Addison�s Disease

About

Do you know what Osama bin Laden and John F Kennedy(1^✔) have in common? They are both Addisonians!

Addison's disease, named after British physician, Dr. Thomas Addison, who first described it in 1855(2^✔). It is a rare endocrine disorder that occurs when the adrenal glands fail to produce the cortisol hormones -glucocorticoids and mineralocorticoids. It is also refered as hypocortisolism or adrenal insufficiency, this life-threatening condition occurs at a frequency of 1 in 100,000, especially in those between the ages of 30 to 50. It occurs when adrenal cortex on both the sides undergoes damage, leading to decreased adrenocortical hormones, which may include cortisol, aldosterone, and androgens. However, it is also known to affect children(3^✔).

The adrenal glands are situated at the top of the kidneys and are composed of an interior medulla and an outer cortex(4^✔). The medulla produces adrenaline-like hormones (catecholamines, epinephrine, and norepinephrine) while the cortex produces the corticosteroids (glucocorticoids and mineralocorticoids) and the male sex hormones - the androgens(5^✔). The failure of adrenal cortex to deliver it's function is termed as Addison's disease.

Types

1. Primary adrenal insufficiency
2. Secondary adrenal insufficiency

Primary adrenal insufficiency(3^✔):

It occurs when the adrenal gland produces insufficient amount of cortisol and aldosterone.

Causes of Addison's Disease?

Causes of primary adrenal insufficiency are:

• When the adrenal glands failed to develop adequately (Adrenal dysgenesis)
• When the glands are present but are unable to produce cortisol (Impaired steroidogenesis)
• Adrenal destruction due to a disease such as:
• An autoimmune condition
• Infections of the adrenal glands
• Cancer spreading to the adrenal glands
• Tuberculosis
• Bleeding into the adrenals

Secondary adrenal insufficiency:

It occurs when the adrenocorticotropic hormone (ACTH) is produced in inadequate amount by the pituitary gland, leading to failure in stimulation of adrenal cortext to produce the adrenal hormones irrespective of the condition of the adrenal cortex(6^✔). Secondary adrenal insufficiency also occurs in people who are on corticosteroids (as a part of their treatment for asthma or arthritis) and there is an abrupt stop of the supplement.

What are the Symptoms and Signs of Adrenal Insufficiency?

Some of the common symptoms include(7^✔):

• Fatigue, dizziness
• Muscle weakness
• Decrease in appetite
• Anxiety
• Weight loss
• Excessive skin pigmentation (hyperpigmentation)
• Low blood BP/ Low blood sugar
• Salt craving / Irritability
• Muscular and joint pains
• Nausea/ diarrhea/ vomiting
• Depression

White patches on skin (Vitiligo) and Goiter are conditions that often occur along with Addison's disease.

What is Addisonian Crisis?

In some situations acute adrenal failure also known as 'Addisonian crisis' Addisonian crisis, also known as adrenal crisis or acute adrenal insufficiency, is an endocrinologic emergency with a high mortality rate secondary to physiologic derangements from an acute deficiency of the adrenal hormone cortisol, requiring immediate recognition and treatment to avoid death. The signs and symptoms of which may include Pain in the lower back, abdomen or legs, severe vomiting, diarrhea which can lead to dehydration, fever, decreased blood pressure, high levels of potassium and calcium, low sugar, loss of consciousness, convulsions, confusion, lethargy and psychosis(8^✔).

How Can We Diagnose Addison's Disease?

Addison's disease is diagnosed with some of the diagnostic modalities mentioned below:

• Blood tests- Blood tests are carried out to measure the levels of sodium, potassium, cortisol and ACTH in the blood. It also evaluates the antibodies if the Addison's disease is caused by an autoimmune condition(2^✔).
• ACTH stimulation test -Here the level of cortisol in the blood is measured before and after administering synthetic ACTH which stimulates the adrenal glands to produce cortisol. This test helps in assessing the extent of damage in the adrenal glands(9^✔).

• Insulin-induced hypoglycemia test- In case of secondary adrenal insufficiency a dose of insulin is administered after which blood glucose and cortisol levels are checked at various intervals. In healthy individuals, the glucose levels deteriorate while the cortisol levels elevate.
• Imaging tests. Computerized tomography (CT) scan of the abdomen can assess the size of the adrenal glands and an MRI scan of the pituitary gland may be carried out in case of secondary adrenal insufficiency(2^✔).

How Can We Treat Addison's Disease?

Treatment for Addison's disease involves taking cortisol hormones in the form of medications or injections.

To replace the cortisol in the body, hydrocortisone (Cortef), prednisone, cortisone acetate are used(6^✔).

To replace the alderosterone, Fludrocortisone (Florinef) is used as it plays an essential role in the treatment of primary and secondary adrenocortical insufficiency(10^✔).

If the condition is Secondary, then the underlying problem has to be addressed.

What is the Prognosis of Addison's Disease?

Despite individual differences the overall prognosis for individuals with Addison's disease is quite good provided the patient closely co ordinates with his doctor and adjusts his medications according to his need. Routine monitoring and follow up is absolutely necessary. Extra caution must be exercised when an affected individual falls ill, becomes pregnant, or undergoes a surgery.

References:

1. President John F Kennedy's medical history: coeliac disease and autoimmune polyglandular syndrome type 2 - (https://pubmed.ncbi.nlm.nih.gov/32341184/)
2. Thomas Addison - (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1079500/)
3. Addison Disease - (https://www.ncbi.nlm.nih.gov/books/NBK441994/)
4. Development of adrenal cortex zonation - (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4486052/)
5. Physiology, Adrenal Gland - (https://www.ncbi.nlm.nih.gov/books/NBK537260/)
6. Adrenal Insufficiency - (https://www.ncbi.nlm.nih.gov/books/NBK441832/)
7. Addison's disease - (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3636818/)
8. Addisonian Crisis - (https://www.ncbi.nlm.nih.gov/books/NBK441933/)
9. Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline - (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4880116/)
10. Fludrocortisone - (https://www.ncbi.nlm.nih.gov/books/NBK564331/)

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