Cushing’s Syndrome Treatments

Posted on January 7, 2026 by MaryO
Medications, Surgery, and Other Treatments for Cushing’s Syndrome

Written by | Reviewed by Daniel J. Toft MD, PhD

Treatment for Cushing’s syndrome depends on what symptoms you’re experiencing as well as the cause of Cushing’s syndrome.

Cushing’s syndrome is caused by an over-exposure to the hormone cortisol. This excessive hormone exposure can come from a tumor that’s over-producing either cortisol or adrenocorticotropic hormone (ACTH—which stimulates the body to make cortisol). It can also come from taking too many corticosteroid medications over a long period of time; corticosteroids mimic the effect of cortisol in the body.

The goal of treatment is to address the over-exposure. This article walks you through the most common treatments for Cushing’s syndrome.

Gradually decreasing corticosteroid medications: If your doctor has identified that the cause of your Cushing’s syndrome is corticosteroid medications, you may be able to manage your Cushing’s syndrome symptoms by reducing the overall amount of corticosteroids you take.

It’s common for some people with certain health conditions—such as arthritis and asthma—to take corticosteroids to help them manage their symptoms. In these cases, your doctor can prescribe non-corticosteroid medications, which will allow you to reduce—or eliminate—your use of corticosteroids.

It’s important to note that you shouldn’t stop taking corticosteroid medications on your own—suddenly stopping these medications could lead to a drop in cortisol levels—and you need a healthy amount of cortisol. When cortisol levels get too low, it can cause a variety of symptoms, such as muscle weakness, fatigue, weight loss, and low blood pressure, which may be life-threatening.

Instead, your doctor will gradually reduce your dose of corticosteroids to allow your body to resume normal production of cortisol.

If for some reason you cannot stop taking corticosteroids, your doctor will monitor your condition very carefully, frequently checking to make sure your blood glucose levels as well as your bone mass levels are normal. Elevated blood glucose levels and low bone density are signs of Cushing’s syndrome.

Surgery to remove a tumor: If it’s a tumor causing Cushing’s syndrome, your doctor may recommend surgery to remove the tumor. The 2 types of tumors that can cause Cushing’s are pituitary tumors (also called pituitary adenomas) and adrenal tumors. However, other tumors in the body (eg, in the lungs or pancreas) can cause Cushing’s syndrome, too.

Pituitary adenomas are benign (non-cancerous), and most adrenal tumors are as well. However, in rare cases, adrenal tumors can be malignant (cancerous). These tumors are called adrenocortical carcinomas, and it’s important to treat them right away.

Surgery for removing a pituitary tumor is a delicate process. It’s typically performed through the nostril, and your surgeon will use tiny specialized tools. The success, or cure, rate of this procedure is more than 80% when performed by a surgeon with extensive experience. If surgery fails or only produces a temporary cure, surgery can be repeated, often with good results.

If you have surgery to remove an adrenal tumor or tumor in your lungs or pancreas, your surgeon will typically remove it through a standard open surgery (through an incision in your stomach or back) or minimally invasive surgery in which small incisions are made and tiny tools are used.

In some cases of adrenal tumors, surgical removal of the adrenal glands may be necessary.

Radiation therapy for tumors: Sometimes your surgeon can’t remove the entire tumor. If that happens, he or she may recommend radiation therapy—a type of treatment that uses high-energy radiation to shrink tumors and/or destroy cancer cells.

Radiation therapy may also be prescribed if you’re not a candidate for surgery due to various reasons, such as location or size of the tumor. Radiation therapy for Cushing’s syndrome is typically given in small doses over a period of 6 weeks or by a technique called stereotactic radiosurgery or gamma-knife radiation.

Stereotactic radiosurgery is a more precise form of radiation. It targets the tumor without damaging healthy tissue.

With gamma-knife radiation, a large dose of radiation is sent to the tumor, and radiation exposure to the healthy surrounding tissues is minimized. Usually one treatment is needed with this type of radiation.

Medications for Cushing’s syndrome: If surgery and/or radiation aren’t effective, medications can be used to regulate cortisol production in the body. However, for people who have severe Cushing’s syndrome symptoms, sometimes medications are used before surgery and radiation treatment. This can help control excessive cortisol production and reduce risks during surgery.

Examples of medications your doctor may prescribe for Cushing’s syndrome are: aminoglutethimide (eg, Cytadren), ketoconazole (eg, Nizoral), metyrapone (eg, Metopirone), and mitotane (eg, Lysodren). Your doctor will let you know what medication—or combination of medications—is right for you.

