Kassey passed away on June 30, 2016. Her sister said she died in her sleep. She was in the hospital due to a crisis on June 21st. Kassey was only 20 years old.
Kim is from Wisconsin. She was recently diagnosed with Cushing’s after about three years of testing. This is in addition to a diagnosis of Lipedema a little over a year ago.
Cushing’s disease (CD) is rare in pediatric patients. It is characterized by elevated plasma adrenocorticotropic hormone (ACTH) from pituitary adenomas, with damage to multiple systems and development. In recent years, genetic studies have shed light on the etiology and several mutations have been identified in patients with CD. A girl presented at the age o […]
Isturisa is a cortisol synthesis inhibitor indicated for the treatment of adult patients with Cushing’s disease for whom pituitary surgery is not an option or has not been curative.
Juilliard graduate Samantha Cohn, 34, crawled out a window in her 16th-floor apartment at West 71st Street and Broadway and jumped at 10:10 a.m. Her mother told investigators she had been diagnosed with Cushing’s syndrome, police sources said.
Diana Lynn Alexander Crosley, age 58, of Sidney, passed away peacefully on Wednesday, June 18, 2014, at 10:10 p.m. at her residence surrounded by her loving family. She was a long-time Cushie who'd had a BLA at the NIH in 2002.
Blood tests and an MRI confirmed that Yawn had a tumour in her pituitary gland — a small, pea-sized organ at the base of the brain — that caused the gland to release excess adrenocorticotropic hormones. As a result, she became inundated with cortisol, a steroid the body releases in response to danger or stress. This combination of factors led to her diagnosi […]
Cushing's disease causes numerous metabolic disorders, cognitive decline, and sarcopenia, leading to deterioration of the general health in older individuals. Cushing's disease can be treated with transsphenoidal surgery, but thus far, surgery has often been avoided in older patients.
Since 1987, NORD has provided assistance programs to help patients obtain life-saving or life-sustaining medication they could not otherwise afford. These programs provide medication, financial assistance with insurance premiums and co-pays, diagnostic testing assistance, and travel assistance for clinical trials or consultation with disease specialists.
Sarah had surgery to remove a tumor from her pituitary gland in the hopes of treating her Cushing's Disease. She died on June 13, 2011 after a brief illness at the age of 28.
In this video exclusive, Maria Fleseriu, MD, FACE, reviews the pituitary research presented at the annual meeting of the Endocrine Society in Atlanta. Among the hottest pituitary topics at the meeting, according to Fleseriu, were dilemmas in pituitary tumors and data for new drugs for Cushing’s syndrome.
Carola is from Santa Cruz, CA. On December 26, 2014 she went to a local urgent care clinic with pneumonia, confirmed by an x-ray, for which she was treated. Carola received a phone call from the urgent care clinic a few days afterwards explaining that the radiologist had seen something unusual that needed further examination. After numerous tests her susp […]
A 22-year-old woman with a three-month history of an increase in appetite, binge eating, and weight gain. After two weeks of her initial symptoms, she started to have grandiose and persecutory delusions, auditory hallucinations, decreased need for sleep, agitation, irritability, and aggression
Let’s keep the ball rolling: the more members in the community, the smarter the insights. We're about 1,468 contributors away from being able to tell which treatments were reported to work better for different subgroups with common aspects. ~~~ The popular website "How Stuff Work"s is doing a survey of all kinds of diseases and Cushing's […]
Stress-related brain disorders can be associated with glucocorticoid disturbance and hippocampal alteration. However, it remains largely unknown how cortisol affects the structure and function of hippocampus. Cushing's disease (CD) provides a unique “hyperexpression model” to explore the effects of excessive cortisol on hippocampus as well as the relati […]
Data from LINC3 and LINC4 provide insight into the impact of dosing titration schedules on risk of hypocortisolism-related adverse events associated with osilodrostat use in patients with Cushing’s disease.
Data from a pair of phase 3 studies presented at the American Academy of Clinical Endocrinology’s 30th Annual Meeting (AACE 2021) is providing insight into the effect of dose titration schedules with use of osilodrostat (Isturisa) in patients with Cushing’s disease.
Presented by Maria Fleseriu, MD, of Oregon Health and Science University, the analysis of the LINC3 and LINC4 demonstrated the more gradual titration occurring in LINC4 resulted in a lower proportion of hypocortisolism-related adverse events, suggesting up-titration every 3 weeks rather than every 2 weeks could help lower event risk without compromising mean urinary free cortisol (mUFC) control.
