Last video, we talked about the functions of cortisol and aldosterone, as well as how
a lack of these corticosteroids cause Addison’s disease.
What happens though, when there is instead too much cortisol?
Join me in this episode of Medicurio where we will discuss Cushing’s syndrome, the
counterpart of Addison’s disease.
There are two types of Cushing’s syndrome depending on whether the excess cortisol is
from inside or outside the body.
Unlike Addison’s disease, aldosterone is not involved.
In endogenous Cushing’s syndrome, the body itself is producing too much cortisol.
Recall from the previous video how the body regulates cortisol production in the adrenal
glands: when the hypothalamus releases CRH in times of stress, the anterior pituitary
releases ACTH in response, which stimulates the adrenal glands to release cortisol.
The released cortisol then stops the anterior pituitary and hypothalamus from releasing
their hormones, which then stops cortisol production.
Clearly, there is a feedback mechanism to prevent non-stop cortisol release, so why
does it occur in Cushing’s syndrome?
Well, if there is a tumor in the anterior pituitary, more cells are producing ACTH,
which stimulates more cortisol release.
What’s more, these anterior pituitary tumors are unresponsive to cortisol and continue
to produce ACTH despite cortisol being released, eliminating the feedback mechanism.
When endogenous Cushing’s syndrome is due to an anterior pituitary tumor, it is known
as Cushing’s disease.
Though tumors in the hypothalamus and the adrenal glands can also lead to high cortisol
levels, either due to high CRH or high cortisol, Cushing’s disease is the most common form
of endogenous Cushing’s syndrome.
However, all of these tumors are rare, with around 1 in 1 million people suffering from
endogenous Cushing’s syndrome, with more women than men affected.
Let’s look at the other type of Cushing’s syndrome.
In exogenous Cushing’s syndrome, medication is the source of excess cortisol.
Corticosteroid medication is not only used to treat Addison’s disease, but also immune
system diseases such as asthma, arthritis, gout, and other autoimmune diseases.
This is because aside from energy production, cortisol also has the function of suppressing
the immune system, which can treat these autoimmune diseases
where the immune system is out of control.
However, too much corticosteroid medication can over-inhibit the body’s natural defenses
and result in one of the symptoms of Cushing’s syndrome: increased risk of infections.
The incidence of exogenous Cushing’s syndrome varies depending on the incidence of the diseases
the medication is treating, but it is much more commonly seen than endogenous Cushing’s syndrome.
In addition to being more susceptible to infections, Cushing’s syndrome has many other symptoms:
weight gain, bone weakness, and high blood pressure.
Recall the other function of cortisol in our body discussed in the previous video: when
released in stressful situations, it stimulates energy production so that you have enough
energy to fight or run away.
What happens though after that stress is gone?
Cortisol increases appetite so that you eat more food to replenish the energy stores that
were used up.
Most of us have experienced this increased appetite during or after a stressful situation,
colloquially known as “stress eating”.
However, sustained, increased levels of cortisol from Cushing’s syndrome cause stress eating
in the absence of a stressful situation.
Therefore, since the energy stores were never used up, increased appetite and eating causes
rapid weight gain on the face, neck, and stomach.
Not only can this rapid weight gain result in stretch marks on the belly, called striae,
when the blood vessels near the skin stretch and burst, it can also lead to diabetes and
eventually death.
Another function of cortisol is bone breakdown, which is why another symptom of Cushing’s
syndrome is osteoporosis, or weak bones.
Bones, aside from providing structural support, also act as storage for calcium.
Calcium ions are extremely important because they allow muscles to contract.
Therefore, in times of stress, when cortisol is secreted, calcium is released from bone
so that muscles can contract to fight or run.
Normally, this calcium is replenished when the stressful situation ends, but if cortisol
is continuously released such as in Cushing’s syndrome, bones will constantly release their
calcium and become weaker and weaker, resulting in osteoporosis.
Finally, many with Cushing’s syndrome suffer from high blood pressure.
This is because cortisol and aldosterone are very similar in structure.
When cortisol is at extremely high levels as seen in Cushing’s syndrome, it can also
stimulate aldosterone receptors in the cell to cause effects similar to those of aldosterone.
Since aldosterone increases blood pressure, high blood pressure is a common symptom of
Cushing’s syndrome.
In addition, cortisol itself has a property of causing blood vessels to squeeze and get
narrower, which further increases blood pressure.
High blood pressure will damage the heart, blood vessels, brain, and kidneys, all of
which can lead to premature death.
The main method of treating both exogenous and endogenous Cushing’s syndrome is to
decrease cortisol levels.
Treating exogenous Cushing’s syndrome is quite simple – decrease the dose of the
corticosteroid medications, or perhaps discontinue it altogether and look for an alternative treatment
for whatever disease the medication was treating.
One thing to watch out for when discontinuing corticosteroid treatment is to avoid suddenly
stopping the medication.
Recall that cortisol, either produced by the body or from medication, inhibits ACTH release.
This is a natural response to prevent too much cortisol production.
However, because there is very little ACTH released, the adrenal glands are rarely stimulated
and waste away from disuse.
If medication is suddenly stopped and ACTH begins to be released again, the adrenal glands
are often so wasted away that they cannot produce cortisol,
leading to an Addisonian crisis.
Therefore, it is important to slowly decrease cortisol medication and allow time for the
adrenal glands to recover.
On the other hand, treating endogenous Cushing’s syndrome, such as Cushing’s disease, is
more difficult.
By surgically removing the tumors, for example on the anterior pituitary, excessive ACTH
is no longer produced, resulting in normal cortisol levels.
If the tumor is too large, the entire anterior pituitary may have to be removed, resulting
in the body now no longer producing any ACTH and as a consequence, no cortisol.
Therefore, the patient must be supplemented with cortisol to prevent Addison’s disease.
Cushing’s syndrome and Addison’s disease are both opposite and intertwined with each
other – treating one of them may lead to the other if not done correctly.
Since in most of the cases Cushing’s syndrome is due to excess steroid medications, this
disease teaches us a valuable lesson: follow instructions carefully when taking medication,
and contact your doctor immediately if you are experiencing side effects.
Thanks for watching, and see you next time for another explanation of a disease on Medicurio.