You may also need to take medication after surgery to remove a pituitary tumor or adrenal tumor. Your doctor will most likely prescribe a cortisol replacement medication. This medication helps provide the proper amount of cortisol in your body. An example of this type of medication is hydrocortisone (a synthetic form of cortisol).

Experiencing the full effects of the medication can take up to a year or longer. But in most cases and under your doctor’s careful supervision, you can slowly reduce your use of cortisol replacement medications because your body will be able to produce normal cortisol levels again on its own. However, in some cases, people who have surgery to remove a tumor that causes Cushing’s syndrome won’t regain normal adrenal function, and they’ll typically need lifelong replacement therapy.2

Treating Cushing’s Syndrome Conclusion
You may need one treatment or a combination of these treatments to effectively treat your Cushing’s syndrome. Your doctor will let you know what treatments for Cushing’s syndrome you’ll need.

From https://www.endocrineweb.com/conditions/cushings-syndrome/cushings-syndrome-treatments

Filed under: adrenal, Cushing's, pituitary, Treatments | Tagged: , , , , , , , , , , , , , | Leave a comment »

On Becoming Empowered

Posted on January 1, 2026 by MaryO

This is kind of a “cheat” post since it’s a compilation of other posts, web pages, message board posts and some original thoughts.  

For all of my early life, I was the good, compliant, patient.  I took whatever pills the doctor prescribed, did whatever tests h/she (most always a he) wrote for.  Believed that whatever he said was the absolute truth.  He had been to med school.  He knew what was wrong with me even though he didn’t live in my body 24/7 and experience what I did.

I know a lot of people are still like this.  Their doctor is like a god to them.  He can do no wrong – even if they don’t feel any better after treatment, even if they feel worse.  “But the doctor said…”

Anyway, I digress.

All this changed for me in 1983.

At first I noticed I’d stopped having my periods and, of course, I thought I was pregnant. I went to my Gynecologist who had no explanation. Lots of women lose their periods for a variety of reasons so no one thought that this was really significant.

Then I got really tired, overly tired. I would take my son to a half hour Choir rehearsal and could not stay awake for the whole time. I would lie down in the back of the van, set an alarm and sleep for the 30 minutes.

A whole raft of other symptoms started appearing – I grew a beard (Hirsuitism), gained weight even though I was on Weight Watchers and working out at the gym nearly every day, lost my period, everything hurt, got what is called a “moon face” and a “buffalo hump” on the back of my neck. I also got stretch marks. I was very depressed but it’s hard to say if that was because of the hormone imbalance or because I felt so bad and no one would listen to me.

I came across a little article in the Ladies Home Journal magazine which said “If you have these symptoms…ask your doctor about Cushing’s”. After that, I started reading everything I could on Cushing’s and asking my doctors. Due to all my reading at the library and medical books I bought, I was sure I had Cushing’s but no one would believe me. Doctors would say that Cushing’s Disease is too rare, that I was making this up and that I couldn’t have it.

I asked doctors for three years – PCP, gynecologist, neurologist, podiatrist – all said the now-famous refrain.  It’s too rare.  You couldn’t have Cushing’s.  I kept persisting in my reading, making copies of library texts even when I didn’t understand them, keeping notes.  I just knew that someone, somewhere would “discover” that I had Cushing’s.

My husband was on the doctors’ sides.  He was sure it was all in my mind (as opposed to all in my head!) and he told me to just think “happy thoughts” and it would all go away.

A Neurologist gave me Xanax. Since he couldn’t see my tumor with his Magnetic Resonance Imaging (MRI) machine there was “no possibility” that it existed. Boy was he wrong!

Later in 1986 I started bruising incredibly easily. I could touch my skin and get a bruise. On New Year’s Day of 1987 I started bleeding under the skin. My husband made circles around the outside perimeter each hour with a marker, like the rings of a tree. When I went to my Internist the next day he was shocked at the size. He now thought I had a blood disorder so he sent me to a Hematologist/Oncologist.

Fortunately, the Hematologist/Oncologist ran a twenty-four hour urine test and really looked at me. Both he and his partner recognized that I had Cushing’s. Of course, he was sure that he did the diagnosis.  No matter that I had been pursuing this with other doctors for 3 years.

It was not yet determined if it was Cushing’s Disease (Pituitary) or Syndrome (Adrenal). However, he couldn’t help me any further so the Hematologist referred me to an Endocrinologist.

