Endoscopic v. Microscopic pituitary surgery

I am learning new things about Cushing's even six years after first seeing the word in print. I did not fully understand the surgical difference and thus possible benefits of endoscopic surgery. For the life of me, I can't remember which I had on my two surgeries, and not much slips by me. I feel like neurosurgeons and even endocrinologists don't emphasize this difference. This made other patients and me believe we were getting the same surgery while at different facilities, but we are not. 

As I continue to determine my next step for treatment after two failed pituitary surgeries and six long years seeking diagnosis and treatment, my mind gets tangled in all the unknowns. I wonder what small change could have led to cure. It might not be helpful, but it does keep me researching and sharing what I find here.

 

Patient's Symptoms Of Cushing's Disease 

Beginning To Abate After 

Endoscopic Pituitary Cure

http://www.medicalnewstoday.com/releases/90154.php

How chronic pain has made me happier

The difficulty in recovering from Cushing's is that for some, it fails to leave us -- despite multiple surgeries or even cortisol-lowering drug therapies. I have room for improvement in this area.

In the article below, Rob Heaton offers an insightful look into chronic pain, and he captures the feelings and emotions surrounding those issues well and turns them into happiness.

When Rob Heaton say chronic pain is like mental illness, I want to add the uncured Cushing's often causes chronic pain and mental illness.

I'll share this short excerpt with you, then please read the entire piece regarding how Rob got happy with chronic pain.

"Chronic pain is like mental illness. It is a squeamish, taboo class of affliction that few people know how to deal with, so you and others dance around the issue and you don't have to admit to any fragility."

How chronic pain has made me happier | Robert Heaton

http://lifehacker.com/5991778/

http://robertheaton.com/

Cortisol and Tinnitus

I had my second pituitary tumor resection surgery done at MD Anderson Cancer Center on April 20, 2011. My ears have been ringing with tinnitus ever since. My first evening I awoke after being in recovery, I asked my husband to close the curtains to block out the light and try to be quiet. All sound was bothering me. I woke a little later to see my mother and two sisters whispering in the room. They had come to see me after surgery and my husband relayed my requests. When i returned home, my husband hammered blankets across our bedroom windows to block out sunlight and noise. It was nearly blacked out, and it was my favorite part of the house and vital to my recovery after surgery.

Even today though, I don't like a lot of noise or light in the house. My windows are covered with different blankets but still blacked out. While my husband is at work, I keep the TV off. I hate all the chattering and noise from commercials. I don't listen to music in the car anymore. It's too noisy. I hate it. Yes, this classically-trained-vehicle-singer no longer likes it or does it. My radio is off while on the road.

Since my surgery, for nearly two years, I

have faced tinnitus on a daily basis--loud nonstop buzzing. It is not pulsatile with my heart beat (like another cause of tinnitus). It is not localized in my ears. It is difficult to describe, but I feel like I am wearing a headband that buzzes. I hear the buzzing in both ears, around the top of my head and through my brain. Tonight it is so loud, it sounds like a bug zapper.

I have mentioned my tinnitus to several endocrinologists and neurosurgeons. None have asked follow up questions and none have related it to my fluctuating adrenal hormones. Last week, one stated it was unrelated to the pituitary.

Then I find this article below which states:

"Tinnitus is a frequent, debilitating hearing disorder associated with severe emotional and psychological suffering. Although a link between stress and tinnitus has been widely recognized, the empirical evidence is scant."

Why can't my doctors help me?  Why don't they know what I stumble across on the Internet as medical fact?  Why must I continue to put the pieces together for them to see the diagnostic picture? The Art of Diagnosis is not only exhausting me; it is draining my life light right out of me.

When will someone sweep me off my crippled feet and discover the treatment that will return me to my vibrant self?

************

BMC Ear, Nose and Throat Disorders 2012, 12:4 doi:10.1186/1472-6815-12-4

Cortisol suppression and hearing thresholds in tinnitus after low-dose dexamethasone challenge

Veerle L Simoens^1,2,3 and Sylvie Hébert^3,4,5*

• * Corresponding author: Sylvie HébertSylvie.hebert@umontreal.ca

Background

Tinnitus is a frequent, debilitating hearing disorder associated with severe emotional and psychological suffering. Although a link between stress and tinnitus has been widely recognized, the empirical evidence is scant. Our aims were to test for dysregulation of the stress-related hypothalamus-pituitary adrenal (HPA) axis in tinnitus and to examine ear sensitivity variations with cortisol manipulation.