“For patients with Cushing’s disease, osilodrostat should be initiated at the recommended starting dose with incremental dose increases, based on individual response/tolerability aimed at normalizing cortisol levels,” concluded investigators.
With approval from the US Food and Drug Administration in March 2020 for patients not eligible for pituitary surgery or have undergone the surgery but still have the disease, osilodrostat became the first FDA-approved therapy address cortisol overproduction by blocking 11β-hydroxylase. Based on results of LINC3, data from the trial, and the subsequent LINC4 trial, provide the greatest available insight into use of the agent in this patient population.
The study presented at AACE 2021 sought to assess whether slow dose up titration might affect rates of hypocortisolism-related adverse events by comparing titration schedules from both phase 3 trials. Median osilodrostat exposure was 75 (IQR, 48-117) weeks and 70 (IQR, 49-87) weeks in LINC3 and LINC4, respectively. The median time to first mUFC equal to or less than ULN was 41 (IQR, 30-42) days in LINC3 and 35 (IQR, 34-52) days in LINC4.
Adverse events potentially related to hypocortisolism were more common among patients in LINC3 (51%, n=70) than LINC4 (27%, n=20). Upon analysis of adverse events, investigators found the most commonly reported type of adverse event was adrenal insufficiency, which included events of glucocorticoid deficiency, adrenocortical insufficiency, steroid withdrawal syndrome, and decreased urinary free cortisol.
Results incited the majority of hypocortisolism-related adverse events occurred during the dos titration periods of each trial. In LINC3, 54 of the 70 (77%) hypocortisolism-related adverse events occurred by week 26. In comparison, 58% of hypocortisolism-related adverse events occurring in LINC4 occurred prior to week 12. Investigators noted most of events that occurred were mild or moderate and managed with dose interruption or reduction of osilodrostat or concomitant medications.
The UCSF website in an obituary from Kate Vidinsky reads “He took a particular interest in pituitary disorders, those affecting the pea-sized ‘master gland’ at the base of the brain responsible for controlling the body’s hormone levels. He was a pioneer of transsphenoidal surgery – the endonasal approach for removing pituitary tumors – and performed more than 3,300 of these procedures at UCSF Medical Center.”
The New York Times in an obituary published yesterday described him as “a pioneering and virtuosic San Francisco neurosurgeon”.
Endocrine Today, October 2017 Brooke Swearingen, MD; Stephanie L. Lee, MD, PhD, ECNU
A 63-year-old man was referred to the Massachusetts General Hospital Neuroendocrine & Pituitary Tumor Clinical Center for management of a pituitary macroadenoma. He experienced increasingly severe retro-orbital headaches in the past year. He reported no double vision, fatigue, orthostatic dizziness, change in beard growth or reduction in libido. An outside head CT scan showed an enlarged pituitary gland.
Imaging and laboratory tests
A pituitary MRI with magnified pituitary slices and gadolinium contrast was ordered. A well-circumscribed “snowman-shaped” sellar mass was identified, measuring 2.6 cm x 2 cm x 1.8 cm (anteroposterior x transverse x craniocaudal) with suprasellar extension (Figure 1). The lesion was heterogeneous on T1-weighted scans after enhancement with IV gadolinium contrast. An area of hypointensity in the superior margin was consistent with a small area of cystic or hemorrhagic degeneration.
Although the mass did not extend laterally into the cavernous sinus, the sellar mass extended upward into the suprasellar cistern through a hole in the dural, the diaphragma sellae, to compress the optic chiasm. The restriction of adenoma growth by the diaphragma sellae results in the snowman shape of the macroadenoma. The optic chiasm and infundibulum (pituitary stalk) could not be identified on coronal or sagittal images (Figure 1). Visual field on confrontation suggested lateral field deficits (bilateral lateral hemianopsia) that were confirmed on formal Goldmann kinetic perimetry visual fields.
Figure 1. Preoperative MRI scan. A large “snowman-shaped” pituitary adenoma (green arrow) has heterogeneous enhancement after gadolinium contrast administration. A small hypodense area in the adenoma likely represented hemorrhage/cystic degeneration (yellow arrow). The tumor does not surround the carotid siphon, an S-shaped portion of the internal carotid artery (red arrows) within the cavernous sinus located laterally from the sella turcica where the pituitary gland resides. (A) Coronal image. (B) Sagittal image. Abbreviation: SS = spenoid sinus.