The Endocrinologist, of course, didn’t trust the other tests I had had done so I was back to square one. He ran his own multitude of tests. He had to draw blood at certain times like 9 AM. and 5 PM. There was a dexamethasone suppression test where I took a pill at 10 p.m. and gave blood at 9 am the next day. I collected gallons of urine in BIG boxes (Fun in the fridge!). Those were from 6 a.m. to 6 a.m. to be delivered to his office by 9 a.m. same day. I was always worried that I’d be stopped in rush hour and the police would ask about what was in that big container. I think I did those for a week. He also did standard neurological tests and asked lots of questions.

When the endo confirmed that I had Cushing’s in 1987 he sent me to a local hospital where they repeated all those same tests for another week and decided that it was not my adrenal gland (Cushing’s Syndrome) creating the problem. The doctors and nurses had no idea what to do with me, so they put me on the brain cancer ward.

When I left this hospital after a week, we didn’t know any more than we had before.

As luck would have it, NIH (National Institutes of Health, Bethesda, Maryland) was doing a clinical trial of Cushing’s. I live in the same area as NIH so it was not too inconvenient but very scary at first to think of being tested there. At that time I only had a choice of NIH, Mayo Clinic and a place in Quebec to do this then-rare pituitary surgery called a Transsphenoidal Resection. I chose NIH – closest and free. After I was interviewed by the Doctors there, I got a letter that I had been accepted into the clinical trial. The first time I was there was for 6 weeks as an inpatient. More of the same tests.

There were about 12 of us there and it was nice not to be alone with this mystery disease. Many of these Cushies (mostly women) were getting bald, couldn’t walk, having strokes, had diabetes. One was blind, one had a heart attack while I was there. Towards the end of my testing period, I was looking forward to the surgery just to get this whole mess over with. While I was at NIH, I was gaining about a pound a day!

The MRI still showed nothing, so they did a Petrosal Sinus Sampling Test. That scared me more than the prospect of surgery. (This test carries the risk of stroke and uncontrollable bleeding from the incision points.) Catheters were fed from my groin area to my pituitary gland and dye was injected. I could watch the whole procedure on monitors. I could not move during this test or for several hours afterwards to prevent uncontrolable bleeding from a major artery. The test did show where the tumor probably was located. Also done were more sophisticated dexamethasone suppression tests where drugs were administered by IV and blood was drawn every hour (they put a heplock in my arm so they don’t have to keep sticking me). I got to go home for a weekend and then went back for the surgery – the Transsphenoidal Resection. I fully expected to die during surgery (and didn’t care if I did) so I signed my will and wrote last letters to those I wanted to say goodbye to. During the time I was home just before surgery, a college classmate of mine (I didn’t know her) did die at NIH of a Cushing’s-related problem. I’m so glad I didn’t find out until a couple months later!

November 3, 1987, the surgeon, Dr. Ed Oldfield, cut the gum above my front teeth under my upper lip so there is no scar. He used tiny tools and microscopes. My tumor was removed successfully. In some cases (not mine) the surgeon uses a plug of fat from the abdomen to help seal the cut. Afterwards, I was in intensive care overnight and went to a neurology ward for a few days until I could walk without being dizzy. I had some major headaches for a day or two but they gave me drugs (morphine) for those. Also, I had cotton plugs in my nostrils. It was a big day when they came out. I had diabetes insipidus (DI) for a little while, but that went away by itself – thank goodness!

I had to use a foam product called “Toothies” to brush my teeth without hitting the incision. Before they let me go home, I had to learn to give myself an injection in my thigh. They sent me home with a supply of injectible cortisone in case my level ever fell too low (it didn’t). I was weaned gradually off cortisone pills (scary). I now take no medications. I had to get a Medic Alert bracelet. I will always need to tell medical staff when I have any kind of procedure – the effects of my excess cortisone will remain forever.

I went back to the NIH for several follow-up visits of a week each where they did all the blood and urine testing again. After a few years NIH set me free. Now I go to my “outside” endocrinologist every year for the dexamethasone suppression test, 24-hour urine and regular blood testing.

As I get further away from my surgery, I have less and less chance that my tumor will grow back. I have never lost all the weight I gained and I still have the hair on my chin but most of my other symptoms are gone. I am still and always tired and need a nap most days. I do not, however, still need to take whole days off just to sleep.

I consider myself very lucky that I was treated before I got as bad as some of the others on my floor at NIH but think it is crazy that these symptoms are not taken seriously by doctors.

