What is Adrenal Insufficiency?
The adrenal gland is composed of two parts: the cortex and the medulla. The adrenal cortex creates hormones needed for normal body function; a lack of these hormones can lead to what’s known as adrenal insufficiency. The cortex specifically produces hormones called glucocorticoids, mineralocorticoids, and androgens. Adrenal insufficiency typically occurs because of damage or dysfunction to the adrenal cortex which leads to a deficiency of glucocorticoids and mineralocorticoids. This type of adrenal insufficiency is often referred to as autoimmune adrenalitis or Addison disease.
Adrenal insufficiency can have symptoms ranging from mild, nonspecific signs to life-threatening shock. Diagnosis can be difficult due to varying symptoms and conditions, and doctors should always keep it in mind as a possibility. Decreased adrenal function may not be apparent until a stressful event or illness triggers a crisis.
Adrenal insufficiency can be caused by three different factors, classified as primary, secondary, or tertiary. Primary adrenal insufficiency happens when there’s a disease affecting the adrenal gland itself. Secondary adrenal insufficiency is caused by a decreased level of a hormone called ACTH, which the pituitary gland releases. Tertiary adrenal insufficiency is the result of a decreased level of CRH, another hormone that the hypothalamus releases.
It’s noteworthy to understand the presence of a mineralocorticoid deficiency in these patients. Those with secondary or tertiary adrenal insufficiency usually have regular mineralocorticoid function because there are separate systems that control it. Mineralocorticoid levels are managed by a system that’s not dependent on signals from the hypothalamus or pituitary.
One crucial factor to know is the difference between the acute and chronic nature of the disease. Acute adrenal insufficiency patients often come in critically ill, while chronic adrenal insufficiency can sneak up slowly and go unnoticed.
What Causes Adrenal Insufficiency?
Primary adrenal insufficiency is a condition where the adrenal glands located on top of the kidneys aren’t able to produce enough of certain hormones, namely aldosterone and cortisol. This can occur suddenly, potentially resulting in a serious condition named adrenal crisis, or it can be a long-term condition known as Addison’s disease.
The primary cause of this condition is often the body’s immune system mistakenly attacking and damaging the adrenal glands. Autoantibodies, which are created by the immune system, target a specific enzyme in the adrenal glands in about 90% of patients afflicted with this condition. Other causes can include bleeding in the adrenal glands, certain types of cancer, infections (like HIV, syphilis, or tuberculosis), or specific drugs such as etomidate, ketoconazole, fluconazole, or metyrapone. Certain medications like phenytoin and rifampin can speed up the metabolism of cortisol, potentially causing adrenal insufficiency in susceptible people.
Adrenal bleeding can occur in patients who are on blood-thinning medication, patients with a propensity for bleeding or in those recovering from surgery.
Primary adrenal insufficiency can also be present from birth. This is associated with a condition called congenital adrenal hyperplasia. Several genetic conditions and panhypopituitarism, a condition characterized by a decrease in pituitary hormone production, can also lead to adrenal insufficiency. Sometimes, if there is bleeding or blockage in the pituitary gland (a condition known as Sheehan syndrome), it can cause secondary adrenal insufficiency. Other reasons might include pituitary tumors, the removal of the pituitary gland, and receiving high doses of radiation.
Brain tumors and the sudden discontinuation of long-term steroid use can result in a condition known as tertiary adrenal insufficiency.
Risk Factors and Frequency for Adrenal Insufficiency
Addison’s disease is thought to affect up to 144 million people in the developed world. With the right treatment, these persons can lead a near-normal lifespan. However, those who don’t receive appropriate treatment face a high risk of death.
The autoimmune type of adrenal insufficiency (which is another name for Addison’s disease) can occur in both males and females, but the form it takes can be different. Women are more likely to have a form of the disease that affects several glands while, for males, the disease typically damages only the adrenal gland, especially during the first two decades of life. As age advances to the fourth decade, this isolated form becomes more common in women.
There are various causes of adrenal insufficiency, so there isn’t a specific group of people who are at a higher risk.
