Addison disease

Addison disease is a rare endocrine disorder characterized by primary adrenal insufficiency. It results from the destruction or dysfunction of the adrenal cortex, leading to decreased production of cortisol and aldosterone. Early recognition and management are essential to prevent life-threatening complications.

Etiology and Pathophysiology

Causes

The causes of Addison disease are diverse and can be classified as follows:

• Autoimmune Adrenalitis: The most common cause in developed countries, involving autoimmune destruction of adrenal cortical cells.
• Infectious Causes: Infections such as tuberculosis, HIV, or fungal infections can damage the adrenal glands.
• Hemorrhagic Destruction: Conditions like Waterhouse-Friderichsen syndrome result in acute adrenal hemorrhage and insufficiency.
• Genetic Causes: Congenital adrenal hyperplasia and other inherited disorders can impair adrenal function.

Pathophysiology

In Addison disease, the adrenal cortex fails to produce adequate hormones, leading to several physiological consequences:

• Impaired Cortisol Production: Leads to fatigue, weakness, and inability to respond adequately to stress.
• Aldosterone Deficiency: Results in sodium loss, potassium retention, hypotension, and dehydration.
• Secondary Hormonal Effects: Elevated ACTH levels occur due to lack of negative feedback, often causing hyperpigmentation of the skin and mucous membranes.

Clinical Features

General Symptoms

Patients with Addison disease often present with nonspecific symptoms that develop gradually over time:

• Chronic fatigue and generalized weakness
• Unintentional weight loss
• Anorexia and gastrointestinal disturbances such as nausea, vomiting, and abdominal pain

Specific Signs

Certain signs are more characteristic of Addison disease and can aid in clinical diagnosis:

• Hyperpigmentation: Darkening of the skin and mucous membranes, particularly in areas exposed to friction or sunlight.
• Hypotension: Low blood pressure and orthostatic dizziness due to aldosterone deficiency.
• Electrolyte Abnormalities: Hyponatremia, hyperkalemia, and mild hypoglycemia are common laboratory findings.

Laboratory Findings and Diagnostic Workup

Biochemical Tests

Initial evaluation includes measurement of hormone levels and electrolytes to confirm adrenal insufficiency:

• Serum cortisol: typically low in the morning
• Plasma ACTH: elevated in primary adrenal insufficiency
• Electrolytes: hyponatremia, hyperkalemia
• Blood glucose: may be mildly decreased

Dynamic Tests

Dynamic testing helps confirm the diagnosis and differentiate primary from secondary adrenal insufficiency:

• ACTH (cosyntropin) stimulation test: measures adrenal response to synthetic ACTH
• Insulin-induced hypoglycemia test: rarely used, assesses cortisol response to stress

Imaging Studies

Imaging may be indicated to evaluate the adrenal glands or investigate secondary causes:

• CT or MRI of the adrenal glands to detect structural abnormalities, infections, or hemorrhage
• Pituitary imaging if secondary adrenal insufficiency is suspected

Differential Diagnosis

Several conditions can mimic Addison disease, and careful evaluation is necessary to establish an accurate diagnosis:

• Secondary adrenal insufficiency due to pituitary or hypothalamic dysfunction
• Hypothyroidism, which can present with fatigue, weight loss, and hypotension
• Chronic fatigue syndrome, often causing generalized weakness and malaise
• Other endocrine disorders such as diabetes mellitus or hypopituitarism

Complications

Adrenal Crisis

An adrenal crisis is a life-threatening complication characterized by acute adrenal insufficiency. It can be triggered by stress, infection, trauma, or abrupt discontinuation of corticosteroid therapy.

Cardiovascular Collapse

Severe hypotension and shock may occur due to fluid and electrolyte imbalances, requiring urgent medical intervention.

Electrolyte Disturbances

Hyponatremia, hyperkalemia, and hypoglycemia are common and can exacerbate weakness, confusion, and cardiovascular instability.

Chronic Comorbidities

Long-standing untreated Addison disease may lead to chronic fatigue, decreased quality of life, and increased susceptibility to infections.

Treatment and Management

Glucocorticoid Replacement

Glucocorticoid therapy is the cornerstone of treatment for Addison disease, aiming to replace deficient cortisol and control symptoms:

• Hydrocortisone is commonly used due to its similarity to natural cortisol.
• Prednisone or dexamethasone may be alternatives depending on patient preference and dosing convenience.
• Dosing strategies involve dividing the total daily dose to mimic the natural circadian rhythm of cortisol secretion.

Mineralocorticoid Replacement

Replacement of aldosterone is necessary in patients with primary adrenal insufficiency to maintain sodium balance and blood pressure:

• Fludrocortisone is the standard mineralocorticoid used.
• Regular monitoring of blood pressure, electrolytes, and body weight is essential to adjust the dose appropriately.

Management of Adrenal Crisis

Adrenal crisis is a medical emergency requiring immediate intervention:

• Rapid administration of intravenous hydrocortisone.
• Fluid resuscitation with isotonic saline to correct hypotension and dehydration.
• Correction of electrolyte imbalances and monitoring of vital signs.

Lifestyle and Patient Education

Patient education is vital to prevent complications and maintain health:

• Stress dosing of corticosteroids during illness, surgery, or trauma.
• Recognition of early signs of adrenal insufficiency.
• Medical alert identification and adherence to prescribed therapy.

Prognosis and Follow-Up

Long-Term Outcomes

With appropriate hormone replacement therapy, patients with Addison disease can have a normal life expectancy. Regular monitoring and adherence to treatment are crucial to prevent complications.

Monitoring for Complications

Ongoing follow-up includes:

• Regular assessment of electrolytes, blood pressure, and body weight.
• Monitoring for signs of over- or under-replacement of corticosteroids.
• Screening for associated autoimmune conditions, which may coexist with Addison disease.

Importance of Patient Compliance

Compliance with medication regimens and stress-dosing instructions is essential to avoid adrenal crises and maintain quality of life. Patient education and support play a key role in successful long-term management.

References

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