What would Harvey Cushing say about Cushing’s disease today?

Posted on April 3, 2014 by MaryO

harvey-book

(BPT) – More than 80 years ago renowned neurosurgeon, Dr. Harvey Cushing, discovered a tumor on the pituitary gland as the cause of a serious, hormone disorder that leads to dramatic physical changes in the body in addition to life-threatening health concerns. The discovery was so profound it came to be known as Cushing’s disease. While much has been learned about Cushing’s disease since the 1930s, awareness of this rare pituitary condition is still low and people often struggle for years before finding the right diagnosis.

Read on to meet the man behind the discovery and get his perspective on the present state of Cushing’s disease.

* What would Harvey Cushing say about the time it takes for people with Cushing’s disease to receive an accurate diagnosis?

Cushing’s disease still takes too long to diagnose!

Despite advances in modern technology, the time to diagnosis for a person with Cushing’s disease is on average six years. This is partly due to the fact that symptoms, which may include facial rounding, thin skin and easy bruising, excess body and facial hair and central obesity, can be easily mistaken for other conditions. Further awareness of the disease is needed as early diagnosis has the potential to lead to a more favorable outcome for people with the condition.

* What would Harvey Cushing say about the advances made in how the disease is diagnosed?

Significant progress has been made as several options are now available for physicians to use in diagnosing Cushing’s disease.

In addition to routine blood work and urine testing, health care professionals are now also able to test for biochemical markers – molecules that are found in certain parts of the body including blood and urine and can help to identify the presence of a disease or condition.

* What would Harvey Cushing say about disease management for those with Cushing’s disease today?

Patients now have choices but more research is still needed.

There are a variety of disease management options for those living with Cushing’s disease today. The first line and most common management approach for Cushing’s disease is the surgical removal of the tumor. However, there are other management options, such as medication and radiation that may be considered for patients when surgery is not appropriate or effective.

* What would Harvey Cushing say about the importance of ongoing monitoring in patients with Cushing’s disease?

Routine check-ups and ongoing monitoring are key to successfully managing Cushing’s disease.

The same tests used in diagnosing Cushing’s disease, along with imaging tests and clinical suspicion, are used to assess patients’ hormone levels and monitor for signs and symptoms of a relapse. Unfortunately, more than a third of patients experience a relapse in the condition so even patients who have been surgically treated require careful long-term follow up.

* What would Harvey Cushing say about Cushing’s disease patient care?

Cushing’s disease is complex and the best approach for patients is a multidisciplinary team of health care professionals working together guiding patient care.

Whereas years ago patients may have only worked with a neurosurgeon, today patients are typically treated by a variety of health care professionals including endocrinologists, neurologists, radiologists, mental health professionals and nurses. We are much more aware of the psychosocial impact of Cushing’s disease and patients now have access to mental health professionals, literature, patient advocacy groups and support groups to help them manage the emotional aspects of the disease.

Learn More

Novartis is committed to helping transform the care of rare pituitary conditions and bringing meaningful solutions to people living with Cushing’s disease. Recognizing the need for increased awareness, Novartis developed the “What Would Harvey Cushing Say?” educational initiative that provides hypothetical responses from Dr. Cushing about various aspects of Cushing’s disease management based on the Endocrine Society’s Clinical Guidelines.

For more information about Cushing’s disease, visit www.CushingsDisease.com or watch educational Cushing’s disease videos on the Novartis YouTube channel at www.youtube.com/Novartis.

 

From http://www.jsonline.com/sponsoredarticles/health-wellness/what-would-harvey-cushing-say-about-cushings-disease-today8087390508-253383751.html

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No High-Quality Studies for Cushing’s Drugs

Posted on October 4, 2013 by MaryO

By Salynn Boyles, Contributing Writer, MedPage Today

Reviewed by Zalman S. Agus, MD; Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse Planner

There is a paucity of clinical trial data supporting the efficacy of most drugs used to treat Cushing’s disease, researchers reported.

Just one drug — pasireotide — has been evaluated in a randomized, double-blind trial, but even it was judged by the researchers to have only a ‘moderate’ level of evidence supporting its effectiveness and safety.