My story goes on and if you’re interested some is on this blog and some is here:

Forbes Magazine | MaryO’s bio | Cushing’s and Cancer Blog | Cushing’s Awareness Day Testimonial Archive |

Because of this experience in getting a Cushing’s diagnosis – and later, a prescription for growth hormone – I was concerned that there were probably other people not being diagnosed with Cushing’s. When I searched online for Cushing’s, all the sites that came up were for dogs and horses with Cushing’s.  Not what I was looking for!

In July of 2000, I was talking with my dear friend Alice, who ran a wonderful menopause site, Power Surge, wondering why there weren’t many support groups online (OR off!) for Cushing’s.  This thought percolated through my mind for a few hours and I realized that maybe this was my calling.  Maybe I should be the one to start a network of support for other “Cushies” to help them empower themselves.

I wanted to educate others about the awful disease that took doctors years of my life to diagnose and treat – even after I gave them the information to diagnose me.  I didn’t want anyone else to suffer for years like I did.  I wanted doctors to pay more attention to Cushing’s disease.

The first website (http://www.cushings-help.com) went “live” July 21, 2000.  It was just a single page of information. The message boards began September 30, 2000 with a simple message board which then led to a larger one, and a larger.  Today, in 2010, we have over 7 thousand members.  Some “rare disease”!

The message boards are stillactive and we have weekly online text chats, weekly live interviews, local meetings, conferences, email newsletters, a clothing exchange, a Cushing’s Awareness Day Forum, podcasts, phone support and much more. Because I wanted to spread the word to others not on “the boards” we have extended out to social networking sites – twitter groups, facebook groups, twines, friendfeeds, newsletters, websites, chat groups, multiply.com, and much, much more.

People are becoming more empowered and participating in their own diagnoses, testing and treatment.  This have changed a lot since 1983!

When I had my Cushing’s over 40 years ago (AARRGGHH!), I never thought that I would meet another Cushing’s patient in real life or online. Back then, I’d never even been aware that there was anything like an “online”. I’m so glad that people struggling with Cushing’s today don’t have to suffer anymore thinking that they’re the only one who deals with this.

Because of my work on the websites – and, believe me it is a ton of work! – I have had the honor of meeting over a hundred other Cushies personally at local meetings, conferences, at NIH (the National Institutes of Health in Bethesda, MD where I had my final diagnosis and surgery). It occurred to me once that this is probably more than most endocrinologists will ever see in their entire career. I’ve also talked to countless others on the phone. Amazing for a “rare” disease!

I don’t know what pushed me in 1983, how I got the confidence and self-empowerment to challenge these doctors and their non-diagnoses over the years.  I’m glad that I didn’t suffer any longer than I did and I’m glad that I have a role in helping others to find the medical help that they need.

What do *YOU* think?  How are you becoming empowered?

Filed under: Clinical trials, Cushing's, General Health, Health Care, pituitary | Tagged: , , , , , , , , , , , , , , , , , , , | 1 Comment »

Medic Alert Bracelets

Posted on December 16, 2025 by MaryO

Since the last topic was about Adrenal Insufficiency, it seemed that a great next topic would be about Medic Alert Bracelets.

Many doctors insist that everyone who has had pituitary or adrenal surgery have a bracelet – and some will even tell patients what they should say on them.

While I was still a patient at the NIH (National Institutes of Health) after my pituitary surgery, I was given my first bracelet along with my kit in care of adrenal crisis.  I had to learn to give myself a shot before I could go home.

Now, my endo checks mine at every visit to be sure I’m wearing my bracelet and reads it to be sure it’s still legible and checks to see what the text says.

He feels that the bracelets – and he insists that they LOOK like medic alert bracelets, not disguised as jewelry – are life savers.

I’m not so sure – I read stories on the message boards that people have gone into AI (adrenal insufficiency and no one has ever looked at their bracelet.  That was certainly the case for young Sam.  Her mom had instructions everywhere, none were heeded and the situation rapidly turned disastrous.

