Cortisol gets a bad rap these days. (Guilty!) Yes, this hormone surges when you’re stressed. And yes, chronic stress is bad news for your health. But while too much cortisol can lead to all sorts of stress-related side effects, too little cortisol is equally debilitating.
Just ask someone with Addison’s disease. If you suffer from this condition, your adrenal glands fail to make adequate amounts of cortisol, says Betul Hatipoglu, MD, an endocrinologist at Cleveland Clinic.
Cortisol plays a role in regulating your blood pressure, heart function, digestion, and a lot else, Hatipoglu explains. So if your adrenal glands poop out and your cortisol levels plummet, a lot can go wrong. (In as little as 30 days, you can be a whole lot slimmer, way more energetic, and so much healthier just by following the simple, groundbreaking plan in The Thyroid Cure!)
Here’s what you need to know about this condition—starting with its craziest symptom.
It can make your teeth appear whiter.
Hatipoglu once met with a patient who was suffering from fatigue, belly pain, and mild weight loss. “Her doctors thought she was depressed,” Hatipoglu recalls. Toward the end of their appointment, Hatipoglu noticed the woman’s teeth looked very white. She realized they looked white because the woman’s skin was tan. “I asked her if she’d been on vacation, and she said she hadn’t been in the sun, and that’s when I knew,” Hatipoglu says. Some Addison’s-related hormone shifts can make the skin appear darker, almost like a tan. “Addison’s is the only disease I know of that can cause darkening of the skin,” she says.
Its (other) symptoms are popular ones.
Along with darker skin, other symptoms of Addison’s include nausea, mild-to-severe abdominal or bone pain, weight loss, a lack of energy, forgetfulness, and low blood pressure, Hatipoglu says. Of course, those same symptoms are linked to many other health issues, from thyroid disease to cancer. “It’s very easy to confuse with other disorders, so many people see a lot of doctors before finally receiving a proper diagnosis,” she says. (One exception: For young women who develop Addison’s disease, loss of body hair is a warning sign, Hatipoglu adds.)
It’s rare.
Doctors also miss or misinterpret the symptoms of Addison’s disease because it’s very uncommon. “I’m not sure if it’s quite one in a million, but it’s very rare,” Hatipoglu says. “It makes sense that many doctors don’t think of it when examining a patient with these symptoms.”
It’s often confused with adrenal insufficiency.
A lot of online resources mention Addison’s disease and adrenal insufficiency as though they were two names for the same condition. They’re not the same, Hatipoglu says. While a thyroid issue or some other hormone-related imbalance could mess with your adrenal function, Addison’s disease refers to an autoimmune disorder in which your body attacks and destroys your adrenal glands.
That destruction can happen quickly.
While it takes months or even years for some Addison’s sufferers to lose all hormone production in their adrenal glands, for others the disease can knock out those organs very rapidly—in a matter of days, Hatipoglu says. “That’s very uncommon,” she adds. But compared to other less-severe adrenal issues, the symptoms of Addison’s tend to present more dramatically, she explains. That means a sufferer is likely to experience several of the symptoms mentioned above, and those symptoms will continue to grow worse as time passes.
Anybody can get it.
Addison’s is not picky. It can strike at any age, regardless of your sex or ethnicity, Hatipoglu says. While there’s some evidence that genetics may play a role—if other people in your family have the disease or some other endocrine disorder, that may increase your risk—there’s really no way to predict who will develop the disease, she adds.
Screening for Addison’s is pretty simple.
If your doctor suspects Addison’s, he or she will conduct a blood test to check for your levels of cortisol and another hormone called ACTH. “Usually the results of that screening are very clear,” Hatipoglu says. If they’re not, some follow-up tests can determine for sure if you have the condition.
There are effective treatments.
Those treatments involve taking oral hormone supplements. In extreme cases, if the patient’s body does not properly absorb those supplements, injections may be necessary, Hatipoglu explains. “But patients live a normal life,” she adds. “It’s a treatable disease, and the treatments are effective.”
