John D. Carmichael, MD, an endocrinologist at Keck Medicine of USC, shares information about the USC Pituitary Center, a multidisciplinary center focused on the clinical care of patients with pituitary disease and research of pituitary tumors.
Mm, Hi. My name is John Carmichael and I'm an endocrinologist kept medical center of U. S. C. And I am the co director of the U S. C. Pituitary center. Today, we're going to be talking about a focus on your own endocrinology first a little bit about myself. I did my endocrinology fellowship at the School of Medicine and worked in the GNU neuroendocrine unit during my fellowship. And after my fellowship was completed, I stayed on and did clinical research with Y you. I conducted clinical research and growth hormone, and healthy adults also conducted clinical trials in growth hormone replacement and clinical trials in acromegaly treatment. After that, I moved to Los Angeles and started working at Cedars Sinai of the Pituitary Center there. During that time, I've completed a fellowship in translational research, worked with Cedar Sinai with their clinical scholars program, and this all led to an early career development of expertise in clinical trial design. And I had the benefit of career mentorship from giants in the field, such as David Kleinberg and Shalom Element. Once I moved to U. S. C, we adopted a USC pituitary center model that benefitted patients in providing multidisciplinary care. This is a multi disciplinary clinic with neural endocrinology and neurosurgery seeing patients in the same office at the same time. Care is provided by unified team of schedulers, office staff, nurses and physicians. We all collaborate to provide the care to the patient with simultaneous care as best we can referrals toe one specialty or reviewed for appropriateness toe offer joint visits with both specialists and we review records and data prior to the visit so that we can accomplish anything that we need to do for the patients in the time leading up to the visit, Imaging is reviewed prior to the visit at a neuro radiology conference with the pituitary center. Neural radiologist on a weekly basis, scheduling is able to provide same day Marie ophthalmology and a joint consultation with endocrinology and neurosurgery, all to provide optimal multidisciplinary care for patients at USC. We have also focused our efforts on research and education in clinical trials with Cushing's disease, acromegaly growth hormone deficiency as well as novel methods of diagnosis and treatment. We maintain a comprehensive database for tracking and reporting outcomes and a program of translational science with genetics and drug development We also maintain ah, high quality lecture, Siri's and CMI events to train the next generation of endocrinologists and service, an educational resource for the immigrant community at large. All of this work is based on the idea of a pituitary tumor center of excellence. This pituitary tumor center of excellence is an idea that has been promoted by the pituitary society, of which I am member and board. A member of the board of directors. We focus our efforts on building a team on the endocrinologist and the neurosurgeon as the principal members of the team, all supported by neuro radiology, neuropathology, radiation, oncology and neuropathology. These centers of excellence rely on external endocrine units, the endocrinologists in the community with referral patterns to the center of excellence to conduct care. And this is all done in an effort to provide excellent care for patients with pituitary disease. This results in the ability to publish our scientific findings and to return these patients once cared for at USC to the external endocrine units. As I said, this goal is to provide the best care for patients with pituitary tumors and to organize a multidisciplinary clinical team that's focused on the management of all of the patients needs. There is a central rural central role for the experienced neurosurgeon and expert neuro endocrinologist, but they work constantly with supporting specialties, and they trained fellows in the management of pituitary tumors. It is of utmost importance to provide courses, publications and lectures so that our findings could be disseminated throughout. I'm going to now talk about the management of pituitary disease and talk about our approach toward pituitary tumors. We're going to discuss the diagnosis and treatment of Cushing's disease, acromegaly care, treatment of Prolactin, Omagh's and Hypo Pituitary ism. Management of utmost importance is Theo evaluation of the seller Mass with structural and hormonal assessments. Structural findings rely on memory of the pituitary in the Cella, as well as visual field testing. When appropriate. My role capitalizes on the hormonal assessment of patients with pituitary tumors looking for findings of hormonal excess or hormonal deficiency. We evaluate to determine if the tumorous accreting too much or excess hormones. This is done primarily with history and physical exam to guide the index of suspicion. This is followed then by hormonal assessments looking for excess growth hormone and acromegaly excess cortisol in Cushing's disease from a pituitary tumor. Excess prolactin from a prolactin oma and the rare cases of thyroid trope in excess from a thyroid trope in secreting pituitary tumor or functional Gonna trophy adenomas, which are extremely rare, causing elevations of testosterone and estrogen. The basic screening labs that are employed to evaluate patients with pituitary disease. Our prolactin i G. F one looking for growth hormone. Excess assessment of genital axis with lutin izing hormone and follicle stimulating hormone, as well as a measurement of total testosterone and men. For women, menstrual history is of utmost importance and, in fact, is probably superior to hormonal testing. In the pre menopausal women. Thyroid assessment relies on TSH and can common it measure of free T four, and court is all excess is assessed clinically, followed by screening test if indicated, and we'll go into that further as we talk about Cushing's disease. Adrenal insufficiency likewise is assessed clinically in. The index of suspicion is raised by the presence of other hormonal deficiencies. When needed, we check a morning cortisol and rely on stimulation, testing for establishment of the adrenal reserve if necessary. Cushing's disease is, I think, by far one of our most complicated diseases to treat. It is a challenging diagnosis to make, not only because the complexity of the testing involved but because the features of Cushing's disease are very similar to those found in the general population is of utmost importance to exclude exogenous glucocorticoids exposure and to then perform testing of urine. Excretion of cortisol, of suppression of cortisol from two Meral or non to Meral sources assessment of late night salivary cortisol to obtain an estimate of diurnal variation of cortisol. And once these things are complete and once we have established that the patients have Cushing's syndrome and elevation of cortisol, it is a that time that we start looking for the source of the abnormal cortisol secretion. Cushing's syndrome symptoms are sometimes very