Source: Stephanie L. Lee, MD, PhD, ECNU. Reprinted with permission.
Initial hormonal evaluation was normal and included morning adrenocorticotropic hormone 18 pg/mL, cortisol 13.64 µg/dL, thyroid-stimulating hormone 2.14 uIU/mL, free thyroxine 1.2 ng/dL and prolactin 12.6 ng/mL. The patient’s morning testosterone level was normal at 324 ng/dL, with follicle-stimulating hormone 2.4 mIU/mL and luteinizing hormone 1.6 mIU/mL. His insulin-like growth factor I level was normal at 124 ng/mL.
Tumor resection
The patient was treated preoperatively with stress-dose hydrocortisone 50 mg. He then underwent transsphenoidal pituitary tumor resection. After the surgeon believed there was an adequate excision of the tumor, the extent of tumor resection was confirmed by an intraoperative MRI (Figure 2 on page 8).
Figure 2. Intraoperative MRI scan. The large macroadenoma is not seen after transsphenoidal surgery. The optic chiasm (yellow arrow) can be seen after removal of the tumor. (A) Coronal image. (B) Sagittal image. Abbreviation: SS = spenoid sinus.
The operation was concluded after the imaging confirmed the complete resection of the pituitary adenoma. The patient’s postoperative course was uneventful. Imaging 4 weeks after the resection confirmed complete resection of the suprasellar mass with residual enhancement of the resection bed and sphenoid sinuses (Figure 3 on page 8). The postoperative MRI revealed a normal optical chiasm and a downward tending of the infundibulum to the residual pituitary gland located inferiorly along the sella turcica (pituitary fossa) of the sphenoid bone. Pathology confirmed a pituitary adenoma. His anterior and posterior pituitary function were normal 6 weeks postoperatively, and his visual field deficit improved.
Intraoperative MRI
Imaging like that used in this case occurs in a specially designed operating room that allows MRI scans during surgery without moving the patient from the surgical table. The MRI is kept in a shielded enclosure during the procedure and then moved along a track into the operating room for imaging. Clinical indications for the use of intraoperative MRI in neurosurgery include resection of pituitary macroadenomas. In the past, these tumors underwent transsphenoidal resection, and the postoperative MRI was performed after 1 or more days after the procedure to check for complete removal. If residual tumor was found, the patients underwent watchful waiting, external radiation or repeat surgery.
The strategic advantage of an intraoperative MRI is that the imaging is performed during the operative procedure, and if there is any residual tumor, surgery can be resumed after the MRI is moved back into the shielded enclosure.
Figure 3. Four-week postoperative MRI scan. The large macroadenoma is not seen after the transsphenoidal survey. The optic chiasm and infundibulum (pituitary stalk) can be seen after resection of the tumor. The pituitary stalk is deviated to the left of the sella where the residual normal thyroid is locate along the sella turcica. The floor of the sella enhances with gadolinium infusion after surgery due to postoperative inflammation. (A) Coronal image. (B) Sagittal image. Abbreviation: SS = spenoid sinus.
It has been reported that the use of intraoperative MRI does not increase complication rates compared with conventional transsphenoidal surgery. Reports on the improvement of gross tumor resection using intraoperative MRI are variable, perhaps due to the expertise of the surgeon. Several reports suggest the use of intraoperative MRI allowed additional resection of noninvasive macroadenomas in 67% to 83% of the patients with a gross tumor resection. These results suggest that a substantial volume reduction and increased gross tumor resection of pituitary macroadenomas occurs with the use of intraoperative MRI compared with standard surgery. One study demonstrated that the gross tumor resection rates of invasive tumors was also improved with the use of intraoperative MRI compared with usual preoperative imaging and surgery (25% vs. 7%).
The use of intraoperative MRI, especially with transsphenoidal reoperations for invasive and noninvasive pituitary macroadenomas, leads to significantly higher “gross tumor resection” rates. This method prevents additional operations or treatment, such as radiation, because it reduces the number of patients with residual adenoma after surgery. This technology is usually found in specialized tertiary care hospitals but should be considered for reoperation for large pituitary macroadenomas or initial operation for large invasive pituitary macroadenomas.
