Gabapentin's alarming impact on adrenal function and infection risk

Med News: A recent case report has shed light on a lesser-known complication associated with the use of gabapentin, a common medication prescribed for nerve pain and seizures. This Med News report discusses how gabapentin can potentially lead to adrenal insufficiency and increase the risk of infection, especially in patients undergoing surgery. Researchers from the 1st Department of Orthopaedics at P. & A. Kyriakou Children’s Hospital in Athens-Greece, in collaboration with the Medical School at the National and Kapodistrian University of Athens, reported a case of a young patient who developed significant complications after receiving gabapentin as part of his pain management treatment.

 Gabapentin's alarming impact on adrenal function and infection risk

Gabapentin: More Than Just a Pain Reliever
Gabapentin (GBP) is widely known for its ability to relieve nerve pain and seizures. It mimics the neurotransmitter gamma-aminobutyric acid (GABA) and has been found to have various off-label uses, including the management of chronic pain. However, this article discusses how GBP can also interfere with the body's stress response by affecting the hypothalamic-pituitary-adrenal (HPA) axis, which regulates cortisol production. This disruption of the HPA axis can have serious consequences, especially for patients who are already under significant stress, such as those undergoing surgery.
 
The Case of Adrenal Insufficiency
The study detailed the case of a 17-year-old male patient who had been diagnosed with osteosarcoma, a type of bone cancer. Following the surgical removal of his tumor and the placement of a prosthesis, he was prescribed gabapentin to manage post-operative pain. Over time, the patient developed a series of complications, including adrenal insufficiency, which is a condition where the adrenal glands do not produce enough cortisol. Cortisol is essential for managing stress and inflammation, especially after surgery.
 
The patient’s cortisol levels dropped to alarmingly low levels, necessitating immediate intervention. The medical team had to administer hydrocortisone, a synthetic cortisol replacement, to help the patient manage this insufficiency. As the patient’s surgery-related stress peaked, so did the complications associated with his adrenal insufficiency, and his ability to fight off infections weakened.

Gabapentin's Role in Cortisol Suppression
Gabapentin’s role in the suppression of cortisol production is still being studied, but what we do know is that it can have a significant effect on how the body handles stress. Cortisol, produced by the adrenal glands, is often referred to as the “stress hormone” because it plays a crucial role in helping the body respond to stressful situations, such as surgery or infection.
 
The study found that gabapentin may blunt this response, making it harder for the body to produce the cortisol it needs to manage the stress of surgery. As cortisol levels drop, patients become more susceptible to infections, and healing becomes more difficult. In this case, the patient devel oped a series of infections, including those caused by Staphylococcus hominis and Staphylococcus xylosus, which are bacteria that are normally harmless but can become dangerous when the immune system is weakened.
 
Infection Risk in Immunocompromised Patients
One of the most troubling aspects of this case was the increased risk of infection linked to gabapentin-induced adrenal insufficiency. The patient developed a significant wound infection after surgery, caused by Staphylococcus hominis, a bacterium that is typically not a major threat but can cause serious infections in immunocompromised individuals. Following this, a more unusual infection with Staphylococcus xylosus occurred, further complicating his recovery.
 
Both of these infections are rare in healthy individuals but pose a serious threat to those with weakened immune systems, as was the case with this patient. The weakened immune response can be attributed to the gabapentin's impact on cortisol production, making it difficult for the body to mount an effective defense against these pathogens.
 
The Importance of Monitoring Cortisol Levels
The findings of this study highlight the need for doctors to carefully monitor cortisol levels in patients who are prescribed gabapentin, particularly those undergoing surgery or who are otherwise at risk for adrenal insufficiency. This patient’s experience underscores the importance of individualized care, where doctors must consider the potential risks of medications like gabapentin, especially when used in high-stress situations.
 
The medical team in this case was able to address the patient's adrenal insufficiency with hydrocortisone, but this came after the patient had already experienced serious complications. Moving forward, more research is needed to determine how doctors can better anticipate and prevent these kinds of issues in patients who are prescribed gabapentin.
 
Broader Implications for Gabapentin Use
The potential for gabapentin to interfere with cortisol production and the body's stress response raises broader questions about its use in certain populations. While gabapentin is generally considered safe, this case highlights the importance of being cautious when prescribing it to patients who are already under significant physiological stress. Surgical patients, in particular, may be at increased risk for complications like adrenal insufficiency and infection if their cortisol levels are not closely monitored.
 
Several studies have explored the relationship between gabapentin and cortisol levels. For instance, research has shown that gabapentin can significantly lower cortisol levels in post-surgical patients, reducing their ability to handle the stress of surgery. In one study, women undergoing abdominal hysterectomy who were given gabapentin showed a significant reduction in cortisol levels 24 hours after surgery, compared to a control group. This reduction in cortisol can be beneficial in terms of pain management, but it also has the potential to increase the risk of complications, as seen in the current case.
 
Conclusion: The Need for Vigilant Monitoring
This case report emphasizes the complex relationship between gabapentin use and adrenal insufficiency, particularly in high-stress environments like surgery. Doctors must weigh the benefits of using gabapentin to manage pain against the risks of suppressing the body’s stress response. Regular monitoring of cortisol levels in patients receiving gabapentin is crucial to catching and addressing adrenal insufficiency before it leads to more serious complications, like infection.

In summary, while gabapentin remains a valuable tool in managing pain and seizures, its potential impact on adrenal function and infection risk warrants careful consideration. Clinicians should remain vigilant, particularly in perioperative settings or in patients with pre-existing conditions that could predispose them to adrenal insufficiency.
 
The study findings were published in the peer-reviewed journal: Pharmaceuticals.
https://www.mdpi.com/1424-8247/17/9/1174
 
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