For this special issue, we wanted to ask some of our Medical Advisory Board members for their thoughts on several topics: What led them to work in endocrinology and specialize in Cushing’s?  When did they first learn about Cushing’s and have their first patient?  What are some challenges and inspirations?  What changes in medicine and technology give you the best hope for the future of treatment?  We got three endocrinologists and three neurosurgeons to share with us:

 

Dr. Martin Weiss

Professor of Neurosurgery, University of Southern California

These thoughts go back more than 50 years to the time when I was a student/resident when we (in the early 60s) were approaching the pituitary via the trans-cranial route and had little understanding about the physiology underlying Cushing’s Disease.  My career spanned the transition to sophisticated radio-immuno-assays, imaging  technology, immunohistochemical pathological analysis and profound changes in surgical technique.  I’m proud that we played a role in these processes.

As a medical student in the early 1960s, I was privileged to work with Dr. Bronson Ray, the undisputed premier pituitary neurosurgeon in North America, and Dr. Olaf Pearson, one of the first pituitary-focused endocrinologists.  Dr. Ray stimulated my interest in pituitary surgery, and that was cemented during my residency when our program became one of the first in the US to adopt the transsphenoidal approach to the pituitary.

When I was subsequently recruited to USC in 1973, I found that there was no neurosurgeon in Southern California performing transsphenoidal surgery, and only Dr. Charles Wilson in San Francisco had similar significant experience with that technique.  As a consequence, referrals for pituitary surgery allowed us to accumulate a series of greater than 4,200 transsphenoidal surgeries when I turned my practice over to my colleague, Dr. Gabe Zada, in 2017.

During our years at USC, we were privileged to introduce modifications of the standard sub-labial microscopic technique, publishing the first North American manuscript describing endoscopic pituitary surgery (JNS 1977) and the extended trans-sphenoidal approach (1987) that provided better access to the suprasellar and retro-sellar areas.  These techniques have now become part of the routine armamentaria of pituitary surgeons.

As I reflect upon this experience, it is apparent that patients with Cushing’s Disease have perhaps been the most challenging of all pituitary tumor patients.  Firstly, in the series that we published, we found that 26% of patients with both clinical and biochemical Cushing’s Disease have normal high resolution (3T) MRI scans of the pituitary so that one has to rely upon studies of cavernous sinus/inferior petrosal sinus blood samples to confirm “central Cushing’s”.  In such cases dependent upon dural sinus sampling for confirmation, the surgical cure rate is significantly lower than those cases in which a tumor is identified by MRI scan.   Our new 7T MRI scanner has demonstrated increased sensitivity in identifying previously missed small tumors as recently reported in The Journal of Neurosurgery.  When such equipment becomes generally available, our “yield” of surgical cures will hopefully correspondingly increase.

Secondly, the recognized delay in establishing the diagnosis of Cushing’s Disease results in our patients frequently harboring life challenging co-morbidities such as severe hypertension, diabetes mellitus and morbid obesity.  Hopefully, the persistent efforts of the CSRF will continue to alert both patients and physicians to consider the diagnosis before the profound co-morbidities arise.

Many years ago, Dr. Olaf Pearson coined the phrase “malignant endocrinopathy” to describe the consequences of unresolved Cushing’s Disease.  We sincerely hope that the work of the CSRF and its panel of scientific advisors will bring this problem to resolution.

 

Dr. Theodore Schwartz

Department of Neurological Surgery, Weill Cornell Pituitary Clinic

I have been taking care of patients with Cushing’s Disease for over 20 years. It is truly a remarkable disease that such a small benign tumor can wreak such havoc throughout the body. The diagnosis is challenging and the treatment can be even more challenging. However, I look forward to seeing patients with Cushing’s in my clinic. There is nothing more satisfying than curing a patient with Cushing’s with surgery. Not only is the surgery itself minimally invasive and low risk, but the impact on the patients’ lives is no less than astounding.   Some patients come to me as a last resort after having had several surgeries from other surgeons. These are the most satisfying of all patients since a cure in this scenario is even more rewarding.  I can see a future just around the corner where patients are given a specific radioisotope to label their tumors that can be seen on an imaging study and which fluoresces in the operating room to be seen by the surgeon. Cure rates will be rapidly increased with this new cutting edge technology.

 

Dr. Mary Lee Vance

Professor of Medicine and Neurosurgery, Division of Endocrinology and Metabolism, University of Virginia

What led you to want to work in endocrinology, and more specifically, to make a difference in the Cushing’s space?

The exquisite beauty of the endocrine system, the intellectual challenges.  Cushing’s is such a devastating disease that goes unrecognized for a long time in many patients who need appropriate diagnosis and treatment(s).

 

When did you first learn about Cushing’s, and what made it stand out to you above other specialties?

Medical School and Internal Medicine Residency. Stand out: the challenge of diagnosis and the difficulties regarding treatments.

 

How long have you been a Cushing’s specialist?

For over 30 years

 

When did you have your first Cushing’s patient?