Methods

Twenty-one tinnitus participants and 21 controls comparable in age, education, and overall health status but without tinnitus underwent basal cortisol assessments on three non-consecutive days and took 0.5 mg of dexamethasone (DEX) at 23:00 on the first day. Cortisol levels were measured hourly the next morning. Detection and discomfort hearing thresholds were measured before and after dexamethasone suppression test.

Results

Both groups displayed similar basal cortisol levels, but tinnitus participants showed stronger and longer-lasting cortisol suppression after DEX administration. Suppression was unrelated to hearing loss. Discomfort threshold was lower after cortisol suppression in tinnitus ears.

Conclusions

Our findings suggest heightened glucocorticoid sensitivity in tinnitus in terms of an abnormally strong glucocorticoid receptor (GR)-mediated HPA-axis feedback (despite a normal mineralocorticoid receptor (MR)-mediated tone) and lower tolerance for sound loudness with suppressed cortisol levels. Long-term stress exposure and its deleterious effects therefore constitute an important predisposing factor for, or a significant pathological consequence of, this debilitating hearing disorder.

******

FREE:  The electronic version of this article is the complete one and can be found at:

http://www.biomedcentral.com/1472-6815/12/4

Reoccurrence: A Cushie's Worst Nightmare

Hooray. You somehow heard the word

Cushing's. Someone finally ran the right tests at the right time. You finally got some highs in cortisol and low ACTH (adrenal tumor) or high ACTH (pituitary tumor). A little spot doesn't light up on your mri ("hypointensity") and it is suspicious for a tumor. Ah ha. This is your surgical target.You finally found a genius neurosurgeon but s/he is three states away from you. You organize coverage for the house and kids while your parents and spouse go off to surgery with you. You are finally getting a surgery. You can believe it is finally happening. You wonder if you will every make it out alive and in what condition, what cortisol condition. 

Within a week or a few months, you start suspecting a reoccurrence. This is so unfair. You had surgery yet you still have Cushing's. Returning symptoms don't lie. Lab values don't lie. Doctors even neurosurgeons don't often know what to do with you-- they said they got all the tumor out, so... ?  They don't understand why the labwork shows high cortisol and high ACTH, I mean, they removed pituitary tumor out of your head!

This is one of many moments of true despair in a Cushie's life.

Every Cushing's patient worries about it, and most doctors deny it even is possible. "One surgery will remove the tumor and you'll be back to normal. No problem."  

Yeah, we wish.

This article gives some parameters for

post op ACTH levels - not just cortisol -  that may indicate a cure versus the dreaded reoccurrence. 

All Cushies study articles like this, hoping that their post op numbers fall within the magical range of cured Cushies. We are looking for hope even when there is none to be found.

Note: this is a small study with only 55 patients. Not a large sample size, but hey. Maybe they are on to something.

------------------

Recurrences of ACTH-Secreting Adenomas After Pituitary Adenomectomy Can Be Accurately Predicted by Perioperative Measurements of Plasma ACTH Levels

• Received November 15, 2012.
• Accepted February 4, 2013.

• Copyright © 2013 by The Endocrine Society
• 
  

 Authors

1. Dima Abdelmannan,
2. Joumana Chaiban,
3. Warren R. Selman and
4. Baha M. Arafah

1. Division of Clinical and Molecular Endocrinology, Department of Neurological Surgery, University Hospitals Case Medical Center, Louis Stokes Cleveland Veterans Medical Center And Case Western Reserve University, Cleveland, Ohio 44106

1. Address all correspondence and requests for reprints to: Baha M. Arafah, MD, Division of Clinical and Molecular Endocrinology, University Hospitals Case Medical Center, 11100 Euclid Avenue, Cleveland, Ohio 44106. E-mail:baha.arafah@case.edu.

Abstract

Background: Adenomectomy is the treatment of choice for ACTH-secreting adenomas. Although the development of ACTH deficiency immediately after adenomectomy suggests surgical success, disease recurrence was reported in patients who developed hypocortisolism postoperatively. In the current study, we examined the value of measuring perioperative plasma ACTH and cortisol levels in predicting disease recurrence of patients with ACTH-secreting adenomas.

