Diagnosis, Treatment, and Management of Adrenal Insufficiency

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In our previous issue, we discussed adrenal insufficiency (AI), types of AI, symptoms, and complications, including adrenal crisis. AI is one of the manifestations of X-linked adrenoleukodystrophy (X-ALD) and can sometimes develop before neurological symptoms appear. This makes early recognition, diagnosis, and appropriate management particularly important for individuals with X-ALD.

In this article, we will briefly look at how AI is diagnosed, the treatments available, and some important precautions that individuals and families can take to manage the condition.

This article is intended for educational purposes and does not replace individualized medical advice. Always consult your healthcare provider or endocrinologist for diagnosis, treatment, and emergency management recommendations.

How is AI diagnosed?

Healthcare providers may recommend a combination of blood tests and other investigations to evaluate adrenal function and identify the underlying cause. AI may cause changes in certain blood measurements, as shown in the table below. These changes are not present in every individual.

Common investigations include:

• Cortisol: A hormone produced by the adrenal glands that helps the body respond to stress. This is measured through a blood test taken in the morning. 

• Adrenocorticotropic hormone (ACTH): A hormone produced by the pituitary gland that signals the adrenal glands to produce cortisol. Measuring ACTH alongside cortisol helps identify the type of AI.

• ACTH stimulation test: Evaluates how well the adrenal glands respond to ACTH and is commonly used to confirm AI.

• Aldosterone: A hormone that helps regulate sodium, potassium, and blood pressure.

• Renin: A hormone produced by the kidneys that helps regulate blood pressure and salt balance.

• Blood glucose, urea, and electrolytes: Including sodium, potassium, and calcium.

• Anti-21-hydroxylase antibodies: Immune system markers that may help identify autoimmune primary AI.

Additional investigations, such as adrenal imaging (CT or MRI), may be recommended depending on the suspected underlying cause. These are not routinely required for every individual. Other laboratory differences, including changes in thyroid-stimulating hormone (TSH) and white blood cell counts, may occasionally occur but are not specific indicators of AI.

Important notes for families: Normal electrolyte levels do not rule out AI. Blood glucose, sodium, potassium, calcium, and urea are supportive findings rather than diagnostic tests on their own. Anti-21-hydroxylase antibody testing helps identify an autoimmune cause and is not required to diagnose X-ALD-related AI.

For individuals with X-ALD, regular monitoring of cortisol and ACTH levels is particularly important in boys and men, even when no symptoms are present. The frequency of testing depends on age and the recommendations of the treating endocrinologist.

How is AI treated?

Treatment primarily involves replacing the hormones that are not produced in sufficient quantities by the adrenal glands. Not everyone with AI requires all types of hormone replacement. Treatment depends on the type of AI, the hormones affected, and the individual's medical needs.

Two important groups of hormones produced by the adrenal cortex (the outer layer of the adrenal glands) are glucocorticoids, such as cortisol, and mineralocorticoids, such as aldosterone.

1. Glucocorticoid replacement 

Hydrocortisone is commonly prescribed to replace cortisol. Other medications, such as prednisolone and dexamethasone, may be used in certain circumstances. The medication and dosage are individualized based on factors such as age, body size, clinical needs, and response to treatment. 

2. Mineralocorticoid replacement:

Fludrocortisone is prescribed when the body does not produce enough aldosterone. It helps maintain blood pressure and regulate sodium and potassium levels. Individuals requiring mineralocorticoid replacement may also need adequate dietary salt intake, as advised by their healthcare provider.

3. Androgen (sex hormone) replacement:

DHEA (dehydroepiandrosterone) is an adrenal hormone that acts as a precursor to sex hormones like testosterone and estrogen. In some women with primary AI, DHEA may be considered when symptoms such as low energy, reduced sexual well-being, or mood concerns persist despite optimized hormone replacement. It is not routinely required for everyone.

Why is sick-day management important?

During times of physical stress, such as illness, fever, infection, injury, or surgery, the body normally produces additional cortisol to meet its increased demands. However, individuals with AI may be unable to produce this additional cortisol naturally. Therefore, they may need temporary adjustments to their glucocorticoid medication, commonly referred to as sick-day rules or stress dosing.

Families should work with their healthcare providers to establish an individualized sick-day management plan, including instructions for when to increase medication, when to use emergency hydrocortisone, and when to seek urgent medical care. If an individual is vomiting repeatedly or cannot keep their medication down, an emergency hydrocortisone injection may be necessary, followed by immediate medical evaluation.

How can families prepare for an adrenal emergency?

As discussed in our previous issue, adrenal crisis is a life-threatening medical emergency that requires immediate treatment. Individuals with AI and their caregivers should be prepared to recognize situations that may increase the risk of adrenal crisis.

Some important precautions include:

• Wearing a medical alert bracelet or necklace identifying the condition.

• Carrying an emergency medical information card in a wallet or on a phone.

• Keeping a prescribed emergency hydrocortisone injection kit readily accessible.

• Ensuring that family members, caregivers, and other relevant individuals know when and how to administer emergency hydrocortisone.

• Keeping an updated medication list and emergency care plan.

• Attending regular follow-up appointments to monitor treatment and make adjustments when needed.

If an adrenal crisis is suspected, seek immediate medical attention. Call 911 in the United States/Canada or your local emergency number.

Adrenal insufficiency is a serious but treatable condition. With appropriate hormone replacement, regular medical follow-up, and an individualized sick-day management plan, many individuals with AI can lead active and fulfilling lives. Understanding the condition, taking medications consistently, and being prepared for emergencies are important steps in preventing complications and supporting long-term health.

References:

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3. Primary adrenal insufficiency - Symptoms, diagnosis and treatment | BMJ Best Practice US. (n.d.). https://bestpractice.bmj.com/topics/en-us/56 

4. National Library of Medicine. (n.d.). Addison Disease. Adrenal Insufficiency | MedlinePlus. https://medlineplus.gov/addisondisease.html#cat_95 

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