…We have dealt with Addison’s for 7 years; but I have handled everything. Apparently the vials of solu-cortef with step-by-step instructions hanging on the bulletin board in the kitchen, medicine cabinet and in every vehicle somehow missed his attention…  (read the whole story at survive the journey: Stars Go Blue)

A Paramedic wrote on the message boards:

I’d like to add a couple things from the perspective of a Paramedic…

A lot of us are not taught about adrenal insufficiency during our education….nor do many of us (if any at all) have a protocol to administer Injectable for AI unless we are able to contact the ER doctor for permission. So…if any of you should have an AI crisis please gently nudge your paramedic to contact the receiving physician for permission to administer the medication. I know this sounds like a lot of responsibility on the part of the patient…but you have to realize that we’re taught to recognize the most common life threats and endocrine disorders (other than diabetes) most usually do not present with life threats (we all know that as cushing’s is more recognized that this will change)…and our protocols cover the most common life threats….so while we may recognize that you are hypotensive and need fluids (IV) and are sweaty, nauseated, decreased level of responsiveness etc…we are not equipped to deal with the actual cause unless you help educate us….

Also…please don’t get angry with us….if we are having problems understanding…just gently insist that a call be made to your doctor or the receiving ED (usually not feasible for us to call your doctor since they do not come to the phone for just anybody but if you have access to them, as many cushies do, it would be great to talk to them)…

Paramedicine is evolving….someday soon, hopefully, our education will include more diagnostic skills…untill just in the past 5 years or so we were NEVER to make a diagnosis at all…just treat the symptoms!!!! So there is hope out there for futher understanding of such a critical problem for those without adrenal (or asleep adrenals) glands….

The medical alert jewerly is a life-saver and we do look for it….

So, the questions for discussion are:

  • Do you have a medical alert bracelet
  • Does your doctor check on it or suggest proper wording.
  • If you have one, has any medical staff read it during a crisis
  • And… what does yours say?

Filed under: adrenal crisis, Cushing's, pituitary | Tagged: , , , , | 15 Comments »

Cushing’s, Cancer and Other Serious Diseases

Posted on December 2, 2025 by MaryO

I was drawn to this blog post because the author mentioned that she had both Cushing’s and cancer, a kind of unusual combination.

1974 to Today: Seal it up
By Experience
I still haven’t heard what the consensus is on my aftercare: Cushing’s and Cancer. I don’t know what I will be expecting to feel like after surgery. My endocrinologist said that I should get sick after the surgery and need some kind of …
1974 to Today – http://1974totoday.blogspot.com/

I don’t usually comment on blog posts but I did on this one because we seem to share so much, disease-wise.

I said

Hi, I was drawn to your blog post because I have a blog with the same name, Cushings & Cancer.

I had my Cushing’s long ago and my cancer (kidney aka renal cell carcinoma) was 3 years ago but I sure know where you’re coming for.

My surgeon contacted my endo for the amounts of steroids during surgery (they came through the IV) then post-op, they kept cutting my dose in half until I was back down to normal.
Generally, you stress-dose after surgery if you feel like you have a flu coming on. Has your endo given you Cortef or another steroid to take for emergencies like this? Sometimes, they will give you an injectible to be faster acting.

Best of luck with the cancer surgery AND your Cushing’s.
MaryO

I sure hope that this isn’t a trend, Cushies getting cancer although I know of a couple others on the boards getting cancer.

I suppose Cushing’s doesn’t make us any more immune to other diseases but it seems like it should.

Haven’t we already “done our time”?

OTOH, I have a friend with a serious cancer (aren’t they all?)  who recently learned that she has a second, unrelated, cancer.  Makes you wonder sometimes.

What other diseases have you had in addition to your Cushing’s?

Filed under: Cancer, Cushing's, Rare Diseases | Tagged: , , , | Leave a comment »

Co-Occurrence of Endogenous and Exogenous Cushing’s Syndromes: Does “Double Cushing Syndrome” Really Exist? A Case Report

Posted on December 1, 2025 by MaryO

ABSTRACT

Double Cushing syndrome exists: exogenous steroid use can mask concurrent adrenal hypercortisolism. When symptoms persist and cortisol remains high after tapering or stopping prescribed glucocorticoids, an endogenous source is likely. Early recognition with ACTH testing, dexamethasone suppression, and adrenal imaging reduces misdiagnosis, favors timely surgery, and supports safe tapering.

1 Introduction

Cushing syndrome (CS) is a non-physiological increase in plasma glucocorticoids [1]. In most cases, the source of increased plasma glucocorticoids is caused by exogenous steroid administration, which is quite common, and about 1% of the world population is on long-term (more than 3 months) oral glucocorticoids [1, 2]. On the contrary, endogenous overproduction of glucocorticoids is rare, and annually, only two to eight per million people are diagnosed with endogenous CS [3]. The simultaneous occurrence of endogenous and exogenous CS is an exceptionally uncommon phenomenon. This dual manifestation has been reported in a few case reports, highlighting its rarity and the complex diagnostic and therapeutic challenges it poses [4, 5]. Therefore, in this study, we discuss a patient who presented with cushingoid features and was simultaneously diagnosed with both endogenous and exogenous CS or, as it is called, double CS.

