Overview

The two adrenal glands are situated above the kidneys. They are made up of two parts: the cortex on the outside and the medulla on the inside. The cortex secretes three types of hormones known as corticosteroids.

Cortisol is a glucocorticoid, a corticosteroid that regulates glucose (blood sugar), inhibits the immunological response, and is secreted in reaction to stress. The pituitary gland, located right below the brain, regulates cortisol production. Cortisol is required for survival. Acute adrenal crisis is a medical emergency induced by a cortisol deficiency. Lightheadedness or dizziness, weakness, sweating, stomach discomfort, nausea and vomiting, or even loss of consciousness may occur in patients.

Adrenal crisis occurs when the adrenal gland deteriorates (Addison's disease, primary adrenal insufficiency), when the pituitary gland is injured (secondary adrenal insufficiency), or when adrenal insufficiency is not treated appropriately. Physical stress such as illness, dehydration, trauma, or surgery, adrenal gland or pituitary gland damage, and discontinuing steroid medication such as prednisone or hydrocortisone too soon are all risk factors for adrenal crisis.

How Common are Adrenal Crises?

Adrenal crises are uncommon. According to studies, 42% of persons with adrenal insufficiency will have an adrenal crisis. Adrenal insufficiencies impact one in every 100,000 persons in the United States.

According to some research, up to 25% of persons who have an adrenal crisis die as a result of it.

Structure of the Adrenal Glands

An adrenal gland is made of two main parts:

• The adrenal cortex is the biggest and most visible component of the adrenal gland. It is separated into three zones: the zona glomerulosa, the zona fasciculata, and the zona reticularis. Each zone is in charge of manufacturing certain hormones.
• The adrenal medulla is found inside the adrenal cortex in the middle of an adrenal gland. It secretes "stress hormones," such as adrenaline.

The adrenal cortex and medulla are surrounded by an adipose capsule, which creates a protective barrier surrounding the adrenal gland.

Hormones of the Adrenal Glands

The adrenal glands in your body are responsible for releasing various hormones straight into your bloodstream. Many of these hormones have to do with how the body reacts to stress, and some are necessary for survival. Both the adrenal cortex and the adrenal medulla perform different and independent activities in the adrenal glands.

A different hormone is secreted by each zone of the adrenal cortex. The adrenal cortex produces the following hormones:

• Cortisol:

Cortisol is a glucocorticoid hormone generated by the zona fasciculata that serves a number of functions in the body. It aids in the regulation of the body's usage of lipids, proteins, and carbs; suppresses inflammation; controls blood pressure; raises blood sugar; and can reduce bone growth.

This hormone is also in charge of the sleep/wake cycle. It is produced under stressful situations to assist your body gain energy and better handle an emergency crisis.

Adrenal glands create hormones in response to signals from the pituitary gland in the brain, which in turn responds to signals from the hypothalamus in the brain. The hypothalamus pituitary adrenal axis is responsible for this. For example, in order for the adrenal gland to create cortisol, the following events occur:

• Corticotropin-releasing hormone (CRH) is produced by the brain and stimulates the pituitary gland to release adrenocorticotropin hormone (ACTH).
• The adrenal glands are then stimulated by ACTH to produce and release cortisol hormones into the bloodstream.
• Normally, both the hypothalamus and the pituitary gland can detect if the blood has a enough quantity of cortisol. When cortisol levels are too high or too low, these glands adjust the quantity of CRH and ACTH secreted. This is known as a negative feedback loop.
• Excess cortisol production can result from adrenal nodules or excess ACTH synthesis from a pituitary tumor or other cause.

• Aldosterone:

This mineralocorticoid hormone generated by the zona glomerulosa regulates blood pressure and some electrolytes (sodium and potassium). Aldosterone signals the kidneys, causing them to take more salt into the circulation and release potassium into the urine. This means that aldosterone also serves to maintain blood pH by managing electrolyte levels in the blood.

• DHEA and Androgenic Steroids:

These zona reticularis-produced hormones are weak male hormones. They are precursor hormones that are transformed into female hormones (estrogens) in the ovaries and male hormones in the testes (androgens). The ovaries and testes, on the other hand, generate far more estrogens and androgens.

• Epinephrine (Adrenaline) and Norepinephrine (Noradrenaline):

The adrenal medulla, or inner section of the adrenal gland, regulates hormones that trigger the flight or fight response. The major hormones released by the adrenal medulla are epinephrine (adrenaline) and norepinephrine (noradrenaline), which have comparable roles.

