Addison’s Disease – Causes, Risks and Treatments

Endocrine glands don’t contain ducts so they are called ductless glands. Hormones are the secretions produced by them. The hormone is a chemical messenger produced in endocrine glands. They are released directly into the blood(because they are ductless) and carried to a distantly situated target organ. These Hormones act as intercellular messengers and are non-nutrient chemicals. These are produced in minute quantities. In  Invertebrates endocrine system is very uncomplicated with lesser hormones whereas in vertebrates many chemicals act as hormones and maintain coordination.

The endocrine glands and cells or groups of cells (tissues) that produce hormones situated in various parts of the human body together constitute the endocrine system. Examples of organized endocrine glands are pineal, thyroid, adrenal, pituitary, pancreas, thymus, parathyroid, and gonads ( ovary in females and testis in males).In addition to these, there are other organs like the kidney, heart, gastrointestinal tract, liver, heart also makes a few hormones. 

Adrenal Glands

These are glands located on the apex of both kidneys (yellow in color in the above picture). An adrenal gland contains two parts: the outer part is the adrenal cortex and the inner or central part is the adrenal medulla. The adrenal medulla produces catecholamines. They contain two hormones known as (adrenaline or epinephrine) and (noradrenaline or norepinephrine).

During emergency conditions or stress conditions, Adrenaline and noradrenaline are quickly produced by the adrenal medulla. Hence these are known as emergency hormones. They are also called Fight or Flight hormones. These hormones increase perceptiveness, dilation of the pupil, piloerection (bristling of hairs), sweating, etc. Both the hormones raise the rate of heartbeat and enhance heart contraction strength and respiration rate.

These hormones trigger glycogen metabolism resulting in an increase in glucose concentration in the blood. In addition, they also trigger the metabolism of lipids and proteins.

The adrenal cortex contains three layers, called the Inner layer (zona reticularis),  Middle layer (zona fasciculata), and Outer layer (zona glomerulosa).

Hormones secreted by the adrenal cortex are generally known as corticoids. They are 2 types- Glucocorticoids and Mineralocorticoids

Glucocorticoids

Glucocorticoids are involved in the metabolism of carbohydrates. In the human body, the main glucocorticoid is Cortisol. Glucocorticoids triggers –

• Gluconeogenesis – a process in which non-carbohydrates (such as lactate, amino acids, and glycerol) are converted into glucose.
• Lipolysis– a process in which triacylglycerols (TAGs) through hydrolysis are converted into fatty acids and glycerol  
• Proteolysis – is a process in which peptide bonds undergo a hydrolysis reaction and proteins are converted into small peptides and/or residues of amino acids. and inhibit cellular uptake and utilization of amino acids.

Cortisol also plays important role in managing the cardio-vascular system and renal functions.  Cortisol is also responsible for anti-inflammatory reactions and suppresses the immune response. Cortisol also triggers the production of RBC.

Mineralocorticoids

Corticoids that maintain the balance of electrolytes and water in the human body are known as Mineralocorticoids.

The key mineralocorticoid in the human body is Aldosterone. Aldosterone mainly shows its effects on renal tubules and enhances the reabsorption of Sodium ions Na+ and water and helps in the excretion of Potassium K+ and phosphate ions. Hence, aldosterone plays a key role in the balancing of electrolytes, the volume of body fluids, blood pressure, and osmotic pressure. Minute quantities of androgenic steroids are also produced by the adrenal cortex. During puberty, these androgenic hormones play an important in the growth of facial hair, axial hair, and Pubic hair.

Symptoms

Addison’s disease symptoms generally develop in a gradual manner, it makes takes many months. Signs and symptoms are as follows:

• Extreme fatigue
• Decreased appetite and Weight loss 
• Hyperpigmentation of skin
• Low blood pressure causes fainting
• Low blood sugar leading to hypoglycemia)
• Carving of salt
• Disturbance of gastrointestinal tract causing diarrhoea or Nausea, vomiting
• Deep  pain in the abdomen
• Muscular and joint pains
• Irritability
• Depression and behavioural symptoms
• Hair loss and impotency  in women’s

Causes 

Addison’s disease causes include:

• Adrenal gland Injury 
• Infection due to TB, AIDS, and fungus
• Autoimmune response
• Cancer cells from other parts attacking the adrenal glands
• Adrenal glands bleeding 
• Removal of  adrenal glands through a surgical procedure
• Amyloidosis (an excessive increase of proteins in the organs)
• Genetic issues

Acute Adrenal Failure (Addisonian crisis)

In some conditions like Acute adrenal failure which is an Addisonian crisis causes the signs and symptoms of Addison’s disease may appear suddenly. This Addisonian crisis may cause life-threatening shock. It involves the following signs and symptoms:

• Severe weakness
• Delirium(disturbances in mental abilities))
• Pain in lower back and legs
• Severe abdominal pain, diarrhea, vomiting causing dehydration
• Reduced blood pressure
• Hyperkalemia(High potassium levels) and Hyponatremia(Low sodium levels)

Diagnosis

Physical examination: The doctor will check the symptoms of the patient and will do a physical exam. Dark patches on your skin may act as a sign for the doctor to consider further investigation to confirm Addison’s disease.

