A plain-language guide

Addison disease

What's known, what's still uncertain, and what's actively debated, written plainly, and built only from published medical research.

Growing map · 34 sourced statements Every statement names its source Updated 2026-08-04
Please read this first. This guide is a companion to your medical team, not a replacement, and it is not medical advice. Everything here is tied to published research. If something you expected is not here, it almost always means we have not mapped a source for it yet, not that it is unknown to medicine. Addison disease is an early, growing map, so it will look incomplete on purpose: we would rather show less and have every line be something you can check than fill the page with claims we cannot stand behind. For anything about your own situation, your clinicians hold the full picture. How this guide is built and why.

What's Addison disease?

Addison's disease is primary adrenal insufficiency: the adrenal glands cannot make enough of their key hormones, especially cortisol and usually aldosterone. In most cases in higher-income countries the cause is autoimmune, where the immune system attacks the adrenal glands. Because cortisol is essential for handling stress, illness, and salt balance, untreated Addison's can become life-threatening, but it is very manageable with daily hormone replacement.

Also indexed asORPHA:85138, MONDO:0100480
Features mapped17
Treatments mapped4
Published sources11
Last reviewed2026-08-04

Signs and symptoms

Salt craving

A craving for salt is one of the symptoms that can develop in Addison's disease, alongside tiredness, nausea, vomiting, belly pain, aching muscles, and weight loss.

Limited evidenceSource: PMID:40720873
Evidence ratingweak
Study designontology_import
Confidence (0-1)0.7
Replicationunreplicated
Supporting sourcesPMID:41419241, ORPHA:85138
Notesplain_language confirmed from PMID:41419241 via curation 2026-06-13. plain_language confirmed from PMID:40720873 via curation 2026-06-25 [claude-draft]. | regrounded primary ORPHA:85138 -> PMID:40720873 on 2026-06-26 [Carrie Schluter, BCPA]
Last reviewed2026-06-26

Orthostatic hypotension

Initial vital signs showed tachycardia and orthostatic hypotension with hyponatremia identified during work up.

Limited evidenceSource: PMID:41405598
Evidence ratingweak
Study designontology_import
Confidence (0-1)0.7
Replicationunreplicated
Supporting sourcesORPHA:85138
Notesplain_language confirmed from PMID:41405598 via curation 2026-06-17. | regrounded primary ORPHA:85138 -> PMID:41405598 on 2026-06-26 [Carrie Schluter, BCPA]
Last reviewed2026-06-26

Tachycardia

A fast heartbeat can occur in Addison's disease, often together with low blood pressure on standing and low blood sodium.

Limited evidenceSource: PMID:40720873
Evidence ratingweak
Study designontology_import
Confidence (0-1)0.7
Replicationunreplicated
Supporting sourcesPMID:41405598, ORPHA:85138
Notesplain_language confirmed from PMID:41405598 via curation 2026-06-17. plain_language revised from PMID:41405598 via curation 2026-06-18 [carrie (claude rewrite)]. | regrounded primary ORPHA:85138 -> PMID:40720873 on 2026-06-26 [Carrie Schluter, BCPA]
Last reviewed2026-06-26

Increased circulating ACTH level

The pituitary gland, sensing the cortisol shortage, pumps out more of its signal hormone ACTH. The high ACTH confirms the problem is in the adrenal glands and also drives the characteristic skin darkening.

Limited evidenceSource: PMID:41048694
Evidence ratingweak
Study designontology_import
Confidence (0-1)0.7
Replicationunreplicated
Supporting sourcesPMID:41102963, ORPHA:85138
Notesplain_language confirmed from PMID:41102963 via curation 2026-06-13. | regrounded primary ORPHA:85138 -> PMID:41048694 on 2026-06-26 [Carrie Schluter, BCPA]
Last reviewed2026-06-26

Decreased circulating aldosterone concentration

In Addison's disease, the immune system damages the adrenal glands, causing low levels of both cortisol and a hormone called aldosterone that helps control salt and fluid balance.

