Iatrogenic Cushing syndrome is a condition that develops when the body has an excessive amount of the hormone cortisol due to external medical factors. The term “iatrogenic” specifically indicates that the condition is a side effect of medical treatment. Cortisol, often called the “stress hormone,” is a natural steroid produced by the adrenal glands that helps regulate various bodily functions, including blood pressure, blood sugar, and inflammation. This syndrome manifests as physical and psychological signs that appear together because of prolonged exposure to high cortisol levels.
Understanding Its Development
Iatrogenic Cushing syndrome predominantly arises from sustained exposure to exogenous corticosteroids, which are human-made drugs structurally similar to the body’s own cortisol. These medications are widely utilized for their potent anti-inflammatory and immune-suppressing properties. They are commonly prescribed for chronic inflammatory disorders such as asthma, autoimmune diseases like lupus and rheumatoid arthritis, inflammatory bowel disease, and to prevent organ rejection after transplantation.
These corticosteroid medications, including common examples like prednisone, hydrocortisone, and dexamethasone, are available in various forms, such as oral tablets, injections, topical creams, and inhaled preparations. When these drugs are taken, they mimic the action of natural cortisol, signaling the body to reduce its own production of the hormone. This external input leads to the suppression of the hypothalamic-pituitary-adrenal (HPA) axis, the intricate system responsible for regulating the body’s natural cortisol levels.
With prolonged use, the HPA axis becomes less active, and the adrenal glands, which typically produce cortisol, may reduce their function. The continuous presence of these synthetic corticosteroids maintains a state of excess cortisol-like activity in the body, leading to the development of iatrogenic Cushing syndrome. The likelihood of developing the syndrome is influenced by the dose and duration of corticosteroid treatment, with higher doses and longer periods generally increasing the risk. In some instances, even herbal products adulterated with undisclosed glucocorticoids have been identified as a cause.
Common Symptoms
Iatrogenic Cushing syndrome presents with a range of noticeable physical and psychological changes due to the excess cortisol. A common physical manifestation is weight gain, particularly around the trunk, face (often described as a “moon face”), and between the shoulders, forming a “buffalo hump.” In contrast, the arms and legs may appear thin due to muscle weakness and fat loss.
Characteristic skin changes include the development of purple or pink stretch marks (striae) on the abdomen, thighs, breasts, and arms. The skin may become thin and fragile, leading to easy bruising and slow wound healing, while acne can also appear. Women might experience increased facial and body hair growth (hirsutism) and menstrual irregularities. Muscle weakness, particularly in the hips and shoulders, can make daily activities challenging.
The syndrome can also affect metabolic processes, potentially leading to elevated blood pressure and the development or worsening of type 2 diabetes. Low potassium levels in the blood may also occur. Psychological and cognitive symptoms are frequently reported, including depression, anxiety, irritability, and significant mood swings. Individuals may also experience difficulty concentrating, memory problems, and issues with sleep. These diverse symptoms contribute to a reduced quality of life and can impact daily functioning.
Diagnosis and Treatment Approaches
Diagnosing iatrogenic Cushing syndrome involves a thorough review of a person’s medical history, with particular attention to current and past medication use, especially corticosteroids. If corticosteroid use is identified as the likely cause, further extensive testing may not be necessary. However, if the cause is unclear or to rule out other forms of Cushing syndrome, several diagnostic tests can measure cortisol levels.
Diagnostic tests to measure cortisol levels include:
24-hour urinary free cortisol test, which measures cortisol excreted in urine over a full day.
Late-night salivary cortisol tests, as cortisol levels are typically low at night.
Blood tests to assess cortisol and ACTH (adrenocorticotropic hormone) levels.
Low-dose dexamethasone suppression test, where a cortisol-like drug is given to see if it suppresses the body’s natural cortisol production, which would not happen in Cushing syndrome.
Imaging studies, such as CT or MRI scans, might be used to examine the pituitary and adrenal glands if other causes are suspected.
The primary treatment for iatrogenic Cushing syndrome is the gradual reduction and eventual discontinuation of the offending corticosteroid medication, always under close medical supervision. Abruptly stopping corticosteroids can lead to a potentially serious condition called adrenal insufficiency or glucocorticoid withdrawal syndrome, characterized by symptoms like severe fatigue, joint pain, muscle aches, and nausea. Therefore, a slow tapering process is essential to allow the body’s own HPA axis to gradually recover its ability to produce cortisol. During this tapering, especially in times of illness or stress, patients may require temporary increases in their steroid dose to prevent adrenal crisis. Supportive care for lingering symptoms is also an important part of management.
Path to Recovery and Long-Term Considerations
Recovery from iatrogenic Cushing syndrome typically involves the gradual resolution of symptoms as the corticosteroid medication is carefully reduced and eventually discontinued. The body’s natural cortisol production, previously suppressed by the external medication, slowly begins to normalize as the hypothalamic-pituitary-adrenal (HPA) axis regains its function. This recovery process can be prolonged, often requiring several months to a year, and sometimes even longer, depending on the prior duration and dosage of corticosteroid use.
During this period, some individuals may still experience lingering effects. While many physical manifestations like weight gain and skin changes generally improve, certain psychological symptoms, such as depression or cognitive challenges, may endure and necessitate continued support. Existing health issues like osteoporosis or high blood pressure, developed from chronic cortisol excess, may also require ongoing medical management. Consistent monitoring by healthcare professionals is important to ensure complete HPA axis recovery and address any persistent health concerns.