The review of the literature evaluating drug treatments for Cushing’s disease, a rare pituitary disorder, is the first to employ a rigorous systematic approach with strict, predefined inclusion criteria and formal analysis of the quality of evidence using an established standard, researcher Monica Gadelha, MD, PhD, of Brazil’s Federal University of Rio de Janeiro, and colleagues wrote in the journal Clinical Endocrinology.

“This systematic review indicates that the majority of medical therapies currently used in the treatment of Cushing’s disease are supported by a low level of evidence,” the researchers wrote. “Further well-designed prospective studies of medications in Cushing’s disease would help to inform clinical practice further.”

Cushing’s disease is the most common form of endogenous Cushing’s syndrome, a hormonal disorder resulting from persistent exposure to abnormally high levels of the hormone cortisol. In the case of Cushing’s disease, the cortisol is secreted by a pituitary adenoma.

Prolonged exposure to high levels of cortisol raises the risk for diabetes mellitus, cardiovascular disease, osteoporosis and nephrolithiasis. Patients with persistent Cushing’s disease have a 3- to 5-fold higher mortality than the general population.

Surgery to remove the pituitary adenoma is the first-line treatment for Cushing’s disease in the U.S., and when the procedure is performed by an experienced surgeon, remission rates in patients with smaller tumors range from 65% to 90%. The long-term remission rate is lower, however, because many patients develop recurrent disease.

Several medical therapies are widely used to treat patients who are not candidates for surgery or who experience relapse following surgery.

Novartis Oncology’s somatostatin analog drug pasireotide (Signifor) became the only drug approved for this indication in December of last year. And the progesterone-blocking drug mifepristone, best known as the abortion pill once called RU-486, was approved in February of 2012 for the treatment of Cushing’s disease-associated hyperglycemia.

Other drugs — including metyrapone, mitotane, cabergoline, and ketoconazole — are also used off-label in the treatment of Cushing’s, and several have shown better response rates than pasireotide in small studies.

In their systematic review, Gadelha and colleagues identified 15 studies that included at least 10 adults with Cushing’s disease and reported treatment responses as the proportion of patients reaching a specified definition of response. Studies examining combinations of medications were excluded from the analysis, as were studies with indefinite diagnoses of Cushing’s disease.

For medications other than mifepristone, studies had to report the proportion of patients with normalized urinary free cortisol (UFC), midnight salivary cortisol or midnight serum cortisol.

The studies were scored according to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system for rating quality of evidence.

Ten of the 15 included studies reported outcomes specifically for patients with Cushing’s disease and the remaining five included patients with other forms of Cushing’s syndrome.

The researchers reported that:

  • Pasireotide was the only treatment assessed in a randomized trial, and it was judged to have a ‘moderate’ level of evidence supporting its use. Response rates from three prospective studies of the drug ranged from 17% to 29%.
  • The remaining medications were supported by a ‘low’ or ‘very low’ level of evidence.
  • The highest response rates were reported in a small retrospective studies of metyrapone (75%, one study) and mitotane (72%, one study).
  • Response rates were 25% to 50% for cabergoline (four studies) and 45% for ketoconazole (one study).
  • Among studies that included patients with other forms of Cushing’s syndrome, response rates were 53% to 88% for ketoconazole (three studies), 70% for mitotane (one study), 57% for metyrapone (one study), and 38% to 60% for mifepristone (one study).

 

But the researchers urged caution in comparing the drugs, citing the variability in the study designs and patient selection endpoints, among other limitations in the research literature.

“The wide variation in the time-frames over which response to treatment was measured makes comparison a challenge,” they wrote. “Comparison of response rates reported in the included studies is also complicated by the variation in methodology used to assess response.”

They noted that well-designed clinical trials are needed to determine which drugs or drug combinations are most effective in the treatment of Cushing’s disease patients.

“Combinations of medical therapies with different modes of action might aid in optimizing the balance of efficacy and safety,” they wrote. “Investigational medications, such as bexarotene, LC1699 and retinoic acid, may help to expand the range of future therapeutic options.”

