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Cushing’s disease, moon face, hypercortisolism, and more – Cushing Syndrome

Cushing Syndrome is a disease that causes distinct physical traits, as moon face. Still, the source of it can differ between people. Basically, for all of the cases, there is a hormone blood level impairment, its name is cortisol.

This disease is highly associated with complications in the long run. Therefore, it is vital to acknowledge the recognizable risk factors and symptoms for an early assessment and diagnosis. Please, just keep reading through for an in-depth knowledge directly from a doctor about Cushing Syndrome.

What is the endocrine system, and how does it work?

The endocrine system functions through molecules that travel within the blood, allowing body tissues to communicate and accomplish tasks. Mainly, in this system, an organ that produces molecules is an endocrine organ, and the molecule’s name is a hormone; it travels through the bloodstream and reaches a receptor in other tissue. The union between the hormone and the receptor provides changes, in the end, defining the hormone function.

In this case, I am going to talk about a specific portion of the large endocrine system, which is the hypothalamic-pituitary-adrenal axis. This loop is in charge of cortisol production in the body. Firstly, two structures within the skull, the hypothalamus, and the pituitary gland are in charge of the corticotropin-releasing hormone (CRH), and the adrenocorticotropic hormone (ACTH), respectively. The CRH incites the pituitary for ACTH secretion, which travels through the bloodstream to a gland that its location is above the kidney, the adrenal gland. Then, ACTH stimulates this gland for finally producing hormone cortisol.

This process is in constant regulation; for that, there is a relatively stable cortisol level in blood. The cortisol, when increased, negatively regulates the hormone production by the two upper structures, as you can see in the image below. Therefore, the system design is virtually perfect. There is a constant production of the cortisol hormone that you are going to comprehend its extensive list of functions in the next question. And, when there is too much of it. The cortisol decreases the CRH and ACTH, for lessening its own blood levels.

Of course, even though it looks like a perfect system, a disease could raise when one of its elements fails. So, let’s keep reading.

File:HPA Axis Diagram (Brian M Sweis 2012).png
HPA axis
CC: BrianMSweis / CC BY-SA (

What are the steroid hormones?

The steroid hormone is a hormone that contains cholesterol molecules, which allows them to move freely through the body, so it is possible to find them virtually anywhere. Two classes of them exist, as sex steroids or corticosteroids. From those, both classes derive five types, and each one of them plays essential roles in every aspect of human life.

Two types of corticosteroids are produced in the cortex of the adrenal gland, mineral corticosteroids, and glucocorticoid hormones, but the latter is specifically relevant to this disease. From all the glucocorticoid hormones, the cortisol hormone is the one with most importance, and it is in control, by the HPA axis. The ACTH secretion by the pituitary causes cortisol production, and then cortisol level in blood regulates itself above in the skull, although other factors participate in that command also.

Overall, glucocorticoid hormones display a wide range of healthful functions within the body by binding to their specific receptor, such as regulation of metabolism, cognition, mental health, cell wellness, and even control inflammatory responses. Glucocorticoid hormones are so great decreasing swelling that its properties are beneficial in several inflammatory and autoimmune diseases. However, a high cortisol level, in the long term, is linked to several nonhealthy body changes also, as high blood pressure, high blood sugar, or weakened immune system.

Notably, the cortisol level increase during the early morning (highest at about 8 a.m.), and it decreases slightly throughout the day. Nevertheless, cortisol can rise in other situations as stress. The human stress can trigger the hypothalamus to secrete CRH, for then the pituitary discharge ACTH, that will stimulate the adrenal gland. This process would end on high cortisol levels just from pure stress, and I just told, in the long run, it can yield not wanted effects.

What is Cushing Syndrome?

Since the first description by Harvey Cushing in the early 20th century, Cushing Syndrome is the term used for an excessive cortisol level within the body.

