Addison's disease, a rare but dangerous adrenal gland disorder.

 Addison's disease, a rare but dangerous adrenal gland disorder.

Addison's disease definition

Addison’s disease is caused by damage to the adrenal glands—two small, triangular glands that sit above the kidneys and produce cortisol, aldosterone, and, to a lesser degree, sex steroids. This condition is a rare deficiency of adrenal gland hormones. Insufficient cortisol and aldosterone production causes Addison's disease, commonly known as primary adrenal insufficiency.  Immune system issues cause most cases of adrenal insufficiency, but infection, cancer, and other disorders can also cause it.

Glands that sit above the kidneys

Addison's symptoms

Symptoms may start slowly and become severe if untreated.

Common Symptoms 

• Muscle weakness and chronic weariness
• Weight loss, appetite reduction
• Hypotension, especially when standing
• Salt desires
• Skin hyperpigmentation, notably on scars, gums, and folds
• Diarrhea, nausea, vomiting
• Stomach discomfort
• Lack of focus, depression, and irritability
• Low blood glucose
• Body hair loss and decreased sex drive (particularly in women)

The signs of an adrenal crisis (medical emergency)

• Sudden, severe lower back, abdomen, or leg discomfort
• Extreme weariness, weakness
• Dehydration after severe vomiting and diarrhea
• Low blood pressure, fainting
• Confusion or unconsciousness
• Fever

Important: Symptoms can vary in severity and develop gradually, making them easy to misdiagnose. If you have any of these symptoms, visit a doctor for diagnosis and treatment. Life-threatening adrenal crises require emergency medical care.

The cause of Addison's disease

Damage to the adrenal cortex causes insufficient cortisol and aldosterone production, causing Addison's disease. The causes vary, but here's a list:

Most Common Reason:

• Autoimmune Adrenalitis
• The immune system misattacks the adrenal glands.
• An immunological response slowly damages the adrenal cortex.
• Commonly linked to autoimmune diseases like:
• Type 1 diabetes
• Autoimmune thyroid disease
• Pernicious anemia
• Vitiligo2

Infectious causes

• TB was the primary cause worldwide and remains so in underdeveloped nations.
• Other infections: HIV/AIDS-related fungal infections

Other medical causes 

• Cancer metastases to the adrenals
• Sepsis- or meningitis-related adrenal hemorrhage
• Amyloidosis: Protein accumulation affects adrenal tissue.
• Adrenalectomy: adrenal gland removal
• Congenital adrenal hyperplasia is genetic.
• Steroid-interfering drugs (ketoconazole, mitotane)

Secondary adrenal insufficiency (similar to Addison's)

• Low ACTH due to pituitary gland malfunction
• Not stimulating the adrenal glands to create cortisol
• Often because:
• Pituitary tumors
• Brain damage
• Stopping corticosteroids suddenly

Diagnosis for Addison's disease

Clinical evaluation, blood testing, and stimulation tests show adrenal insufficiency and reveal Addison's disease. The overview is structured as follows:

Initial Blood Tests

These detect hormone and electrolyte imbalances:

• Decreased cortisol (particularly in the morning)
• Primary adrenal insufficiency (high ACTH)
• A low aldosterone
• Low sodium, high potassium, low glucose
• In autoimmune Addison's, adrenal antibodies (e.g., 21-hydroxylase antibodies)

Synacthen (ACTH) Stimulation Test

The gold standard for diagnosis:

• Injections of synthetic ACTH
• Cortisol is tested before and 30–60 minutes after.
• Normal response: Significant cortisol spike
• Addison's illness: minimal cortisol rise

Insulin-induced hypoglycemia test

• For suspected pituitary dysfunction:
• Insulin reduces blood glucose to cause stress.
• Usually, cortisol rises.
• A blunted reaction indicates secondary adrenal insufficiency.

The CRH Stimulation Test 

• Distinguishes secondary and tertiary adrenal insufficiency:
• CRH injection, ACTH, and cortisol levels monitored over time

Image tests

Used for cause investigation:

• CT scan of adrenal glands for size, calcification, and tumors
• MRI of the pituitary gland for secondary adrenal insufficiency.

• Additional tests

• Testing thyroid function for coexisting hypothyroidism and TB screening for probable infection.