Methods: Consecutive patients (n = 55; 41 females, 14 males) with clinical, biochemical, and histological documentation of ACTH-secreting adenomas were investigated after pituitary adenomectomy. All patients were followed with clinical monitoring and frequent measurements of plasma ACTH and serum cortisol levels, and none received glucocorticoids unless or until they developed symptoms of adrenal insufficiency or when their serum cortisol levels were ≤3 μg/dL.

Results: Postoperative serum cortisol levels reached ≤3 μg/dL in 46 of 55 and were ≥4 μg/dL in the remaining 9. Simultaneously measured plasma ACTH levels in the latter 9 patients were >40 ng/L when the serum cortisol reached its nadir. In contrast, among the 46 patients who had serum cortisol levels of ≤3 μg/dL, plasma ACTH levels measured simultaneously were ≤20 ng/L in 38 of 46 and >20 ng/L in the remaining 8. During a mean follow-up period of nearly 7 years, patients who had a nadir plasma ACTH of >20 ng/L developed recurrences even though their postoperative serum cortisol levels were ≤3 μg/dL.

Conclusions: Despite profound hypocortisolemia after adenomectomy, a simultaneously measured plasma ACTH level of >20 ng/L in the perioperative period is highly predictive of future recurrence of ACTH-secreting adenomas.

• Received November 15, 2012.
• Accepted February 4, 2013.

• Copyright © 2013 by The Endocrine Society

1. Published online before printFebruary 28, 2013, doi:10.1210/jc.2012-3910 The Journal of Clinical Endocrinology & Metabolism February 28, 2013 jc.2012-3910

http://m.jcem.endojournals.org/content/early/2013/02/28/jc.2012-3910.abstract

Persistent Cushing's

Treatment of Cushing's Disease if Surgery Fails

"Bilateral adrenalectomy is usually reserved and employed as a last resort when all else has failed and the patient is in grave danger due to the consequences of high cortisol levels. However, the success and relatively low risk of complications of laparoscopic bilateral adrenalectomy prompts us to reconsider our attitudes towards adrenalectomy in patients with residual and recurrent Cushing's disease. Perhaps adrenalectomy should be employed earlier in the course of treatment of patients with refractory Cushing's disease."

Guidelines for Doctors and their Patients who have Residual Cushing's Disease

Lewis S. Blevins, Jr. MD and Gwen Stanhope, PA-C

California Center for Pituitary Disorders at University of California, San Francisco 

http://ccpd.ucsf.edu/Patient%20guide%20re%20residual%20Cushing's%20Syndrome.pdf

Patient's Symptoms Of Cushing's Disease Beginning To Abate After Endoscopic Pituitary Cure

Another patient's tale of ofd symptoms, misdiagnosis, and surgical path in hopes for a cure.

Thanks for sharing your story, Kathie.

http://www.medicalnewstoday.com/releases/90154.php

These articles about pituitary tumor tissue located outside the pituitary really make me suspicious about what could be source of my uncured Cushing's.

Extrapituitary Parasellar Microadenoma in Cushing's Disease

https://pubmed.ncbi.nlm.nih.gov/10443699/

The Science of Stress

This Oprah article could easily be entitled: 

The Science of Stress:

5 Things Cortisol is Doing to Your Body

It is all here, in black and white. 

Yet we Cushies suffer in a waiting game for treatment--whether it is our first, second, third, or FOURTH (mine) line of treatment. 

Our bodies are breaking down. 

We are literally losing our minds -- cognitively and emotionally -- as we live each day in a broken body with no end date to look forward to, no time limit to endure. The struggling and suffering is endless. It is heartbreaking.

*****************

The Science of Stress: 5 Things Worrying Is Doing to Your Body
http://www.oprah.com/spirit/Science-of-Stress-What-Stress-Does-to-Your-Body

Loneliness impacts the human body like physical stress

Many Cushies long for a unflinching, strong, support structure that won't let us fall down while we are sick. I believe, actually, that any person facing medical hardships and uncertainty in health revert to a scared person whose best chance to thrive is with many hands to hold. 

Cushies know that many of us do not have these support systems in place. We cry and wish it were different. We reach out for help, and help is not given. Everyone has their own life to live, even parents, siblings, and friends, and maybe that makes stopping to really help and get involved with a sick person difficult. Time has run out for all families.

I just learned that:

 "Loneliness impacts the human body 

      like physical stress."

I was shocked. I often feel forgotten, lonely, isolated, due to hormonal

imbalances but all the lack of community

support. I cried. How will we ever win? 

