Addison’s Disease
- Fysiobasen
- Sep 13
- 6 min read
Addison’s disease, also called primary chronic adrenal insufficiency, is a rare but serious condition in which the adrenal cortex is gradually destroyed and loses its ability to produce vital hormones such as cortisol and aldosterone. Without treatment, this hormone deficiency causes severe disturbances in salt and fluid balance, metabolism, and stress regulation. The condition may present with a serious, and at times life-threatening, clinical picture if not detected and treated in time¹.
Alternative Names and Spellings
In English, the condition is referred to as “Addison’s disease” or “primary chronic adrenal insufficiency.” When the underlying problem is secondary (due to pituitary or hypothalamic dysfunction), the term Addison’s disease is not applied; instead, it is referred to as secondary or tertiary adrenal insufficiency.
Causes and Pathophysiology
Addison’s disease occurs when the adrenal cortex, the outer layer of the adrenal glands, is progressively destroyed and can no longer produce the hormones cortisol (a glucocorticoid) and aldosterone (a mineralocorticoid).
In the Western world, the most common cause is autoimmune destruction, where the immune system mistakenly attacks the adrenal cortex.
Globally, tuberculosis remains a major cause, especially in areas with high infection prevalence².
Other causes include adrenal hemorrhage, metastases from cancer, or hereditary disorders that affect the adrenal glands.
Secondary and tertiary forms of adrenal insufficiency exist, but these are due to disease or damage in the pituitary or hypothalamus and are not classified as Addison’s disease³.
Clinically Relevant Anatomy
The adrenal glands (suprarenal glands) are small endocrine organs located on top of each kidney. They consist of two main parts:
Adrenal cortex (outer layer), which produces steroid hormones:
Zona glomerulosa: produces aldosterone for blood pressure and salt balance regulation
Zona fasciculata: produces cortisol for metabolism and stress response
Zona reticularis: produces androgens (precursors of sex hormones)
Adrenal medulla (inner layer), which produces stress hormones: adrenaline, noradrenaline, and some dopamine⁴
Complete loss of adrenal cortex hormone production leads rapidly to life-threatening fluid and electrolyte imbalances. Without treatment, death may occur within days or weeks⁴.
Prevalence
Addison’s disease is rare. It affects about 1 in 100,000 people in the United States, and approximately 8,400 individuals are diagnosed in the United Kingdom. The condition can occur at any age and in both sexes, but it most often affects middle-aged women⁵.
Symptoms and Clinical Presentation
Symptoms of Addison’s disease often develop gradually and typically do not become apparent until more than 90% of the adrenal cortex is destroyed. Early symptoms are usually diffuse and related to the deficiency of both cortisol and aldosterone.
Common symptoms and findings:
Hyperpigmentation of the skin, especially in exposed areas such as oral mucosa and scars, caused by increased ACTH and MSH production as the body attempts to stimulate the adrenal glands¹².
Slowly progressive weakness and fatigue.
Low blood pressure with dizziness, due to excessive sodium loss (low aldosterone).
Abdominal pain, lower back or bone pain.
Gastrointestinal complaints: nausea, vomiting, weight loss, diarrhea, and loss of appetite.
Low blood sugar, particularly during fasting or physical exertion.
Reduced tolerance to physical or psychological stress (e.g., infections, trauma, surgery).
Strong salt cravings.
Risk of circulatory collapse and shock, especially during infection or injury.
Low-grade fever.
Acute Addisonian crises with vomiting and lethargy triggered by stress, infection, or trauma.
Situations where Addison’s disease should be suspected:
Persistent fatigue, hyperpigmentation, gastrointestinal symptoms, and salt cravings.
Unexplained hypoglycemia in individuals with type 1 diabetes.
Low sodium and high potassium levels on blood tests without an obvious cause.
Worsening symptoms when initiating thyroxine therapy in a patient with hypothyroidism³.
Complications
Addison’s disease can lead to several severe complications:
Addisonian crisis: An acute, life-threatening condition characterized by low blood pressure, shock, fever, altered consciousness, and severe abdominal pain with vomiting.
Hypoglycemia: Particularly in response to infection, fasting, or intense physical exertion.
Chronic hypotension with increased risk of dehydration and electrolyte imbalance.
Osteoporosis: Both the disease itself and long-term steroid use may contribute to bone loss.
Polyglandular autoimmune syndrome: Addison’s disease may coexist with other autoimmune disorders such as type 1 diabetes, hypothyroidism, hypoparathyroidism, vitamin B12 deficiency, vitiligo, and chronic hepatitis⁷.
