidemiology[bmj.com]
  • Google Scholar Steffensen C, Bak AM, Rubeck KZ, Jorgensen JO: Epidemiology of Cushing's syndrome. Neuroendocrinology. 2010, 92 (Suppl 1): 1-5.[ojrd.biomedcentral.com]
  • Epidemiology of Cushing's syndrome. Neuroendocrinology 2010; 92(Suppl 1 ): 1-5. ]. Depending upon the level of plasma ACTH, the causes of Cushing syndrome can be broadly divided into two: 1) ACTH dependent CS and 2) ACTH–independent CS.[benthamopen.com]
  • J Bone Miner Res 15:993–1000 View Article Google Scholar van Staa TP, Leufkens HG et al (2002) The epidemiology of corticosteroid-induced osteoporosis: a meta-analysis.[springerplus.springeropen.com]
Sex distribution
Age distribution

Pathophysiology

  • Louis: Saunders Elsevier; 2009: 481-483. 3.0 3.1 3.2 Harold J Bruyere: 100 Case Studies in Pathophysiology.[physio-pedia.com]
  • Pathophysiology Glucocorticoids’ bioavailability is between 60% and 100%.[emedicine.medscape.com]
  • The pathophysiologic roles of inter-leukin-6 in human disease. Ann Intern Med . 1998;128:127–37. 15. Cushing H. The basophil adenomas of the pituitary body and their clinical manifestations (pituitary basophilism).[aafp.org]
  • The pathophysiological mechanism varies depending upon the cause of CS [ 60 Soffer LJ, Iannaccone A, Gabrilove JL. Cushing's syndrome A study of fifty patients. Am J Med 1961; 30: 129. ].[benthamopen.com]
  • This review summarizes potential pathophysiological mechanisms, diagnostic approaches, and therapies.[ojrd.biomedcentral.com]

Prevention

  • Inhaled corticosteroids and the prevention of readmission to hospital for asthma. Am J Respir Crit Care Med 1998; 158: 126-32. , 6 Suissa S, Ernst P, Benayoun S , et al. Low-dose inhaled corticosteroids and the prevention of death from asthma.[benthamopen.com]
  • Taking medicines to prevent bone loss. This can help reduce the risk of fractures if you develop osteoporosis. Taking medicine to decrease the amount of glucocorticoid medicine that you need.[medlineplus.gov]
  • To prevent weight gain, aerobic exercise is good to increase your heart rate. Examples of aerobic exercise include fast walking, jogging, cycling, and swimming. [6] Education on avoiding falls and removing loose rugs and other hazards in the home.[physio-pedia.com]
  • Because glucocorticoids suppress the immune system, they reduce inflammation and are also frequently given to people who have had organ transplants to prevent the immune cells from attacking the transplant.[endocrinediseases.org]
  • Incomplete spinal cord syndromes Infection prevention and control Infectious mononucleosis Infective endocarditis Infertility Inflammation of the eyelids Inflammatory myopathies Influenza Inguinal hernia Inhalational anesthetics Inherited hyperbilirubinemia[amboss.com]

References

Article

  1. Epperla N, McKiernan F. Iatrogenic Cushing syndrome and adrenal insufficiency during concomitant therapy with ritonavir and fluticasone. Springerplus. 2015 Aug 27;4:455.
  2. Yeoh SW. Iatrogenic Cushing Syndrome from Interaction Between Ritonavir and Oral Budesonide During Direct Acting Antiviral Hepatitis C Therapy. J Clin Exp Hepatol. 2016 Sep;6(3):246-249.
  3. Celik O, Niyazoglu M, Soylu H, Kadioglu P. Iatrogenic Cushing's syndrome with inhaled steroid plus antidepressant drugs. Multidiscip Respir Med. 2012 Aug 29;7(1):26.
  4. Findling JW, Raff H. Cushing's Syndrome: important issues in diagnosis and management. J Clin Endocrinol Metab. 2006 Oct;91(10):3746-3753
  5. Di Somma C, Pivonello R, Loche S, et al. Severe impairment of bone mass and turnover in Cushing’s disease: comparison between childhood-onset and adulthood-onset disease. Clin Endocrinol (Oxf) 2002; 56:153–158.

  6. Magiakou MA, Mastorakos G, Oldfield EH, et al. Cushing’s syndrome in children and adolescents. Presentation, diagnosis, and therapy. N Engl J Med 1994; 331:629–636.

  7. Mann M, Koller E, Murgo A, Malozowski S, Bacsanyi J, Leinung M. Glucocorticoidlike activity of megestrol. A summary of Food and Drug Administration experience and a review of the literature. Arch Intern Med. 1997 Aug 11-25;157(15):1651-1656.
  8. Abuchaibe C, Akhtar ON. SAT-0776: Exogenous Cushing's Syndrome after Use of OTC Joint Supplement. Adrenal Case Reports 1 - CAH and Adrenal Insufficiency. Endocrine Society's 96th Annual Meeting and Expo, June 21–24, 2014 – Chicago. Available at http://press.endocrine.org/doi/abs/10.1210/endo-meetings.2014.AHPAA.1.SAT-0776. Accessed: 4/2/15.
  9. Newell-Price J, Bertagna X, Grossman AB, Nieman LK. Cushing's syndrome. Lancet. 2006 May 13;367(9522):1605-1617.

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Last updated: 2018-06-21 20:16