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  1. Dr. Irmanie Hemphill, who first thought her weight gain was due to having a baby. Doctors at Cleveland Clinic Florida in Weston diagnosed her with a tumor in the pituitary gland in her brain. In the summer of 2019, Irmanie Hemphill gained a lot of weight, developed acne and had high blood pressure. She attributed it to her body adjusting from giving birth just six weeks prior. “I was thinking maybe it was just hormonal changes from having a baby,” said Hemphill, 38, of Pembroke Pines. But when Hemphill, a family medicine physician, saw that her nails were turning dark and she gained five pounds within a week, she knew it was something more serious. Blood tests ordered by her physician came back normal, with the exception of high levels of cortisol detected via a urine cortisol test, which she requested after researching her symptoms online. The next step was to find out where the excess cortisol was coming from: either her kidneys or her adrenal glands, which produce hormones in response to signals from the pituitary gland in the brain. The first MRI of her brain did not detect anything abnormal, so her endocrinologist attributed her symptoms to her body adjusting post-pregnancy. Hemphill sought a second opinion at Cleveland Clinic Weston, where more MRIs of her brain, combined with an Inferior Petrosal Sinus Sampling (IPSS) procedure, detected she had a tumor on her pituitary gland. That led her to be diagnosed with Cushing’s Disease — caused by excess cortisol. TWO TYPES OF PITUITARY TUMORS There are two types of pituitary tumors: those that produce active hormones, like the one Hemphill had, and those that do not, which grow in size over time and do not manifest symptoms right away. Hemphill’s tumor was producing adrenocorticotropic hormone (ACTH), which causes the adrenal gland to produce more cortisol. Many people with Cushing’s Disease experience high blood pressure and high blood sugar, muscle fatigue, easy bruising and brain fog. If left untreated, the condition can lead to pulmonary embolisms, diabetes, osteoporosis, strokes and heart attacks. “It was a little bit of relief but also sadness,” said Hemphill, of finding out her diagnosis. “I was very happy that I got a diagnosis but now it’s like, what’s the next step?” LESS INVASIVE WAY TO REMOVE A PITUITARY TUMOR Hospitals in South Florida are at the forefront in developing new research, techniques and technologies for pituitary tumors. The tiny bean-shaped pituitary gland is located at the base of the brain and controls many of the body’s hormonal and metabolic functions. Last June, neurosurgeon Dr. Hamid Borghei-Razavi of Cleveland Clinic Weston removed Hemphill’s pituitary tumor through her nose. This type of procedure allows surgeons to remove the tumor without damaging the brain. “It’s a less-invasive approach compared to 20 years ago, when pituitary tumors were removed through the cranium,” he said. “Now, with new technologies, more than 95% of pituitary tumors can be removed through the nose.” The procedure takes just a few hours to complete, based on the size and location of the tumor. Patients usually stay at the hospital for one to two days afterward for observation. The removal of Hemphill’s tumor, which was three to four millimeters in size, put an end to her Cushing’s Disease and her symptoms, though it took six months to a year for Hemphill to feel normal. (She was prescribed cortisol for six months until her adrenal glands could restart producing cortisol on their own.) “Sometimes it’s very hard to make a diagnosis for pituitary tumors because we don’t see them in the MRIs,” said Borghei-Razavi. “We call it MRI Negative Cushing’s Syndrome. It means we don’t see it in the MRI, but the cells are there,” he said. Borghei-Razavi and Hemphill credit the Inferior Petrosal Sinus Sampling (IPSS) test as pinpointing her tumor. Cleveland Clinic Weston is among only a handful of medical practices in South Florida that use this technique. Three Ways to Remove the Tumor Most pituitary tumors are benign. The challenge is when it comes to removing the tumor. “Pituitary tumors come in all shapes and sizes,” says Dr. Zoukaa Sargi, a head and neck surgeon at Sylvester Comprehensive Cancer Center at the University of Miami. “There are non-functional tumors that do not secrete hormones that can reach extreme sizes of up to 10 centimeters before coming to medical attention. This is the equivalent of the size of a grapefruit,” he says. “Then there are functional tumors that produce hormones that are typically discovered much sooner and can be only a few millimeters in size before coming to medical attention. A small proportion, less than 1%, are malignant,” he adds. There are three treatment options for pituitary tumors: surgical removal, medical therapy and radiation. “Medical therapy is only applicable in certain functional tumors that produce hormones,” says Dr. Ricardo Komotar, a neurosurgeon who is director of the Sylvester Comprehensive Cancer Center Brain Tumor Initiative. “Radiation is an option primarily for inoperable tumors with high surgical risk. Surgical removal is the optimal treatment in the vast majority of pituitary cases, conferring the greatest benefit with the lowest morbidity,” he says. Dr. Rupesh Kotecha, chief of radiosurgery at Miami Cancer Institute (MCI), part of Baptist Health South Florida, says there are a number of