Limited evidenceSource: PMID:40982814
Evidence ratingweak
Study designontology_import
Confidence (0-1)0.7
Replicationunreplicated
Supporting sourcesPMID:40842744, ORPHA:85138
Notesplain_language confirmed from PMID:40842744 via curation 2026-06-17. | regrounded primary ORPHA:85138 -> PMID:40982814 on 2026-06-26 [Carrie Schluter, BCPA]
Last reviewed2026-06-26

Decreased circulating cortisol level

A low blood cortisol level, especially in the morning when it should be highest, is the central finding. Cortisol helps the body respond to stress and illness, so a shortage leads to fatigue, low blood pressure, and poor tolerance of infection.

Limited evidenceSource: PMID:40982814
Evidence ratingweak
Study designontology_import
Confidence (0-1)0.7
Replicationunreplicated
Supporting sourcesPMID:41102963, ORPHA:85138
Notesplain_language confirmed from PMID:41102963 via curation 2026-06-13. | regrounded primary ORPHA:85138 -> PMID:40982814 on 2026-06-26 [Carrie Schluter, BCPA]
Last reviewed2026-06-26

Primary adrenal insufficiency

The core problem is primary adrenal insufficiency: the failure is in the adrenal glands themselves, not in the pituitary signal telling them to work. That distinction is why the body's signal hormone, ACTH, is high while the adrenal hormones are low.

Limited evidenceSource: PMID:40720873
Evidence ratingweak
Study designontology_import
Confidence (0-1)0.7
Replicationunreplicated
Supporting sourcesPMID:41102963, ORPHA:85138
Notesplain_language confirmed from PMID:41102963 via curation 2026-06-13. | regrounded primary ORPHA:85138 -> PMID:40720873 on 2026-06-26 [Carrie Schluter, BCPA]
Last reviewed2026-06-26

Asthenia

A deep lack of energy and strength (asthenia) was the most common symptom at the start of primary adrenal insufficiency in this group, alongside skin darkening and low blood sodium. Their absence, though, does not rule the condition out.

Limited evidenceSource: PMID:40982814
Evidence ratingweak
Study designontology_import
Confidence (0-1)0.7
Replicationunreplicated
Supporting sourcesPMID:40849756, PMID:39510861, ORPHA:85138
Notesplain_language confirmed from PMID:40849756 via curation 2026-06-17. plain_language revised from PMID:40849756 via curation 2026-06-18 [carrie (claude rewrite)]. plain_language confirmed from PMID:39510861 via curation 2026-06-25 [claude-draft]. | regrounded primary ORPHA:85138 -> PMID:40982814 on 2026-06-26 [Carrie Schluter, BCPA]
Last reviewed2026-06-26

Fatigue

Ongoing fatigue is a common symptom of Addison's disease and often appears alongside low blood pressure and darkening of the skin.

Limited evidenceSource: PMID:40720873
Evidence ratingweak
Study designontology_import
Confidence (0-1)0.7
Replicationunreplicated
Supporting sourcesPMID:40842744, PMID:40891960, ORPHA:85138
Notesplain_language confirmed from PMID:40842744 via curation 2026-06-17. plain_language revised from PMID:40891960 via curation 2026-06-18 [owner]. plain_language revised from PMID:40842744 via curation 2026-06-18 [carrie (claude rewrite)]. | regrounded primary ORPHA:85138 -> PMID:40720873 on 2026-06-26 [Carrie Schluter, BCPA]
Last reviewed2026-06-26

Hyperpigmentation of the skin

Darkening of the skin (hyperpigmentation) is frequently seen in Addison's disease. It is linked to a long-standing rise in adrenocorticotropic hormone (ACTH), the signal the body sends when the adrenal glands are underactive.

Limited evidenceSource: PMID:40982814
Evidence ratingweak
Study designontology_import
Confidence (0-1)0.7
Replicationunreplicated
Supporting sourcesPMID:41419241, PMID:42220732, ORPHA:85138
Notesplain_language confirmed from PMID:41419241 via curation 2026-06-13. plain_language confirmed from PMID:42220732 via curation 2026-06-25 [claude-draft]. | regrounded primary ORPHA:85138 -> PMID:40982814 on 2026-06-26 [Carrie Schluter, BCPA]
Last reviewed2026-06-26

Anti-21-hydroxylase antibody positivity

In autoimmune Addison's disease, a blood test for 21-hydroxylase antibodies is usually positive. These antibodies target an enzyme in the adrenal gland and confirm that the cause is autoimmune, which also raises the chance of other autoimmune conditions.