The Cushing's destroys every aspect of our lives, and people around us get compassion fatigue. After six years with little patient improvement ( prognosis: negative, for the Seinfeld fans), it is difficult for most to stay involved. Their compassion fatigues and their care can runs out of gas.

After reading this article, I'd like to take a moment to say:

It is not my fault I am sick.

It is not my fault I have reoccurring  tumors in my brain and that I am now facing a third surgery in hopes of beating Cushing's.

It is not my fault that I am no longer the worker, friend, wife, daughter, cousin, sister or aunt that I once was, and that you all still want me to be. I have mourned the loss of my self and my spirit every day since from March 2007, when I first discovered my Cushing's diagnosis. That has been 2,160 days of loneliness.  I also mourn my loss of being about to be the kind of friend and family I had been previously. That guilt creeps in, too. In the end, though, I remain lonely and forgotten.

-- Loneliness impacts the body like physical stress. 

-- Cushing's patients have excess cortisol, which hampers all efforts to control and regulate stress.

-- Lack of emotional support leaves Cushies lonely.

-- Loneliness becomes another source of stress that a Cushie's bodies can not process.

Poor support systems actually lower a Cushie quality of life when Cushies feel isolated, lonely, and forgotten.

*-*-*-*

I'll be blunt. If you are not involved in the support or care of your Cushie loved one, you are contributing to their loneliness, and hastening their deaths. 

On the Cushie's death certificate, it could say "primary cause is Cushing's; secondary cause of death is loneliness."

Now what steps will you take to make sure your Cushie doesn't feel forgotten, isolated, and lonely?

Call and ask. Call and care.

How Loneliness Can Harm Your Health
http://www.huffingtonpost.com/douglas-labier/loneliness-health_b_2574810.html

Sent via Flipboard

New Orphan Drug Approved for Cushing's

FDA NEWS RELEASE

For Immediate Release: Dec. 14, 2012

Media Inquiries: Morgan Liscinsky, 301-796-0397; morgan.liscinsky@fda.hhs.gov 

Consumer Inquiries: 888-INFO-FDA

FDA approves Signifor, a new orphan drug for Cushing's disease

The U.S. Food and Drug Administration today approved Signifor (pasireotide diaspartate) injection for the treatment of Cushing's disease patients who cannot be helped through surgery.

Cushing's disease is caused by over-production of cortisol, a hormone made by the adrenal glands. A tumor in the pituitary gland leads to overstimulation of the adrenal gland, which results in excess cortisol production. Cortisol regulates many important functions in the body, including response to stress and injury. Patients with Cushing's disease may have increased weight, glucose intolerance or diabetes, high blood pressure, easy bruising, and increased risk for infections.

 

"Although surgery tends to be first line therapy to treat Cushing's disease, Signifor is a new treatment option for patients when surgery hasn't worked or isn't an option," said Mary Parks, M.D., director of the Division of Metabolism and Endocrinology Products in the FDA's Center for Drug Evaluation and Research.

The safety and effectiveness of Signifor were evaluated in a clinical trial of 162 Cushing's disease patients. Trial participants were randomly chosen to receive one of two dose levels of Signifor over a six-month treatment period. Some patients who safely responded to the medication where allowed to continue treatment. Signifor resulted in decreased cortisol levels as measured in urine collected over a 24-hour period. This reduction was seen as early as one month after starting treatment. About 20 percent of patients in the clinical trial were able to reduce urine cortisol levels into the normal range.

Signifor caused increases in blood sugar levels, which could be detected as early as two weeks after starting treatment. Continued treatment caused or worsened diabetes in some patients; therefore, patients need to be carefully monitored for this side effect and be treated appropriately with anti-diabetic therapies, including insulin.

The FDA is requiring three postmarketing studies for Signifor: a clinical trial to assess high blood sugar (hyperglycemia) management; a long-term prospective observational cohort study (registry) of patients with Cushing's disease treated with Signifor; and focused safety monitoring for reports of serious hyperglycemia, acute liver injury, and adrenal insufficiency.

Signifor is administered under the skin (subcutaneously) twice daily, and will be dispensed with a Medication Guide, including instructions for patients and caregivers that describe the risks and adverse reactions people should be mindful of when using the product.

The most common adverse reactions observed in the clinical trial included hyperglycemia, diarrhea, nausea, abdominal pain, and gallstones.

Signifor is manufactured by Novartis Pharma Stein AG, Stein, Switzerland.

