Addison's Disease (Addisons Disease)

Addisons hyperpigmentation[1]

Addison’s disease is a chronic clinical disease characterized by the progressive decline in the function of the adrenal glands. This potentially fatal disease may result in hyperpigmentation, hypotension, and cardiovascular collapse. Addison’s disease is easily diagnosed clinically and by the use of hormonal assays that reveal an elevated adrenocorticotropic hormone (ACTH) with a low plasma cortisol level.


Addison’s disease has a typical insidious and chronic onset which may take several months. The following signs and symptoms are usually presented by patients with primary adrenal insufficiency:

On occasions, the symptomatology of Addison’s disease may appear acutely or abruptly. The acute onset of adrenal insufficiency symptoms is clinically referred to as Addisonian crisis. The following signs and symptoms are typically observed in acute adrenal failure:


Addison’s disease is primarily investigated by means of an extensive clinical history taking followed by a careful review of the presenting signs and symptoms. When the patients are suspected of having Addison’s disease the following confirmatory tests may be done to ascertain the diagnosis:

  • Serum electrolytes: This blood test will determine the present level of sodium and potassium in the serum because these electrolytes are usually affected in Addison’s disease.
  • Hormonal assays: The hormonal levels of ACTH and cortisol are likewise determined to support the suspicion of Addison’s disease.
  • ACTH stimulation test: This hormonal test monitors the level of cortisol produced in the body after the injection of a synthetic ACTH hormone [8]. A damaged adrenal cortex may not respond to ACTH stimulation at all.
  • Insulin-induced hypoglycemia test: This will test for secondary adrenal insufficiency or those caused by a pituitary dysfunction. This test measures the levels of blood glucose and cortisol levels at the different time intervals after the introduction of synthetic insulin. The normal response of the body is to decrease the glucose level and increase the cortisol level.
  • Imaging: Computed tomography (CT scan) of the abdomen can elucidate the size and pathology of the adrenal gland at the suprarenal region [9]. Magnetic resonance imaging (MRI) may demonstrate the conditions of the pituitary gland in the skull to rule out secondary causes of adrenal insufficiency.


The main goal in the treatment of Addison’s disease is to replace the deficient hormones in the right levels of steroid hormones that the adrenal glands are incapable of maintaining. The following are options used in the treatment of Addison’s disease:

  • Oral corticosteroids: Patients may be given oral hydrocortisone, prednisone, or cortisone acetate to replace the deficient cortisol hormone. In the same way, fludrocortisone may be given to replace the aldosterone deficiency.
  • Injectable corticosteroids: This steroid is given for the same indications. This option is resorted by patients if they are unable to tolerate oral corticosteroids [10].
  • Androgen replacement therapy: This regimen is given to women with low androgen levels. The oral dehydroepiandrosterone is preferentially used to address problems of libido and sexual satisfaction in women.
  • Sodium supplementations: Sodium may be amply given during activities that incurs heavy perspiration like exercises. Excessive diarrhea and vomiting among patients may also benefit from the sodium supplementations.


Addison’s disease presenting with significant adrenal hormone insufficiency can be life threatening if left untreated. Patients undergoing hormone replacement therapy with the deficient mineralocorticoid and glucocorticoid may live a normal life.


The greater majority of cases of Addison’s disease or primary adrenal insufficiency is caused by the idiopathic atrophy of the adrenals, accounting for almost 70% of all cases. The leading theory postulated for the idiopathic atrophy of the adrenals points to an autoimmune origin. There are however, some less common causes of adrenal destruction which include granuloma, tuberculosis, histoplasmosis, amyloidosis, inflammatory necrosis, hemorrhage and tumorous growths. The most common cause of Addison’s disease among children is congenital adrenal hyperplasia (CAH).


In the United States, the recent prevalence rate of Addison’s disease is up to 60 cases per one million population. Addison’s disease is relatively rare internationally. The increase in the mortality and morbidity rates is usually due to the delay in the replacement therapy of the mineralocorticoid and glucocorticoid hormones [2]. Although, primary adrenal insufficiency is already considered serious and potentially life threatening, concomitant illnesses like malignancies, cardiovascular diseases, and infectious diseases influences greatly the increased mortality rate among these patients [3].