Life was good! In fact, life was great! I was married to the love of my life. We had a beautiful little girl. My husband and I had both earned our graduate degrees. I earned my Doctorate in Clinical Psychology and was growing my clinical practice. I loved my work!
In October, 2006, my life was turned upside down when I gained 30 pounds in 30 days! I knew this was not normal at all. I sought answers but my doctor kept insisting that I wasn’t eating the right foods, that I wasn’t exercising hard enough, and finally that it was genetic. However, I was always a thin person, I ate pretty healthy foods, and I was pretty active. Red flags became even greater when my physician put me on prescription weight loss drugs and I STILL gained another 30 pounds. I knew my body and I knew something was wrong but I had no one to validate what was going on.
In January, 2010, to my surprise, I learned that I was miraculously pregnant with our second daughter. I was so sick during that pregnancy and, again, my doctors couldn’t figure out why. My OBGYN was very supportive, yet so concerned. Her solution was to put me on bed rest. I became so ill that she told me that “my only job was to sit still and wait to have a baby”. I did give birth to a healthy baby girl four weeks early. Little did I know, then, how much of a miracle she was.
During the latter part of my pregnancy, while flipping through channels on television, I came across a Cushing’s episode on the health TV show, “Mystery Diagnosis”.
I knew right away that this diagnosis fit everything I had been experiencing: years of weird and unexplained symptoms, gaining 150 pounds for no reason, an onset of diabetes, high blood pressure, and an overall sense of doom.
You see, my friends and family witnessed me go from a vibrant young Clinical Psychologist in practice, to someone whose health deteriorated due to the symptoms of Cushing’s, as I tried for many years to get answers from professionals. As I continued to eat a healthy, 1000 calorie per day diet, engage in exercise with multiple personal trainers, and follow through with referrals to consult with dietitians; I continued to gain weight at a rate of 5 pounds per week and experience rapidly declining health. Finally, after watching that Cushing’s episode of Mystery Diagnosis, I found my answer! Ultimately, I sought the expertise of and treatment from a team of experts at the Seattle Pituitary Center in Seattle, WA. I had brain surgery in Seattle on November 16th, 2011. I want to tell you how I found the people who helped save my life…
On June 9, 2011, I went to my first MAGIC conference. I had never heard of them but someone on one of the online support groups told me about it. At that time, I was working but was very, very sick. We suspected at that time that I had been sick for years! My local endocrinologist was far from a Cushing’s expert. After watching the Cushing’s episode of Mystery Diagnosis, I told the same endocrinologist who had misdiagnosed me for years that I had found my answer. He swore that there was “literally no possible way that I had Cushing’s Disease!” He stated that my “hump wasn’t big enough”, “my stretch marks were not purple enough” and that “Cushing’s patients do not have children!” I told him that I was NOT leaving his office until he started testing me. He finally caved in. To his surprise, I was getting abnormal labs back.
At that time, there was evidence of a pit tumor but it wasn’t showing up on an MRI. So, I had my IPSS scheduled. An IPSS stands for Inferior Petrosal Sinus Sampling. It is done because 60 % of Cushing’s based pituitary tumors are so small that they do not show up on an MRI. Non Cushing’s experts do not know this so they often blow patients off, even after the labs show a high level of ACTH in the brain through blood work. An overproduction of the hormone ACTH from the pituitary communicates to the adrenal glands to overproduce cortisol. Well, the IPSS procedure is where they put catheters up through your groin through your body up into your head to draw samples to basically see which side of your pituitary the extra hormone is coming from, thus indicating where the tumor is. U of C is the only place in IL that does it.
So, back to the MAGIC convention; my husband and I went to this conference looking for answers. We were so confused and scared! Everyone, and I mean everyone, welcomed us with opened arms like we were family! There were brilliant presenters there, including an endocrinologist named Dr. William Ludlam. At that time, he was the director at the Seattle Pituitary Center in Seattle, WA. He is a true Cushing’s expert. Since then, he left in January, 2012 to have a significant impact toward the contribution of research of those impacted by Cushing’s Syndrome. His position was taken over by another brilliant endocrinologist, Dr. Frances Broyles.
