How to Respond to a Classic CAH Adrenal Crisis

Understanding the Challenges of Managing Congenital Adrenal Hyperplasia

Congenital adrenal hyperplasia (CAH) is a lifelong condition that requires careful management to prevent serious complications. One of the most critical issues for patients with CAH is the risk of an acute adrenal insufficiency, also known as an adrenal crisis. This life-threatening event occurs when the body's cortisol levels drop dangerously low, leading to severe symptoms and potentially fatal outcomes.

Adrenal crises are the leading cause of death in individuals with CAH, accounting for up to 42% of excess deaths according to a population-based study from 2014. Experts like Deborah Merke, MD, MS, from the National Institutes of Health (NIH), have emphasized that this fear of adrenal crises is deeply ingrained in the lives of those affected by the condition. Regardless of age or clinical status, patients consistently express concern about the risks associated with adrenal insufficiency. As treatment strategies evolve, particularly with efforts to reduce glucocorticoid doses, it becomes even more important to recognize and address these risks.

Tânia Bachega, MD, PhD, from the University of São Paulo in Brazil, also highlighted the ongoing challenges of managing CAH. While glucocorticoid therapy has significantly improved survival rates, the threat of acute adrenal insufficiency remains a major concern for both patients and healthcare providers.

Causes and Symptoms of Adrenal Crisis

Classic CAH is typically diagnosed at birth and is caused by a genetic mutation affecting the 21-hydroxylase enzyme. This deficiency leads to reduced cortisol production, which prompts the body to overstimulate the adrenal glands, resulting in excessive androgen production. The disruption of hormone levels can lead to a range of symptoms, including low appetite, nausea, dizziness, and fatigue.

An adrenal crisis is triggered when the body experiences unusual stress—such as illness, surgery, or insufficient medication—which causes cortisol levels to drop critically. This leads to problems with blood pressure, blood glucose regulation, and salt depletion. Symptoms of an adrenal crisis include low blood pressure, low blood glucose, severe dehydration, vomiting, diarrhea, weakness, confusion, dizziness, seizures, and fainting.

The salt-wasting form of CAH is particularly dangerous, as it leads to excessive sodium loss in the urine due to reduced aldosterone. This can result in shock and other life-threatening conditions.

Managing Adrenal Crises: Sick-Day Rules and Emergency Protocols

When patients with CAH experience signs of illness, they should follow "sick-day rules" and take extra doses of hydrocortisone. According to guidelines from the Endocrine Society, glucocorticoid dosage should be increased during febrile illness, gastroenteritis with dehydration, major surgery, or trauma.

Sick-day adjustments vary depending on the severity of the illness, the patient’s normal steroid dose, and the type of steroid being used. All patients should have access to a glucocorticoid injection kit and receive education on its use to prevent adrenal crises.

Immediate action is crucial during an adrenal crisis. Short-term administration of high-dose glucocorticoids is never harmful, but failure to treat can be fatal. Guidelines from the U.K. Society for Endocrinology emphasize that hydrocortisone should not be withheld, even in pregnant women. It is inactivated in the placenta and does not harm the unborn baby, but untreated adrenal insufficiency during pregnancy can lead to maternal and fetal death.

It is important to note that increasing glucocorticoid doses is not necessary during mild stress, emotional strain, or routine physical activity.

Prevention and Education: Key to Reducing Risk

Preventing adrenal crises requires consistent education and preparation. Bachega recommends that healthcare providers ask patients with CAH about infections, their knowledge of what to do during an infection, and whether they have an identification card. This should be done at every clinical appointment.

Patients should always carry an emergency letter and wear medical identification indicating their condition. These steps help ensure that healthcare professionals can respond quickly and appropriately in an emergency.

Educating patients and caregivers is essential for recognizing warning signs and knowing how to manage adrenal crises. During childhood, this knowledge often falls under the responsibility of caregivers, making it vital to foster patient autonomy as they transition into adulthood. Transition care plays a key role in teaching patients how to adjust glucocorticoid therapy during sick-day episodes.

Bachega also stressed the need for better education among healthcare providers. She shared a troubling example of losing three patients due to a lack of awareness in emergency departments. Improving provider education is critical to ensuring timely and effective treatment for all patients with CAH.