As a Resident in Medicine in 1978 I saw a 12 year old girl with Cushing’s.  I saw more patients many times during my Endocrinology Fellowship.

 

What are the challenges you hope to help change?

Better and more effective drugs to control the disease. Development of a drug that actually cures Cushing’s. Of course I can’t change this, but have hope for the future.

 

What is it like to work with this difficult disease and its patients?

Exhausting, especially after successful pituitary or adrenal surgery (time for recovery is slow and frustating for the patient), but well worth it when the patient has the correct diagnosis and successful treatment(s) and I don’t recognize her/him with the remarkable changes with recovery (seeing the photos of what they looked like when they came to see me and after treatment(s) is amazing).

 

What keeps you inspired?

The need for these patients to receive a correct diagnosis and treatment(s).

 

What changes have you seen in medicine and technology since you first started that give you the greatest hope for better future outcomes?

Technology: more sensitive MRI development and inferior petrosal sinus sampling.  Medications: currently not so much regarding efficacious and safe drugs.

 

Editor’s Note: Dr. Vance has done a lot of research on recovery post-Cushing’s.  She has observed that a big roadblock to psychological recovery is difficulty in allowing oneself to be finished being a Cushing’s patient.  UVA is well-known for their Cushing’s treatment program, so Dr Vance and her team frequently see patients who have been given the wrong diagnosis and in some cases unnecessary operations by doctors who did not understand or adhere to appropriate testing guidelines.  It is an unfortunate reality but something that she has spent years trying to help patients set right when they reach her.

 

Dr. Eliza Geer

Medical Director, Multidisciplinary Pituitary and Skull Base Tumor Center, Memorial Sloan Kettering Cancer Center

I am drawn to Cushing’s because cortisol affects basically every part of the body and brain, and there is still so much we don’t understand. The more experience I have diagnosing and treating Cushing’s, the more I realize how little we know! I am always learning from my patients. I am inspired, and rewarded, when I am able to make even a small difference for one of my patients. I hope to find ways to improve quality of life and long term outcomes for people with Cushing’s, by focusing more holistically on mental and physical health, and establishing integrated treatment and support systems for patients during the recovery process.

 

Dr. Nicholas Tritos

Neuroendocrine Unit, Massachusetts General Hospital

Since my residency days, I have been touched by the health challenges that so many patients with pituitary tumors often face, especially those who have Cushing’s disease. I have been inspired by our patients’ courage and resilience and have celebrated their amazing recoveries in response to treatment. I have been always amazed at the enormous complexity of the pituitary gland, which beautifully orchestrates so many important functions in the human body despite its minute size.

Over the past several decades, substantial progress has been made in our understanding of the behavior of tumors that cause Cushing’s disease as well as other pituitary tumors. As a consequence, we have better treatment strategies. Overall, our patients are doing better these days, which is very gratifying. However, significant challenges remain. For example, tumors of patients with Cushing’s disease are often very small and hard to find by imaging tests (such as MRI) that are carried out before pituitary surgery, or even on direct inspection of the pituitary gland by the neurosurgeon during surgery. Although almost always benign, tumors that cause Cushing’s disease may grow back after patients undergo initially successful surgery, thus requiring further treatment. These are some of the areas where more research can help us further improve the outlook for our patients.

 

Dr. Raj Mukherjee

Neurosurgeon, Johns Hopkins

What led you to want to work in endocrinology, and more specifically, to make a difference in the Cushing’s space?

Cushing’s disease severely impacts patients’ and families’ quality of life, and, as a surgeon, I have found it extraordinarily rewarding to cure these patients whenever possible. 

When did you first learn about Cushing’s, and what made it stand out to you above other specialties?

I first learned about Cushing’s disease in medical school, nearly two decades ago. The complex underlying pathophysiology of the disease and its impact upon multiple organ systems throughout the body make it stand out to me.

 

How long have you been a Cushing’s specialist?

I have been studying clinical outcomes and treating patients with Cushing’s disease for ~10 years.

 

When did you have your first Cushing’s patient?

I treated my first Cushing’s patient in 2010.

 

What are the challenges you hope to help change?

Managing symptoms in patients with recurrent or residual disease are challenging, and I’d like to help create more patient-centered treatment options that maximize patient’s quality of life while minimizing the morbidity of various treatments.

 

What is it like to work with this difficult disease and its patients?

I find it incredibly rewarding to work and support patients suffering from Cushing’s disease. These patients are often incredibly knowledgeable regarding this condition and extremely grateful when we’re able to provide them with a surgical cure.

 

What keeps you inspired?

Continuing to work with so many resilient patients with Cushing’s disease continues to be an inspiration.

 

What changes have you seen in medicine and technology since you first started that give you the greatest hope for better future outcomes?

Advancements in adjunctive intraoperative visualization techniques with the endoscopic endonasal approach hold incredible promise, as do new devices that help maintain and improve nasal morbidity in Cushing’s disease patients treated surgically.