I was scheduled to get an IPSS at U of C on June 28th, 2011 to locate the tumor. Two days after the IPSS, I began having spontaneous blackouts and ended up in the hospital for 6 days. The docs out here had no clue what was happening and I was having between 4-7 blackouts a day! My life was in danger and they were not helping me! We don’t know why, but the IPSS triggered something! But, no one wanted to be accountable so they told me the passing out, which I was not doing before, was all in my head being triggered by psychological issues. They did run many tests. But, they were all the wrong tests. I say all the time; it’s like going into Subway and ordering a turkey sandwich and giving them money and getting a tuna sandwich. You would be mad! What if they told you, “We gave you a sandwich!” Even if they were to give you a dozen sandwiches; if it wasn’t turkey, it wouldn’t be the right one. This is how I feel about these tests that they ran and said were all “normal”. The doctors kept telling us that they ran all of these tests so they could cover themselves. Yet, they were not looking at the right things, even though, I (the patient) kept telling them that this was an endocrine issue and had something to do with my tumor! Well, guess how good God is?!!!!
You see, Dr. Ludlam had given me his business card at the conference, which took place two weeks prior to the IPSS. I put it away for a while. But, something kept telling me to pull the card out and contact him. I am crying just thinking about it, Lord!
So, prior to my IPSS, I wrote Dr. Ludlam an e mail asking him some questions. At that time, he told me to send him ALL of my records including labs. I sent him 80 pages of records that day. He called me back stating that he concurred with all of the evidence that I definitely have Cushing’s Disease from a pituitary source. He asked me what I planned to do and I told him that I was having the IPSS procedure done in a few days at the University of Chicago. He told me once I got my results to contact him.
Fast forward, I ended up in the hospital with these blackouts after my IPSS. The doctors, including MY local endocrinologist told me there was no medical evidence for my blackouts. In fact, he told the entire treatment team that he even doubted if I even had a tumor! However, this is the same man who referred me for the IPSS in the first place! I was literally dying and no one was helping me! We reached out to Dr. Ludlam in Seattle and told him of the situation. He told me he knew exactly what was going on. For some reason, there was a change in my brain tumor activity that happened after my IPSS. No one, to this day, has been able to answer the question as to whether the IPSS caused the change in tumor activity. The tumor, for some reason, began shutting itself on and off. When it would shut off, my cortisol would drop and would put me in a state of adrenal insufficiency, causing these blackouts!
Dr. Ludlam said as soon as we were discharged, we needed to fly out to Seattle so that he could help me! The hospital discharged me in worse condition then when I came in. I had a blackout an hour after discharge! But get this…The DAY the hospital sent me home saying that I did not have a pit tumor, my IPSS results were waiting for me! EVIDENCE OF TUMOR ON THE LEFT SIDE OF MY PITUITARY GLAND!!!
Two days later, Craig and I were on a plane to Seattle. I had never in my life been to Seattle, nor did I ever think I would go. We saw the man that God used to save my life, Dr. William Ludlam, the same man who we had met at the MAGIC conference for the first time one month prior! He put me on a combo of medications that would pull me out of crisis. Within one month, my blackouts had almost completely stopped! Unfortunately, we knew this was a temporary fix! He was treating me to carry me over to surgery. You see, his neurosurgeon, Dr. Marc Mayberg was just as amazing. He is one of the top neurosurgeons in the US! Statistically, he has one of the highest success rates!
The problem was that our insurance refused to pay for surgery with an expert outside of IL, stating that I could have surgery anywhere in IL! Most people don’t know that pituitary surgeries are very complicated and need the expertise of a “high volume center” which is where they do at least 50 of these surgeries per year. Dr. Mayberg has performed over 5,000 of these surgeries! By this time, we had learned that we need to fight for the best care! It was what would give me the best chance at life! We thought I would have to wait until January when our insurance would change, to see if I could get the surgery I so desperately needed! I was holding on by a thread!