The prevalence of adrenal insufficiency in kids isn’t well known, but it’s most often caused by a condition called Congenital Adrenal Hyperplasia (CAH). This condition is the most common cause of primary adrenal insufficiency in children and affects 1 in every 14,200 live births.
Signs and Symptoms of Adrenal Insufficiency
Adrenal insufficiency, a condition characterized by underperformance of the adrenal glands, often surfaces through various signs and symptoms. These can include low blood pressure, changes in mental states, lack of appetite, vomiting, weight loss, fatigue, and frequent stomach pains. Women may experience reproductive issues, for example missed periods, reduced sexual desire, and less hair in the armpit and pubic regions. Craving for salt and feeling dizzy when standing up (orthostatic hypotension) are common in patients due to the lessened function of the mineralocorticoid hormone. It is important to know if the patient has been using corticosteroid medications, as this can help diagnose the condition, especially in chronic cases.
Physical signs may include dry and loose skin along with unusual skin pigmentation. Patients may also show neuropsychiatric signs. Some physical symptoms resembling Cushing’s syndrome, another adrenal gland disorder, such as thinning skin, stretch marks, swelling, obesity, muscle wastage, and neuropsychiatric disturbances may also be noticeable.
Extreme cases can result in shock without any prior sign of low blood pressure. Low blood pressure can be present in any form of adrenal insufficiency. If a patient develops a fever, it’s important to explore the possibility of infection, though fever can also occur with any form of adrenal insufficiency.
Testing for Adrenal Insufficiency
Diagnosing primary adrenal insufficiency often involves dealing with vague symptoms, so it’s critical to be on the alert. The condition may cause lower sodium and higher potassium and sugar levels in the blood. Checking levels of cortisol, ACTH, renin, aldosterone, and conducting a complete chemistry panel is a part of the diagnostic process. In case of elevated ACTH and plasma renin activity, Serum cortisol level can help in diagnosing the illness. A test called the ACTH stimulation test can also help sort out whether the cause is ‘central’ (in the brain) or ‘peripheral’ (in the adrenal gland itself).
To begin the investigation, doctors generally check for anti-21-hydroxylase antibodies as these are often found attacking and weakening the adrenal cortex (the outer layer of adrenal gland) in cases of primary adrenal insufficiency.
People with secondary adrenal insufficiency are more likely to have lower blood sugar, but they generally do not suffer from dehydration, raised potassium levels, or darker skin.
If adrenal insufficiency starts later in life, it’s usually because of a secondary cause. If the reason is unclear, doctors may look into testing for conditions like HIV and tuberculosis, especially since adrenal insufficiency due to tuberculosis is more common in people from developing countries.
The most common lab results seen in chronic primary adrenal insufficiency include anemia (low red blood cell count), hyponatremia (low sodium levels), and hyperkalemia (high potassium levels).
Treatment Options for Adrenal Insufficiency
Chronic primary adrenal insufficiency is a condition that requires multiple treatments.
1. Glucocorticoid replacement: This involves taking hydrocortisone, prednisone, or dexamethasone orally as prescribed by your doctor. These drugs are taken in divided doses with the largest dose given early in the morning. Your doctor will monitor your symptoms and perform a blood test called an ACTH test as needed.
2. Mineralocorticoid replacement: This involves taking fludrocortisone orally and could also require adjusting your diet to include more salt. Make sure to take into consideration other medications you might be taking, as they might affect the needed dosage of fludrocortisone. As part of this treatment, your doctor will check your blood pressure, pulse, and levels of potassium and a hormone called renin.
3. Androgen replacement: In some cases, women might need to take a medication called dehydroepiandrosterone (DHEA) for psychological wellbeing after their glucocorticoid and mineralocorticoid levels are optimal.
4. Patient education: It’s crucial to understand the illness, manage stress, and learn how to inject certain types of glucocorticoids if required.
5. Emergency precautions: Patients should have an emergency medical alert, information card, and pre-filled syringes with a 4 mg dose of dexamethasone.