2 Case Presentation

The patient was a 46-year-old male with a history of new-onset hypertension and recurrent deep vein thrombosis (DVT) who was referred to our endocrinology clinic with a chief complaint of hip pain and weakness of the lower limbs. In the past 3 years, the patient had been receiving 50 mg/day of oral prednisolone and inhalation powder of Umeclidinium and Vilanterol (62.5/25 μg/dose) because of respiratory complications that started after Coronavirus Disease 2019 (COVID-19) vaccination. After 3 months of corticosteroid treatment, he experienced DVT for the first time when he was started on rivaroxaban. However, while he was on treatment, the second DVT occurred 1 month before his referral, and therefore, rivaroxaban was changed to warfarin 5 mg/day.

The patient also mentioned weight gain with his body mass index (BMI) rising from 26 to 31 kg/m2, progressive weakness of proximal muscles, easy bruising, decreased libido, mood changes with mostly euphoric mood, and irritability during the last 2 years. Moreover, multiple osteoporotic fractures of ribs, clavicle, sternum, and lumbar vertebrae were added to his symptoms in the past 5 months. At that time, he underwent bone densitometry, which revealed osteopenia of the left hip with a Z-score of −1.3 and severe osteoporosis of total lumbar spine with a T-score of −3.9. He started taking calcium and vitamin D3 supplements and received a single injection of 750 μg/3 mL teriparatide 30 days before his referral to our center.

Two months ago, the patient gradually reduced the dosage of prednisolone by tapering the dose to 12.5 mg/day. However, a month later, the hip pain and muscle weakness worsened to such an extent that the patient was unable to walk. Due to his signs and symptoms, the patient was referred to our center for further evaluation of CS. The patient also mentioned a history of nephrolithiasis, new-onset hypertension, and lower limb edema, for which he was started on eplerenone 25 mg and furosemide 20 mg tablets once daily. In his family history, the patient’s mother had type 2 diabetes mellitus, and his two sisters had a history of nephrolithiasis. The patient did not mention any history of allergies to medications or foods. He was addicted to opium and had 15 pack-years of smoking, but he did not mention alcohol consumption.

Upon admission, the patient presented with a blood pressure of 150/83 mmHg, heart rate of 74 bpm, respiratory rate of 20/min, temperature of 36.5°C, oxygen saturation of 93%, and BMI of 31 kg/m2. He was sitting in a wheelchair due to weakness and severe pain in the hip. On physical examination, the patient showed the features of CS, including moon face, buffalo hump, central obesity, facial plethora, thin and brittle skin, acne, and purple stretch marks (striae) on the flanks (Figure 1). Proximal muscle weakness in the lower limbs with a muscle force grade of 4/5 and 3+ edema was also observed. Laboratory investigations are shown in Table 1.

Details are in the caption following the image

De-identified clinical photographs illustrating the Cushingoid phenotype. (A) Overall habitus with marked central (truncal) adiposity. (B) Rounded plethoric face (“moon facies”). (C) Relatively slender distal extremities compared with truncal obesity. (D) Dorsocervical fat pad (“buffalo hump”). (E) Upper thoracic/supraclavicular fat accumulation. (F) Protuberant abdomen with wide violaceous striae.
TABLE 1. Laboratory findings of case report.
Laboratory test Patient value (in-hospital) Patient value (follow-up) Reference range
On admission
Hemoglobin (g/dL) 16.6 13.6 13.5–17.5
Hematocrit (%) 49.5 42.1 42–52
WBC (white blood cells; 103/μL) 11.8 7.1 4.0–11.0
PLT (platelet count; 103/μL) 286 294 150–450
BUN (blood urea nitrogen; mg/dL) 10 11 7–18
Cr (creatinine; mg/dL) 0.9 0.9 0.7–1.3
ALP (alkaline phosphatase; IU/L) 1016 129 44–147
AST (aspartate aminotransferase; IU/L) 48 30 < 31
ALT (alanine transaminase; IU/L) 88 21 < 31
CRP (C-reactive protein; mg/dL) 31 3 < 5
ESR (erythrocyte sedimentation rate; mm/h) 63 24 < 15
Sodium (mEq/L) 148 141 136–145
Potassium (mEq/L) 4.8 4.3 3.5–5
FBS (fasting blood glucose; mg/dL) 97 89 80–100
TC (total cholesterol; mg/dL) 267 182 < 200
TG (triglyceride; mg/dL) 148 104 < 200
LDL (low-density lipoprotein; mg/dL) 138 98 < 130
HDL (high-density lipoprotein; mg/dL) 64 55 30–70
In hospital
Cortisol 8 a.m. fasting (μg/dL) 20.2 14.1 4.3–24.9
ACTH (adrenocorticotropic hormone; pg/mL) < 1 — 7.2–63.3
1 mg Overnight dexamethasone suppression test (μg/dL) 16.5 — < 1.8

