Understanding Addison's Disease: Causes, Symptoms, and Treatment

What is Addison disease?

Adrenal glands, as we know, produce two important hormones, i.e., cortisol & aldosterone.

Addisson's disease is a rare chronic condition in which a person's adrenal gland fails to produce enough of these hormones. The major cause for this particular condition is an autoimmune attack, which is treatable with proper medication and care.

Classification of Addison disease

Addison's disease can be classified into three main categories. 

They are as follows:

• Primary adrenal insufficiency: Affects adrenal gland
• Secondary adrenal insufficiency: Affects pituitary gland
• Tertiary adrenal insufficiency: Affects hypothalamus

Let's look into the definition and causes of each of the above.

Primary Adrenal Insufficiency

Acute destruction of the adrenal gland is the main reason for this condition. Thus, they fail to produce the hormones that they are supposed to produce. Primary adrenal insufficiency is an autoimmune disease. The other major causes of primary adrenal gland insufficiency are as follows:

• Certain infections in the body
• Long-term administration of glucocorticoids (e.g., prednisone)
• Cancer and any sort of abnormal growths in the body (tumors)
• Certain blood thinners are used to check clotting in the blood.

Secondary Adrenal Insufficiency

• Caused when the pituitary gland fails to produce adrenocorticotropic hormone (ACTH), which instructs the adrenal glands when to release the hormones. Adrenal insufficiency can also occur if the patient fails to take the corticosteroid medications prescribed by their doctor. The other major causes of secondary adrenal insufficiency are as follows:
  • Tumors
  • Medications
  • Genetics
  • Traumatic brain injury

Tertiary Adrenal Insufficiency

The major cause is the impaired production of CRH from the hypothalamus. This in turn hampers the secretion of ACTH from the pituitary gland. Another cause of tertiary adrenal insufficiency is long-term steroid therapy.

• Primary adrenal insufficiency: Affects adrenal gland
• Secondary adrenal insufficiency: Affects pituitary gland
• Tertiary adrenal insufficiency: Affects hypothalamus

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What conditions might indicate a higher risk for Addison's disease?

People at higher risk of Addison's disease might have the following conditions:

• Cancer
• Been taking blood thinners/anticoagulants
• Gotten any part of the adrenal gland removed through surgery
• Have had chronic infections like tuberculosis
• Have had type 1 diabetes or Graves' disease (Autoimmune disease)

Risk factors for autoimmune Addison's disease

• A particular variant of the HLA-DRB 1 gene, which is called HLA-DRB*04:04
• Other disease-associated HLA gene variants also contribute to the autoimmune response, which can cause autoimmune Addison disease.

Epidemiology

• Addison's disease is a comparatively rare condition.
• It can affect people of any age, sex, or ethnicity.
• Incidence: 0.6 per 100,000 of the population/year
• In India, it is known to affect 1 in 100,000 individuals.
• Most common age of presentation in adults: 30 to 50 years.
• Women are more likely to get affected by Addison's disease than men.
• Almost 70% of reported cases of Addison's disease occur due to autoimmune reactions that damage the adrenal cortex.

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Pathophysiology

We are aware that adrenal failure due to various reasons is the main cause of Addison's disease. This leads to decreased production of cortisol initially, which is followed by decreased aldosterone production. This results in negative feedback inhibition, which results in the elevation of the following hormones:

• Adrenocorticotropic hormone (ACTH)
• Melanocyte-stimulating hormone (MSH)

Diagnosis

As adrenal insufficiency is considered a rather rare condition, diagnosis is often delayed on average up to 5 years. Clinical diagnosis of adrenal insufficiency includes three steps:

• Determining low sodium, high potassium, or low cortisol levels through blood tests.
• Evaluating of the HPA axis
• Confirming a primary disorder cause.

Diagnosis of Addison's disease includes:

• Asking of medical history and symptoms
• Physical examination
• Lab tests to check potassium and sodium levels
• Measuring hormone levels
• Imaging tests

Imaging Tests

• CT scans or MRIs are used to find out if the normal hormone production of the adrenals or pituitary and hypothalamic regions is affected or not.
• Patients with no autoimmune disease should undergo a CT scan of the adrenal glands.
• MRI of the hypothalamic and pituitary regions is done if secondary or tertiary adrenal insufficiency is suspected.

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Clinical features of Addison's disease

Skin changes related to Addison's disease

• Darkening of the elbow skin surface
• Darkening of palm creases
• Darkening of the gums
• Vitiligo mixed with darkening of skin

Addisonian pigmentation of buccal mucosa

• Muscle weakness
• Skin darkening (Caused by excess ACTH in case of primary adrenal insufficiency)
• Fatigue (Due to low levels of cortisol)
• Low blood sugar levels (Hypoglycemia)
• Decreased appetite and weight loss (Mainly in children due to decreased levels of cortisol)
• Low blood pressure (Lack of aldosterone)
• Decreased heart rate
• Sores in mouth
• Salt craving (Due to lack of cortisol)
• Fainting spells (Due to lack of aldosterone)
• Nausea and vomiting (Due to lack of cortisol)

Neuropsychiatric symptoms of Addison's disease include:

• Depression and mood swings
• Lack of energy
• Disturbances in sleep

If left untreated for a long time, it can lead to an Addisonian crisis. Symptoms include:

• Delirium
• Hallucinations (Visual and auditory)
• Agitation

In case of a life-threatening medical emergency, the person may experience:

• Loss of consciousness
• Change of mental status (Restlessness, fear and confusion)
• Severe fever
• Sudden pain in the lower back, legs, or belly.

Also read: Understanding Cardiac Tamponade: Causes, Symptoms, and Treatment

Treatment

• The type of treatment opted for depends upon the cause of the condition.
• Medications are prescribed to regulate the adrenal glands.

Cortisol replacement

• The most physiological option for cortisol replacement available today is oral hydrocortisone.
• It is the preferred treatment of adrenal insufficiency.
• Changes can be seen within a period of 24 hours.
• A combination of glucocorticoids medication is administered to improve the health of the patient.
• Treatment involves the replacement of the missing cortisol in the form of hydrocortisone tablets or prednisone tablets.
• The aim is to mimic the physiological concentrations of cortisol.
• Fludrocortisone is also administered for the missing aldosterone.
• Commonly prescribed drugs for cortisol replacement therapy are as follows:
  • Hydrocortisone
  • Cortisone acetate
  • Dexamethasone
  • Prednisone
  • Prednisolone
  • Methylprednisolone
  • Hydrocortisone
  • Sodium succinate

Did You Know?

• Addison's disease requires lifelong treatment.
• Increasing the dietary intake of Ca and Vit D can also benefit patients suffering from Addison's disease.
• Patients are advised to increase their medications during illness or when undergoing surgery or dental treatment.

• For some people with Addison's disease, it may take years for the hormone production to get totally disrupted, while for some others it may grow worse very quickly.
• President John F. Kennedy is believed to have Addison's disease along with hypothyroidism.
• Addison's disease was first identified or mentioned in the medical literature in 1855 by a physician named Thomas Addison.
• Women are more likely to get affected by Addison's disease than men.
• Almost 70% of reported cases of Addison's disease occur due to autoimmune reactions that damage the adrenal cortex.

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