We present a young woman with 3 weeks of headaches and cognitive disturbance who subsequently developed florid psychosis requiring multiple admissions under neurology and psychiatry.
It’s unbelievable but the idea for Cushing’s Help and Support arrived 21 years ago late last night. I was talking with my dear friend Alice, who ran a wonderful menopause site called Power Surge, wondering why there weren’t many support groups online (OR off!) for Cushing’s and I wondered if I could start one myself and we decided that I could.
Statistics are that people who are vaccinated have a 1:1,000,000 chance of dying from COVID, while people who are unvaccinated have a 1:500 chance of dying from COVID. I think most people would take the 1:1,000,000 risk. Dr. Friedman has always been a proponent of the COVID-19 vaccine because he is a scientist and bases his decisions on peer-reviewed liter […]
Poor communication between physicians and CS patients may contribute to dissatisfaction with the postsurgical experience. Increased information on recovery, including helpful coping mechanisms, and improved provider-physician communication may improve HRQOL during recovery.
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.
With the goal of reducing false positives for adrenal insufficiency (AI), scientists are recommending a new, more precise diagnostic cutoff of 14-15 μg/dL of serum cortisol, rather than the current 18 μg/dL.
I am trying to find a doctor for my mom. She is located in Monroe, CT. Would prefer someone in Fairfield or New Haven county, but I am willing to drive further if necessary.
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
The ZENEO autoinjector is a revolutionary delivery system, and this product is a terrific strategic fit with our current adrenal insufficiency business. Patients, advocacy groups, and physicians in the adrenal insufficiency community have repeatedly expressed to us the need for a hydrocortisone autoinjector, so we are excited to be partnering with Crossject […]
2021 Living Rare, Living Stronger NORD Patient and Family Forum featuring the Rare Impact Awards The health and well-being of people living with rare diseases, their loved ones and those working to improve their lives continues to remain a top priority for all of us here at NORD. The COVID-19 pandemic brought us new ways to engage with our community and our […]
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.
I have been ill for years & years. Was diagnosed Cushing’s Syndrome in 2010 but now I know what I’m looking for I can honestly say I’ve had bouts of it since childhood.
Amy is from Michigan. She has a great many symptoms, a pituitary microadenoma, an 8 1/2 mm nodule on the adrenal gland and her left kidney has a some type of cyst on the superior pole.
Hi, It's important to respect mother/adult child boundaries, and I am careful about how I interact with my beautiful daughter so that she does not think I am criticizing her, but I'm very worried. She is presenting what is listed as classic Cushing's symptoms. We have a family history of pituitary problems.
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.