We began appealing our insurance. At the time the MAGIC foundation had an insurance specialist who was allowed to help us fight our insurance. Her name is Melissa Callahan and she took it upon herself to fight for us as our patient advocate. It was a long and hard battle! But…we finally WON!!!! On November 16th, 2011, Dr. Marc Mayberg found that hidden tumor on the left side of my pituitary gland! He removed the tumor along with 50% of my pituitary gland.
Recovery was a difficult process. They say that it takes about one full year to recover after pituitary surgery for Cushing’s. I was grateful to be in remission, nonetheless. However, about one year after my brain surgery, the Cushing’s symptoms returned. After seven more months of testing that confirmed a recurrence of the Cushing’s, I was cleared for a more aggressive surgery. This time, I had both of my adrenal glands removed as a last resort. By then, we had learned that I had hyperplasia, which is an explosion of tumor cells in my pituitary. It only takes one active cell to cause Cushing’s. Therefore, I could have potentially had several more brain surgeries and the disease would have kept coming back over and over.
As a last resort, my adrenal glands were removed so that no matter how much these cells try to cause my adrenals to produce excessive amounts of cortisol; the glands are not there to receive the message. As a result, I am Adrenally Insufficient for life, which means that my body cannot produce the life sustaining hormone, cortisol, at all. I had my Bilateral Adrenalectomy by world renowned BLA surgeon, Dr. Manfred Chiang, in Wisconsin on August 21st, 2013. I traded Cushing’s Disease for Addison’s Disease, one of the hardest decisions I have ever had to make in my life. However, I knew that I would die with Cushing’s. Recovery from my last surgery was difficult and involved weaning down to a maintenance dose of steroid to replace my cortisol. Now, on a maintenance dose; I still have to take extra cortisol during times of physical or emotional stress to prevent my body from going into shock.
I promised a long time ago that I would pay it forward…give back because so much has been given to me. This is why I have committed my life to supporting the Cushing’s community. I post videos on YouTube as a way of increasing awareness. My channel can be found at http://www.YouTube.com/drnkarenthames
Karen has made 2 videos about her experiences with Cushing’s:
and
Doc Karen will be our guest in an interview on BlogTalk Radio Friday December 2 at 11:00 AM eastern. The Call-In number for questions or comments is (323) 642-1665 .
The archived interview will be available through iTunes Podcasts (Cushie Chats) or BlogTalkRadio. While you’re waiting, there are currently 90 other past interviews to listen to!
Dear Dr. Roach: I was told that I have Cushing’s disease, which has caused diabetes, high blood pressure, hunger, weight gain and muscle loss. I was never sick before this, and I did not have any of those things. I am told I have a tumor on my right adrenal gland. I have been to numerous doctors, but most have not been too helpful. They seem to try to treat the diabetes or blood pressure, but nothing else. They seem not to be familiar with Cushing’s. I tell them which medication works, but they still give me new medication. I have an endocrinologist and am scheduled to meet a urologist.
I have managed to go to physical therapy, exercise every day and lose over 50 pounds. I am not happy with the advice I’m getting. I was told that surgery to remove the tumor will fix everything, but that I would need to take steroids for either a short term or for life. My body is already making too much cortisol. I have 50 more pounds to lose. I work hard to keep the weight down. I feel like a science experiment. Within a week, I have had three different medications. I could not tell which was causing the side effects and making me dehydrated. I am not sure surgery is right for me, because they said it can be done laparoscopically, but if they can’t do it that way, they will have to cut me all the way across, which may take a long time to heal and may get infected.
Do you know what tests will confirm the diagnosis? Would surgery fix all these problems? I had the 24-hour urine test, the saliva test and blood tests. I want to know if it may be something else instead of Cushing’s. I’m not on anything for the high cortisol levels.
– A.L.
A: It sounds very much like you have Cushing’s syndrome, which is caused by excess cortisone, a hormone that has many effects. It is called Cushing’s disease when the underlying cause is a pituitary tumor that causes the adrenal gland to make excess cortisone. (Cortisone and cortisol are different names for the same chemical, also called a glucocorticoid.) Cushing’s syndrome also may be caused by an adenoma (benign tumor) of the adrenal gland, which sounds like the case in you.