Limited evidenceSource: PMID:41048694
Evidence ratingweak
Study designontology_import
Confidence (0-1)0.7
Replicationunreplicated
Supporting sourcesPMID:40849756, ORPHA:85138
Notesplain_language confirmed from PMID:40849756 via curation 2026-06-13. | regrounded primary ORPHA:85138 -> PMID:41048694 on 2026-06-26 [Carrie Schluter, BCPA]
Last reviewed2026-06-26

Autoimmunity

SARS-CoV-2 infection may act as an environmental trigger that shifts hidden autoimmunity into active disease in people who are genetically prone to it. Whether the virus plays a direct causal role is still uncertain.

Limited evidenceSource: PMID:40720873
Evidence ratingweak
Study designontology_import
Confidence (0-1)0.7
Replicationunreplicated
Supporting sourcesPMID:40849756, ORPHA:85138
Notesplain_language confirmed from PMID:40849756 via curation 2026-06-17. plain_language revised from PMID:40849756 via curation 2026-06-18 [carrie (claude rewrite)]. | regrounded primary ORPHA:85138 -> PMID:40720873 on 2026-06-26 [Carrie Schluter, BCPA]
Last reviewed2026-06-26

Hyperkalemia

High blood potassium (hyperkalemia) is common in Addison's disease, often appearing together with low blood sodium.

Limited evidenceSource: PMID:40720873
Evidence ratingweak
Study designontology_import
Confidence (0-1)0.7
Replicationunreplicated
Supporting sourcesPMID:41102963, ORPHA:85138
Notesplain_language confirmed from PMID:41102963 via curation 2026-06-13. plain_language confirmed from PMID:40720873 via curation 2026-06-25 [claude-draft]. | regrounded primary ORPHA:85138 -> PMID:40720873 on 2026-06-26 [Carrie Schluter, BCPA]
Last reviewed2026-06-26

Dehydration

When the body doesn't make enough aldosterone, it can't properly balance sodium and potassium, which can lead to low blood pressure and dehydration.

Limited evidenceSource: PMID:40982814
Evidence ratingweak
Study designontology_import
Confidence (0-1)0.7
Replicationunreplicated
Supporting sourcesORPHA:85138
Notesplain_language confirmed from PMID:40982814 via curation 2026-06-17. plain_language revised from PMID:40982814 via curation 2026-06-18 [carrie (claude rewrite)]. | regrounded primary ORPHA:85138 -> PMID:40982814 on 2026-06-26 [Carrie Schluter, BCPA]
Last reviewed2026-06-26

Hyponatremia

Low blood sodium (hyponatremia) is common in Addison's disease, often appearing together with high blood potassium.

Limited evidenceSource: PMID:40720873
Evidence ratingweak
Study designontology_import
Confidence (0-1)0.7
Replicationunreplicated
Supporting sourcesPMID:41102963, ORPHA:85138
Notesplain_language confirmed from PMID:41102963 via curation 2026-06-13. plain_language confirmed from PMID:40720873 via curation 2026-06-25 [claude-draft]. | regrounded primary ORPHA:85138 -> PMID:40720873 on 2026-06-26 [Carrie Schluter, BCPA]
Last reviewed2026-06-26

Nausea and vomiting

Nausea and vomiting can be persistent, wearing symptoms in adrenal insufficiency, often together with loss of appetite and feeling full quickly. Because these gut symptoms are not specific, they can be mistaken for another problem early on.

