Medical Therapies in Cushing’s Syndrome

Chapter

The Hypothalamic-Pituitary-Adrenal Axis in Health and Disease

pp 165-179

Date: 03 December 2016

Medical Therapies in Cushing’s Syndrome

Abstract

Medical therapy has an important, albeit secondary, role in patients with Cushing’s syndrome. While medications are not currently used as definitive therapy of this condition, they can be very effective in controlling hypercortisolism in patients who fail surgery, those who are not surgical candidates, or those whose tumor location is unknown. Medical therapies can be particularly helpful to control hypercortisolism in patients with Cushing’s disease who underwent radiation therapy and are awaiting its salutary effects.

Currently available treatment options include several steroidogenesis inhibitors (ketoconazole, metyrapone, mitotane, etomidate), which block one or several steps in cortisol synthesis in the adrenal glands, centrally acting agents (cabergoline, pasireotide), which decrease ACTH secretion, and glucocorticoid receptor antagonists, which are represented by a single agent (mifepristone). With the exception of pasireotide and mifepristone, available agents are used “off-label” to manage hypercortisolism. Several other medications are at various stages of development and may offer additional options for the management of this serious condition.

As more potential molecular targets become known and our understanding of the pathogenesis of Cushing’s syndrome improves, it is anticipated that novel, rationally designed medical therapies may emerge. Clinical trials are needed to further investigate the relative risks and benefits of currently available and novel medical therapies and examine the potential role of combination therapy in the management of Cushing’s syndrome.

Keywords

Cabergoline, Etomidate, Ketoconazole, Levoketoconazole, Metyrapone, Mifepristone, Mitotane, Osilodrostat, Pasireotide, Pituitary adenoma

UAE Patient’s (Pituitary) Brain Tumour Removed Through Nostrils

Dubai: A 34-year-old patient working as a crane operator has undergone a remarkable new procedure of surgery at Thumbay Hospital, Dubai, that facilitated the removal of a brain tumour through the nostrils.

The patient, Mehnaj Khan, a Pakistani crane operator, underwent endoscopic trans-nasal trans-sphenoidal surgery in September, where the tumour was removed through the nose by endoscopic surgery without any cut or stitches on the skin. The father of five children has now made a full recovery, with improved vision, a hospital spokesperson said.

Khan first noticed something was wrong when his eyesight began to diminish, first the right eye, followed by the left eye. Although he had ignored his frequent bouts of headache for two years, Khan was compelled to visit an ophthalmologist due to vision deterioration. When an eye check-up revealed nothing was wrong, he was referred to to Thumbay Hospital, where an MRI scan of the brain revealed that he had a large tumour in the pituitary gland, pressing on the optic apparatus of brain and also hypothalamus, a very vital part of brain. This tumour was pressing on his optic nerves, causing him to slowly lose his sight.

Dr. Ishwar Chandra Premsagar, consultant neurosurgeon at Thumbay Hospital who operated on Khan, said: “Conventionally, such operations require surgeons to open the skull — a procedure known as a craniotomy. Alternatively, affected portions of the brain are reached via major incisions in the side of the face or inside the mouth, leaving behind major scars of the surgery. However, the patient’s tumour was removed by suctioning it out through his nose.”

An ear nose and throat (ENT) surgeon and an eye surgeon were consulted to plan the surgery and save further deterioration of vision while providing a chance for complete recovery.

Khan, who was nearly blind in one eye with the tumour growth, expressed his gratitude to the hospital and the teams of surgeons as he noticed improvement in his vision after the surgery. By the end of the week, he could read too. The patient was very thankful to the team of surgeons.

Dr Premsagar added: “The endoscope provides a close-up view of the pituitary, allowing the surgeon to remove the entire tumour out in one go through the nostrils, causing no disfigurement or damage to the brain. On the other hand, the procedure ensures far less danger of brain damage or stroke, and the patient usually makes a quicker recovery. Although post-surgery, deterioration of vision stops, but one cannot guarantee complete recovery of vision. This patient was lucky as his vision improved, but it may not happen in all patients. Hence, it is extremely important that one should ensure early consultation, diagnosis and surgery to ensure high chances of recovery.”

From http://gulfnews.com/news/uae/health/uae-patient-s-brain-tumour-removed-through-nostrils-1.1933841

Interview with Doc Karen, Pituitary Patient and Cushing’s Advocate

Karen’s Story

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

Additionally, I am working on a Cushing’s documentary. Please like us on Facebook at http://www.facebook.com/Hug.A.Cushie

Thank you for taking the time to read my story!

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!

Helpful Endocrinologist in Pittsburgh, Pennsylvania

Dr. Murray Gordon is an endocrinologist in Pittsburgh, Pennsylvania and is affiliated with multiple hospitals in the area, including Allegheny General Hospital and Washington Hospital. He received his medical degree from Albany Medical College and has been in practice for more than 20 years. Dr. Gordon accepts several types of health insurance, listed below. He is one of 8 doctors at Allegheny General Hospital and one of 3 at Washington Hospital who specialize in Endocrinology, Diabetes & Metabolism.

Dr. Gordon is in private practice and has an  experienced research site that is currently recruiting for a Cushing’s Syndrome Trial.  If interested in this trial, please call Ann at 412-359-5143.

 

420 E North Ave
Suite 205
Pittsburgh, PA 15212

Phone (412) 359-3426

Fax (412) 359-6974

Pituitary dysfunction after traumatic brain injury: are there definitive data in children?

Arch Dis Child doi:10.1136/archdischild-2016-311609

  1. Correspondence toDr Paula Casano-Sancho, Pediatric Endocrinology Unit, Sant Joan de Déu Hospital, Passeig Sant Joan de Déu, Santa Rosa 39-57, Esplugues, Barcelona 08950, Spain; pcasano@hsjdbcn.org
  • Received 14 July 2016
  • Revised 26 October 2016
  • Accepted 27 October 2016
  • Published Online First 21 November 2016

Abstract

In the past decade, several studies in adults and children have described the risk of pituitary dysfunction after traumatic brain injury (TBI). As a result, an international consensus statement recommended follow-up on the survivors. This paper reviews published studies regarding hypopituitarism after TBI in children and compares their results.

The prevalence of hypopituitarism ranges from 5% to 57%. Growth hormone (GH) and ACTH deficiency are the most common, followed by gonadotropins and thyroid-stimulating hormone. Paediatric studies have failed to identify risk factors for developing hypopituitarism, and therefore we have no tools to restrict screening in severe TBI. In addition, the present review highlights the lack of a unified follow-up and the fact that unrecognised pituitary dysfunction is frequent in paediatric population.

The effect of hormonal replacement in patient recovery is important enough to consider baseline screening and reassessment between 6 and 12 months after TBI. Medical community should be aware of the risk of pituitary dysfunction in these patients, given the high prevalence of endocrine dysfunction already reported in the studies. Longer prospective studies are needed to uncover the natural course of pituitary dysfunction, and new studies should be designed to test the benefit of hormonal replacement in metabolic, cognitive and functional outcome in these patients.

From http://adc.bmj.com/content/early/2016/11/21/archdischild-2016-311609.short?rss=1

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