3 Methods (Differential Diagnosis, Investigations, and Treatment)

Initially suspected of having exogenous-induced CS, the patient’s prednisolone was on hold for 3 days. Cortisol 8 a.m. fasting level, measured with Electrochemiluminescence (ECL) and adrenocorticotropic hormone (ACTH) test, was 20.2 μg/dL (585.4 nmol/L) and < 1 pg/mL, respectively. Due to the lack of suppression of serum cortisol despite not using oral glucocorticoids, the absence of adrenal insufficiency symptoms, and the fact that the patient’s symptoms remained unchanged during this period, co-occurrence of endogenous CS was suspected.

A 1 mg overnight dexamethasone suppression test was performed to confirm endogenous CS diagnosis, and the results were reported as 16.5 μg/dL (normal range < 1.8 μg/dL). Considering the possibility of an ACTH-independent CS, the patient underwent an abdominopelvic multidetector computed tomography (MDCT) of abdominopelvic with adrenal protocol, which revealed a well-defined lesion with an approximate size of 32.8 × 38.6 mm in the left adrenal gland with a radiodensity of 90 Hounsfield units and a normal right adrenal gland (Figure 2). Moreover, evidence of previous old fractures as multiple callus formation was seen involving the clavicles, sternum, bilateral ribs, ischium, and pelvic bones. Multilevel old stable compression fractures of thoracic and lumbar vertebral bodies were also present. The differential diagnoses were glucocorticoid secretory adrenal tumors, including adrenal cell carcinoma and lipid-poor adenoma. In order to rule out pheochromocytoma, 24-h urine catecholamines were measured, and the results were negative.

Details are in the caption following the image

Abdominopelvic multidetector computed tomography (MDCT) with adrenal protocol showing a well-defined lesion with an approximate size of 32.8 × 38.6 mm in the left adrenal gland; radiodensity 90 HU. (A) Transverse plane. (B) Coronal plane. (C) Sagittal plane.

Finally, the patient underwent left adrenalectomy and corticosteroid replacement therapy due to the suppression of the other adrenal gland. According to the post-operative pathological investigations, immunohistochemistry markers reported as negative chromogranin, positive melan-A and inhibin, less than 3% Ki-67 marker, and lipid-poor adrenal cortical adenoma without invasions were diagnosed (Figure 3).

Details are in the caption following the image

Immunohistochemistry of the adrenal lesion (all panels acquired with a 100× oil-immersion objective; 10× eyepiece; original magnification ×1000). (A) Positive inhibin, (B) Positive Melan-A, (C) Less than 3% Ki-67 marker, and (D) Negative chromogranin.

4 Results (Outcome and Follow-Up)

Within 3 months after the operation, the patient’s corticosteroid was tapered and then discontinued due to the normalization of the cortisone serum test (14.1 μg/dL). Proximal limb weakness and hip pain, which had deprived the patient of the ability to move, gradually improved so that he could walk easily and perform daily activities. The signs and symptoms related to CS, including the patient’s mood, skin signs, and general appearance, returned to normal. The patient has been followed up for 6 months after the surgery. The patient’s BMI decreased to 24 kg/m2, and he stopped his anti-hypertensive medications with a blood pressure of 100/60 mmHg without previously prescribed drugs. So far, the laboratory tests have been within the normal range, and he has no complaints (Table 1).

