What is Adrenal Crisis (Addisonian Crisis)?
An adrenal crisis, also known as Addisonian crisis, is a serious, life-threatening condition due to sudden insufficiency of adrenal glands. The mortality rate associated with this condition is 0.5 per 100 patient-years. This indicates that it is a leading cause of death for people with adrenal insufficiency. Patients can quickly worsen without prompt treatment, leading to fatal consequences at home or shortly after admission to a hospital.
This medical emergency happens when there is insufficient production of cortisol, a primary hormone produced by the adrenal gland. Causes of this insufficiency can be internal or external factors. Diagnosing this condition early and providing immediate treatment are crucial in saving a patient’s life and increasing their chances of survival.
Doctors must differentiate between adrenal insufficiency and adrenal crisis because failure to treat the latter promptly can be fatal. Even though the characteristics of this condition are well-documented, they are often overlooked, causing delays in treatment and an increase in severe disease and death rates.
Preventing adrenal crises requires educating patients and their families about steps to take when the patient is unwell and ensuring that they have emergency medications like intramuscular hydrocortisone at home.
The exact definition of an adrenal crisis is the subject of ongoing debates among medical experts. However, we will refer to the definition given by Rushworth et al in 2019: It is an abrupt worsening of the patient’s health, associated with one of these conditions: either a significant drop in blood pressure (systolic blood pressure less than 100 mm Hg) or a blood pressure that’s 20 mm Hg lower than the patient’s normal level.
Usually, these symptoms should get better and disappear within one to two hours after receiving emergency treatment. This is manifested by a significant drop in the low blood pressure within the first hour, followed by a gradual improvement in the patient’s condition over the next two hours.
What Causes Adrenal Crisis (Addisonian Crisis)?
The history of adrenal crisis, a severe condition related to low levels of certain hormones, begins with Thomas Addison, who was the first to describe adrenal insufficiency in 1855. The discovery of cortisone in the late 1940s by Hench, Kendall, and Reichstein significantly changed how adrenal insufficiency was treated, greatly improving the life expectancy of those affected by it.
In the 1930s, tuberculosis was the primary cause of adrenal insufficiency, responsible for about 70% of cases. Nowadays, autoimmune adrenalitis, also known as Addison’s disease, is the most common cause in developed countries, while tuberculosis still leads in developing countries.
Up to half of patients previously diagnosed with adrenal insufficiency can have an acute adrenal crisis as the initial sign of their condition. In fact, in one study, about 10% of patients with an adrenal crisis did not have an identifiable cause.
Adrenal crises can be triggered by various factors such as different types of infections, including COVID-19, flu-like illnesses, experiencing severe physical or emotional stress, becoming pregnant or giving birth, undergoing surgery, exposure to extreme temperatures, and not following hormone replacement therapy. Starting treatment for certain conditions like thyroid toxicity in someone with untreated adrenal insufficiency can also cause it, as can taking certain medications that inhibit adrenal function or for cancer treatment.
Risk Factors and Frequency for Adrenal Crisis (Addisonian Crisis)
It’s hard to pinpoint exactly how often adrenal crises occur in the general population. However, it is estimated that about 6% to 8% of people with adrenal insufficiency will experience an adrenal crisis each year. Even those who have received thorough education on how to manage and prevent adrenal insufficiency still have a high occurrence rate. Among these well-informed patients, about 6% will die as a result of an adrenal crisis. The yearly frequency of adrenal crisis in people with Addison’s disease stays around 8%.
There are several factors that can put a person at risk of having an adrenal crisis:
- Having a diagnosed history of adrenal insufficiency or a previous adrenal crisis.
- Being diagnosed with primary adrenal insufficiency, this poses a higher risk than secondary adrenal insufficiency.
- Taking regular GC therapy, including topical and inhaled forms, which could lead to an adrenal crisis if suddenly stopped because it may suppress the hypothalamic-pituitary-adrenal (HPA) axis.
- Taking certain medications that either affect cortisol metabolism or reduce its production, including levothyroxine, phenytoin, phenobarbital, rifampin, carbamazepine, St John’s wort, ketoconazole, etomidate, and fluconazole.
- Using anticoagulation agents which could increase the risk of adrenal hemorrhage.
- Taking additional medications like megestrol acetate and medroxyprogesterone.
- Being pregnant, especially during the last trimester.
- Being advanced in age.
- Having other health issues or conditions.
- Having type 1 diabetes
- Having adrenal metastasis or adrenal hemorrhage
- Having Polyglandular autoimmune syndromes 1 and 2
Signs and Symptoms of Adrenal Crisis (Addisonian Crisis)
An adrenal crisis is a serious condition that can cause a range of symptoms. These may include feeling weak or extremely tired, dropping weight without meaning to, and feeling sick or vomiting. Some people have stomach pain, lose their appetite, or experience back or limb pain. Symptoms can also include feeling dizzy, sleepy, or confused, and sometimes they could even lose consciousness.
