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  1. Laparoscopic adrenalectomy — a minimally invasive procedure that removes the adrenal glands through a tiny hole in the abdomen — can be safely performed in obese patients with Cushing’s syndrome, a retrospective study reports. The surgery resolved symptoms in 95% of cases, reducing cortisol levels, lowering blood pressure, and leading to a significant loss of weight in morbidly obese patients. The study, “Minimally invasive approach to the adrenal gland in obese patients with Cushing’s syndrome,” was published in the journal Minimally Invasive Therapy & Allied Technologies. Cushing’s syndrome results from the prolonged secretion of excess cortisol, the major glucocorticoid hormone. While most cases are caused by tumors in the pituitary gland, up to 27% result from tumors in the adrenal glands. In these cases, the standard therapeutic strategy is to remove one or both adrenal glands, a surgical procedure called adrenalectomy. However, because glucocorticoids are key hormones regulating fat metabolism, Cushing’s syndrome patients are known to be prone to obesity, a feature that is often associated with post-operative complications. In this study, researchers aimed to compare the outcomes of morbidly obese patients versus the mildly obese and non-obese who underwent a minimally invasive procedure to remove their adrenal glands. The approach, called laparoscopic adrenalectomy, inserts tiny surgical tools through a small hole in the abdomen, along with a camera that helps guide the surgeon. The study included 228 patients (mean age 53.4 years). Of them, 62 were non-obese, 87 were moderately obese, and 79 were considered morbidly obese. There were 121 patients with tumors in the right adrenal gland, 96 in the left gland, and 11 in both glands. High blood pressure was the most common symptom, affecting 66.7% of the participants. Surgery lasted 101 minutes on average, and patients remained in the hospital for a median 4.3 days afterward. Six patients had to be converted into an open surgery because of uncontrollable loss of blood or difficulties in the procedure. Post-surgery complications, most of which were minor, were seen in seven patients. One patient had blood in the peritoneal cavity and had to have surgery again; another patient had inflammation of the pancreas that required a longer admission. The analysis showed no statistical differences among the three groups regarding the length of surgery, length of stay in the hospital, or the rate of conversion into open surgery. However, in obese women, surgeons chose a different surgical incision when removing the left adrenal gland, “suggesting that the distribution of visceral fat in these patients could constitute a drawback for the [standard] approach,” researchers said. After the surgery, 95% of patients saw their symptoms resolve, including cortisol levels, high blood pressure, and glucose metabolism, and none had a worsening of symptoms in the 6.3 years of follow-up. Obese patients also showed a significant reduction in their weight — 2 kg by 18 months, and 5 kg by the end of follow-up. Overall, “laparoscopic adrenalectomy is safe and feasible in obese patients affected with Cushing’s disease and it can lead to the resolution of the related symptoms,” researchers said. The benefits of the surgery in patients with Cushing’s syndrome “could be extended to the improvements and in some cases to the resolution of hypercortisolism related symptoms (i.e. hypertension or even morbid obesity),” the study concluded. Adapted from https://cushingsdiseasenews.com/2019/02/07/laparoscopic-removal-of-adrenal-glands-safe-for-obese-cushings-patients/
  2. The effects of obesity on the diagnosis of Cushing’s syndrome and strategies to alter the traditional approaches have been addressed in a new review study. The study, “Diagnosis and Differential Diagnosis of Cushing’s Syndrome,” appeared in The New England Journal of Medicine. The author was Dr. Lynn D. Loriaux, MD and PhD, and a professor of medicine at the Division of Endocrinology, Diabetes and Clinical Nutrition at the School of Medicine, Oregon Health & Science University (OHSU), in Portland, Oregon. Traditionally, exams of patients with glucocorticoid excess focused on the presence of changes in anabolism (the chemical synthesis of molecules). Given the increase in obesity in the general population, changes in anabolism can no longer distinguish Cushing’s syndrome from metabolic syndrome. However, analyses of anti-anabolic changes of cortisol – including osteopenia (lower bone density), thin skin, and ecchymoses (injury that causes subcutaneous bleeding) – are an effective way to make this distinction. The worldwide prevalence of metabolic syndrome in obese people is estimated at about 10%. Conversely, the incidence of undiagnosed Cushing’s syndrome is about 75 cases per 1 million people. Cushing’s and metabolic syndrome share significant clinical similarities, including obesity, hypertension, and type 2 diabetes. Therefore, “making the diagnosis is the least certain aspect in the care of patients with [Cushing’s],” Loriaux wrote. Regarding a physical examination, patients with osteoporosis, reduced skin thickness in the middle finger, and three or more ecchymoses larger than 1 cm in diameter and not associated with trauma are more likely to have Cushing’s. Researchers estimate the probability of people with all three of these symptoms having Cushing’s syndrome is 95%. Measuring 24-hour urinary-free cortisol levels allows the assessment of excess glucocorticoid effects, typical of Cushing’s syndrome. The test, which should be done with the most stringent techniques available, averages the augmented secretion of cortisol in the morning and the diminished secretion in the afternoon and at night. Dexamethasone suppression is one of the currently used screening tests for Cushing’s syndrome. Patients with obesity and depression should not show decreased plasma cortisol levels when dexamethasone is suppressed. However, given its low estimated predictive value (the proportion of positive results that are “true positives”), “this test should not influence what the physician does next and should no longer be used” to screen for Cushing’s, the author wrote. Some patients may show evidence of Cushing’s syndrome at a physical examination, but low urinary free cortisol excretion. This may be due to glucocorticoids being administered to the patient. In this case, the glucocorticoid must be identified and discontinued. Periodic Cushing’s assessments that measure urinary free cortisol should be performed. The opposite can also occur: no clinical symptoms of Cushing’s, but elevated urinary free cortisol excretion and detectable plasma levels of the hormone corticotropin. In these patients, the source of corticotropin secretion, which can be a tumor or the syndrome of generalized glucocorticoid resistance, must be determined. The disease process can be corticotropin-dependent or independent, depending on whether the hormone is detectable. Corticotropin in Cushing’s syndrome can come from the pituitary gland (eutopic) or elsewhere in the body (ectopic). Loriaux recommends that the source of corticotropin secretion be determined before considering surgery. Up to 40% of patients with pituitary adenomas have nonfunctioning tumors (the tumor does not produce any hormones) and the corticotropin source is elsewhere. If misdiagnosed, patients will likely undergo an unnecessary surgery, with a mortality rate of 1%. Patients with an ectopic source of corticotropin should undergo imaging studies in the chest, followed by abdominal and pelvic organs. If these tests fail to detect the source, patients should undergo either the blockade of cortisol synthesis or an adrenalectomy (removal of adrenal glands). However, corticotropin-independent Cushing’s is usually caused by a benign adrenal tumor that uniquely secretes cortisol. “Such tumors can be treated successfully with laparoscopic adrenalectomy,” Loriaux wrote. If the tumor secretes more than one hormone, it is likely malignant. Surgical to remove the tumor and any detectable metastases should be conducted. Overall, “the treatment for all causes of [Cushing’s syndrome], other than exogenous glucocorticoids, is surgical, and neurosurgeons, endocrine surgeons, and cancer surgeons are needed,” Loriaux wrote in the study. “This level of multidisciplinary medical expertise is usually found only at academic medical centers. Thus, most, if not all, patients with [Cushing’s syndrome] should be referred to such a center for treatment.” From https://cushingsdiseasenews.com/2017/10/24/diagnosing-cushings-syndrome-amid-challenge-of-obesity-and-strategies-to-improve-methods/
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