The cortisol causing the disease could come from the own body, which means it is producing it through the adrenal gland, the endogenous crushing’s syndrome. Or people can acquire them by absorbing the cortisol in the form of medicine, for example, exogenous Cushing. Both ways would end on excess cortisol, so their manifestations would be otherwise similar. However, it would depend on the disease-causing the crushing syndrome that other signs may appear. This will become more clear further in the causes section.

By far, the most common cause of this disease is glucocorticoid medication using. Either due to a doctor error, patient self-medication, or a complication from long-term treatment. Even though exogenous Cushing syndrome accounts for more than 99% of the cases, endogenous Cushing syndrome is always a possibility, so ruling it out before treatment is mandatory.

Endogenous Cushing syndrome or hypercortisolism is particular because the hormone production could be either within the adrenal gland or somewhere else. Therefore, the utilization of two terms is a must, and it is core for understanding this disease. Hypercortisolism independent and dependent on ACTH, and let me explain this thoroughly.

Approximately seven of every ten patients with endogenous disease would have it dependent on ACTH, which means the hormone production is in the pituitary. This is the classical expression of the disease, for that the name of Cushing disease, albeit even cancer, like lung cancer, in some scenarios, can produce ectopic ACTH. On the other hand, independent of ACTH implies that the hormone output is in the adrenal gland. The disease mechanism aids the doctor in where to search for the problem.

Who is at risk of Cushing syndrome?

It would depend, there are different risk factors for the different types of Cushing syndrome. For the most common, exogenous Cushing syndrome, people using steroids medication are at high risk, if using them for long periods. For example, patients with progressive conditions as rheumatoid arthritis that sometimes require corticosteroid medication for long periods.

Then, there is endogenous Cushing syndrome, which is more challenging to define who is at more risk. Luckily, some numbers would lead us through. It is way more common in women than in men, approximately five times to one. Nevertheless, men have the highest rate of ectopic ACTH disease because of their similarly large proportion of lung cancer. The age range in which it is more common the Cushing disease is between twenty-five and forty years, albeit lung cancer patients could have it later than that.

Furthermore, some patients may be at more risk, like the ones having characteristic symptoms. For seeing them, move to the signs and symptoms section. Additionally, patients with unusual fractures and vertebral osteoporosis, polycystic ovary syndrome, diabetes, low serum potassium, kidney stones, and strange infections are all high-risk populations. Another crucial clinical feature, for example, is high blood pressure that is not responding well to antihypertensive medication. Sometimes that suggests your doctor look for other causes, and one of them is Cushing syndrome.

How much stress is too much stress to cause increased cortisol levels?

The stress, overall, always triggers a cortisol response. For excellence, the HPA axis is a stress response, and it is necessary. It prepares the body filling it up with energy to resolve a critical situation. This circumstance is excellent if you ask me; it is a problem-solving tool.

However, the question is not how much stress increases cortisol levels? Instead, you should ask, how many times per day, week, or month, are you stressed? The problem arises when it becomes chronic. That continuous increase over time would cause the body changes and disease nobody wants.

If you are looking for a specific amount, for now, there is not. Typically, what the doctor would look at is for any changes in your normal corporal functions as blood pressure, blood sugar, or blood cholesterol, among others. Yet, recent studies support that cortisol level from the hair is a reliable marker of chronic cortisol excess. Therefore, it can forecast diseases like hypertension, depression, or diabetes.

What causes Cushing Syndrome?

Cushing syndrome, as we said, has two sources, exogenous and endogenous. And from the endogenous, there are mechanisms dependent and independent from ACTH. The most common one who acts dependently on ACTH will have in the pituitary gland; a benign tumor called a pituitary adenoma. This pituitary tumor is the real and classical Cushing’s disease, while all the other forms of the disease are just a Cushing syndrome. It has nothing to do with cancer. A tumor means a tissue grew more than it is supposed to, and in this case, is producing ACTH.

Then, there are mechanisms depending on ACTH and not coming from the pituitary gland. It is an ectopic Cushing syndrome. This ectopic ACTH secretion explains the remaining 30% of the cases, depending on ACTH. It is mostly by malignant tumors, as can be with lung cancer. The ectopic tumor starts independently, producing ACTH that stimulates the adrenal gland to generate cortisol; in the end, it is an ectopic ACTH syndrome.