These hormones are capable of boosting the heart rate and power of cardiac contractions, increasing blood supply to the muscles and brain, relaxing airway smooth muscles, and aiding in glucose (sugar) metabolism, among other things. They also govern the constriction of blood vessels (vasoconstriction), which helps to maintain blood pressure and increases it in reaction to stress.

Epinephrine and norepinephrine, like numerous other hormones generated by the adrenal glands, are frequently triggered in physically and emotionally stressful situations when your body need more resources and energy to endure unusual pressure.

What is an Adrenal Crisis?

An adrenal crisis occurs when your adrenal glands do not produce enough of the hormone cortisol. It is a potentially fatal consequence of adrenal insufficiency (Addison's disease). If you feel you are experiencing an adrenal crisis, contact your healthcare professional right away.

The adrenal glands are located immediately above each kidney. They're little and triangle-shaped. They produce hormones such as cortisol. Hormones are molecules that help your body coordinate diverse processes by transporting information through your blood to your organs, skin, muscles, and other tissues. These signals instruct your body on what to do and when.

Cortisol affects almost every organ and tissue in your body. Some of its functions include:

• Regulating your body’s stress response.
• Helping control your metabolism.
• Suppressing inflammation.
• Regulating blood pressure.
• Regulating blood sugar.
• Helping control your sleep-wake cycle.

Other names for an adrenal crisis include Addisonian crisis and acute adrenal crisis.

Why is an Adrenal Crisis An Emergency?

A shortage of blood flow may result from an adrenal crisis (shock). Shock spreads swiftly and might harm your organs. An adrenal crisis can kill up to 20% of persons in shock if they are not treated. An adrenal crisis may also cause seizures or a coma.

• Primary adrenal insufficiency:

The cortex, or outer layer, of the adrenal glands is occasionally injured. The body then becomes unable to produce adequate hormones, a condition known as primary adrenal insufficiency. This is often caused by an autoimmune condition, in which the body attacks itself. People who have Addison's disease are more prone than others to have another autoimmune condition.

Other causes of adrenal gland failure may include:

• Tuberculosis
• Other infections of the adrenal glands
• Spread of cancer to the adrenal glands
• Bleeding into the adrenal glands

• Secondary adrenal insufficiency:

Adrenocorticotropic hormone is produced by the pituitary gland (ACTH). ACTH stimulates the adrenal cortex to produce hormones. Pituitary tumors that aren't malignancy, inflammation, and pituitary surgery can all cause the pituitary gland to produce insufficient ACTH.

Inadequate ACTH levels can cause the adrenal glands to produce insufficient glucocorticoids and androgens. This is referred to as secondary adrenal insufficiency.

Most secondary adrenal insufficiency symptoms are similar to those of initial adrenal insufficiency. Secondary adrenal insufficiency, on the other hand, does not cause darker skin and is less likely to cause severe dehydration or low blood pressure. They are more prone to low blood sugar.

Temporary secondary adrenal insufficiency occurs when patients who take corticosteroids like prednisone to address illnesses like asthma or arthritis abruptly cease taking the medication rather than tapering off.

Symptoms of an Adrenal Crisis

The most common symptoms of an adrenal crisis include:

• Abdominal pain or pain in your side (flank).
• Long-lasting fatigue.
• Loss of appetite.
• Darker patches of skin (hyperpigmentation).
• Weakness.
• Unexplained weight loss.
• Other warning signs of adrenal crisis may include:
• Dehydration.
• Diarrhea.
• Dizziness, confusion, light-headedness, fainting or coma.
• Fever.
• Headache.
• Joint pain.
• Low blood glucose.
• Low blood pressure.
• Nausea and vomiting.
• Rapid breathing (respiratory rate).
• Rapid heart rate.

What can Trigger an Adrenal Crisis?

The following stressors may trigger an adrenal crisis:

• Not receiving treatment for an adrenal insufficiency such as Addison’s disease.
• Damage to your adrenal gland, including adrenal gland diseases or surgery.
• Dehydration.
• Hypopituitarism.
• Infection.
• No longer taking glucocorticoid medications (prednisone) after taking them for a long time.
• Mental or emotional stress.