Maria Fleseriu, MD, who was not involved in the review, agreed that more drug treatments are needed. But she added that Cushing’s patients today have many more drug options than they did just a few years ago.

Fleseriu directs the Pituitary Center at Oregon Health & Science University, where she is an associate professor of medicine and endocrinology.

In a recently published analysis, Fleseriu wrote that pituitary-targeted medical therapies should soon play a more prominent role in treating Cushing’s disease, and may become first-line treatments when surgery fails or is contraindicated.

“We now have one drug approved for Cushing’s and another approved for diabetes symptoms associated with the disease,” she told MedPage Today. “We are moving forward, but we are not where we would like to be. Combination therapy is probably where we are heading, but further studies are needed.”

Financial support for this research was provided by Novartis Pharmaceuticals.

Researcher Monica Gadelha reports receiving speaker fees and participating on advisory boards for Novartis. Gadelha and co-author Leonardo Vieira Neto were investigators in Novartis’ clinical trials of pasireotide.

 

From http://www.medpagetoday.com/Endocrinology/GeneralEndocrinology/42043

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Johns Hopkins’ Dr. Alfredo Quinones-Hinojosa

Posted on August 30, 2013 by MaryO

Johns Hopkins’ Dr. Alfredo Quinones-Hinojosa writes:

In 2006, the ABC show “Hopkins” aired. Episodes 1 and 7 featured my patients. I would like to share these videos with you and encourage you to view them to witness what it is like inside the hospital. The emotions are real and many people who follow this page have experienced this first hand. One day we will find a cure for brain cancer.

Episode 1:

Episode 7:

See all:

 

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One Of A Kind: Despite use of only one lung, right guard Dillon Reagan helps solidify Jacks’ offensive line

Posted on August 28, 2013 by MaryO

The Big Uglies. The Big Nasties. The Hogs.

All terms used to describe a football team’s offensive line.

More often than not, it takes a special breed of player to be willing to do battle in the trenches.

Humboldt State right guard Dillon Reagan can without a doubt be bestowed with the title of special.

From overcoming Cushing’s Syndrome — a rare disease which left him with the use of only one lung — to the depression that was associated with the disorder, the Issaquah, Wash. native has definitely taken the road less traveled.

”The hardest part,” Reagan began, “was the first four months. (Doctors) didn’t know what was necessarily wrong with me. I was misdiagnosed as bipolar.”

Reagan displayed the initial symptoms of Cushing’s in 2009 after earning second-team All-State honors as a freshman at College of the Redwoods. A disorder caused by a tumor on one of the endocrine glands, Cushing’s causes a massive secretion of hormones which can affect behavior and physical appearance.

It did that and more to Reagan.

”I had full-ride scholarships taken away,” he said.

A full-body scan revealed a softball-sized tumor wrapped around his heart and left lung. Open heart surgery remedied the situation but his left lung useless.

In the midst of all this, Reagan also developed diabetes.

It would have been quite easy for the 6-foot-3 kid from Washington to call it quits. No one would have blamed him.

But an offensive lineman never quits.

”I never changed my approach,” Reagan said. “It’s a position of dominance and perseverance. Being an offensive lineman helped me get through all that. It helped me not feel sorry for myself.

”It was a long road back to full speed, but, your body reacts to how you push it.”

And push he did.

Reagan hit the weight room and transformed his body — which ballooned to 380 pounds due to Cushing’s — back to the muscular 300-pound frame he showcased his freshman year. He returned to Redwoods for his sophomore campaign and again displayed the skills that made him a Division I commodity.

”I ended up getting All-California,” Reagan said. “And with the use of only one lung.”

Looking to further his football career at the university level, there was really only one option.

”I wanted to go to a good program,” Reagan said. “That clear answer was Humboldt State.”

Reagan noted the close ties Redwoods and Humboldt shared as a deciding factor. His coach at CR was Duke Manyweather, a former HSU player himself. Reagan also sought the guidance of Humboldt State strength and conditioning coach Drew Petersen during his road to physical recovery.

Reagan asked to join Humboldt State as a non-scholarship athlete during the 2012 Spring semester and head coach Rob Smith and his coaching staff were more than happy to have him.