specific, but often are poor. Discriminate er's of disease. We see patients very commonly who may have Cushing's disease because of the symptoms that they report, such as obesity and her statism changes in fat location, including uh, relocation of the Dorsey's cervical, uh, fat pads and facial fullness that, uh, that is striking feature of Cushing syndrome. But these unfortunately do not discriminate the disease from those patients who do not have elevations of court is all from a to Meral source. We have to rely on specific signs like facial plethora, proximal muscle Weakness, Wide Probe Austria and easy bruising that tell us more likely that the patient has Cushing syndrome, as opposed to findings that were found in the general population. One of the most complex parts of the treatment of patients with Cushing's syndrome is the use of novel medications. For many, many years, there were a few medications that were available to treat patients who were surgical failures for Cushing's disease, Cushing's disease treatment. And recently we have seen approval of several new medications. Unfortunately, these medications or complex in their management there are multiple drug interactions. They're challenging side effect profiles. The efficacy is sometimes limited, and it's uncertain what role these medications will play in the long term management of patients with Cushing syndrome. And so we're left with a highly individualized approach toward each patient, and this is reliant on multimodal care, with incorporation of surgery, sometimes second surgeries and radiation. In many cases, there's also a need for lifelong monitoring, as recurrence can happen in decades to come. After a successful treatment initially acromegaly or growth hormone, and I g F one excess is a complicated and difficult disease to treat. Could be very disfiguring to patients who are suffering from long term exposure to high levels of growth hormone and, unfortunately, takes several years for them to come to medical attention Because of the slow and insidious onset of growth hormone access. The goals of therapy, regardless of the mode of treatment, or to control that growth hormone secretion to normalize age and gender matched GF one levels to a blade or reduce the tumor mass and prevent its recurrence and to reduce symptoms associated with the mass effects of the tumor. All the while, we're trying to alleviate significant co morbid features of the disease and normalize thes patients. Survival time management of acromegaly realize initially on transfer total surgery for most patients from their assessment of disease activity is done, and after the the surgery is complete. If the patient is in remission, we then employ a surveillance of annual monitoring of growth hormone and I G F one levels and imaging findings to make sure that the patient is free of disease. If the disease is persistent, We then have several medications that are available for us for the treatment of of uh, of acromegaly with medical management aimed at suppression of growth hormone secretion, or blockade of growth hormone once it's in the periphery, some of these medication have the end advantage of tumor suppression and control of tumor size as well. If these things fail, we often need to rely on other modes of therapy or combinations of therapy. And in very in very few cases, we need to rely on radiation treatment. As I said, surgery is the initial treatment of choice, and in this case, surgeon experience and degree of invasiveness are key predictors of outcome. Studies have shown that a single surgeon model, rather than multiple surgeons treating patients with acromegaly, have benefitted patients with improved outcomes and higher success rates of surgery. If those patients are still not cured by surgery, there are multiple medical choices, and there are novel and emerging compounds. We continue to participate in ongoing clinical trials and Orel compounds, and there are multiple opportunities for hormonal and tumor control with combination medical therapy. There are also investigations that were undertaking into targeted therapies to control patients disease and to alleviate some of the symptoms of growth hormone excess Prolactin. Omagh's are among the most common secret torrey pituitary tumors that we see patients with symptomatic prolactin, Omagh's air commonly treated with medical therapy as first line therapy. Once these patients or controlled with their disease, we monitor their prolactin level monitor their image ing and visual fields if necessary. Prolactin Omagh's, however, can sometimes be very resistant treatment. And in those cases, or in the cases of intolerance, we need to rely on other modes of therapy. We have employed a clinical protocol of increasing the dose of Coburg, a Lien and Roma Christine toe high doses to control patients with, uh with medical therapy alone. And we've had a great success rate in doing this. When we titrate the dose ing to maximum dose, we get good efficacy with almost all patients controlled with their disease. In some cases, though, we have to rely on surgical excision for treatment of patients with resistant or intolerance to medications. Here's an example of a large pituitary tumor with a very high prolactin level, and even in cases where the tumors or large and the prolactin levels were very high routine doses of Coburg a lien therapy result in normalization of prolactin. In this case, you see in the first three months a dramatic lowering of prolactin in response to medical therapy and over one year's time we see a reduction in tumor mass all due to medical therapy alone. This patient continues to see me as Marie has normalized as well as his prolactin, all with the treatment with medical therapy alone. Hypo Pituitary Ism is another aspect of pituitary care that relies on complex testing and an expertise in management. Many cases rely on dynamic testing timed tests with with agents that are employed to cause secretion of growth hormone, or cortisol. Yeah, so that we can address patients growth hormone or cortisol deficiencies. There's diligent attention to medication interactions, as all of these medications may need to be employed in someone with pituitary failure. These patients also require long term follow up in dozing adjustment with age. We have been part of clinical trials looking at novel medications, both for hormonal replacement formulations as well as new testing agents employed to diagnose patients with pituitary failure, and we continue to participate in ongoing clinical trials in this area. I would like to acknowledge the other members of the U. S. C. Pituitary center team without which our center would not be successful as it is. I would like to thank. Gabriel is out of my co director, as well as our nurse practitioner Emily Rodan and our nurse, Monica Chu, who form the core of our pituitary center team. We also rely on colleagues in neuro ophthalmology nor radiology, radiation, oncology, neural, oncology, oil. They're oncology, and I need to acknowledge our predecessors, Dr Martin Weiss and Dr Peter Singer, who formed the foundation of the USC pituitary Center. With decades of work treating patients with pituitary disease, I'd like to thank you for your attention.