Adrenal Crisis Diagnosis

Laboratory Studies:

• Serum chemistry: Abnormalities are seen in up to 56% of patients. Hyponatremia is prevalent (although not diagnostic); hyperkalemia, metabolic acidosis, and hypoglycemia are also possible. The absence of test abnormalities, however, does not rule out the diagnosis of adrenal crisis.
• Cortisol levels in the blood: Adrenal insufficiency is indicated by less than 20 mcg/dL with extreme stress or following ACTH stimulation.
• ACTH test (diagnostic): Determine baseline blood cortisol levels, then give ACTH 250 mcg intravenous push (IVP), and then take serum cortisol 30 and 60 minutes later. Adrenal insufficiency is diagnosed when the rise is less than 9 mcg/dL.
• CBC: There may be anemia (moderate and nonspecific), lymphocytosis, and eosinophilia (very suggestive).
• Thyroid hormone levels in the blood: Examine the patient for autoimmune, infiltrative, or numerous endocrine problems.
• Blood and other cultures: Blood and other cultures should be performed as clinically needed. A major cause of acute adrenal crisis is infection.

Imaging Studies:

• Chest radiography: Assess for tuberculosis, histoplasmosis, malignant disease, sarcoid, and lymphoma.
• Abdominal CT scanning: Visualize adrenal glands for hemorrhage (as in the image below), atrophy, infiltrative disorders, and metastatic disease. Adrenal hemorrhage appears as hyperdense, bilaterally enlarged adrenal glands.

Other Tests:

Electrocardiography:

• Prolongation of the QT interval can induce ventricular arrhythmias.
• Deep negative T waves have been described in acute adrenal crisis.

What Causes Adrenal Crisis?

However, regardless of the etiology, the adrenal crisis is an acute complication of adrenal insufficiency. There are several causes of adrenal insufficiency, which can be broken down into primary, secondary, and tertiary. 

• Primary causes: Primary causes include etiologies that directly impact the adrenal gland, most notably Addison disease, which can entail the autoimmune destruction of the adrenal gland. Surgical removal, congenital adrenal abnormalities, bilateral adrenal hemorrhage, adrenomyeloneuropathy/adrenoleukodystrophy, and infections such as TB, systemic fungal infection, and acquired immunodeficiency syndrome are all possible underlying causes (AIDS). Waterhouse-Friderichsen syndrome can cause adrenal crises in the presence of meningitis. Other endocrine illnesses should be checked out because adrenal insufficiency is a feature of autoimmune polyglandular endocrinopathies types 1, 2, and 4.

• Secondary causes: Secondary causes of adrenal insufficiency include a disturbance in cortisol control, which is generally caused by a problem with the pituitary gland, which generates adrenocorticotropic hormone (ACTH), which increases cortisol release from the adrenal gland. Chronic exogenous glucocorticoid usage is the most prevalent cause. Pituitary tumors or metastases, pituitary apoplexy, pituitary surgery, radiation, lymphocytic hypophysitis, head trauma, Sheehan syndrome in pregnancy, pituitary infiltrative illness, empty-sella syndrome, and other reasons are also possible of adrenal insufficiency are a disruption of cortisol regulation, usually from the compromise of the pituitary gland that produces adrenocorticotropic hormone (ACTH), which ultimately stimulates cortisol release from the adrenal gland. The most common cause is chronic exogenous glucocorticoid use. Other causes include pituitary tumors or metastasis, pituitary apoplexy, pituitary surgery, radiation, lymphocytic hypophysitis, head trauma, Sheehan syndrome in pregnancy, pituitary infiltrative disease, empty-sella syndrome, etc.

• Tertiary causes: Tertiary reasons include hypothalamic disturbance, which impacts CRH and ACTH release. Exogenous steroids and opiates are notable causes. refer to disruption of the hypothalamus, which in turn affects CRH and ACTH release. Notable causes are exogenous steroids and opiates.

Treatment/Management

The use of glucocorticoids, primarily hydrocortisone, is the definitive therapy for adrenal crisis. The initial dose is 100 mg intravenously or intramuscularly (IV/IM), followed by 100 to 300 mg daily for the next 2 to 3 days, either as boluses every 6 hours or as a continuous infusion until full recovery. Hydrocortisone will also offer enough mineralocorticoid coverage at this dosage. While hydrocortisone is the recommended therapy, prednisolone or methylprednisolone and dexamethasone administration has been recorded. These patients require extensive hydration and vasopressor treatment in addition to medical therapy.