The following season, Reagan showed why.

As a junior, Reagan started 11 games for the Jacks providing a stabilizing force for a unit which paved the way for running backs to gain 2,152 total yards. He also earned second-team all conference honors.

It is amazing how high Reagan has risen after seeing how far he had fallen. An inspiration and uplifting athlete, it is easy to label him special.

Just don’t tell Reagan that.

”It takes me a little longer to warm up and get to game speed. But I don’t want to be treated differently than my teammates,” he said.

Entering his senior season, Reagan is being counted upon to be a stalwart right guard as he is only one of two returning starters (center and good friend David Kulp the other) from last season’s road graders.

Reagan is more than ready.

”As an offensive lineman, you show up every day, no matter what happens outside of practice, no matter what’s going on at home, no matter how beat up you are. You do it again and do it every day,” he said. “We set the tempo for the rest of the practice, rest of the game. If we don’t know up, it’s hard for everyone else to show up.”

Three positions are up for grabs on the Jacks’ front line. Reagan likes what he is seeing from the player stepping up to the plate.

”Start with tackle,” Reagan began, “(Jonathon) Rowe has made tremendous contributions at camp. He’s really growing up for his in a short time. Jonathan Bajet, he’s moving over from the defensive line, and he’s been really neck-and-neck for a starting guard position. David (Kulp), he’s a great guy to play next too, a great guy to have in your corner. It just works. We don’t have to say anything, we know what we’re doing. And (Jarrett) Adams has stepped up a bit. In the last few weeks he’s learned how to play right tackle.”

Humboldt is still knee-deep in competition in preparation for the Sept. 7 season-opening home contest against Simon Fraser. Reagan notes practicing daily against a defensive line which features returners Alex Markarian, Silas Sarvinski and Tommy Stuart, to name a few, helps both the O and D.

”They are adapting to our fast offense,” Reagan said. “You’re only as good as you practice. No one shows up game day and plays good. We challenge each other every day. It gets intense. But it’s all out of competition. Competition is a thing that drives a football team.”

If everything falls into place, all the Jacks’ hard work will result in one thing: Great Northwest Athletic Conference supremacy.

There’s simply no better lasting impression for Reagan.

”A GNAC Championship,” he said. “That puts you down in the books forever, that GNAC Championship.”

Title or not, it’s a pretty safe bet Reagan has already left a lasting impression.

 

Ray Aspuria can be reached evenings at 707-441-0527 or raspuria@times-standard.com. Follow him at twitter.com/AirUpsa707

 

From The Times-Standard

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Improved Quality of Life After Bilateral Laparoscopic Adrenalectomy for Cushing’s Disease

Posted on August 11, 2013 by MaryO
Ann Surg. 2007 May; 245(5): 790–794.
A 10-Year Experience
Sarah K. Thompson, MD,* Amanda V. Hayman, MD, MPH,* William H. Ludlam, MD, PhD,† Clifford W. Deveney, MD,* D Lynn Loriaux, MD, PhD,† and Brett C. Sheppard, MD*

Objective:

To determine long-term quality of life after bilateral adrenalectomy for persistent Cushing’s disease after transsphenoidal pituitary tumor resection.

Summary Background Data:

Bilateral adrenalectomy for symptomatic relief of persistent hypercortisolism appears to be an effective treatment option. However, few studies have examined long-term outcomes in this patient population.

Methods:

Retrospective review of 39 patients treated by bilateral laparoscopic adrenalectomy for Cushing’s disease from 1994 to 2004. Patients completed a follow-up phone survey, including our Cushing-specific questionnaire and the SF-12v2 health survey. Patients then refrained from taking their steroid replacement for 24 hours, and serum cortisol and ACTH levels were measured.

Results:

Three patients died at 12, 19, and 50 months following surgery from causes unrelated to adrenalectomy. The remaining 36 patients all responded to the study questionnaire (100% response rate). Patients were between 3 months and 10 years post-adrenalectomy. We had zero operative mortalities and a 10.3% morbidity rate. Our incidence of Nelson’s syndrome requiring clinical intervention was 8.3%; 89% of patients reported an improvement in their Cushing-related symptoms, and 91.7% would undergo the same treatment again. Twenty of 36 (55%) and 29 of 36 (81%) patients fell within the top two thirds of the national average for physical and mental composite scores, respectively, on the SF-12v2 survey. An undetectable serum cortisol level was found in 79.4% of patients.

