Addison’s disease is an endocrine disorder where the adrenal glands fail to produce enough steroid hormones, like cortisol and aldosterone. Symptoms often develop slowly and include weakness, weight loss, and abdominal pain. A more distinct sign is the development of dark patches inside the mouth, known as oral pigmentation. This can be an early indicator of adrenal insufficiency, appearing months or years before other symptoms.
The Hormonal Mechanism Behind Pigmentation
Hyperpigmentation in Addison’s disease results from a hormonal feedback loop. The pituitary gland releases adrenocorticotropic hormone (ACTH) to signal the adrenal glands when more cortisol is needed. In Addison’s disease, the adrenal glands fail to produce cortisol, so the pituitary gland continues to produce large quantities of ACTH in an attempt to stimulate the unresponsive glands.
This pigmentation occurs because ACTH and melanocyte-stimulating hormone (MSH), which governs skin pigment, are derived from the same precursor molecule, pro-opiomelanocortin (POMC). When the pituitary gland increases POMC production to create more ACTH, it also generates an excess of MSH.
The surplus MSH stimulates pigment-producing cells (melanocytes) to increase their production of melanin. Melanin is the natural pigment responsible for the color of skin, hair, and mucous membranes. This overproduction leads to the darkening of the skin and the patchy discoloration inside the mouth.
Characteristics of Oral Pigmentation in Addison’s Disease
The patches are typically multifocal and irregular, presenting as blotchy macules rather than uniform spots. The color can vary, ranging from a light brown to a deep gray or even a bluish-black hue. These discolorations are painless and do not alter the texture of the mucosal surface.
This pigmentation is frequently observed on the inside of the cheeks (buccal mucosa). Other common sites include the gums (gingiva), the roof of the mouth (palate), and the tongue. The pattern can be spotty or appear in streaks, sometimes alternating with areas of normal-colored tissue.
While some individuals naturally have melanin in their oral tissues, known as physiological pigmentation, its appearance is different. Physiological pigmentation tends to be more symmetrical and uniform in color, whereas the macules in Addison’s disease are scattered and patchy. The sudden appearance of new, irregular patches in an adult can be an indicator of the underlying systemic condition.
Pigmentation as Part of a Larger Symptom Profile
While oral pigmentation can be one of the first and most visible signs of Addison’s disease, it seldom occurs in isolation. The same hormonal process causing oral discoloration also leads to hyperpigmentation of the skin.
This skin darkening is often more pronounced in areas exposed to the sun, but it also appears in skin creases, such as those on the palms of the hands, as well as on knuckles, elbows, and knees. Old scars that were previously faded may darken, and areas of friction can also become discolored.
Beyond changes in skin color, individuals with Addison’s disease commonly experience persistent fatigue, muscle weakness, and unintentional weight loss. Many also develop low blood pressure, which can cause dizziness upon standing, a condition known as orthostatic hypotension. A distinct craving for salty foods is related to the loss of aldosterone, a hormone that regulates the body’s balance of sodium and potassium.
Diagnostic Significance and Management
New, blotchy pigmentation in the mouth often prompts a physician to investigate for Addison’s disease. Because these oral signs can precede other symptoms, a dental professional may be the first to suspect the condition. Diagnosis is confirmed through laboratory tests that measure hormone levels, which will show low cortisol and high ACTH. An ACTH stimulation test, which measures the adrenal glands’ response to synthetic ACTH, is often used to confirm the diagnosis.
Treatment focuses on the underlying disease, as the pigmentation is a symptom. Management of Addison’s disease involves hormone replacement therapy to compensate for what the adrenal glands can no longer produce. Patients are prescribed daily doses of hydrocortisone to replace cortisol.
By managing the underlying hormonal deficiency, the stimulus for excess pigment production is removed. Over time, this can lead to the fading or even complete resolution of the oral and skin hyperpigmentation, although the degree to which this occurs can vary among individuals.