The high amounts of cortisone produced by the adrenal tumor cause high blood pressure, glucose intolerance or frank diabetes, increased hunger, obesity (especially of the abdomen – large bellies and skinny limbs are classic), dark-colored striae (stretch marks), easy bruising, a reddish face and often weakness of arm and leg muscles. When full-blown, the syndrome is easy to spot, but many people don’t have all the characteristics, especially early in the course of the disease.
Your endocrinologist is the expert in diagnosis and management, and has done most of the tests. I am somewhat surprised that you haven’t yet seen a surgeon to have the tumor removed. Once it is removed, the body quickly starts to return to normal, although losing the weight can be a problem for many.
I have seen cases in my training where, despite many tests, the diagnosis was still uncertain. The endocrinologist orders a test where the blood is sampled from both adrenal veins (which contain the blood that leaves the adrenal glands on top of the kidneys). If the adrenal vein on the side of the tumor has much more cortisone than the opposite side, the diagnosis is certain.
Gafni RI, Papanicolaou DA, Nieman LK.
Developmental Endocrinology Branch, National Institute of Child Health and Human Development, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892-1862, USA.
OBJECTIVE: There is currently no optimal test to screen for endogenous Cushing’s syndrome (CS) in children. Traditional 24-hour urine or midnight serum cortisol values may be difficult to obtain or elevated by venipuncture stress. We hypothesized that salivary cortisol measurement is a reliable way to screen for CS in children.
STUDY DESIGN: Sixty-seven children (5-17 years) were studied: 24 obese volunteers, 29 non-obese volunteers, and 14 children with CS. Saliva was obtained at 7:30 AM, bedtime, and midnight for measurement of free cortisol by radioimmunoassay.
RESULTS: Salivary cortisol was detectable in all morning and evening samples from patients with CS but was frequently undetectable in healthy children at bedtime (66%) and at midnight (90%). With cut points that excluded healthy children, a midnight salivary cortisol value of 7.5 nmol/L (0.27 microg/dL) identified 13 of 14 patients with CS, whereas a bedtime value >27.6 nmol/L (1 microg/dL) detected CS in 5 of 6 patients. The diagnostic accuracies of midnight salivary cortisol and urinary free cortisol per square meter were the same (93%).
CONCLUSION: Salivary cortisol measurement at bedtime or midnight rules out CS in nearly all cases. Nighttime salivary cortisol sampling is thus a simple, accurate way to screen for hypercortisolism in children. PMID: 10891818 [PubMed – indexed for MEDLINE]
THE PRINCIPLE RESEARCHER FOR SALIVARY CORTISOLS IS HERSHEL RAFF AT THE UNIVERSITY OF WISCONSIN. HE IS A RESEARCH SCIENTIST, NOT A DOCTOR. YOU CAN CONTACT HIM DIRECTLY FOR ORDERING INFO.
Salivary Cortisol: A Screening Technique
By: Dr. Hershel Raff
Cushing’s syndrome – endogenous hypercortisolism – is characterized by a loss of circadian rhythmicity. In normal patients, cortisol levels peak in the early morning hours and decrease to substantially lower levels at night. Rather than the normal decrease in late evening cortisol, patients with Cushing’s syndrome of any cause fail to decrease cortisol secretion in the late evening. Therefore, the measurement of elevated late evening cortisol is helpful in the diagnosis of Cushing’s syndrome. Obtaining a late night, unstressed plasma cortisol is virtually impossible in most clinical practices. Salivary cortisol is in equilibrium with the free, biologically active portion of cortisol in the plasma. Therefore, if one obtains a saliva sample in patients at bedtime in their homes under unstressed conditions, one can make the diagnosis of endogenous hypercortisolism.
A simple way to sample saliva is by using a Salivette made by the Sarstedt Company (Newton, NC). This device consists of a cotton tube and plastic tubes. The patient only has to chew the cotton tube for 2-3 minutes and place it in the plastic tube. The tube is then transported to our lab for analysis.