Conclusions:

Laparoscopic bilateral adrenalectomy for symptomatic Cushing’s disease is a safe and effective treatment option. The majority of patients experience considerable improvement in their Cushing’s disease symptoms, and their quality of life equals that of patients initially cured by transsphenoidal pituitary tumor resection.

harvey-cushing-memorial

Harvey Cushing first described Cushing’s disease (hypercortisolism caused by an ACTH-secreting pituitary adenoma) in 1912 in his book entitled: The Pituitary Body and its Disorders. Endogenous glucocorticoid excess causes devastating sequelae in the patient, including marked central obesity, facial fullness, proximal muscle weakness, hypertension, diabetes, hypogonadism, osteoporosis, mood disorders, and cognitive impairment.1–4 Transsphenoidal pituitary tumor resection is without dispute the best first line treatment option for these patients. Unfortunately, 10% to 30% of patients will fail to achieve long-term remission of their Cushing’s disease.5 Four treatment options exist for these patients: 1) repeat transsphenoidal resection, 2) medical therapy, 3) radiation therapy, and 4) bilateral laparoscopic adrenalectomy. Optimum treatment or sequence of different treatments has not yet been established in the literature and often presents a considerable challenge to both the patient and the physician.5

Few studies examine long-term outcomes, including quality of life, in patients requiring additional therapy for persistent Cushing’s disease.6,7 At our institution, patients who fail repeated transsphenoidal adenomectomy are offered bilateral laparoscopic adrenalectomy in the hopes of minimizing the adverse effects caused by chronic hypercortisolism.

The purpose of this study was to determine the safety, efficacy, and long-term outcomes in patients who underwent bilateral laparoscopic adrenalectomy for persistent Cushing’s disease. We assessed all patients for biochemical cure of their Cushing’s disease and evaluated their quality of life with both a general and a Cushing-specific questionnaire.

METHODS

Selection of Patients and Variables

After approval from our Institutional Review Board, all patients who underwent a bilateral laparoscopic adrenalectomy for persistent Cushing’s disease were identified from Oregon Health & Science University (OHSU)’s centralized administrative hospital discharge database. As the first laparoscopic adrenalectomy was reported in 1992 by Gagner et al,8 our first patient dates back to November 1994. OHSU is an ideal setting for a study of this nature as there are large neuroendocrine and neurosurgical units subspecializing in Cushing’s disease management. Therefore, patients in this study were accrued from direct referral from these 2 units, and include patients from adjacent and remote states as well as from Oregon. Inclusion criteria included: confirmed diagnosis of Cushing’s disease, minimum of 3 months follow-up, and bilateral laparoscopic adrenalectomy (BLA) done at OHSU. Our surgical technique has been previously reported6 and is the standard transperitoneal approach in lateral decubitus position. Medical records were reviewed to obtain patient demographics, operative reports, pathologic data, and postoperative events.

A total of 39 patients qualified for our study. Their characteristics at study entry are listed in Table 1. The majority of patients were female (34 of 39), and mean age at time of BLA was 41.5 years. Our follow-up ranged from 3 months to 10 years, with a mean follow-up of 3.6 years following BLA. Three patients died at 12, 19, and 50 months after BLA from cardiac failure (1), pneumonia (1), and stroke (1) as reported by Hawn et al.6 These patients were more than 65 years of age at the time of BLA, and their deaths occurred well outside of the perioperative time period. Patients with Cushing’s disease have a high prevalence of atherosclerosis and maintain increased cardiovascular risk even 5 years after cure.2–4

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TABLE 1. Patient Characteristics

The remaining 36 patients all responded to our phone questionnaire (100% response rate). We achieved a 100% response rate by contacting patient’s primary physician, their endocrinologist, and/or their next-of-kin contact (in case of emergency) if a patient was not available at their listed phone number. Thirty-five of 36 patients complied with biochemical testing (97.2% of available study sample). All patients had undergone at least one transsphenoidal pituitary tumor resection, with the mean number of resections calculated at 1.5. Most patients had a time interval of at least 2 years between their last pituitary tumor resection and BLA. Four patients had had failed pituitary irradiation (10.3%).