Diagnostic Tests and Laboratory Findings
The diagnosis of Addison’s disease relies on a combination of clinical symptoms, laboratory tests, and stimulation tests to confirm hormone deficiency and determine the underlying cause.
Key laboratory tests and findings:
ACTH stimulation test: The most important and commonly used test. Cortisol is measured in blood or urine before and after administration of synthetic ACTH.
In normal adrenal function, cortisol levels rise significantly after stimulation.
In Addison’s disease, there is little or no increase in cortisol.
Diagnosis is confirmed with high ACTH (≥ 50 pg/mL) and low cortisol (< 5 μg/dL or < 138 nmol/L)⁹¹⁰.
CRH stimulation test: Performed if ACTH testing yields unclear results. Cortisol is measured after intravenous CRH administration.
Addison’s disease typically shows high ACTH but no cortisol response⁹.
Blood chemistry:
Serum sodium < 135 mmol/L
Serum potassium > 5 mmol/L
Sodium:potassium ratio < 30:1
Fasting blood glucose < 2.8 mmol/L
Bicarbonate < 15–20 mmol/L
BUN (urea) > 7.1 mmol/L
Hematology:
Elevated hematocrit
Low white blood cell count
Increased lymphocytes and eosinophils
Imaging:
X-ray or ultrasound of the abdomen may reveal adrenal calcifications or structural changes, particularly in cases of suspected tuberculosis or cancer.
Medical Treatment
The treatment of Addison’s disease requires lifelong hormone replacement therapy to substitute for the adrenal cortex hormones that are no longer produced. The goal is to mimic the body’s natural hormone rhythm and ensure stable fluid and electrolyte balance throughout the day.
Most common medications:
Hydrocortisone is usually the first choice for glucocorticoid (cortisol) replacement. Tablets are often divided into two or three daily doses to mimic the body’s circadian rhythm, although this can still cause fluctuations in hormone levels.
Prednisolone or dexamethasone may be used as alternatives, especially when it is desirable to avoid major swings in cortisol levels, as these drugs have a longer duration of action.
Fludrocortisone is prescribed as mineralocorticoid replacement to maintain blood pressure and normal electrolyte balance.
Dehydroepiandrosterone (DHEA) may be considered in selected cases, particularly in women with signs of androgen deficiency. This is not standard treatment and should only be used after specialist evaluation³.
Adrenal Crisis
An adrenal crisis is a rare but acute and life-threatening complication where the adrenal glands suddenly fail to produce enough cortisol. It can be triggered by stress, infection, trauma, or medication errors, and requires immediate medical intervention.
Typical signs of adrenal crisis:
Severe dehydration
Nausea and vomiting
Abdominal pain
Loss of appetite, chills, and general malaise
If untreated, rapid progression to shock, high fever, and seizures
This is a medical emergency that must be treated with urgent intravenous fluids and high-dose hydrocortisone⁷
Physiotherapy
Although research on physiotherapy in Addison’s disease is limited, clinical experience shows that many patients suffer from reduced endurance, weakness, and fatigue even after treatment has begun.
The physiotherapist’s role includes:
Gradually tailored exercise and activity programs to prevent overexertion and worsening fatigue.
Focus on strengthening muscles, improving balance, and enhancing cardiovascular fitness, all adapted to daily condition and disease status.
Support in coping with long-term fatigue and reduced physical capacity, enabling participation in daily activities.
Guidance on activity regulation and energy conservation strategies.
Particular attention to the increased risk of osteoporosis in patients on long-term steroid therapy, incorporating weight-bearing exercise whenever possible.
Key symptoms the physiotherapist should monitor:
Gradually increasing weakness and fatigue
Persistent pain in the abdomen, back, or bones
Unexplained tiredness and reduced functional capacity
Generalized muscle complaints
Differential Diagnosis
Several conditions can mimic Addison’s disease and must be excluded through careful clinical evaluation and laboratory testing.
Common differential diagnoses include:
Heavy metal poisoning: especially arsenic, which may cause skin hyperpigmentation.
Hemochromatosis: iron overload leading to bronze or gray skin pigmentation and liver damage.
Peutz-Jeghers syndrome: a hereditary disorder with mucocutaneous pigmentation and intestinal polyps, often causing abdominal pain and blood in stool.
Hypothyroidism: also presents with fatigue and low energy but typically with weight gain (as opposed to weight loss in Addison’s).
Hypopituitarism: ACTH deficiency can mimic Addison’s but usually without hyperpigmentation.
Other autoimmune, infectious, or chronic systemic conditions¹⁰¹³¹⁴¹⁵.
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