ACTH Stimulation Test: In this test, a shot of artificial ACTH is given to test the adrenal glands’ response to adrenal glands. After the shot If the adrenal glands produce a minute quantity of cortisol, it indicates the poor function of the adrenal glands.

Blood Tests: Blood tests will be performed to check the levels of ACTH, cortisol, sodium, and potassium, in patients’ blood samples.

X-rays: These are used to check evidence of calcium deposits over adrenal glands.

Computed Tomography: A CT scan might be recommended to analyze the adrenals and pituitary gland. For example, it can detect the current situation of adrenal glands and the extent of damage caused to it.

Treatment

Addison’s disease is treated with pills of hydrocortisone as a substitute for the cortisol hormone. 

If there is insufficient quantity of  aldosterone, fludrocortisone acetate pills are prescribed.

Adrenal exhaustion

Adrenal glands fail to work properly due to damage and disease. For example, damage to adrenal glands leads to the production of a lesser amount of cortisol and aldosterone than the required quantity this insufficiency causes Addison’s disease. According to some studies, even the high stress due to modern life is also identified as the culprit for poorly functioning adrenal glands. Because continuous excess stimulation of the adrenal medulla results in its fatigued (adrenal exhaustion ). This prevents it from working at full capacity. According to a few scientists opinion it can be treated using adrenal extracts.

Adrenal extracts

Glands of animals like cows and pigs are collected from slaughterhouses and converted into the form of adrenal extracts. These extracts are prepared from the entire gland or made just from the outside parts. Hydrocortisone hormone is the key active ingredient in the adrenal extract. At the beginning of the 20th century, These extracts of the adrenal gland were used for different types of purposes and were mostly they were available in the form of injection. Along with Addison’s disease, These adrenal extracts were used to treat surgical shock, morning sickness, allergies, burns, and asthma.

Conceptual Questions

Question 1: If in a person’s adrenal gland suddenly stops producing glucocorticoids due to a sudden injury then it affects which process?

Answer:

Carbohydrate metabolism- Glucocorticoids play a key role in the metabolism of carbohydrates. The main glucocorticoid in the human body is Cortisol. If glucocorticoids are not produced then it will affect processes like Gluconeogenesis, lipolysis, and proteolysis.

Question 2: If due to a disease condition or malfunction adrenal gland suddenly stops producing Mineralocorticoids then it affects which process in the human body?

Answer: 

Electrolytes and water balance 

• Mineralocorticoids maintain the balance of electrolytes and water in the human body.
• The main hormone of this type in the human body is Aldosterone. It enhances the reabsorption of Sodium ions Na+ and water and helps in the removal of Potassium K+ and phosphate ions from renal tubules. 

Question 3: What are the effects produced in a person if his adrenal gland undergoes acute failure?

Answer: 

Acute adrenal failure is also called an Addisonian crisis-This Addisonian crisis may lead to shock that is life-threatening. It involves the following signs and symptoms:

• Severe weakness
• Delirium(disturbances in mental abilities))
• Pain in lower back and legs
• Severe abdominal pain, diarrhea, vomiting causing dehydration
• Reduced blood pressure
• Hyperkalemia(High potassium levels) and Hyponatremia(Low sodium levels)

Question 4: What are the uses of the adrenal extract?

Answer: 

Adrenal extracts were used for different purposes in the early 20th century and were mostly they were available in the form of injections. These were used to treat surgical shock, morning sickness, allergies, burns, asthma along with Addison’s disease, 

Question 5: What are the diagnostic procedures to identify Addison’s disease?

Answer:  

Diagnosis involves- Physical examination, ACTH stimulation test to identify the efficiency of the adrenal gland, Blood tests to measure deficiency of ACTH, CT scan to identify the extent of damage that occurred to the adrenal gland, and  X-Rays to detect calcium deposits.

Question 6: What are fight or flight hormones?

Answer: 

During emergency conditions or stress conditions Adrenaline and noradrenaline are quickly produced by adrenal medulla .Hence these are known as  emergency hormones .They are also called Fight or Flight hormones. These hormones increases perceptiveness, dilation of pupil , piloerection (bristling of hairs), sweating etc. Both the hormones raises the rate of  heart beat and enhances heart contraction strength and the  respiration rate.