Blood test results for Addison's

Doctors use hormone and electrolyte blood testing and stimulation tests to diagnose Addison's disease. What those results usually show:

Important Blood Test Results

• Low cortisol: Especially in early morning samples (8 AM cortisol).
• Elevated ACTH: Provides evidence of Addison's illness.
• Low aldosterone: Seen in primary cases

Electrolyte imbalances:

• Hyponatremia
• Potassium overload
• Hypochloremia
• Low blood glucose, especially fasting

A high BUN and creatinine: 

• Dehydration reduces renal perfusion.
• Autoimmune markers: 21-hydroxylase or adrenal cortex antibodies in autoimmune Addison's.

ACTH Stimulation Test

• Cortisol response after synthetic ACTH injection
• Normal response: Significantly elevated cortisol
• Addison's illness: Minimal cortisol rise

🧠 Additional tests (if required)

• Insulin tolerance test: Secondary adrenal insufficiency, pituitary function test.
• The CRH stimulation test: Differentiates secondary and tertiary causes

How to treat Addison's disease

Taking steroid drugs every day (usually pills) to replace the missing adrenal hormones is the main way to treat Addison's disease.

Life must have these steroid hormones.  People with Addison's disease have to take hormone pills every day for the rest of their lives.

Addison's therapies

Replace deficient hormones—primarily cortisol and aldosterone—to restore balance and prevent adrenal crises in Addison's disease. Treatment is lifelong and personalized.

Key Medications

• Hydrocortisone, prednisone, methylprednisolone:
• Cortisol replacement, used 2–3 times daily to match natural rhythms
• Fludrocortisone acetate: Aldosterone replacement regulates sodium, potassium, and blood pressure

Adjustments to lifestyle

• Take more salt: In hot weather, with hard exertion, or with intestinal difficulties.
• Manage stress: Illness, surgery, or stress may require dose increases.

Prepare for emergencies:

• Ensure you have a medical alert bracelet and a steroid emergency card for emergencies. Extra adrenal crisis medication and an injectable corticosteroid kit

Treating Adrenal Crisis

• Instant IV corticosteroids, saline, and glucose in hospitals
• Severe exhaustion, vomiting, low blood pressure, and confusion are early indications.

Monitor and follow up

• Regular endocrinologist visits
• Associated autoimmune disease screening annually
• Dose adjustments for stress, illness, or lab results

Although Addison's disease is incurable, most patients live long, active lives with adequate care.

Life expectancy with Addison's

Most individuals with Addison's disease can lead a full and active life, achieving a life expectancy similar to that of the average population when they receive adequate therapy and management. However, various factors affect results:

Life expectancy insights

• According to a 2009 survey, women have an average life expectancy of 75.7 years.
• 64.8 years male
• For women, this is 3.2 years shorter than the general population, and for males, it is 11.2 years shorter.
• Access to care, treatment adherence, and adrenal crisis avoidance affect these figures.

Factors that lower life expectancy

• Adrenal crisis: An abrupt, life-threatening hormone decline, affecting ~8% of patients annually and resulting in 0.5-2% fatality.
• Infections: Long-term steroid use suppresses the immune system, increasing the risk.
• Individuals may fail to adhere to their medication regimen or postpone dose adjustments due to illness or stress.
• Management may be complicated by autoimmune disorders such as thyroid disease and diabetes.
• Depressive disorders can impact the consistency of treatment.

How to Increase Longevity

• Hydrocortisone and fludrocortisone should be taken regularly and adjusted with stress.
• Wear an alarm bracelet and carry emergency corticosteroid injections.
• Inform family and caregivers about adrenal crisis symptoms.
• Endocrinologist visits should be regular.

Who is most affected?

Women predominate.

• Typically, the diagnosis occurs between the ages of 30 and 50.
• It's linked to autoimmune disorders, potentially elevating the risk.

Why It's Often Ignored

• Slow-developing symptoms resemble weariness and despair.
• Due to its rarity, doctors may not suspect it.
• Although rare, Addison's disease is well understood and curable when discovered early. 

Also, read https://patient.info/signs-symptoms/tiredness-fatigue/addisons-disease.

Conclusion

Addison's disease, a rare but dangerous adrenal gland disorder, reduces cortisol and aldosterone production. The gradual and nonspecific symptoms, which include fatigue, low blood pressure, and skin pigmentation, can be lethal if left untreated. Tuberculosis, cancer metastases, and autoimmune assaults are causes. Early detection, continuous treatment, and crisis planning make Addison's tolerable.