In kids, an adrenal crisis could lead to weight loss and slow growth. This could also be accompanied by other symptoms, like low blood sugar, which can cause seizures. Less common symptoms across all age groups could include feeling like you have a serious stomach problem, or symptoms such as craving salt, missed periods, losing interest in sexual activity, and feelings of depression.
If a doctor is checking for an adrenal crisis, they’ll look at your basic body functions, like your temperature, heart rate, and blood pressure. They can change if you’re having an adrenal crisis. During a physical exam, the doctor might see that you look visibly unwell. If you have primary adrenal insufficiency, you might have signs like darker skin and scars around your mouth.
To figure out if you’re having an adrenal crisis, the doctor needs to know your full medical history, including any past surgeries. They’ll also need to know what medications and supplements you’ve been taking at home.
It’s also important to identify anything that might have triggered an adrenal crisis. The doctor must know if you have a history of using glucocorticoids long-term since stopping suddenly or getting sick could lead to an adrenal crisis. They’ll also want to know if you have any other autoimmune diseases, as people with multiple autoimmune disorders can show signs of adrenal insufficiency. If you have type 1 diabetes and frequently have low blood sugar while taking insulin, that could indicate adrenal insufficiency. Typically, patients with an adrenal crisis usually experience unexplainable shock that does not improve even with standard fluid replacement and medicines that narrow blood vessels.
Testing for Adrenal Crisis (Addisonian Crisis)
In the event of an adrenal crisis, several laboratory tests may show abnormal results. Classic signs in these test results might include:
* Low sodium levels (hyponatremia), caused by a lack of the hormone mineralocorticoid
* High potassium levels (hyperkalemia), also caused by a lack of mineralocorticoid
* Low blood sugar levels (hypoglycemia), due to decreased sugar production and use in the body
* Low or average levels of ACTH (a hormone), found in cases of secondary adrenal insufficiency
* High or average levels of ACTH, found in cases of primary adrenal insufficiency
* High calcium levels (hypercalcemia), due to a decrease in blood volume
* Increased creatinine levels, a waste product signifying prerenal failure
* Low aldosterone levels, caused by a lack of mineralocorticoid in primary adrenal insufficiency
* High renin levels, usually seen in primary adrenal insufficiency due to the loss of sodium in urine and decreased blood volume
A blood test may also reveal normal size and color of red blood cells, as well as increased numbers of lymphocytes and eosinophils, caused by a deficiency in adrenal hormones. Additionally, an increase in thyroid-stimulating hormone (TSH) levels could signal underactive thyroid coinciding with conditions of multiple gland disorders or due to the absence of cortisol’s inhibitory effect on TSH production.
Evaluating Cortisol Levels
In adrenal crises, it’s crucial that treatment isn’t delayed for the sake of completing laboratory tests. The swift administration of hydrocortisone is vital for managing these crises. But, if speed isn’t expected to be an issue, blood work can be done swiftly before starting hydrocortisone treatment.
For treating adrenal crises, healthcare providers might suggest the following blood tests:
* ACTH: High ACTH levels paired with low levels of cortisol and aldosterone suggest primary adrenal insufficiency, while low ACTH levels with low cortisol hint at secondary or tertiary adrenal insufficiency.
* Basic metabolic panel: This blood test includes a glucose test and is also recommended.
* Other blood tests: These might be used to determine the levels of cortisol, aldosterone, and renin in the body.
Under circumstances where the diagnosis of adrenal crisis is uncertain and cortisol levels are borderline, conducting an ACTH stimulation test in the acute setting is not advised until the patient’s condition has stabilized.
Treatment Options for Adrenal Crisis (Addisonian Crisis)
The confirmed treatment method for adrenal crisis involves administering glucocorticoids (GCs), especially a drug called hydrocortisone. When patients with a history of adrenal insufficiency present symptoms matching an adrenal crisis, treatment should start straight away. When a patient’s health is rapidly declining and there’s a suspicion of adrenal insufficiency or crisis, “stress dose” of steroids must be administered immediately. The doses of stress steroids and fluid resuscitation vary for children and adults.
For adults in an emergency, healthcare providers typically recommend an initial dose of hydrocortisone, delivered through an injection into a muscle or vein. This is followed by an additional amount of hydrocortisone over 24 hours. Those experiencing low blood sugar are given a saline or dextrose solution, followed by maintenance fluids for hydration.
For children, the dosage of hydrocortisone is calculated based on the child’s body surface area. An equal amount is given over the next 24 hours, divided into doses every six hours. If a child has low blood sugar, they are given normal saline and potentially additional dextrose depending on their weight.
Recent studies suggest that administering hydrocortisone continuously rather than in intermittent doses is better for managing adrenal crises. This is because it helps to keep the cortisol levels within the desired range.