6. Managing minor febrile illness or stress: During periods of illness or stress, patients might need to increase their glucocorticoid dose. But modifications to the mineralocorticoid dose are not needed. If the condition worsens or continues for more than three days, patients should contact their doctor.
7. Emergency treatment for severe stress or trauma: Patients should always have injectable drugs, sterile normal saline and syringes on hand.
If patients have an adrenal crisis (a severe and potentially life-threatening condition), the primary steps that medical professionals will take include:
1. Establishing intravenous access (placing a needle in a vein) for drug administration and fluid replacement.
2. Conducting lab tests to check electrolyte levels, glucose, and hormones (cortisol and ACTH).
3. Starting an infusion of isotonic saline or 5% dextrose in isotonic saline as quickly as possible.
4. Administrating 100 mg of hydrocortisone intravenously, followed by 50 mg every 6 hours for the first 24 hours.
5. Correcting electrolyte imbalances, especially hyponatremia (low sodium levels).
After stabilizing the patient, the following measures will be taken:
1. Continued isotonic saline infusion, but at a slower rate.
2. Diagnosis and treatment of possible infections that could have caused the adrenal crisis.
3. If the patient’s adrenal insufficiency status is unknown, an ACTH stimulation test will be performed to establish the diagnosis.
4. If there are no contraindications, glucocorticoid will be tapered over 1 to 3 days to the oral maintenance dose.
5. Mineralocorticoid replacement with fludrocortisone will be started once the saline infusion is stopped.
What else can Adrenal Insufficiency be?
The following conditions might be considered by healthcare professionals when diagnosing adrenal gland-related issues:
- Adrenal crisis (a severe drop in adrenal hormone levels)
- Adrenal hemorrhage (bleeding in the adrenal glands)
- Congenital adrenal hyperplasia (a group of inherited disorders affecting the adrenal glands)
- Eosinophilia (a high number of eosinophils, a type of white blood cell)
- Histoplasmosis (a fungal infection)
- Hyperkalemia (high potassium level in the blood)
- Sarcoidosis (an inflammatory disease affecting various organs)
- Tuberculosis (an infectious disease targeting mainly the lungs)
A doctor will carefully consider these conditions and use appropriate tests to get to the bottom of the patient’s health issues.
What to expect with Adrenal Insufficiency
Adrenal insufficiency doesn’t have to restrict a person’s life if it’s managed correctly. With the right treatment and routine check-ins, individuals with this condition can lead a normal and active life. This is true even for children, who can grow normally and reach puberty without any issues when properly monitored and treated.
Possible Complications When Diagnosed with Adrenal Insufficiency
The most severe complication of adrenal insufficiency, known as an adrenal crisis, can be life-threatening if not properly managed. This crisis can lead to various symptoms and abnormal laboratory results. If left untreated, it can result in death, and it can also increase the risk of a hypoglycemic shock, which is a condition characterised by low blood sugar levels.
Symptoms and Laboratory Results of Adrenal Crisis:
- Extreme thirst and dehydration
- Low blood pressure or shocks more severe than expected from the current illness
- Nausea and vomiting accompanied by weight loss
- Abdominal pain
- Low blood sugar (hypoglycemia) without an obvious reason
- Unexplained fever
- Abnormal blood levels of sodium (hyponatremia), potassium (hyperkalemia), waste product (azotemia), calcium (hypercalcemia), or certain type of white blood cells (eosinophilia)
- Any other autoimmune endocrine deficiency, like hypothyroidism
- Changes in skin color (Pigmentation abnormalities)
Preventing Adrenal Insufficiency
It’s important for patients and their families to learn about the signs of an adrenal crisis. Catching this condition early and treating it quickly can greatly improve the chances of recovery. After talking with their doctors, patients should always keep an emergency medicine shot on hand.
Lastly, anyone who’s been diagnosed with adrenal insufficiency should be encouraged to wear a medical ID bracelet. This simple accessory can provide critical information to healthcare professionals in case of an emergency.
