Metabolomic profiling reveals adrenal suppression due to inhaled corticosteroid treatment for asthma

Inhaled cortical steroids (ICS) can help patients manage asthma symptoms, and recent updates to asthma treatment guidelines have expanded recommended, low-dose treatment. But concerns persist that ICS may reduce production of the steroid hormone cortisol in the body leading to adrenal suppression. While initial adrenal suppression symptoms are subtle, continued progression can lead to fatigue, headache, abdominal pain, vomiting and psychiatric symptoms.

Until now, studies of ICS and adrenal suppression have been limited and have produced conflicting findings. To better understand the association between ICS and adrenal suppression, researchers from Brigham and Women's Hospital and the University of Cambridge conducted the largest metabolomic study of asthma to date. By analyzing the blood plasma of 14,000 individuals from four independent study cohorts, the team identified 17 steroid metabolites that were reduced in individuals with asthma and found that, even among patients taking low-dose ICS, ICS usage was associated with reduced cortisol levels. The researchers also found significant associations between adrenal insufficiency symptoms, including fatigue and anemia, in asthma patients taking ICS treatment compared to those who were not.

The use of ICS has been instrumental in reducing asthma exacerbations and improving overall quality of life. However, while their effectiveness should not be understated, our findings suggest that the risks of ICS usage must also be considered."

Jessica Lasky-Su, ScD, co-senior author, Channing Division of Network Medicine, Brigham and Women's Hospital

"Our work suggests that simple measures, such as regular cortisol monitoring and prescription of the lowest effective ICS dose, may help to mitigate the systemic side effects of ICS use," said co-senior author Claudia Langenberg, MD, PhD, of the MRC Epidemiology Unit at the University of Cambridge, UK, and Berlin Institute of Health at Charité Universitätsmedizin, Germany.

 

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New genetic study offers hope for asthma sufferers

A new study has offered fresh hope for asthma sufferers by identifying a genetic variant that could improve the safety and effectiveness of corticosteroids, drugs that are used to treat a range of common and rare conditions including asthma, and chronic obstructive pulmonary disease (COPD).
Corticosteroids are very effective in the treatment of asthma and COPD, with more than 20 million prescriptions issued in the UK annually. Unfortunately, corticosteroids can also cause side effects, one of which is adrenal suppression, seen in up to 1/3 of people tested. People with this condition do not make enough cortisol. Cortisol helps the body respond to stress, recover from infections and regulate blood pressure and metabolism.

Adrenal suppression can be very difficult to diagnose, as it can present with a spectrum of symptoms from non-specific symptoms such as tiredness, to serious illness and death. The majority of patients do not develop adrenal suppression, and the reasons why some do, and while other don’t, despite using similar doses of corticosteroids were not previously understood.

In a world first, the researchers, conducted a genome-wide association study (GWAS) to pinpoint the genes responsible for increasing the risk of a person developing adrenal suppression.

This method searches a person’s DNA (genome) for small variations, called single nucleotide polymorphisms (SNPs). Each person carries about three million SNPs, but if a particular SNP occurs more frequently in people with a particular condition than in people without the condition, it can pinpoint the underlying reason for the difference.

The researchers identified two groups of children with asthma, and one group of adults with chronic obstructive pulmonary disease (COPD), all of whom used inhaled corticosteroid medications. Each patient’s adrenal function was tested. This is the largest published cohort of children ever tested for adrenal suppression (580 children in total).

Individuals who had a particular variation in a specific gene (platelet derived growth factor D; PDGFD) had a markedly increased risk of adrenal suppression, both in the children with asthma and adults with COPD. This risk increased if the patient had two copies of the variation (one from their mother, one from their father). Children with two copies of the high risk variation in PDGFD were nearly six times more likely to develop adrenal suppression than children with no copies.

A researcher said: “Our highly novel findings offer the potential to develop personalised approaches therapy. This could involve screening patients to avoid or minimise steroid use if they are at high risk, or if steroids are needed, developing a specific plan to monitor their adrenal function.”

“However, it is important to stress that steroids are effective medications, and patients should not stop taking these medicines without medical input. If you are worried about any side effects, please consult your doctor, nurse or pharmacist looking after you.”

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