different hormones that the pituitary gland can secrete. “Prolactin is the most common form of pituitary adenoma that’s functioning and accounts for 30% to 50%,” he said. Excess prolactin can cause the production of breast milk in men and in women who are not pregnant or breastfeeding. Kotecha said the next most common are growth-hormone secreting tumors, which occur in 10% of patients. ACTH-secreting adenomas — the kind that Hemphill had — account for 5% of patients, while 1% secrete TSH, which causes the thyroid gland to be overactive. MCI’s Proton Therapy delivers high-dose radiation that treats the tumor’s area, allowing for surrounding tissues and organs to be spared from the effects of radiation. “The pituitary gland essentially sits in the middle of the brain,” says Kotecha. “It’s sitting in the middle of all of these critical structures.” From https://www.miamiherald.com/living/health-fitness/article251653033.html
  2. Minimally invasive diagnostic methods and transnasal surgery may lead to remission in nearly all children with Cushing’s disease, while avoiding more aggressive approaches such as radiation or removal of the adrenal glands, a study shows. The study, “A personal series of 100 children operated for Cushing’s disease (CD): optimizing minimally invasive diagnosis and transnasal surgery to achieve nearly 100% remission including reoperations,” was published in the Journal of Pediatric Endocrinology and Metabolism. Normally, the pituitary produces adrenocorticotropic hormone (ACTH), which stimulates the adrenal glands to produce cortisol. When a patient has a pituitary tumor, that indirectly leads to high levels of cortisol, leading to development of Cushing’s disease (CD). In transnasal surgery (TNS), a surgeon goes through the nose using an endoscope to remove a pituitary tumor. The approach is the first-choice treatment for children with Cushing’s disease due to ACTH-secreting adenomas — or tumors — in the pituitary gland. Micro-adenomas, defined as less than 4 mm, are more common in children and need surgical expertise for removal. It is necessary to determine the exact location of the tumor before conducting the surgery. Additionally, many surgeons perform radiotherapy or bilateral adrenalectomy (removal of both adrenal glands) after the surgery. However, these options are not ideal as they can be detrimental to children who need to re-establish normal growth and development patterns. Dieter K. Lüdecke, a surgeon from Germany’s University of Hamburg, has been able to achieve nearly 100% remission while minimizing the need for pituitary radiation or bilateral adrenalectomy. In this study, researchers looked at how these high remission rates can be achieved while minimizing radiotherapy or bilateral adrenalectomy. Researchers analyzed 100 patients with pediatric CD who had been referred to Lüdecke for surgery from 1980-2009. Data was published in two separate series — series 1, which covers patients from 1980-1995, and series 2, which covers 1996-2009. All the surgeries employed direct TNS. Diagnostic methods for CD have improved significantly over the past 30 years. Advanced endocrine diagnostic investigations, such as testing for levels of salivary cortisol in the late evening and cortisol-releasing hormone tests, have made a diagnosis of CD less invasive. This is particularly important for excluding children with obesity alone from children with obesity and CD. Methods to determine the precise location of micro-adenomas have also improved. The initial methodology to localize tumors was known as inferior petrosal sinus sampling (IPSS), an invasive procedure in which ACTH levels are sampled from the veins that drain the pituitary gland. In series 1, IPSS was performed in 24% of patients, among which 46% were found to have the wrong tumor location. Therefore, IPSS was deemed invasive, risky, and unreliable for this purpose. All adenomas were removed with extensive pituitary exploration. Two patients in series 1 underwent early repeat surgery; all were successful. Lüdecke introduced intraoperative cavernous sinus sampling (CSS), an improved way to predict location of adenomas. This was found to be very helpful in highly select cases and could also be done preoperatively for very small adenomas. In series 2, CSS was used in only 15% of patients thanks to improved MRI and endocrinology tests. All patients who underwent CSS had correct localization of their tumors, indicating its superiority over IPSS. In series 2, three patients underwent repeat TNS, which was successful. In these recurrences, TNS minimized the need for irradiation. The side effects of TNS were minimal. Recurrence rate in series 1 was 16% and 11% in series 2. While Lüdecke’s patients achieved a remission rate of 98%, other studies show cure rates of 45-69%. Only 4% of patients in these two series received radiation therapy. “Minimally invasive unilateral, microsurgical TNS is important functionally for both the nose and pituitary,” the researchers concluded. “Including early re-operations, a 98% remission rate could be achieved and the high risk of pituitary function loss with radiotherapy could be avoided.” From https://cushingsdiseasenews.com/2018/09/04/minimally-invasive-methods-yield-high-remission-in-cushings-disease-children/