The primary idiopathic and autoimmune form of Addison’s disease is more commonly seen in children and females. There is no racial predilection to Addison’s disease. The mean age of onset is 30 to 50 years old but may present earlier among the infantile cases of congenital adrenal hyperplasia.

Sex distribution
Age distribution


The pathogenesis of Addison’s disease or adrenal insufficiency is primarily due to the destruction of the adrenal cortex. Cortical destruction may either be inflammatory, necrotic, neoplastic, infectious, or hemorrhagic in nature. Signs and symptoms of adrenal insufficient usually present clinically when 90% or more of the adrenal cortex has been rendered dysfunctional or destroyed. The main systemic pathology is brought about by the lack of glucocorticoid and mineralocorticoid hormone secretion that is essential to the body.


The congenital form of primary adrenal insufficiency cannot be prevented, although; new born screening may detect congenital adrenal hyperplasia in the first two days of life. The prompt diagnosis and hormone replacement therapy of Addison’s disease can prevent untoward complications and death.


Addison’s disease is a serious disorder that occurs when the adrenal glands are unable to produce sufficient hormones needed for proper metabolism. In this disorder, the hormones aldosterone and cortisol are insufficiently secreted from the suprarenal glands. For this reason, Addison’s disease is also referred to as primary adrenal insufficiency [1]. Hormonal treatment is the standard approach to this disease to mimic the natural function of the deficient adrenal hormone.

Patient Information


Addison’s disease is a serious disorder that occurs when the adrenal glands is unable to produce sufficient mineralocorticoid and glucocorticoid hormones needed for normal functioning.


The most common cause of Addison’s disease is idiopathic autoimmune adrenal atrophy. The other causes include granuloma, tuberculosis, histoplasmosis, amyloidosis, inflammatory necrosis, hemorrhage and tumors.


Patients usually present with anorexia, nausea and vomiting. Muscular fatigue and weakness are fairly common with hyperpigmentation of the skin. Signs of hypotension and hypoglycemia may also be observable.


Diagnostics for Addison’s disease starts with blood test of electrolytes and hormones. ACTH stimulation tests and Insulin-induced hypoglycemia tests, imaging studies with CT scan and MRI may follow.

Treatment and follow-up

The cornerstone in the treatment of Addison’s disease is the active hormonal replacement of the deficient hormones. Glucocorticoids are replaced with oral and injectable steroids, mineralocorticoids are replace by fludrocortisone. Androgen replacement therapy for afflicted women can allay the signs of androgen deficiency.


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  1. Addison T. On the Constitutional and Local Effects of Disease of the Supra-renal Capsules. London, UK: Samuel Highley; 1855.
  2. White K, Arlt W. Adrenal crisis in treated Addison's disease: a predictable but under-managed event. Eur J Endocrinol. Jan 2010; 162(1):115-20.
  3. Kyriazopoulou V. Glucocorticoid replacement therapy in patients with Addison's disease. Expert Opin Pharmacother. Apr 2007; 8(6):725-9.
  4. Bergthorsdottir R, Leonsson-Zachrisson M, Oden A, et al. Premature mortality in patients with Addison's disease: a population-based study. J Clin Endocrinol Metab. Dec 2006; 91(12):4849-53.
  5. McBrien DJ. Steatorrhea in Addison's disease. Lancet. 1963; Vol I: 25-6.
  6. Barnett AH, Espiner EA, Donald RA. Patients presenting with Addison's disease need not be pigmented.Postgrad Med J. Nov 1982; 58(685):690-2.
  7. McBrien DJ. Steatorrhea in Addison's disease. Lancet. 1963; Vol I: 25-6.
  8. Kyriazopoulou V, Parparousi O, Vagenakis AG. Rifampicin-induced adrenal crisis in addisonian patients receiving corticosteroid replacement therapy. J Clin Endocrinol Metab. Dec 1984; 59(6):1204-6.
  9. Likhari T, Magzoub S, Griffiths MJ, et al. Screening for Addison's disease in patients with type 1 diabetes mellitus and recurrent hypoglycaemia. Postgrad Med J. Jun 2007; 83(980):420-1.
  10. Ma ES, Yang ZG, Li Y, et al. Tuberculous Addison's disease: morphological and quantitative evaluation with multidetector-row CT. Eur J Radiol. Jun 2007; 62(3):352-8.

Media References

  1. Addisons hyperpigmentation, CC0 1.0