In cases of adrenal crisis, it is important to consult an endocrinologist for proper management and guidance. Once the patient’s condition improves, healthcare providers will gradually reduce the dosage of steroids. This helps to avoid sudden stoppage of the treatment and makes for a smoother transition to lower doses.
Whether a patient needs mineralocorticoid replacement is decided on a case-by-case basis in consultation with an endocrinologist. If the dosage of glucocorticoids given to the patient is more than 50 mg, mineralocorticoid replacement isn’t needed.
In situations where hydrocortisone isn’t available, other types of glucocorticoids can be considered, such as prednisolone, methylprednisolone, or dexamethasone.
In patients where an infection triggered the adrenal crisis, it is crucial to administer suitable antibiotics promptly to treat the underlying infection.
What else can Adrenal Crisis (Addisonian Crisis) be?
An adrenal crisis, a severe medical condition, usually doesn’t occur on its own. Its diagnosis may need to take into account a wide range of possibilities based on the patient’s symptoms and the underlying cause. Common symptoms during an adrenal crisis may include changes in mental state, stomach pain, nausea, vomiting, and fever. However, low blood pressure is often the most significant symptom. If a patient with a known history of adrenal issues experiences such symptoms, an adrenal crisis is the most likely diagnosis.
Further tests are needed to find the exact cause of the adrenal crisis. This could involve checking for conditions like severe infections, septic or circulatory shock (extreme reactions to infections in the body), myxedema coma (a life-threatening condition due to severe low thyroid function), injury, stress, heart attack, or certain kinds of triggers. If a patient, who doesn’t have a known adrenal disorder, shows a persistent low blood pressure that is not responding to fluids or medications to raise it, adrenal crisis should be strongly considered as a diagnosis.
What to expect with Adrenal Crisis (Addisonian Crisis)
Adrenal crisis, although rare, has a high mortality rate even with quick treatment using corticosteroids. Because it doesn’t occur frequently, many healthcare workers might not be very familiar with how to spot and handle this condition.
A study from the United Kingdom found that adrenal crises were responsible for 10% of deaths among patients who suffer from primary and secondary adrenal insufficiency. This shows how crucial it is for healthcare professionals to understand and promptly react to this condition.
Possible Complications When Diagnosed with Adrenal Crisis (Addisonian Crisis)
An adrenal crisis is a serious medical condition that can be life-threatening, even if it’s detected early and treated right. It can also lead to other complications. These can include abnormal electrolyte levels, which result in too little sodium, too much potassium, and too little glucose in the blood. These imbalances can cause other severe problems like seizures, irregular heartbeats, and even comas. If left untreated, low blood pressure from an adrenal crisis can lead to inadequate blood supply to the organs, which can cause multiple organ failures. Additionally, the initial disease or event that caused the adrenal crisis can bring about other complications.
- Can be life-threatening
- Abnormal electrolyte levels
- Too little sodium
- Too much potassium
- Too little glucose
- Seizures
- Irregular heartbeats
- Comas
- Low blood pressure
- Inadequate blood supply to organs
- Multiple organ failures
- Additional complications from initial disease or event
Preventing Adrenal Crisis (Addisonian Crisis)
Many patients suffering from adrenal crises do not know they have adrenal insufficiency (a condition where the adrenal glands don’t produce enough hormones). Therefore, healthcare professionals should be well-equipped with knowledge about diagnosing this and using stress dose steroids to manage it effectively.
It’s important that patients also understand the following rules:
* When sick, patients should double or triple their usual daily dose of glucocorticoids. This helps replicate the natural response of the body increasing cortisol levels during stress.
* If a patient has a fever over 38 °C, they should double their normal dosage of oral corticosteroids. If their fever exceeds 39 °C, they should triple it.
* Patients should understand how and when to administer stress dosages during stressful times, such as trauma, surgery, and severe illness. During times of extreme emotional stress (for example, the death of a loved one or an important exam), patients may need to take an extra 10 mg of hydrocortisone.
Patients should also be informed about the signs and symptoms of adrenal insufficiency, like nausea, vomiting, abdominal pain, unintentional weight loss, dizziness, and a diminished sense of well-being, among others. They should wear a medical alert bracelet or necklace, which can provide critical information to healthcare providers during an emergency.
Patients should have a home emergency kit including hydrocortisone and syringes. A steroid card with instructions for managing an adrenal crisis should be readily available, especially during emergencies. This card should contain dosage information for adrenal crisis management.
Patients should regularly see an endocrinologist. Adults should have appointments annually, and children should have them every 3 to 6 months.
Table 2 outlines strategies to prevent an adrenal crisis. For example, when a patient has a high fever or requires surgery, they should adjust their steroid dose according to the table. During emotional stress or intensive exercise, they should take an extra 10-20 mg of hydrocortisone depending on the situation.
Remember, it’s important for patients to educate themselves on their medications and when to adjust doses under certain situations. Always have an emergency kit prepared, and regularly follow up with a healthcare professional.