For more information:

• FDA Approved Drugs: Questions and Answers 
• FDA: Drug Innovation  

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation's food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

#

http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm332351.htm

--------

See http://www.signifor.us/index.jsp for more information.

Spotlight on Cushing's: Lori on Dr Oz

Be sure to watch Lori's heartbreaking 

and informative segments 

on the Dr Oz show.

Thank you Dr Oz!

Out of Control Obesity: 

One Woman's Struggle with 

Cushing's Disease

http://www.doctoroz.com/videos/out-control-obesity-one-womans-struggle-cushings-disease-pt-1

My Friend Lori Featured in News

Doctors, Patient From Ohio State Wexner Medical Center To Be Featured On 'Dr. Oz' Show

Wednesday December 19, 2012 5:39 PM

COLUMBUS, Ohio - An innovative operation conducted at The Ohio State University Wexner Medical Center will be featured on "The Doctor Oz Show."

Doctors used the operation to treat Cushing's Disease, an illness Lori Genser Burkhoff has suffered from for most of her life.

Cushing's Disease is caused by a tumor on the pituitary gland, the master gland of the body. Burkhoff was diagnosed when she was 14, when she gained 60lbs in a few months.

"The shape of my face was sort of as if somebody injected air into it. I was weak. I was losing my hair. I was just falling apart," Burkhoff said.

Doctors operated on her pituitary gland three times, but the problems persisted.

"Having a fourth pituitary surgery is sort of unheard of in the medical community, and there are very few doctors in the country who would even attempt to do this," Burkhoff said.

Then Burkhoff, a New York resident, heard of a new way to remove brain tumors, pioneered at the OSU Wexner Medical Center.

Instead of cutting open her head to reach the tumor and remove it, doctors went in through her nose. A brain surgeon worked through one nostril, while Dr. Ricardo Carrau, an ear nose and throat doctor, worked through the other.

"The advantage of doing is through the nose is you have an actual corridor. The nose has some air space. The sinuses have some air space," Carrau said. "So if you can connect the two, you can get to the pituitary gland."

Carrau said that avoiding incisions during surgery helps patients heal faster.

"They recover incredibly better than what they were doing before," Carrau said.

Burkhoff needed two surgeries. CBS' Dr. Oz was there to see for himself how it was done.

Now Burkhoff said she plans to come home to her husband and daughter.

"I'm hoping for a real start to 'Act Two,'" she said.

Doctors removed Lori's entire pituitary gland and part of the nearby bone to avoid a return of Cushing's Disease. Since the surgery, Lori has lost 30 pounds.

The Dr. Oz Show will have Lori's full story Thursday at 4 p.m. on 10TV.

 

©2012 by 10TV.com. All rights reserved. 

http://www.10tv.com/content/stories/2012/12/19/columbus-woman-to-appear-dr-oz-cushings-disease.html

Cushing's to be Featured in National News

In September 2012, Dr. Oz from the Dr Oz Show joined my dear friend Lori and her amazing surgical team for her 4th (and ultimately 5th) brain surgery in Columbus, Ohio.  Lori has been battling Cushing's for 20 years.  

Please tune in to/ DVR this network television show this Thursday, December 20 to learn more about Cushing's. Check your local listings.

(Show lists the topics as sextuplets and Marlo Thomas/ cancer).

From the Dr Oz Show:

"Can you imagine gaining so much weight, despite a healthy lifestyle, that it would eventually lead you to die from obesity?  It's a real illness, and it's called Cushing's Disease.  Dr. Oz met Lori, a woman desperate to survive this devastating and rare condition, and he joined her in the operating room as she underwent the dangerous surgery that could end her life or improve it forever. Dr. Oz shares his journey and he introduces Dr. Daniel Prevedello from Ohio State University Medical Center who performed Lori's ground-breaking procedure."

Lori has also created a web site crushingcushings.com to help share her story. 

I hope you will be able to watch. This is a big day in Cushie World.

Melissa

Australian Pituitary Foundation

Our friends in Hobart, Tasmania, Australia gathered to discuss the pituitary gland today.

Click here for more program details.

http://www.gpsouth.com.au/Consumers/News/Pituitary%20in%20Tassie.pdf

Click here for brochure:
http://www.pituitary.asn.au/portals/0/pdfs/resources/APF%20Brochure.pdf

Images courtesy of Australian Pituitary Foundation. 

http://www.pituitary.asn.au/  

All rights reserved.

