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].

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.

The primary treatment for iatrogenic Cushing Syndrome is to gradually reduce the dose of glucocorticoid medication under medical supervision. Abrupt cessation can lead to adrenal insufficiency, a potentially life-threatening condition. In some cases, alternative medications with fewer side effects may be considered. Supportive treatments may include managing symptoms such as high blood pressure or diabetes, if present.

The prognosis for iatrogenic Cushing Syndrome is generally good if the condition is recognized early and managed appropriately. Most symptoms improve with the reduction or cessation of glucocorticoid therapy. However, some effects, like osteoporosis or cardiovascular issues, may require long-term management.

The etiology of iatrogenic Cushing Syndrome is the administration of glucocorticoids, which are often prescribed for conditions like asthma, rheumatoid arthritis, lupus, and other inflammatory or autoimmune diseases. The risk increases with higher doses and longer duration of treatment.

Iatrogenic Cushing Syndrome is relatively common due to the widespread use of glucocorticoids in medical practice. It can affect individuals of any age or gender, although those on long-term steroid therapy are at higher risk. The exact prevalence is difficult to determine, as it depends on prescribing practices and patient adherence to medication regimens.

The pathophysiology of iatrogenic Cushing Syndrome involves the suppression of the hypothalamic-pituitary-adrenal (HPA) axis due to external glucocorticoid administration. This suppression leads to decreased production of endogenous cortisol by the adrenal glands. The excess glucocorticoids cause the characteristic symptoms by affecting various metabolic processes, including protein and fat metabolism, and altering immune responses.

Preventing iatrogenic Cushing Syndrome involves careful management of glucocorticoid therapy. This includes using the lowest effective dose for the shortest possible duration and considering alternative treatments when appropriate. Regular monitoring and follow-up with healthcare providers can help identify early signs of the syndrome.

Iatrogenic Cushing Syndrome is a condition caused by prolonged exposure to glucocorticoid medications. It presents with symptoms like weight gain, skin changes, and high blood pressure. Diagnosis involves recognizing the use of glucocorticoids, and treatment focuses on reducing or stopping these medications. With proper management, the prognosis is generally favorable.

If you are taking glucocorticoid medications and notice symptoms such as unusual weight gain, changes in your skin, or mood swings, it is important to discuss these with your healthcare provider. They can help determine if these symptoms are related to your medication and adjust your treatment plan accordingly. Regular check-ups and open communication with your doctor are key to managing your health effectively.

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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.
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