Study Protocol

Once consented, patients were submitted to a two-step study:

Clinical Study

Patients were asked to complete a two-page phone questionnaire by an independent investigator (A.V.H.) that identified patient’s preoperative and postoperative body mass index (BMI), comorbidities, preoperative and postoperative Cushing’s disease symptoms, and satisfaction with surgery. Cushing’s disease-specific symptoms were subcategorized into 4 categories: physical appearance (9 items), hematologic/immunologic (3 items), comorbidities (3 items), and neuropsychiatric (10 items) (questionnaire available upon request). Patients were asked to describe their symptoms both preoperatively and currently on a linear scale from 1 point (no symptom) to 5 points (extreme symptom). We then calculated the increase or decrease in number of points from preoperatively to the present time. This was reported as a mean increase or decrease in the overall number of points for each category of symptoms. The SF-12v2 questionnaire (QualityMetric Inc, Lincoln, NE) was also administered during the same interview.

Biochemical Study

Patients were instructed to cease their steroid replacement for 24 hours, and then have a morning serum cortisol level drawn to confirm biochemical cure. A serum cortisol level less than 1 μg/dL was considered a “cure.” Any patient who had a level over 1 μg/dL was asked to change their steroid replacement regimen to dexamethasone (0.5 mg orally once a day) and to undergo repeat cortisol level testing. If their serum cortisol levels were still detectable (>1 μg/dL) after continuing on dexamethasone replacement for 3 days, the patients were deemed to have endogenous cortisol production.

Statistical Analysis

SPSS for Windows, version 11.0 (SPSS Inc., Chicago, IL) was used to perform data analysis. Data were expressed as mean (range) or mean ± SD as appropriate. Results from the SF12v2 health survey were compared with published values for the U.S. population using t tests. Postoperative variables associated with an elevated cortisol level were evaluated by bivariate logistic regression.

RESULTS

Surgical outcomes are listed in Table 2. We had no surgical mortalities, and 4 of 39 (10.3%) patients had significant complications, including urosepsis, distal pancreatitis, and 2 conversions to an open procedure. One patient was converted for bleeding from a splenic injury, and the second patient was converted to an open procedure for hepatomegaly and inability to visualize the adrenal vein safely. One patient had a minor vena caval injury requiring only pressure to control. Mean operating time was 273 minutes (excluding 35 minutes of repositioning time), and estimated blood loss was less than 100 mL for 25 of 39 (75.8%) patients. Mean length of stay was 4.2 days. Twenty-seven of 39 (69%) adrenal glands showed diffuse or nodular hyperplasia on pathology, while 9 of 39 (25%) adrenal glands were hypertrophic only. Three adrenal glands (8.3%) were normal on pathology. More than 50% of patients had never experienced an adrenal crisis. Approximately 20% had had one adrenal crisis, and the rest had had more than one episode of cortisol insufficiency.

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TABLE 2. Surgical Outcomes

Nelson syndrome is characterized by: 1) growing residual pituitary adenoma, 2) ACTH concentration >300 mg/dL, and 3) hyperpigmentation of the skin following bilateral adrenalectomy.9,10 Twenty-six of 35 patients (74.3%) had a serum ACTH level less than 300 pg/mL and 9/35 patients (25.7%) had an elevated ACTH level (Table 3). Three of 35 patients (8.6%) had MRI evidence of growing residual pituitary adenoma, and 4 of 36 patients (11.1%) complained of significant skin darkening (and an additional 7 of 36 patients, 19.4%, noted mild skin darkening). In our patient population, 3 of 36 (8.3%) required further pituitary surgery or irradiation for some or all of these components of Nelson syndrome.

