Addison’s Disease and Corticosteroids (Part 1)

Addison’s Disease and Corticosteroids (Part 1)

November 2, 2019 21 By Jose Scott


If you ask someone to think of steroids, they’ll probably think of… …this. But in science, the term steroid is used to
describe molecules consisting of four rings arranged in a specific orientation, like this. There are many types of steroids found in
our body. For example, cholesterol is a steroid involved in cell
membrane structure, while testosterone and estrogen are steroid hormones that are involved
in reproduction and secondary sex characteristics. In fact, the synthetic steroids that are used
to build muscle mass, called anabolic steroids, are very similar to testosterone. But the steroids that we will focus on in
this video are the corticosteroids: cortisol and aldosterone, which are essential to life. Join me in this two-part video on Medicurio
where we will discuss the two diseases that occur if a person has too little or too much
of these corticosteroids: Addison’s disease and Cushing’s Syndrome. The symptoms of Addison’s disease are due
to a lack of cortisol and aldosterone. You may have heard of cortisol as the “stress
hormone” because it is produced and released in times of stress – for example, a wild bear encounter. Specifically, cortisol causes the breakdown of
fats, carbohydrates, and proteins to supply the body with energy, often by converting
some of the breakdown products into a high energy sugar called glucose – a process
known as gluconeogenesis, which increases blood sugar levels. In doing so, the body produces energy to use
to fight or run away The release of cortisol involves three organs
in your body: the hypothalamus and the anterior pituitary, both of which are found within
the brain, and the adrenal glands above the kidneys. These three areas constantly communicate with
each other through chemical messengers, or hormones. During times of stress, the hypothalamus releases
corticotropin-releasing hormone, which tells the anterior pituitary to release adrenocorticotropic hormone, which then tells the adrenal glands to release cortisol. When then hypothalamus and the anterior pituitary
detect cortisol, they then stop releasing their respective hormones so that the body does
not produce too much cortisol. This may seem like a lot of terminology, but it’ll become useful later on in this video. Aldosterone is also released from the adrenal
gland and is involved in increasing blood pressure. It does this by increasing the amount of sodium-potassium pumps in the membrane of renal cells that lie between blood vessels and the tubes where urine passes through. These pumps transport 3 sodium ions out of the cell and into the blood in exchange for 2 potassium ions into the cell. Since there is a net gain of ions into the blood, water flows into the blood through osmosis. Since there is more water in blood, blood volume increases, which increases blood pressure. Since both of these corticosteroids are produced
by the adrenal glands, damage to the adrenal glands leads to less production of these corticosteroids,
causing Addison’s disease. In the developed world, this damage is most
commonly due to autoimmune disease, while in less developed areas, tuberculosis infections
are the main culprit. A less common cause is cancer cells from other
areas in the body that have spread to the adrenal glands and have multiplied, which damages the surrounding cells. In rare situations, genetic mutations may
interfere with the proper development of the adrenal glands or cause enzymes that produce these
corticosteroids to become dysfunctional. Addison’s disease affects around 1 in 100,000
people, and is not influenced by sex or gender. It is, however, more common in middle-aged people. To summarize, cortisol is primarily involved
in energy generation, while aldosterone is primarily involved in increasing blood pressure. Damage to adrenal glands causes the symptoms
for Addison’s disease. With less cortisol, the body is less capable
of generating energy, so it makes sense that the patient would feel tired and weak. Decreased appetite often accompanies tiredness,
which leads to weight loss. Blood sugar is low from decreased gluconeogenesis. With less aldosterone, less water reabsorption
occurs, causing low blood pressure. Lightheadedness from suddenly standing up
is often a direct consequence of low blood pressure, since the blood flows out of the
brain due to gravity more easily. A craving for salt may be present since less
sodium reabsorption occurs. Finally, the most interesting symptom is darkening
of the skin, called hyperpigmentation, particularly in old scars, creases in the hand, and the
inside of the mouth. Recall the signaling pathway involved in cortisol
release we discussed earlier. With damaged adrenal glands, the anterior
pituitary constantly releases ACTH in the hopes of causing cortisol release, but to
no avail. Constant release of ACTH means more ACTH needs
to be made, which requires more of its precursor molecule. This precursor molecule can also be converted
into melanocyte-stimulating hormone, or MSH. MSH, as its name implies, stimulates melanocytes, which are these octopus-looking cells underneath the skin. When activated, they produce a dark pigment
called melanin, which causes skin to darken as if you got a tan. These symptoms usually develop slowly. However, people with Addison’s disease are
more likely to suffer from a life-threatening Addisonian crisis, which is a rapid drop in
blood sugar and blood pressure, accompanied by fatigue and fainting – essentially, these
are simply the symptoms discussed earlier but occurring not over the span of years,
but in the span of hours. In addition, low sodium levels and high potassium
levels are observed due to less aldosterone. Other symptoms include abdominal and side
pain, vomiting, and diarrhea. Most Addisonian crises are triggered by physical
trauma, such as injury, infection, or surgery. A person undergoing an Addisonian crisis needs
immediate treatment. Since Addison’s disease is due to less cortisol
and aldosterone, it makes sense that replenishing those corticosteroids will reverse the symptoms. This can be done by injecting cortisol, which
is called hydrocortisone if it is a drug, as well as taking fludrocortisone which has
similar structure and effects as aldosterone. Additionally, a saline and glucose solution
also needs to be injected to treat low blood volume and low blood glucose, respectively. If this treatment is administered quickly
enough, most people will recover. For those who are diagnosed with Addison’s
disease, they need to take those steroid supplements, usually orally, throughout their life to maintain
healthy corticosteroid levels and avoid an Addisonian crisis. Ultimately, most people with Addison’s disease
are able to live normal lives. However, since symptoms usually develop
slowly and are shared with many other diseases, often it is the unexpected Addisonian crisis
that causes death among those who are unaware that they have this disease. Therefore, it is important to raise awareness
for this disease to prevent these avoidable deaths. Consult a physician if you suspect that you
or someone you know may have Addison’s disease. Thanks for watching, and see you next time
on Medicurio to discuss Part 2 of this video, Cushing’s syndrome, which is caused by too
much corticosteroids.