Addison's disease

Addison's disease
Name	Addison's disease
Synonyms	Primary adrenal insufficiency, chronic adrenal insufficiency, hypocortisolism, hypocorticism
Caption	The adrenal glands, located atop the kidneys, are the primary site of pathology.
Field	Endocrinology
Symptoms	Fatigue, weight loss, hyperpigmentation, low blood pressure
Complications	Addisonian crisis, severe hypotension, shock
Onset	Any age
Duration	Lifelong
Causes	Autoimmune disease, tuberculosis, adrenal hemorrhage, metastatic cancer
Risks	Other autoimmune diseases
Diagnosis	ACTH stimulation test, renin and aldosterone levels, autoantibody testing
Differential	Secondary adrenal insufficiency, anorexia nervosa, chronic fatigue syndrome
Treatment	Hydrocortisone, fludrocortisone
Prognosis	Good with consistent treatment
Frequency	0.8–1.4 per 100,000 in developed countries

Addison's disease. It is a rare, chronic endocrine disorder resulting from primary insufficiency of the adrenal cortex. This leads to deficient production of crucial glucocorticoid and mineralocorticoid hormones, most notably cortisol and aldosterone. The condition requires lifelong hormone replacement therapy to manage its systemic effects and prevent life-threatening complications.

Signs and symptoms

The onset is often insidious, with non-specific symptoms like profound fatigue, anorexia, and unintentional weight loss. A cardinal sign is hyperpigmentation, most noticeable in sun-exposed areas, skin creases like the palmar crease, and mucous membranes, due to elevated proopiomelanocortin and adrenocorticotropic hormone (ACTH). Hypotension, particularly orthostatic hypotension, and salt craving are common due to aldosterone deficiency. Gastrointestinal disturbances such as nausea, vomiting, and abdominal pain are frequent. An acute, life-threatening exacerbation known as an Addisonian crisis can present with severe hypotension, hyponatremia, hyperkalemia, fever, and hypoglycemia, often triggered by physical stress like infection or surgery.

Causes

In developed nations, the most common cause is autoimmune adrenalitis, where the body's immune system attacks the adrenal cortex. This is often part of autoimmune polyendocrine syndrome type 1 or type 2, which may involve other glands like the thyroid in Hashimoto's thyroiditis or the pancreas in type 1 diabetes. Historically, tuberculosis was a leading cause worldwide and remains significant in endemic regions. Other infectious causes include fungal infections like histoplasmosis and HIV-associated infections such as cytomegalovirus. Bilateral adrenal hemorrhage, which can occur in settings of sepsis like Waterhouse-Friderichsen syndrome from meningococcal disease, is a rarer cause. Infiltrative diseases like amyloidosis, hemochromatosis, and metastatic cancer, particularly from lung cancer or breast cancer, can also destroy adrenal tissue.

Diagnosis

Diagnosis involves a combination of clinical suspicion and specific laboratory tests. The definitive test is the ACTH stimulation test (cosyntropin stimulation test), which demonstrates a blunted cortisol response. Elevated plasma ACTH levels confirm the primary adrenal origin. Simultaneously, measurement of renin and aldosterone levels typically shows elevated renin with low aldosterone. Detection of 21-hydroxylase autoantibodies supports an autoimmune etiology. Imaging with computed tomography (CT) of the adrenal glands may reveal atrophy in autoimmune cases or enlargement in infectious or hemorrhagic causes. It is crucial to distinguish it from secondary adrenal insufficiency, which involves the pituitary gland or hypothalamus.

Treatment

Lifelong hormone replacement therapy is essential. Glucocorticoid deficiency is treated with oral hydrocortisone or prednisone, typically administered in divided doses to mimic the body's circadian rhythm. Mineralocorticoid replacement is achieved with fludrocortisone. During periods of physical stress, such as illness, injury, or surgery, glucocorticoid doses must be increased significantly to prevent crisis; patients are advised to carry a steroid emergency card and often an emergency injection of hydrocortisone. Management of an acute Addisonian crisis is a medical emergency requiring immediate intravenous hydrocortisone, aggressive fluid resuscitation with normal saline, and correction of hypoglycemia.

Epidemiology

Addison's disease is uncommon, with an estimated prevalence of 93–140 per million and an incidence of 0.8–1.4 per 100,000 per year in developed countries like the United Kingdom and Scandinavia. Autoimmune adrenalitis shows a female predominance and is frequently associated with other autoimmune diseases. The age of onset for autoimmune cases often peaks in the third to fourth decades of life. Geographic variation exists, with infectious causes like tuberculosis remaining predominant in regions such as parts of Africa and India.

History

The disease is named after Thomas Addison, a British physician at Guy's Hospital in London, who first provided a classic clinical description in his 1855 publication *On the Constitutional and Local Effects of Disease of the Suprarenal Capsules*. His work was corroborated by colleagues like Richard Bright and Thomas Hodgkin. For decades, the condition was uniformly fatal until the groundbreaking work of American chemists Edward Calvin Kendall and Tadeus Reichstein and Swiss chemist Philip Showalter Hench, who isolated and synthesized cortisone; their research earned them the Nobel Prize in Physiology or Medicine in 1950. The subsequent development of synthetic fludrocortisone in the 1950s by David A. K. Black completed the modern replacement regimen, transforming a fatal disease into a manageable chronic condition.

Category:Autoimmune diseases Category:Endocrinology Category:Rare diseases