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TABLE 3. Nelson’s Syndrome

Postoperative Cushing’s disease symptom resolution postadrenalectomy is listed in Table 4. Thirty-three of 36 patients (92%) experienced weight loss following BLA, with a mean decrease in BMI from 35 to 29.6. The highest mean points improvement in Cushing symptoms was reported for physical appearance and neuropsychiatric complaints, 11.1 and 9.8 points, respectively. Patients also reported some improvement in their hematologic/immunologic complications and systemic comorbidities, 2.8 and 3.1 points, respectively. Twenty-eight of 36 patients (78%) reported a moderate or significant improvement in their symptoms, while 4 of 36 (11.1%) experienced only mild improvement, and 4 of 36 (11.1%) had no improvement or were worse.

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TABLE 4. Postoperative Symptom Resolution

Thirty-one of 36 patients (86.1%) were either satisfied or very satisfied with their BLA (Table 5). Four patients (11.1%) were dissatisfied or very dissatisfied with BLA. An overwhelming 33 of 36 patients (91.7%) said they would undergo the same treatment again if needed. The mean Physical Composite Score for the SF-12v2 was 36 (range, 16–60) compared with 48 for U.S. women 45 to 54 years of age. The mean Mental Composite Score was 45 (range, 14–64) compared with 49 for U.S. women 45 to 54 years of age. Six of 36 patients (16.7%) were above the 50th percentile for U.S. population in physical categories, while 16 of 36 patients (44.4%) were above the 50th percentile in mental categories. Twenty of 36 (56%) and 29 of 36 (81%) patients fell within the top two thirds of the national average for physical and mental composite scores, respectively. By comparison with another chronic disease, namely diabetes, 23 of 36 (64%) and 28 of 36 (78%) of the BLA patients fell within the top two thirds of the diabetic patient average for physical and mental composite scores, respectively.

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TABLE 5. Postoperative Quality of Life

Postoperative biochemical results are listed in Table 6. Twenty-seven of 34 patients (79.4%) had no detectable endogenous cortisol after ceasing exogenous steroids for 24 hours. Seven of 34 patients (20.6%) were confirmed to have endogenous cortisol production with a detectable serum cortisol level after both cessation of steroids for 24 hours and after 3 days of dexamethasone.

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TABLE 6. Postoperative Biochemical Outcomes

DISCUSSION

The main objective of this study was to evaluate quality of life (QOL) after bilateral laparoscopic adrenalectomy for persistent Cushing’s disease. Thirty-nine patients have had this therapy for chronic hypercortisolism over the past 10 years at OHSU and, of those patients still alive, we had a 100% response rate. To our knowledge, this is the largest series of long-term follow-up of patients with persistent Cushing’s disease treated by BLA. The degree of willingness of this patient group to assist the medical community in studying this disease likely reflects the impact Cushing’s disease has had on these patients and the enormity of the decisions they have had to make regarding their health over the course of their disease.

Our center published preliminary QOL results on our initial 18 patients.6 In this study, there was a 66% response rate, and scores on all 8 parameters of the SF-36 were significantly reduced from general population values. We significantly improved our response rate by doing telephone surveys as opposed to mail-out questionnaires, and by contacting all those necessary to locate a “missing patient.” In the present study, we though it would be more representative to compare our patient’s SF-12 values to U.S. women 45 to 54 years of age as well as to patients with diabetes (a patient population also with a chronic disease). In both cases, Cushing’s disease patients that are treated with BLA have significant improvement in their Cushing-related problems and most have regained a relatively normal QOL. Furthermore, we created a Cushing-specific symptom questionnaire as there is no disease-specific QOL questionnaire available for Cushing’s disease. This Cushing-specific questionnaire shows that 89% of patients experience improvement in their symptoms after BLA and, consequently, marked improvement in their QOL.

The results of this study show that, while the mean physical composite score was significantly lower than that of age- and gender-matched U.S. citizens (36 vs. 48), the mean mental composite score was close to that of U.S. women 45 to 54 years of age (45 vs. 49). A recent paper by van Aken et al7 reports similar findings in patients successfully treated by transsphenoidal surgery. They found, using 4 different questionnaires including the SF-36, that several aspects of QOL are reduced, particularly in areas of physical ability. It would seem, therefore, that patients who undergo BLA for persistent Cushing’s disease have, at the very least, an equal QOL to those patients who are successfully treated by initial transsphenoidal pituitary tumor resection.