Therapy of Adrenal Insufficiency

This new article from our friends in Italy is a comprehensive yet easy-to-read look at adrenal insufficiency. I find this information so valuable in understanding the mechanics of sufficient and timely cortisol replacement for Cushies post-op pituitary surgery or, for me, combined with nighttime ketaconazole as a medical therapy for persistent Cushing's disease. I applaud the authors for their wondrous graphs and tables highlighting the most important aspects of cortisol control. In particular, my heart sang when reading about the future of cortisol replacement section. Hope is on the way.

*******

Therapy of adrenal insufficiency: an update

• Alberto Falorni, 
• Viviana Minarelli, 
• Silvia Morelli

Endocrine

November 2012

Abstract

Adrenal insufficiency may be caused by the destruction or altered function of the adrenal gland with a primary deficit in cortisol secretion (primary adrenal insufficiency) or by hypothalamic-pituitary pathologies determining a deficit of ACTH (secondary adrenal insufficiency). The clinical picture is determined by the glucocorticoid deficit, which may in some conditions be accompanied by a deficit of mineralcorticoids and adrenal androgens. The substitutive treatment is aimed at reducing the signs and symptoms of the disease as well as at preventing the development of an addisonian crisis, a clinical emergency characterized by hypovolemic shock. The oral substitutive treatment should attempt at mimicking the normal circadian profile of cortisol secretion, by using the lower possible doses able to guarantee an adequate quality of life to patients. The currently available hydrocortisone or cortisone acetate preparations do not allow an accurate reproduction of the physiological secretion pattern of cortisol. A novel dual-release formulation of hydrocortisone, recently approved by EMEA, represents an advancement in the optimization of the clinical management of patients with adrenal insufficiency. Future clinical trials of immunomodulation or immunoprevention will test the possibility to delay (or prevent) the autoimmune destruction of the adrenal gland in autoimmune Addison's disease.

View the complete article in .pdf form here:

http://download.springer.com/static/pdf/580/art%253A10.1007%252Fs12020-012-9835-4.pdf?auth66=1354599590_c8e2d487dd479af815146acdc2d7e633&ext=.pdf

or view HTML:

http://link.springer.com/article/10.1007%2Fs12020-012-9835-4

Aggressive Cushing's

I have been so sick for the 75 days with adrenal insufficiency. As a result, I have been unable to determine the right ketoconazole dose at 8 pm and 10 pm or stabilize my Cortef/ hydrocortisone replacement at 8 am. Only in the last few days have I even thought of looking to the medical journals for more knowledge. Today, I share this full article (pdf).

Journal of Oncololgy. 2012; 2012: 685213.

Published online 2012 August 9.

Management Strategies for Aggressive Cushing's Syndrome: From Macroadenomas to Ectopics

Carlotta Pozza, Chiara Graziadio, Elisa Giannetta, Andrea Lenzi, and Andrea M. Isidori^*

Abstract

Cushing's syndrome (CS) is a rare but severe clinical condition represented by an excessive endogenous cortisol secretion and hence excess circulating free cortisol, characterized by loss of the normal feedback regulation and circadian rhythm of the hypothalamic-pituitary axis due to inappropriate secretion of ACTH from a pituitary tumor (Cushing's disease, CD) or an ectopic source (ectopic ACTH secretion, EAS). The remaining causes (20%) are ACTH independent. As soon as the diagnosis is established, the therapeutic goal is the removal of the tumor. Whenever surgery is not curative, management of patients with CS requires a major effort to control hypercortisolemia and associated symptoms. A multidisciplinary approach that includes endocrinologists, neurosurgeons, oncologists, and radiotherapists should be adopted. This paper will focus on traditional and novel medical therapy for aggressive ACTH-dependent CS. Several drugs are able to reduce cortisol levels. Their mechanism of action involves blocking adrenal steroidogenesis (ketoconazole, metyrapone, aminoglutethimide, mitotane, etomidate) or inhibiting the peripheral action of cortisol through blocking its receptors (mifepristone "RU-486"). Other drugs include centrally acting agents (dopamine agonists, somatostatin receptor agonists, retinoic acid, peroxisome proliferator-activated receptor γ"PPAR-γ" ligands) and novel chemotherapeutic agents (temozolomide and tyrosine kinase inhibitors) which have a significant activity against aggressive pituitary or ectopic tumors.

---

Articles from Journal of Oncology are provided here courtesy of Hindawi Publishing Corporation

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3425913/pdf/JO2012-685213.pdf