The other mechanism that is independent of ACTH is the direct affection of the adrenal gland. So, in this disease, the ACTH level will be low, because there is too much cortisol giving negative feedback to the pituitary gland. The most common scenario is an adrenal adenoma, which is the same I told you before in the pituitary gland. A benign tumor that grows and starts overproducing its hormone, in this case, cortisol. However, it is less common but possible to have a malignant adrenal tumor as an adrenal carcinoma. It has particular features, as expressing other hormones besides cortisol.

These adrenal tumors account for less than 5% of the cases in children above five years. Nevertheless, in younger children, independent of ACTH mechanisms could explain nearly half of the diseases.

What are Cushing syndrome and Cushing disease?

Cushing syndrome is referred to as the broad scenario of hypercortisolism and the changes it carries to the body. It comprises many diseases or steroid medication use, and it is just referring to cortisol excess. So it does not matter where the cortisol is coming from.

On the contrary, Cushing’s disease refers to a unique scenario from all the possibles in a Cushing syndrome. It indicates an endogenous Cushing’s syndrome by a pituitary ACTH overproduction, specifically. What does this mean? Only those patients with a Cushing syndrome because of a pituitary tumor secreting ACTH would get the name “Cushing disease.”

What are the signs and symptoms of Cushing syndrome?

The signs and symptoms have two different categories, ones that really helps the doctor to make a diagnosis, and others that are so general that makes it challenging to think in Cushing syndrome. Typically, these symptoms have been occurring for about 4 or 5 years because, for a doctor, disease recognition is difficult. For the reason that not all the patients have clear and distinctive symptoms as could be the moon face. Most of them could have mild symptoms, and when they progress over time and become bothering, then make the typical disease changes. Next, they assist to a doctor.

The signs that better help to find Cushing syndrome are various. Easy bruising, sudden face redness (facial plethora), muscle weakness, reddish-purple stretch mark, and in children, weight gain with a decreasing growth velocity. However, many signs exist, such as upper back fat pad (“buffalo hump”), facial fullness (moon face), obesity, poor skin healing, hair growing in places where it is not commonly supposed to, and female balding. The symptoms include depression, fatigue, weight gain, back pain, decreased sexual desire, short term memory impairment, trouble sleeping, irritability, and menstrual alteration.

Nevertheless, what should really raise the suspicious in regards to Cushing syndrome, is the appearance of chronic disease, pretty common in the elderly, but now in relatively young people such as hypertension, as mentioned earlier or diabetes, and osteoporosis. These changes are typical from an excessive cortisol hormone for an extended period.

Moon face
Ozlem Celik, Mutlu Niyazoglu, Hikmet Soylu and Pinar Kadioglu / CC BY (

Does this condition put me at risk for any others?

Indeed, the cortisol virtually affects all the systems in the body. As you saw, it can cause high blood pressure (hypertension), diabetes, osteoporosis (bone loss that leads to bone fractures). However, it is not all; there are way more.

Cushing syndrome’s primary cause of death is due to cardiovascular disease. It promotes a state of damage that substantially increases the chances of a heart infarction, heart failure, and thromboembolism.

The depression due to Cushing syndrome can cause death by suicide, and it is an essential factor in the disease. Also, the weakened immune system in this disease predisposes to more and severe infections. This situation can lead to life-threatening conditions such as sepsis, organ failure, and death.

When a patient is recovering from the Cushing syndrome, and the cortisol levels are decreasing. It could trigger an underlying autoimmune disease, like rheumatoid arthritis. Damage to the reproductive system in both women and men is also a fact.

How do doctors diagnose Cushing syndrome?

Considering that, more than 99% of the Cushing syndromes are from exogenous causes. Firstly, to find out through a well-elaborated interrogation if the patient is taking any kind of steroid medication is a must.  