Late-evening salivary cortisol is not intended to replace the current standard screening test – measurement of a 24 hr urine free cortisol. However, the salivary cortisol test can be extremely useful for patients suspected of having intermittent Cushing’s syndrome. Due to the convenience of sample collection, the patient can sample saliva several evenings in a row. In fact, our clinical endocrinologists routinely order 2-3 consecutive late-evening salivary cortisol samples.
Our research (Raff H, Raff JL, Findling JW. 1998 LATE-NIGHT SALIVARY CORTISOL AS A SCREENING TEST FOR CUSHING’S SYNDROME. J Clin Endocrinol Metab. 83:2681-2686) has shown that the combination of late-evening salivary cortisol and urine free cortisol is very accurate in diagnosing Cushing’s syndrome in most patients. Doctors can obtain a kit by contacting ACL Client Services at 1-800-877-7016.
Editor’s Note: DR. HERSHEL RAFF, PH.D. IS A PROFESSOR OF MEDICINE AND PHYSIOLOGY AT THE MEDICAL COLLEGE OF WISCONSIN’S ENDOCRINE RESEARCH LABORATORY AT ST. LUKE’S MEDICAL CENTER IN MILWAUKEE, WISCONSIN.
In adults with adrenal incidentaloma, adiponectin levels may help predict the presence of subclinical Cushing’s disease, according to recent findings.
Asli Dogruk Unal, MD, of the department of endocrinology and metabolism at Memorial Atasehir Hospital in Istanbul, and colleagues analyzed data from 40 patients with adrenal incidentaloma (24 women; mean age, 61 years) and 30 metabolically healthy adults without adrenal adenomas or hyperplasia (22 women; mean age, 26 years). All patients with type 2 diabetes were newly diagnosed and not on any antidiabetic therapies; included patients were not using statin therapy for about 12 weeks.
Participants provided blood samples
Among patients with adrenal incidentaloma, eight (20%) were diagnosed with subclinical Cushing’s syndrome; median adenoma diameter in these patients was 3.05 cm. The remaining patients were classified as nonfunctional adrenal incidentaloma. Compared with patients who had nonfunctional adrenal incidentaloma, patients with subclinical Cushing’s syndrome had a higher median midnight cortisol level (9.15 µg/dL vs. 5.1 µg/dL; P = .004) and urinary free cortisol level (249 µg per 24 hours vs. 170 µg per 24 hours; P = .007).
In two group comparisons, researchers found that only adiponectin level was lower in the subclinical Cushing’s syndrome group vs. the nonfunctional adrenal incidentaloma group (P = .007); there were no observed between-group differences for age, BMI, waist circumference, insulin levels, homeostasis model assessment for insulin resistance (HOMA-IR) or lipid profiles.
Adiponectin level was negatively associated with insulin level, HOMA-IR, triglyceride level and midnight cortisol level, and was positively associated with body fat percentage, HDL and adrenocorticotropic hormone levels. In linear regression analysis, age was found to be an increasing factor, whereas sex, HOMA-IR, LDL, waist circumference and presence of subclinical Cushing’s syndrome were decreasing factors.
In evaluating the receiver operating characteristic analysis, researchers found that adiponectin level had a predictive value in determining the presence of subclinical Cushing’s syndrome (area under the curve: 0.81; 95% CI, 0.67-0.96). Sensitivity and specificity for an adiponectin value of 13 ng/mL or less in predicting the presence of subclinical Cushing’s syndrome were 87.5% and 77.4%, respectively; positive predictive value and negative predictive value were 50% and 96%, respectively.
“Presence of [subclinical Cushing’s syndrome] should be considered in case of an adiponectin level of 13 ng/mL in [adrenal incidentaloma] patients,” the researchers wrote. “Low adiponectin levels in [subclinical Cushing’s syndrome] patients may be important in treatment decision due to the known relation between adiponectin and cardiovascular events. In order to increase the evidences on this subject, further prospective follow-up studies with larger number of subjects are needed.” – by Regina Schaffer
Disclosure: The researchers report no relevant financial disclosures.
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