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Addison's Disease: A Deceptive Presentation

A patient presents with vague complaints of fatigue, nausea, vomiting and slight diarrhea. During the physical assessment, he is tachycardic and hypotensive.


The patient has cool, clammy, brownish skin with hyperpigmentation along areas of friction: the flexor creases of the palms, elbows and knees.1


These common signs and symptoms could be dismissed as viral gastroenteritis or the common flu, but do they signal something more serious?


The answer is "yes." The symptoms described above can all be signs of Addison's disease, a life-threatening, renal crisis that is frequently missed. In western countries, the incidence of Addison's disease is estimated at 120 per 1 million people.2



Addison's disease, also known as adrenal insufficiency, occurs most often in adults between the ages of 30-60.3 The cause of most cases is an autoimmune mechanism that is more common in women.3 (A small number of cases result from fungal infections, cancer or surgical removal of the adrenal glands.)


Addison's disease is characterized by inadequate corticosteroid and mineralcorticoid synthesis that leads to adrenal crisis.3


When adrenal crisis occurs, serum adrenocorticotropin hormone (ACTH) rises, causing hypofunction of the adrenal cortex and, ultimately, hypocortisolism.3 The glucocorticoids mediate glucose metabolism and have an inflammatory effect.3 Mineralcorticoids maintain electrolyte balance and extracellular volume.3 The absence or suppression of these corticosteroids increases the risk for adrenal crisis.3 Hyperfunction of the adrenal gland may also occur, caused by a catecholamine-producing tumor called pheochromocytoma.3 


Signs and Symptoms

In most patients, the slow loss of cortisol and aldosterone that occurs in Addison's disease produces a chronic, steadily worsening fatigue, appetite loss and some weight loss. Blood pressure lowers and falls further upon standing, leading to lightheadedness. Nausea, vomiting and diarrhea are also common. Muscles may weaken, and emotional changes may occur. The patient may crave salt - so much so that he or she may want to eat salt out of a shaker or even drink pickle juice.4 Decreased libido may also be reported.4


The slow, progressive symptoms are usually missed or ignored until a sudden event, such as viral infection, an accident or surgery, prompts a downturn because of the adrenal gland's deficient response to these stresses.


Quick recognition of Addisonian crisis is essential to avoid life-threatening events. Common signs and symptoms of adrenal crisis include sudden pain in the lower back, abdomen or legs, severe nausea and vomiting, headache, weakness, fatigue, and chronic diarrhea.4


Upon physical exam, hyperpigmentation may be evident on the buccal mucosa, knees and the soles of the feet.1 Flexor surfaces such as knuckles, elbows, areola and palm creases may appear tanned. The hyperpigmentation results from the high plasma corticotropin concentrations that occur with decreased cortisol feedback.1  


The patient may report axillary and pubic hair loss. Vitiligo - white, patchy areas of depigmentation on the skin - is also a sign of an adrenal crisis.1 Hypotension may occur due to decreased blood volume from hypoaldosteronism and cause increasing renal sodium loss.3  


Laboratory Findings

Several serum laboratory results can be elevated or suppressed in adrenal crisis. Urine and serum levels of ketosteroids, aldosterone and cortisol are decreased, and ACTH levels are increased.3 Blood urea nitrogen and hematocrit levels are increased related to dehydration. Hyperkalemia can cause mild to severe alkalosis.3  


Several other biochemical abnormalities associated with Addison's disease include hyponatremia, hypoglycemia, high antidiuretic hormone levels, lymphocytes and eosinophilia.5  


Mineralcorticoid deficiency causes hyponatremia and hyperkalemia.6  Hypoglycemia may also occur and can be life threatening, leading to seizures, coma and even death.1  Adrenal insufficiency is diagnosed based on low levels of cortisol at 8 a.m., along with elevated ACTH levels.2



Addison's disease can mirror many illnesses. The common symptoms of nausea, vomiting and diarrhea can mimic gastroenteritis. Hair loss, fatigue and general malaise are also signs of a thyroid disorder. Adrenal crisis can also affect mood and be mistaken as depression or panic and anxiety disorders. Excessive thirst and salt cravings could be mistaken for dehydration or diabetes mellitus.


Hypotensive states may be diagnosed as hypovolemia. But these symptoms may actually be the absence of circulating glucocorticoids and adrenal steroids that can ultimately lead to shock and death.6  


Tuberculosis is a common cause of adrenal insufficiency worldwide, but it may be difficult to identify as the cause of an adrenal crisis.7  


The adrenal gland can be enlarged as a result of diseases such as malignancies of the lung, breast or gastrointestinal system, as well as from AIDS and opportunistic infections.1  



Since Addison's disease is caused by a lack of cortisol and aldosterone, the treatment is to replace these with similar steroids. In the acute setting, dexamethasone (6-10 mg) may be given intravenously every 6-8 hours.


Once stabilized, patients require treatment with hydrocortisone or cortisone every morning and in the afternoon. The initial dose of hydrocortisone is 20 mg in the morning and 10 mg in the evening.1  The ultimate goal is to use the lowest dose possible to avoid any weight gain or osteoporosis. The patient requires education about the possibility of increasing the dose when stressful events occur.


Lifelong steroid therapy is necessary for all patients with Addison's disease. Patients require thorough education about this need, as well as an understanding of how to adjust their dose when stress or illness occurs.3  


Patients should have an emergency plan for medical crises. They should wear a medic alert bracelet that describes their medical regimen and specific treatment, and they should carry ampules of self-injectable steroids.


Addison's At a Glance


Signs and Symptoms


  • Fatigue
  • Low blood pressure
  • Muscle weakness
  • Nausea, vomiting, diarrhea
  • Appetite loss, some weight loss
  • Sometimes, darkening of skin

Diagnostic Markers


  • Low cortisol level at 8 a.m., along with elevated adrenocorticotropin hormone
  • Decreased urine and serum levels of ketosteroids, aldosterone and cortisol
  • High antidiuretic hormone levels
  • Increased blood urea nitrogen and hematocrit



  • Lifelong steroid therapy


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