Then, assess the cortisol level in the patient’s body for evidence of its elevation. There are many types of tests available for determining cortisol levels, such as Twenty-four-hour urinary free cortisol assay, Low-dose dexamethasone suppression test, and measuring late-night salivary cortisol levels. For now, the dexamethasone suppression test is one of the most used because of its simplicity. The patient takes 1 mg of oral dexamethasone between 23.00 and 24.00 h, and their serum cortisol is measured between 8.00 and 9.00 h the following morning.

Furthermore, to determine if the Cushing syndrome is dependent or independent of the ACTH, measuring it, would yield increased or decreased ACTH, respectively. So if the ACTH level is high, very probably the cause is within the pituitary, a Cushing disease perhaps. And if the ACTH level is low, then very likely the root of the disease will be in the adrenal gland.

If the ACTH level is high, further confirmation tests are often necessary. An invasive procedure, inferior petrosal sinus sampling, is a direct sampling from the veins that drain the pituitary gland in the skull. This test helps to confirm that the high ACTH level, indeed, is in the pituitary gland. If this test results negative, then other sources of ACTH secretion must be looked for, like lung cancer. Also, the noninvasive CRH stimulation test is used for differentiating between the two most common ACTH dependent Cushing syndromes.

Additionally, if an ACTH dependent Cushing Syndrome is suspected, a magnetic resonance image (MRI) of the head, focused in the pituitary gland, is necessary to identify any abnormal growth.

How do doctors treat Cushing syndrome?

Nearly all the causes of Cushing Syndrome have treatment, although the underlying disease must be found first. The overall purpose of each treatment would be to reduce the cortisol level and effects.

In the exogenous Cushing Syndrome, a change in the amount and form that steroid medicine is received must exist even if it requires to stop or change the medication. But, when steroids treatment has been for a long term ending it out of the sudden could trigger severe life-threatening conditions, as acute adrenal insufficiency. Therefore, this situation must be handled very carefully by professionals.

Then, for all the diseases prompting endogenous Cushing syndrome. The treatment of choice here is the tumor resection. Because most of the time, it would be a hormone-secreting tumor, by eliminating it, also the hormone excess would go away. The Cushing disease treatment is a transsphenoidal surgery, while for adrenal tumors, it is adrenalectomy. Even if it requires to eliminate both adrenal glands, it would be bilateral adrenalectomy, when there are tumors in both of them.

However, there are situations in which tumor resection is not possible, or in others as ectopic ACTH secretion. For that, there is a medication attempting to control hypercortisolism, although its failure is pretty common.

What should you do if your Cushing syndrome is caused by your medication?

The general aim is to do stepwise removal of the drug. If possible, eliminate it completely. However, this must be done carefully because of a stress episode affecting the patient could cause complications. A complication, as an adrenal crisis, can lead to death if not treated. Therefore, referring to a doctor when attempting to do this is essential.

I am presenting symptoms of it, what can I do?

I did a Cushing Syndrome symptoms checker for helping you to determine how likely it is that your symptoms are by this condition. It is free, and would only take a few minutes.

What do you think?

Written by Dr. Esteban Kosak

Doctor of Medicine - MD Recently Graduated from Medical School and inspired to aid the global population during this situation. I think that we shall no longer be waiting to see a doctor when we feel sick. Several times we feel disease searches in Google drive us to a rabbit hole and come out thinking that we may die of cancer or something very serious, given that symptoms may seem to fit a wide variety of illnesses. Since I recently graduated from medical school. I have all the medical information fresh in my mind. My thorough experience as an expert researcher allows me to very-well known the different diseases and conditions that affect human bodies. Empowered by the United Nations 17 Sustainable Development Goals (SGDs). I think that we all can provide a grain of sand to help humanity. That's why we created Symptoms.Care a place where you can come and screen your symptoms and find what different illnesses can be related to them. Armed with the right information you can instantly, discretely, secure and from the comfort of your home talk with a Doctor that can Evaluate your Symptoms and help you seek the right treatment.


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