References:
Boellis A, et al. J Magn Reson Imaging. 2014;doi:10.1002/jmri.24414.
Fomekong E, et al. Clin Neurol Neurosurg. 2014;doi:10.1016/j.clineuro.2014.09.001.
Tandon V, et al. J Clin Neurosci. 2017;doi:10.1016/j.jocn.2016.10.044.
For more information:
Stephanie L. Lee, MD, PhD, ECNU, is an Endocrine Today Editorial Board Member. She is associate professor of medicine and director of thyroid health in the Section of Endocrinology, Diabetes and Nutrition at Boston Medical Center. She can be reached at Boston Medical Center, 88 E. Newton St., Boston, MA 02118; email: stephanie.lee@bmc.org.
Brooke Swearingen, MD, is associate professor of surgery (neurosurgery) at Harvard Medical School and co-director of the neurological ICU at Massachusetts General Hospital. He can be reached at bswearingen@partners.org.
Disclosures: Lee and Swearingen report no relevant financial disclosures.
Ed started as Senior Staff Fellow in the Surgical Neurology Branch at the NIH (1981). After 5 years, Ed would become the Chief of the Surgical Neurology Branch. He would stay on as Branch Chief and lead the neurosurgical effort at the NIH for the next 21 years. During his tenure, he developed clinical, research, and training programs in epilepsy, congenital malformations, syringomyelia, nervous system neoplasia, drug delivery, and vascular malformations. The strength of these programs was his leadership and their multidisciplinary nature, which incorporated physicians and scientists across the basic, translational, and clinical arenas. Research investigation was always targeted at defined clinical problems. Under his direction, these programs shaped understanding of the studied neurological disorders, as well as improving patient care.
Please let us know your experiences with this new program!
Hallmark Health and Tufts Medical Center have established a new neurosurgery program at Melrose-Wakefield Hospital to bring advanced care and services to the community. Fellowship-trained neurosurgeon Mina G. Safain, MD, has been jointly hired by Hallmark Health and Tufts Medical Center to lead the new program. He will provide care at both Melrose-Wakefield Hospital and Tufts Medical Center.
The neurosurgery program is an example of clinical integration of services between Hallmark Health and Tufts Medical Center since Hallmark Health joined Wellforce as a third founding member this past January. At that time, leaders from the organizations discussed finding ways to bring specialized care traditionally performed at academic medical centers into the community hospital setting for the benefit and convenience of patients.
“Offering neurosurgery provides a service for our patients that few community hospitals can offer,” said Steven Sbardella, MD, chief medical officer at Hallmark Health. “Our clinical relationship with Tufts Medical Center enables us to bring more highly specialized care options to our patients.”
“We are extremely excited to work with the physicians at Melrose-Wakefield Hospital and look forward to increasing the services available to care for patients with neurologic diseases,” said Carl Heilman, MD, neurosurgeon-in-chief at Tufts Medical Center. “Dr. Safain is an exceptionally talented and compassionate neurosurgeon and the perfect person to spearhead the launch of this new program.”
Dr. Safain’s clinical interests include all diseases affecting the brain, spine and peripheral nervous system. He has specific interests in minimal access procedures for degenerative, infectious and oncologic spine disorders, as well as minimally invasive treatments for brain tumors, including neuro-endoscopy.
“The opportunity to practice in the community is very important to me,” said Dr. Safain. “I look forward to working with the esteemed staff and providers at Melrose-Wakefield Hospital and Lawrence Memorial Hospital and treating the patients in the surrounding communities.”
“Welcoming such a highly-respected neurosurgeon as Mina Safain to our team is a tremendous benefit for our communities and patients across our system including Lawrence Memorial Hospital in Medford and Melrose-Wakefield Hospital,” said Dr. Sbardella.
Dr. Safain, together with Ran Ku, PA, a neurosurgery physician assistant with more than 12 years of experience, will provide neurosurgery coverage and expertise five days a week.
Dr. Safain received his medical degree from Yale University School of Medicine. He completed his neurosurgery residency at Tufts Medical Center serving as chief resident during his final year. Dr. Safain also completed fellowship training in pituitary and neuro-endoscopic surgery at Brigham and Women’s Hospital.
Dr. Safain has published and presented nationally on a range of topics related to neurosurgical diseases and minimally invasive treatments for brain tumors.
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