Two other findings are worthy of discussion in this study. First, the surgical outcomes for these patients were favorable, with zero mortalities, and a 10% morbidity rate. Our operative times (mean, 273 minutes), and length of stay (mean, 4.2 days) were longer than most other series of laparoscopic adrenalectomies.11,12 However, this can be explained by a Canadian study that compared surgical outcomes in 3 different categories of patients13: 1) Cushing’s disease, 2) pheochromocytoma, and 3) unilateral adrenalectomy for nonpheochromocytoma. Poulin et al13found that patients in the first group had longer operating time (median, 255 minutes) and a long postoperative stay (median, 4 days). This is likely secondary to the high BMI of this patient population and the added operative time inherent in repositioning the patient. The extended postoperative stay is in part due to the need to establish homeostasis in fluids and electrolytes following removal of both adrenal glands. It is also due to the need for steroid taper and regulation, as well as the delayed healing these patients experience due to the catabolic nature of cortisol. Our results show that this is a safe, effective option for patients with persistent Cushing’s disease after transsphenoidal pituitary tumor resection.

Second, approximately 20% of our study sample had evidence of endogenous cortisol production following BLA. Evidence of detectable cortisol levels after BLA is reportedly rare; however, there is a paucity of literature on this subject. Possible etiologies include incomplete adrenal resection or functional ectopic adrenal remnants in the adrenal fossa or elsewhere. In 2 patients undergoing BLA for Cushing’s disease (from this current series), we have documented extracortical adrenal tissue remote from the adrenal gland in the retroperitoneal fat. Since then, we have changed our operative conduct to include complete removal of the retroperitoneal fat in the adrenal bed to avoid inadvertently leaving behind extracortical adrenal tissue. Since changing our technique, we have identified one other patient with an extracortical adrenal rest in the left adrenal fossa.

We have also done reoperative laparoscopic explorations in 2 of 7 patients with detectable serum cortisol levels, clinical evidence of hypercortisolism (and subsequent loss of postoperative need for steroid replacement), and positive NP-59 radioscintigraphy scans. The source of alleged endogenous cortisol production, as directed by NP-59 scanning, was in the adrenal fossa in one patient and on the left ovary in the second patient. Pathology demonstrated only fibrous tissue. The source of cortisol production following BLA remains to be determined and will be the subject of future investigation. We currently do not advise routine reexploration for symptomatic endogenous cortisol production without a positive NP-59 scan.

The present study does have one important limitation. We do not have preoperative QOL surveys on the majority of our patients. Therefore, we are relying on patients to remember their preoperative status and compare it with their current state of health. However, bias toward the patient feeling obliged to report a positive outcome was avoided by using an independent investigator (A.V.H.) with no involvement in the patient’s perioperative care to complete all telephone questionnaires. As well, there was no variation in response according to time interval between BLA and our study or between number of preoperative transsphenoidal treatments and BLA, suggesting that memory (or lack thereof) is not an independent predictor of postoperative improvement.

CONCLUSION

Our study shows that BLA for persistent Cushing’s disease provides patients with considerable improvement in their Cushing-related symptoms with concordant increase in their quality of life. After BLA, patients may attain the same (or better) quality of life as patients initially cured by transsphenoidal pituitary tumor resection. We think that BLA is a safe and effective treatment of the 10% to 30% of patients who fail initial therapy for Cushing’s disease, and should be considered preferentially over other available therapies.

ACKNOWLEDGMENTS

The authors thank Karin Miller and Chris Yedinak for all their help in coordinating and collecting biochemical data on our patients.

Footnotes

Reprints: Brett C. Sheppard, MD, Department of Surgery, Oregon Health & Science University, Mail Code: L223A, Portland, OR 97239. E-mail: sheppard@ohsu.edu.

REFERENCES

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Articles from Annals of Surgery are provided here courtesy of Lippincott, Williams, and Wilkins

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