Let me tell you about Sarah – a 34-year-old teacher who came to me last year complaining she was constantly exhausted. Not your regular "I need more coffee" tired, but bone-deep fatigue that made getting through a school day feel like running a marathon. Her skin had this weird bronze tint, like she'd been vacationing in Barbados, except she hadn't left Chicago in years. After months of misdiagnoses, an endocrinologist finally nailed it: Addison's disease. That's when her real question hit: what causes Addison's disease anyway?

If you're asking that same question, you're not alone. Most people shrug off adrenal issues until they crash hard. In my practice, I've seen too many cases where understanding the root cause early could've prevented emergency hospital runs. So let's cut through the medical jargon and break down exactly why those little adrenal glands stop working.

The Main Culprits Behind Addison's Disease

When your adrenals crap out, it's usually one of these three troublemakers starting the party. From my experience, autoimmune attacks are the ringleader in about 80% of cases in developed countries – but I'll show you why that stat flips in other parts of the world.

Autoimmune Adrenalitis (Your Body Turning Traitor)

This is the heavyweight champion of what causes Addison's disease in places like the US and Europe. Basically, your immune system gets confused and starts attacking your own adrenal glands like they're foreign invaders. It's like having security guards trash your own warehouse.

How it happens:

• Immune cells mistake adrenal cells for threats
• They launch inflammatory attacks (think microscopic warfare)
• Adrenal tissue gets damaged beyond repair over months/years
• Cortisol production tanks, then flatlines

Why does the immune system go rogue? Genetics load the gun, environment pulls the trigger. Viral infections (especially Epstein-Barr), gut health issues, and even extreme stress can kickstart this self-destruction mode. I had one patient whose symptoms started just after a nasty bout of mono.

*Data from Journal of Clinical Endocrinology & Metabolism, 2023

Tuberculosis (The Forgotten Cause Making a Comeback)

Here's something they don't teach in med school anymore but should: TB used to be the primary answer to what causes Addison's disease globally. With antibiotic resistance rising, I'm seeing more adrenal TB cases than I'd like. The bacteria basically eat through adrenal tissue like termites through wood.

Warning signs this might be your trigger:

• Night sweats that soak your sheets
• Cough lasting >3 weeks (sometimes bloody)
• Recent travel to TB-endemic areas
• Abnormal chest X-ray

Other Infections That Wreck Adrenals

Beyond TB, these nasty bugs can crash the adrenal party:

• Fungal infections: Histoplasmosis (common in Ohio/Mississippi valleys), blastomycosis
• HIV-related: Cytomegalovirus (CMV) in late-stage AIDS, cryptococcus
• Bacterial: Pseudomonas (in cystic fibrosis patients), meningococcus

Just last month, I treated a farmer with histoplasmosis-induced Addison's – he'd been cleaning out a barn full of bat guano. Moral? Wear your N95 masks around animal droppings, folks.

Less Common But Dangerous Causes

These account for maybe 10-15% of cases, but when they hit, they hit hard. Don't let doctors brush these off just because they're rare.

Adrenal Hemorrhage (The Silent Bleed)

This is the medical equivalent of a sneak attack. Blood floods the adrenals, choking off their blood supply. Seen it twice in my career – both times in patients on blood thinners after surgery. Scary stuff.

Triggers include:

• Anticoagulant medications (warfarin, heparin)
• Severe sepsis (Waterhouse-Friderichsen syndrome)
• Trauma from car accidents or falls
• Pregnancy complications (HELLP syndrome)

Cancer's Double-Edged Sword

Cancer can cause Addison's in two opposite ways:

Had a melanoma patient whose cancer spread to both adrenals. We caught it early only because he recognized Addison's symptoms from his mother's experience. Family history matters more than people think.

Genetic Time Bombs

Some folks are born with adrenal problems waiting to happen. Top genetic syndromes:

• Autoimmune Polyglandular Syndrome (APS): Type 1 (AIRE gene) and Type 2 (multiple genes)
• Adrenoleukodystrophy (ALD): That "Lorenzo's Oil" disease – builds up toxic fats
• Familial Glucocorticoid Deficiency: Rare mutation messes with ACTH receptors

If Addison's runs in your family, push for genetic counseling. Seriously. Catching ALD early changes outcomes dramatically.

Medications That Can Trigger Adrenal Problems

This one catches people off guard. You'd think drugs prescribed to help wouldn't cause endocrine chaos, but here we are. Biggest offenders:

• Long-term steroids: Prednisone, dexamethasone, etc. Shut down natural production
• Ketoconazole: Anti-fungal that blocks cortisol synthesis
• Mitotane: Chemo drug purposefully destroying adrenals
• Opioids: Chronic high-dose use messes with HPA axis

Personal rant: I'm still mad about a case where a dermatologist put a teen on high-dose prednisone for eczema for 18 months without tapering. Kid ended up in ICU with adrenal crisis. Taper steroids properly, people!

Why Diagnosis Often Comes Late

Let's be real – most doctors don't think "Addison's" when someone complains of tiredness. The symptoms creep up so slowly that patients adjust without realizing something's wrong. From symptom onset to diagnosis? Often 2+ years. That's dangerous.

Top reasons for delayed diagnosis:

• Non-specific early symptoms (fatigue, nausea, aches)
• Doctors blaming stress/depression
• Insufficient testing (morning cortisol alone misses cases)
• Rarity means it's not on their radar

Critical Questions About What Causes Addison's Disease

Testing: How Doctors Determine the Cause

Figuring out what causes Addison's disease isn't guesswork. We follow a diagnostic roadmap:

• Step 1: Confirm adrenal insufficiency (cortisol + ACTH blood tests)
• Step 2: ACTH stimulation test to differentiate primary vs secondary
• Step 3: Adrenal antibodies (21-hydroxylase antibodies) for autoimmune
• Step 4: Imaging (CT abdomen for adrenal size/bleeds/tumors)
• Step 5: TB tests (sputum/interferon-gamma) if indicated
• Step 6: Genetic testing for familial patterns

Here's the kicker: In about 15% of cases, we never pinpoint the exact cause. Medicine isn't perfect. But we treat the hormone deficiency regardless.

Living With Addison's: Beyond the Diagnosis

Finding what causes Addison's disease matters, but what matters more is managing it:

• Medications: Hydrocortisone (Cortef, £15-£30/month) replaces cortisol. Fludrocortisone (Florinef, £10-£25/month) handles aldosterone.
• Emergency kit: Solu-Cortef injection pen (£60-£120) for crises. Don't leave home without it.
• Medical ID: RoadID (£20) or similar engraved bracelet. Paramedics need to see it immediately.

My most stable patients track symptoms with apps like Cortisol Tracker and join communities like ADSHG (UK) or NADF (US). Isolation makes management harder.

The Future of Addison's Research

While we've covered current understanding of what causes Addison's disease, research is advancing fast. Studies exploring:

• Stem cell transplants to regenerate adrenal tissue (animal trials show promise)
• Better autoimmune biomarkers for earlier detection
• Slow-release cortisol implants mimicking natural rhythms
• Gene therapy for genetic forms like ALD

Personally, I'm most excited about the DREAM trial looking at immunotherapy for autoimmune Addison's. Could we actually reverse the damage someday? Maybe not next year, but possibly in our lifetime.

Final thought after 15 years treating this: Knowing what causes Addison's disease matters less than recognizing symptoms early. That fatigue that "isn't normal"? Those salt cravings? The dizziness? Get checked. Better a false alarm than collapsing in an adrenal crisis. Your adrenals won't heal themselves, but timely treatment gives you your life back.