Endocrinologists and gastroenterologists at Mount Sinai have joined forces to describe treatment protocols and raise awareness of a common but under-recognized and undertreated clinical problem: Secondary adrenal insufficiency (AI) arising from glucocorticoid treatment in patients with inflammatory bowel disease (IBD).
Corticosteroids are widely used to treat inflammatory conditions, including Crohn’s disease and ulcerative colitis. The increasing use of biologic agents for chronic treatment of those two conditions has meant that corticosteroids are typically reserved for intermittent use during flares. The intermittent use of steroids due to these more efficacious therapies has actually uncovered a new issue—secondary adrenal insufficiency when corticosteroids are withdrawn.
This glucocorticoid-induced AI (GC-AI) is often missed because there are no specific guidelines for gastroenterologists regarding checking adrenal function in these patients. Moreover, the symptoms of AI—nausea, vomiting, abdominal pain, and decreased appetite—can mimic those of an IBD flare.
“We had a patient with Crohn’s disease come in who was very sick, who had been on and off steroids and turned out to have adrenal insufficiency, but it wasn’t recognized initially,” says Alice C. Levine, MD, Professor of Medicine (Endocrinology, Diabetes and Bone Disease) at the Icahn School of Medicine at Mount Sinai. “We discovered there was a lack of knowledge on the part of gastroenterology about how to test for and treat this phenomenon.”
To address this condition, physician-scientists in Gastroenterology and Endocrinology organized a multidisciplinary initiative, including a three-hour virtual symposium in May 2023. The event was co-chaired by Dr. Levine and Jean-Frédéric Colombel, MD, Director of the Leona M. and Harry B. Helmsley Charitable Trust Inflammatory Bowel Disease Center at Icahn Mount Sinai.
In the symposium, Dr. Colombel and two gastroenterology fellows provided overviews about use of corticosteroids to treat IBD in adults and children. Dr. Levine and two endocrinology fellows, Rachel Sheskier, MD, and Natalia Viera Feliciano, MD, along with other staff, spoke about the clinical presentation and management of secondary adrenal insufficiency due to exogenous steroid use.
“For endocrinologists, this is a big opportunity for us to teach our peers in different specialties about how the medications they are prescribing might be affecting the endocrine system.”
Rachel Sheskier, MD
From left: Rachel Sheskier, MD, Alice C. Levine, MD, and Natalia Viera Feliciano, MD,
Following the symposium, Dr. Sheskier, Dr. Viera-Feliciano, and two medical residents conducted a systematic review and meta-analysis and drafted an expert consensus manuscript to be submitted for publication in a gastroenterology journal.
The multidisciplinary aspect is key, Dr. Sheskier says. “Mount Sinai is a big center with world-renowned people, but we often tend to stay in our lanes. Yet many medications cross over and may produce side effects that require the expertise of other specialists. There is so much education that everyone can receive with multidisciplinary talks and conferences.”
The consensus document includes results from the meta-analysis, in which the pooled prevalence of AI in patients with IBD following corticosteroid use was about 25.6 percent. However, there was a wide range across different types of glucocorticoids, doses, and durations of treatment.
Nine total recommendations about testing and management are provided, including during surgery and pregnancy. “AI after discontinuation of steroids is common in patients with IBD, adults and pediatric alike,” the document said. “The threshold to test steroid users for AI should be low in clinical practice.”
According to Dr. Levine, “low threshold” means “any patient with IBD who has a history of being on steroids, which is most of them. And if they come in with an acute illness, you really have to check whether part of that illness is secondary AI.”
Testing should involve measurement of a morning serum cortisol, but it will only be accurate if the patient is on a low dose of glucocorticoid in the weeks prior and the drug is held for a minimum of 24 hours prior to measurement. Guidance is also given for variable dosing of glucocorticoid replacement for patients who are asymptomatic, symptomatic, and those who require “stress dosing” during acute illness.
Of course, GC-AI is not limited to IBD or gastroenterology. Corticosteroids are commonly used in other fields, including pain medicine, rheumatology, dermatology, orthopedics, pulmonology, and oncology.
Dr. Levine notes that in many fields of medicine, these are given in “steroid-sparing” regimens that are believed to cause less systemic absorption but have also been linked to GC-AI. “Budesonide was always thought to be an oral steroid that doesn’t really get absorbed in the GI tract and just works locally, but that turns out to be a fallacy. It’s really a very big issue,” she says.
The endocrinology team is considering embarking on similar projects with other specialties. If they do, pain medicine, with its heavy use of intra-articular steroid injections, would be a likely next candidate, Dr. Sheskier says. “Patients in general are exposed to a lot of different steroids,” she says. “For endocrinologists, this is a big opportunity for us to teach our peers in different specialties about how the medications they are prescribing might be affecting the endocrine system, and particularly the adrenals.”