Inhaled steroids (IS) are a common and effective treatment for chronic respiratory diseases. However, patients and healthcare providers must be aware of their potential to interfere with the body’s natural hormone production. These drugs can cause adrenal insufficiency (AI), though this complication is rare when the medication is used at low or moderate doses. The risk increases with prolonged use of high doses or when certain patient and drug factors are present. Recognizing this association is crucial for managing a condition that can range from vague symptoms to a life-threatening medical emergency.
Understanding Inhaled Steroids and Adrenal Insufficiency
Inhaled steroids (ICS) are synthetic versions of the body’s natural anti-inflammatory hormones. They are the primary treatment for conditions like asthma and Chronic Obstructive Pulmonary Disease (COPD), delivered directly to the airways via an inhaler to reduce chronic inflammation. This local delivery mechanism is designed to maximize therapeutic effect in the lungs.
Adrenal insufficiency (AI) occurs when the adrenal glands, located atop the kidneys, fail to produce adequate amounts of the hormone cortisol. Cortisol is a glucocorticoid that plays a fundamental role in maintaining blood pressure, regulating metabolism, and enabling the body to respond appropriately to stress, such as illness or injury. When AI is caused by an external medication like an inhaled steroid, it is referred to as secondary adrenal insufficiency.
How Inhaled Steroids Suppress Hormone Production
Inhaled steroids lead to adrenal insufficiency by interfering with the Hypothalamic-Pituitary-Adrenal (HPA) axis, a complex hormonal feedback loop. Normally, the hypothalamus releases Corticotropin-Releasing Hormone (CRH), signaling the pituitary gland to release Adrenocorticotropic Hormone (ACTH). ACTH then prompts the adrenal glands to synthesize and release cortisol.
When an inhaled steroid is used, a small portion is absorbed into the systemic circulation. This absorbed synthetic glucocorticoid acts as an exogenous source of cortisol, exerting a potent negative feedback signal on the HPA axis. The hypothalamus and pituitary gland interpret this signal as sufficient glucocorticoids and reduce or stop the release of CRH and ACTH.
Prolonged suppression of ACTH causes the adrenal glands to lose necessary stimulation and become dormant, a condition known as adrenal suppression (AS). This suppression prevents the glands from rapidly increasing cortisol production when faced with a physical stressor. If the medication is suddenly stopped or the body encounters a severe stressor, the resulting lack of endogenous cortisol can precipitate a crisis.
Factors That Increase Systemic Risk
The risk of developing adrenal insufficiency from inhaled steroids depends on several factors. A primary determinant is the total daily dosage and the duration of therapy, as higher doses used over long periods increase systemic absorption and HPA axis suppression. Some specific steroid compounds, such as fluticasone, are associated with higher risk compared to others. This is attributed to their greater potency and lipophilicity, which leads to increased systemic absorption and a longer half-life.
Patient-specific factors also contribute to systemic risk.
- Children may absorb a higher effective dose relative to their body surface area.
- Concurrent use of other steroid medications, including nasal sprays or oral courses, compounds the total systemic glucocorticoid load.
- Strong inhibitors of the CYP3A4 liver enzyme can slow the breakdown of the inhaled steroid, leading to higher drug levels in the bloodstream and increasing the risk of adrenal suppression.
Recognizing the Signs of Adrenal Crisis
Adrenal insufficiency can present with vague and non-specific symptoms, making it challenging to identify in its early stages. Common complaints include persistent fatigue, generalized weakness, loss of appetite (anorexia), and unintentional weight loss. Patients may also experience gastrointestinal symptoms such as nausea, vomiting, or abdominal pain.
The condition becomes an acute adrenal crisis when the body faces a significant physiological stressor, such as an infection, major injury, or surgery. In this emergency state, the suppressed adrenal glands cannot produce the surge of cortisol required to cope with the stress. Symptoms escalate rapidly, including profound weakness, severe hypotension, and signs of shock. The lack of cortisol impairs vascular tone and metabolic function, potentially resulting in dangerously low blood sugar (hypoglycemia) and confusion.
In children, a noticeable deceleration in linear growth velocity or delayed onset of puberty may indicate chronic HPA axis suppression. Any high-risk patient experiencing severe, uncharacteristic symptoms during stress should seek immediate medical attention.
Diagnosis, Monitoring, and Treatment
Diagnosis of inhaled steroid-induced adrenal insufficiency often begins with a high index of suspicion, followed by specific laboratory testing to evaluate HPA axis function. An initial screening test measures the early morning serum cortisol level, which reflects the hormone’s natural peak. A low morning cortisol level suggests adrenal suppression, but a definitive diagnosis requires a dynamic test.
The most common confirmatory test is the ACTH stimulation test (short Synacthen test). This involves administering a synthetic version of ACTH and measuring the cortisol response in the blood. A blunted or inadequate rise in cortisol confirms that the adrenal glands are suppressed and cannot respond appropriately to stimulation.
For high-risk patients, such as those receiving long-term high-dose therapy, regular monitoring is recommended to detect suppression before symptoms occur. If adrenal insufficiency is confirmed, the primary treatment is hydrocortisone replacement therapy, an oral corticosteroid. Patients must be educated about “stress dosing,” meaning they temporarily increase their oral steroid dose when sick or undergoing surgery to prevent a life-threatening adrenal crisis. Providing patients with a steroid card ensures medical personnel are aware of their condition during an emergency.