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.
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 . Together with oral budesonide, it resulted in weakness, muscle wasting, and other characteristic symptoms in a hepatitis sufferer . Inhaled fluticasone propionate taken together with antidepressants was reported to result in the rapid development of symptoms of Cushing’s syndrome .
The increased prevalence of obesity can make it difficult to identify a patient with true Cushing’s syndrome , 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 , 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 .
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 . Herbal products have also been reported to contain glucocorticoids .
Laboratory workup shows signs of adrenal suppression (early morning cortisol and ACTH levels being low   ), owing to low ACTH output caused by the exogenous glucocorticoids. However, it should be remembered that hydrocortisone increases cortisol levels . Dehydroepiandrosterone sulfate levels are also low. ACTH stimulation tests are also below normal  . Tests for 24-h urinary cortisol tend to be normal, at the lower values of the normal range  . Patients are often hypokalemic, and blood glucose may be high . Bone mineral density measurement will determine the level of osteopenia or osteoporosis.