Limited evidenceSource: PMID:40720873
Evidence ratingweak
Study designontology_import
Confidence (0-1)0.7
Replicationunreplicated
Supporting sourcesPMID:41405598, PMID:41241120, ORPHA:85138
Notesplain_language confirmed from PMID:41405598 via curation 2026-06-17. plain_language revised from PMID:40720873 via curation 2026-06-18 [owner]. plain_language revised from PMID:41405598 via curation 2026-06-18 [carrie (claude rewrite)]. plain_language confirmed from PMID:41241120 via curation 2026-06-25 [claude-draft]. | regrounded primary ORPHA:85138 -> PMID:40720873 on 2026-06-26 [Carrie Schluter, BCPA]
Last reviewed2026-06-26

Adrenal crisis

In Addison disease, a sudden severe shortage of cortisol can cause an adrenal crisis, a life-threatening emergency. Steroid replacement helps prevent it.

Limited evidenceSource: PMID:37694439
Evidence ratingweak
Confidence (0-1)0.7
Replicationunreplicated
Notesplain_language confirmed from PMID:37694439 via curation 2026-06-25 [claude-draft].
Last reviewed2026-06-25

How it is diagnosed

Addison disease

Diagnosed using: Morning serum cortisol.

Limited evidenceSource: PMID:41700239
The source text this rests on
“Endocrine evaluation confirmed primary adrenal insufficiency (PAI), evidenced by markedly reduced morning cortisol, elevated adrenocorticotropic hormone (ACTH), and positive adrenal cortex antibodies.”
An excerpt quoted verbatim from the source named above, shown as recorded. The full sentence is in the linked source.
Evidence ratingweak
Confidence (0-1)0.7
Replicationunreplicated
Notesconfirmed from PMID:41700239 via curation 2026-06-25
Last reviewed2026-06-25

Addison disease

Diagnosed using: Plasma ACTH.

Limited evidenceSource: PMID:41700239
The source text this rests on
“Endocrine evaluation confirmed primary adrenal insufficiency (PAI), evidenced by markedly reduced morning cortisol, elevated adrenocorticotropic hormone (ACTH), and positive adrenal cortex antibodies.”
An excerpt quoted verbatim from the source named above, shown as recorded. The full sentence is in the linked source.
Evidence ratingweak
Confidence (0-1)0.7
Replicationunreplicated
Notesconfirmed from PMID:41700239 via curation 2026-06-25
Last reviewed2026-06-25

Addison disease

Diagnosed using: Adrenal cortex antibodies.

Limited evidenceSource: PMID:41700239
The source text this rests on
“Endocrine evaluation confirmed primary adrenal insufficiency (PAI), evidenced by markedly reduced morning cortisol, elevated adrenocorticotropic hormone (ACTH), and positive adrenal cortex antibodies.”
An excerpt quoted verbatim from the source named above, shown as recorded. The full sentence is in the linked source.
Evidence ratingweak
Confidence (0-1)0.7
Replicationunreplicated
Notesconfirmed from PMID:41700239 via curation 2026-06-25
Last reviewed2026-06-25

Addison disease

Diagnosed using: ACTH stimulation test.

Limited evidenceSource: PMID:29260252
The source text this rests on
“…the ACTH stimulation test for the diagnosis of adrenal cortex…”
An excerpt quoted verbatim from the source named above, shown as recorded. The full sentence is in the linked source.
Evidence ratingweak
Confidence (0-1)0.7
Replicationunreplicated
Notesconfirmed from PMID:29260252 via curation 2026-06-25
Last reviewed2026-06-25

Treatment and management

What the research describes, not a recommendation. Treatment decisions belong with your clinician.

This covers treatments that appear in the published research mapped here. Investigational and experimental therapies are not included, so their absence is a boundary of this map, not a sign they do not exist.

hydrocortisone

An adrenal crisis is treated promptly with intravenous fluids, support for blood pressure, and a stress dose of hydrocortisone given into a vein. This emergency hydrocortisone replaces the cortisol the body cannot make.

Used to help with: Addison disease.

Limited evidenceSource: PMID:40842744
The source text this rests on
“Addison's disease management involved hydrocortisone…”
An excerpt quoted verbatim from the source named above, shown as recorded. The full sentence is in the linked source.
Evidence ratingweak
Confidence (0-1)0.7
Replicationunreplicated
Supporting sourcesPMID:40720873
Notesconfirmed from PMID:40842744 via curation 2026-06-13
Last reviewed2026-06-13

fludrocortisone

Fludrocortisone is the mineralocorticoid replacement used in primary adrenal insufficiency. It stands in for aldosterone, the hormone that helps the body hold on to salt and keep blood pressure and potassium in balance.