  3. By: SHERRY BOSCHERT, Family Practice News Digital Network SAN FRANCISCO – The size of a pituitary tumor on magnetic resonance imaging in a patient with ACTH-dependent Cushing’s syndrome can’t differentiate between etiologies, but combining that information with biochemical test results could help avoid costly and difficult inferior petrosal sinus sampling in some patients, a study of 131 cases suggests. If MRI shows a pituitary tumor larger than 6 mm in size, the finding is 40% sensitive and 96% specific for a diagnosis of Cushing’s disease as the cause of adrenocorticotropic hormone (ACTH)-dependent Cushing’s syndrome, and additional information from biochemical testing may help further differentiate this from ectopic ACTH secretion, Dr. Divya Yogi-Morren and her associates reported at the Endocrine Society’s Annual Meeting. Pituitary tumors were seen on MRI in 6 of 26 patients with ectopic ACTH secretion (23%) and 73 of 105 patients with Cushing’s disease (69%), with mean measurements of 4.5 mm in the ectopic ACTH secretion group and 8 mm in the Cushing’s disease group. All but one tumor in the ectopic ACTH secretion group were 6 mm or smaller in diameter, but one was 14 mm. Because pituitary "incidentalomas" as large as 14 mm can be seen in patients with ectopic ACTH secretion, the presence of a pituitary tumor can’t definitively discriminate between ectopic ACTH secretion and Cushing’s disease, said Dr. Yogi-Morren, a fellow at the Cleveland Clinic. That finding contradicts part of a 2003 consensus statement that said the presence of a focal pituitary lesion larger than 6 mm on MRI could provide a definitive diagnosis of Cushing’s disease, with no further evaluation needed in patients who have a classic clinical presentation and dynamic biochemical testing results that are compatible with a pituitary etiology (J. Clin. Endocrinol. Metab. 2003;88:5593-602). The 6-mm cutoff, said Dr. Yogi-Morren, came from an earlier study reporting that 10% of 100 normal, healthy adults had focal pituitary abnormalities on MRI ranging from 3 to 6 mm in diameter that were consistent with a diagnosis of asymptomatic pituitary adenomas (Ann. Intern. Med. 1994;120:817-20). A traditional workup of a patient with ACTH-dependent Cushing’s syndrome might include a clinical history, biochemical testing, neuroimaging, and an inferior petrosal sinus sampling (IPSS). Biochemical testing typically includes tests for hypokalemia, measurement of cortisol and ACTH levels, a high-dose dexamethasone suppression test, and a corticotropin-releasing hormone (CRH) stimulation test. Although IPSS is the gold standard for differentiating between the two etiologies, it is expensive and technically difficult, especially in institutions that don’t regularly do the procedure, so it would be desirable to avoid IPSS if it’s not needed in a subset of patients, Dr. Yogi-Morren said. The investigators reviewed charts from two centers (the Cleveland Clinic and the M.D. Anderson Cancer Center, Houston) for patients with ACTH-dependent Cushing’s syndrome seen during 2000-2012. ACTH levels were significantly different between groups, averaging 162 pg/mL (range, 58-671 pg/mL) in patients with ectopic ACTH secretion, compared with a mean 71 pg/mL in patients with Cushing’s disease (range, 16-209 pg/mL), she reported. Although there was some overlap between groups in the range of ACTH levels, all patients with an ACTH level higher than 210 pg/mL had ectopic ACTH secretion. Median serum potassium levels at baseline were 2.9 mmol/L in the ectopic ACTH secretion group and 3.8 mmol/L in the Cushing’s disease group, a significant difference. Again, there was some overlap between groups in the range of potassium levels, but all patients with a baseline potassium level lower than 2.7 mmol/L had ectopic ACTH secretion, she said. Among patients who underwent a high-dose dexamethasone suppression test, cortisol levels decreased by less than 50% in 88% of patients with ectopic ACTH secretion and in 26% of patients with Cushing’s disease. Most patients did not undergo a standardized, formal CRH stimulation test, so investigators extracted the ACTH response to CRH in peripheral plasma during the IPSS test. As expected, they found a significantly higher percent increase in ACTH in response to CRH during IPSS in the Cushing’s disease group, ranging up to more than a 1,000% increase. In the ectopic ACTH secretion group, 40% of patients did have an ACTH increase greater than 50%, ranging as high as a 200%-300% increase in ACTH in a couple of patients. "Although there was some overlap in the biochemical testing, it is possible that it provides some additional proof to differentiate between ectopic ACTH secretion and Cushing’s disease," Dr. Yogi-Morren said. In the ectopic ACTH secretion group, the source of the secretion remained occult in seven patients. The most common identifiable cause was a bronchial carcinoid tumor, in six patients. Three patients each had small cell lung cancer, a thymic carcinoid tumor, or a pancreatic neuroendocrine tumor. One patient each had a bladder neuroendocrine tumor, ovarian endometrioid cancer, medullary thyroid cancer, or a metastatic neuroendocrine tumor from an unknown primary cancer. The ectopic ACTH secretion group had a median age of 41 years and was 63% female. The Cushing’s disease group had a median age of 46 years and was 76% female. Dr. Yogi-Morren reported having no financial disclosures. sboschert@frontlinemedcom.com On Twitter @sherryboschert From Famiiy Practice News
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