5 Discussion

The described case was diagnosed with a cortisol-producing adrenocortical adenoma accompanied by exogenous CS. CS is an uncommon clinical condition caused by prolonged exposure to increased cortisol levels, which can be due to endogenous or exogenous factors [6]. Endogenous CS is infrequent and is classified as ACTH-dependent (80% of cases) or ACTH-independent (20% of cases) [7]. In the ACTH-independent category, adrenal adenoma accounts for 60% of cases and only 12% of cases of endogenous CS [7, 8]. Exogenous CS mainly occurs due to prolonged administration of glucocorticoids, which are used to manage a broad spectrum of diseases such as inflammatory, autoimmune, or neoplastic disorders and are the most common cause of CS worldwide [9]. Multiple factors, including formulation, duration of administration, pharmacokinetics, affinity, and potency of exogenous glucocorticoids, affect the probability of exogenous CS, but all forms of glucocorticoids can induce CS [10].

In the setting of cushingoid clinical features with chronic administration of high-dose glucocorticoids, especially oral prednisolone, the probability of exogenous CS is remarkably high; therefore, CS diagnostic approaches suggest that the first step after confirmation of cortisol excess is ruling out exogenous glucocorticoid administration [7, 8, 10]. Therefore, the possibility of co-occurrence of endogenous CS with iatrogenic CS is extremely low, and the diagnosis requires high clinical suspicion [4].

Differentiating endogenous and exogenous CS based on clinical features can be challenging and far-fetched. However, a few points can help physicians distinguish between these two. First, exogenous CS symptoms tend to be more striking, while endogenous CS appears more gradually. Second, hypertension, hypokalemia, and features of androgen excess, such as acne and hirsutism, are more common in endogenous CS [4, 10]. In addition, endogenous CS should be suspected if the patient’s symptoms continue after corticosteroid discontinuation or if the serum cortisol level is high despite corticosteroid cessation. In our case, the patient had a high cortisol level despite stopping prednisolone for 3 days, and he did not have any symptoms of adrenal insufficiency despite stopping prednisolone suddenly. Consequently, it was suspected that glucocorticoids might come from an endogenous source. Because ACTH was suppressed concurrently with elevated cortisol, non-ACTH-dependent CS was suspected, and MDCT of abdominopelvic confirmed it.

So far, few similar cases of simultaneous endogenous and exogenous CS have been reported. The first case was a 23-year-old woman with juvenile idiopathic arthritis who was administered high doses of triamcinolone for 16 years [4]. The development of cushingoid features that favored endogenous CS, such as hirsutism and acne, strengthened the suspicion of endogenous CS, and a CT scan revealed hypercortisolism with a bulky and nodular left adrenal gland, and a double CS was confirmed [4]. The second case was a 66-year-old woman diagnosed with exogenous CS after consumption of Traditional Chinese medicine (TCM) for a year [5]. The cessation of TCM did not significantly improve her cushingoid features, and she developed additional CS complications, including hypertension, diabetes mellitus, and osteoporotic fractures over the next 8 years. CS workup revealed a right-sided adrenal adenoma, and after the adrenalectomy, her clinical cushingoid features markedly improved [5]. These cases suggest that exogenous and endogenous CS can exist simultaneously in the same person. Although it is very rare, it should be considered in a person who still complains of CS symptoms after corticosteroid cessation. We suggest clinicians evaluate the patients for the disappearance of exogenous CS symptoms after tapering and stopping glucocorticoids. If the symptoms remain, they should be evaluated for endogenous CS.

6 Conclusion

The co-occurrence of an endogenous CS in the setting of an exogenous CS is curious. The diagnosis is based on a high clinical suspicion. Clinicians should evaluate patients for symptom resolution after tapering and discontinuing corticosteroids. Clinical cushingoid features that do not resolve after discontinuing exogenous glucocorticoids and high cortisol levels despite discontinuing corticosteroids should raise clinicians’ suspicion of the co-occurrence of exogenous and endogenous CS.

Author Contributions

Reza Amani-Beni: investigation, methodology, writing – original draft, writing – review and editing. Atiyeh Karimi Shervedani: methodology, writing – original draft. Bahar Darouei: conceptualization, validation, writing – review and editing. Matin Noroozi: methodology, writing – original draft. Maryam Heidarpour: conceptualization, supervision, validation, writing – review and editing.

Acknowledgments

The authors have nothing to report.

Consent

Written informed consent was obtained from the patient to publish this report, including de-identified clinical photographs, in accordance with the journal’s patient consent policy.

Conflicts of Interest

The authors declare no conflicts of interest.

Data Availability Statement

The data that supports the findings of this study are available on request of the corresponding author. The data are not publicly available due to privacy restrictions.

https://onlinelibrary.wiley.com/doi/10.1002/ccr3.71419

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