Used to help with: Addison disease.

Limited evidenceSource: PMID:40842744
The source text this rests on
“…management involved hydrocortisone…”
An excerpt quoted verbatim from the source named above, shown as recorded. The full sentence is in the linked source.
Evidence ratingweak
Confidence (0-1)0.7
Replicationunreplicated
Supporting sourcesPMID:35947299
Notesconfirmed from PMID:40842744 via curation 2026-06-13
Last reviewed2026-06-13

corticosteroid replacement therapy

Corticosteroid replacement therapy is the mainstay of treatment for Addison's disease, replacing the hormones the adrenal glands can no longer make. Even with it, the condition still carries higher mortality and a reduced quality of life, which is why ongoing care matters.

Used to help with: Addison disease.

Limited evidenceSource: PMID:41587556
The source text this rests on
“Despite the use of corticosteroid replacement therapy, people with Addison's disease have increased mortality and reduced quality of life.”
An excerpt quoted verbatim from the source named above, shown as recorded. The full sentence is in the linked source.
Evidence ratingweak
Confidence (0-1)0.7
Replicationunreplicated
Notesconfirmed from PMID:41587556 via curation 2026-06-25
Last reviewed2026-06-25

stress-dose (sick-day) glucocorticoid

People on a steady replacement routine still need higher doses during illness or physical stress, such as a viral infection or surgery. These extra stress doses (sick-day dosing) cover the body's increased need for cortisol and help head off an adrenal crisis.

Used to help with: Addison disease.

Limited evidenceSource: PMID:40720873
The source text this rests on
“Patients who have stabilized their replacement regimens will also require increased doses during periods of illness or stress, such as viral infections or surgery.”
An excerpt quoted verbatim from the source named above, shown as recorded. The full sentence is in the linked source.
Evidence ratingweak
Confidence (0-1)0.7
Replicationunreplicated
Notesconfirmed from PMID:40720873 via curation 2026-06-25
Last reviewed2026-06-25

How to read the evidence labels

Widely acceptedSpecialists broadly agree on this.
Strong evidenceBacked by solid, repeated research.
Moderate evidenceReasonable evidence, still being confirmed.
Limited evidenceSome evidence, but not yet convincing.
Early evidenceAn early finding that needs more study.
Experts disagreeResearchers actively disagree about this.
No longer supportedLater, stronger evidence or guidance overturned this.

Where this comes from

This guide is built from 11 published source(s). Every claim above links back to one of them. Click any source ID to read the original on PubMed.

ORPHA:85138 · Orphanet/HPO annotations for Addison disease
PMID:29260252 · [Functional diagnostics in endocrinology].
PMID:35947299 · Renin and electrolytes indicate the mineralocorticoid activity of fludrocortisone: a 6 year study in primary adrenal ins
PMID:37694439 · Challenges in managing disorders of sex development associated with adrenal dysfunction.
PMID:40720873 · Adrenal Insufficiency: A Case Study.
PMID:40842744 · Diagnostic and Therapeutic Challenges in Concurrent Addison's Disease and Acromegaly.
PMID:40982814 · A DESCRIPTION OF ADDISON'S DISEASE, AND ITS NEUROPSYCHIATRIC MANIFESTATIONS COMPARING THE DISEASE AS IT IS NOW TO THE DISEASE AS EXPERIENCED BY SAINT ELIZABETH OF THE TRINITY IN 1906.
PMID:41048694 · Autoimmune Primary Adrenal Insufficiency in a Pregnant Patient Without Autoimmune Comorbidities.
PMID:41405598 · Dizziness and orthostatic hypotension in a college student.
PMID:41587556 · Clinical features, investigation, and management of Addison's disease.
PMID:41700239 · Addison's Disease Presenting with Hypercalcaemia, Acute Kidney Injury, and Anxiety.

Take it further

Printed, source-linked documents built from this condition's graph — ready to bring to an appointment or attach to a coverage request. Every claim carries its published source, the same as this guide.