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  • Christine Ahn MD
    Carl Allen DDS, MSD
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ContentsSynopsisCodesLook ForDiagnostic PearlsDifferential Diagnosis & PitfallsBest TestsManagement PearlsTherapyAssociated MedicationsReferencesView all Images (17)
Addison disease - Oral Mucosal Lesion
See also in: Skin
Other Resources UpToDate PubMed

Addison disease - Oral Mucosal Lesion

See also in: Skin
Print Images (17)
Contributors: Carl Allen DDS, MSD, Sook-Bin Woo MS, DMD, MMSc
Other Resources UpToDate PubMed


Addison disease is a chronic primary adrenocortical insufficiency resulting from dysfunction of the adrenal glands. This can be due to a variety of causes, which include autoimmune diseases, infections (tuberculosis), and neoplasms (metastatic cancer). The most common associated autoimmune diseases are Type I diabetes mellitus, Hashimoto thyroiditis, and vitiligo. Patients with acquired immunodeficiency syndrome may develop Addison disease due to cytomegalovirus infection. Other less common causes are drugs (antifungals), congenital adrenal hypoplasia, and disorders such as sarcoidosis and amyloidosis. Some cases are idiopathic. Patients with loss-of-function mutations in sphingosine-1-phosphate lyase may have nephrosis with ichthyosis and adrenal insufficiency.

The adrenal insufficiency leads to decreased levels of glucocorticoids (the most common), mineralocorticoids, and adrenal androgens. The disease is characterized by general symptoms of fatigue, weight loss, weakness, vomiting, dizziness, cold intolerance, and muscle aches. Because these symptoms are nonspecific, the diagnosis may go unrecognized until the patient presents with a life-threatening adrenal crisis (severe hypotension and even coma).

The cutaneous manifestation of patients with chronic Addison disease is hyperpigmentation of skin and mucous membranes. Skin pigmentation, which appears as "bronzing" of the skin, is generalized and mainly affects sun-exposed areas. Oral mucosal lesions present as dark brown to black macules and frequently are the first sign of disease. These and the other clinical signs of the disease appear only after 90% of the adrenal gland is nonfunctioning. The hyperpigmentation is due to increased production of melanocyte-stimulating hormone (MSH), which is part of the adrenocorticotrophic hormone (ACTH) molecule; ACTH production in the pituitary increases in response to decreased cortisol production, leading also to an increase in MSH levels and melanosis.

Men and women are equally affected, and although all ages are affected, it is more common between the ages of 30 and 50. Estimated prevalence of the disease is at 120 per million.

Addisonian Crisis:
Acute adrenal failure presents with severe penetrating abdominal pain accompanied by vomiting and diarrhea, low blood pressure, and loss of consciousness. This is a life-threatening emergency that must be managed aggressively.


E27.1 – Primary adrenocortical insufficiency

363732003 – Addison disease

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Differential Diagnosis & Pitfalls

Diseases that produce pigmentation of the oral mucosa have to be differentiated from Addison disease.
  • Physiologic pigmentation (see multifocal or diffuse mucosal pigmentation) – Although this appears similar to pigmentation of Addison disease, this is not of acute onset and is unaccompanied by systemic symptoms.
  • Heavy metal pigmentation (see multifocal or diffuse mucosal pigmentation) – This is usually located at the gingival margin.
  • Peutz-Jeghers syndrome shows peri-orificial peppered pigmentation (small macules) and intestinal polyposis.
  • McCune-Albright syndrome and neurofibromatosis are both associated with oral melanotic macules and café au lait skin pigmentation.
  • Post-inflammatory hypermelanosis and smoker's melanosis occur as a result of inflammation and appear gradually over time; it is particularly common in areas of lichen planus that develop in dark-skinned patients.
  • Melanoacanthosis may be a form of post-inflammatory hypermelanosis that has a sudden onset, spreads rapidly, and then resolves.
  • Oral melanotic macules are common on the vermilion, palatal mucosa, and gingiva and are solitary or multi-focal, appearing gradually over time.
  • Medications such as minocycline, anti-malarials, clofazimine, and imatinib may cause pigmentation, often on the palatal mucosa. Tetracycline pigmentation of teeth show through the mucosa as a grayish macular discoloration.

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Last Updated: 03/07/2017
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Addison disease - Oral Mucosal Lesion
See also in: Skin
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Addison disease (Common Features) : Abdominal pain, Fatigue, Hyperkalemia, Muscle weakness, Weight loss, Anorexia, Darkening skin lesion, BP decreased, Hyperpigmentation, Na decreased, Depression
Clinical image of Addison disease
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