A comprehensive search for the etiology should also be conducted, and empiric antibiotics should be explored. In the critical care unit (ICU), close monitoring is essential. If the patient is pregnant, hydrocortisone is the recommended drug, and the patient should be released on hydrocortisone rather than cortisone acetate.

Guidelines for Managing Adrenal Crisis During an Emergency:

• If the patient displays clinical and biochemical signs of an adrenal crisis, give 100 mg hydrocortisone IV, followed by another 100 mg IV every 6 to 8 hours.
• Because dehydration and hypovolemia are typical precipitating factors, the patient must be rehydrated with normal saline 0.9%. This will address hypovolemia and prerenal failure as well. One liter of normal saline should be given in the first hour, and the need for further intravenous fluid resuscitation should be addressed based on the patient's hemodynamic condition (typically 4 to 6 liters are required in the first 24 hours).
• Correction of hypoglycemia with intravenous dextrose is required, as does regular blood glucose monitoring.
• To avoid osmotic demyelination syndrome, avoid quick correction of hyponatremia of more than 6 to 8 meq in the first 24 hours. Remember that cortisol replacement might cause water diuresis and inhibit antidiuretic hormone.
• It is necessary to evaluate urine output.
• Please contact your endocrinologist as soon as possible for more guidance.
• Only taper steroids when clinical improvement has occurred. Tapering should be done gradually.

How Can I Prevent an Adrenal Crisis?

Learn what factors might cause an adrenal crisis if you have adrenal insufficiency. Mental or emotional stress, dehydration, illness, or failing to take your glucocorticoid drugs as advised by your healthcare professional are all examples.

Adrenal insufficiency can be caused by surgery or pregnancy. Before undergoing any operation, inform your doctor that you have adrenal insufficiency. If you intend to get pregnant, consult with your physician.

Carry a medical identity card, necklace, or bracelet indicating adrenal insufficiency. Your identifying documents should also specify the sort of medication you require as well as the precise dosage. This information can assist your healthcare providers in providing timely treatment.

Check your blood pressure and weight on a regular basis. Inform your doctor if you lose weight or if your blood pressure becomes too high or too low.

Your doctor may administer an emergency cortisol injection. They'll teach you when and how to administer cortisol to yourself. Keep this medicine and the instructions for using it on hand at all times. Teach a family member or close friend how to give you the cortisol shot if you are unable to do so yourself.

It's also a good idea for you and your doctor to devise a strategy in case you can't take your hydrocortisone tablets due to nausea or vomiting.

What Can I Expect if I Have an Adrenal Crisis?

If you think you're suffering an adrenal crisis, get help right once. Over time, high dosages of glucocorticoids are not detrimental. If you do not get prompt care, you may die.

The majority of persons who have experienced an adrenal crisis will need to take hydrocortisone medications for the rest of their lives. Always have additional medicine on hand in case you fall unwell and require more.

Contact your healthcare provider immediately if you have symptoms of an adrenal crisis.

See your healthcare provider if you experience major stress — such as an injury, illness or mental or emotional stress. You may need to adjust your medication.

Questions should I ask my healthcare provider:

• How can you tell that I’m having an adrenal crisis?
• If I’m not having an adrenal crisis, what other condition might I have?
• What stressors triggered my adrenal crisis?
• How long will it take me to recover?
• What medications do you recommend?
• How should I properly store my medications?
• Do the medications have any side effects?

Conclusion

Adrenal crisis, also known as acute adrenal insufficiency, is a life-threatening illness that has a fatality rate of 0.5/100 patient-years and is a leading cause of death in patients with adrenal insufficiency. 

Patients may rapidly decline, culminating in death at home or shortly after admission to the hospital. It is an endocrine emergency caused by an internal or external process in the presence of a known or unknown absence of production of the major glucocorticoid, cortisol. Early detection and treatment can save a patient's life and improve their chances of survival. 

Clinicians must distinguish between adrenal insufficiency and adrenal crisis, as the latter is lethal if neglected. While this condition is thoroughly documented, it is sometimes difficult to identify, and treatment may be delayed, resulting in significant morbidity and mortality. Adrenal crises can be avoided by educating patients and their families about sick day policies and having intramuscular hydrocortisone available at home.