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Cushing’s syndrome patients who undergo adrenal surgery are more likely to have venous thromboembolism — blood clots that originate in the veins — than patients who have the same procedure for other conditions, a study suggests. Physicians should consider preventive treatment for this complication in Cushing’s syndrome patients who are having adrenal surgery and maintain it for four weeks after surgery due to late VTE onset. The study, “Is VTE Prophylaxis Necessary on Discharge for Patients Undergoing Adrenalectomy for Cushing Syndrome?” was published in the Journal of Endocrine Society. Cushing’s syndrome is a condition characterized by too much cortisol in circulation. In many cases, it is caused by a tumor in the pituitary gland, which produces greater amounts of the cortisol-controlling adrenocorticotropic hormone (ACTH). In other cases, patients have tumors in the adrenal glands that directly increase cortisol production. When the source of the problem is the pituitary gland, the condition is known as Cushing’s disease. The imbalance in cortisol levels generates metabolic complications that include obesity, high blood pressure, diabetes, and cardiovascular complications. Among the latter, the formation of blood clots in the deep veins of the leg, groin or arm — a condition called venous thromboembolism (VTE) — is higher in both Cushing’s disease and Cushing’s syndrome patients. VTE is believed to be a result of excess coagulation factors that promote blood clot formation, and is thought to particularly affect Cushing’s disease patients who have pituitary gland surgery. Whether Cushing’s syndrome patients who have an adrenalectomy — surgical removal of one or both adrenal glands — are at a higher risk for VTE is largely unknown. This is important for post-operative management, to decide whether they should have preventive treatment for blood clot formation. Researchers at the National Cancer Institute in Maryland did a retrospective analysis of a large group of patients in the American College of Surgeons National Quality Improvement Program database. A total of 8,082 patients underwent adrenal gland surgery between 2005 and 2016. Data on these patients included preoperative risk factors, as well as 30-day post-surgery mortality and morbidity outcomes. Patients with malignant disease and without specified adrenal pathology were excluded from the study. The final analysis included 4,217 patients, 61.8% of whom were females. In total, 310 patients had Cushing’s syndrome or Cushing’s disease that required an adrenalectomy. The remaining 3,907 had an adrenal disease other than Cushing’s and were used as controls. The incidence of VTE after surgery — defined as pulmonary embolism (a blockage of an artery in the lungs) or deep-vein thrombosis — was 1% in the overall population. However, more Cushing’s patients experienced this complication (2.6%) than controls (0.9%). Those diagnosed with Cushing’s syndrome were generally younger, had a higher body mass index, and were more likely to have diabetes than controls. Their surgery also lasted longer — 191.2 minutes versus 142 minutes — as did their hospital stay – 2.4 versus two days. Although without statistical significance, the researchers observed a tendency for longer surgery time for patients with Cushing’s syndrome than controls with VTE. They saw no difference in the time for blood coagulation between Cushing’s and non-Cushing’s patients, or postoperative events other than pulmonary embolism or deep-vein thrombosis. In addition, no differences were detected for VTE incidence between Cushing’s and non-Cushing’s patients according to the type of surgical approach — laparoscopic versus open surgery. These results suggest that individuals with Cushing syndrome are at a higher risk for developing VTE. “Because the incidence of VTE events in the CS group was almost threefold higher than that in the non-CS group and VTE events occurred up to 23 days after surgery in patients with CS undergoing adrenalectomy, our data support postdischarge thromboprophylaxis for 28 days in these patients,” the researchers concluded. From https://cushingsdiseasenews.com/2019/02/14/cushings-syndrome-patients-blood-clots-adrenal-surgery/
Patients with subclinical hypercortisolism, i.e., without symptoms of cortisol overproduction, and adrenal incidentalomas recover their hypothalamic-pituitary-adrenal (HPA) axis function after surgery faster than those with Cushing’s syndrome (CS), according to a study. Moreover, the researchers found that an HPA function analysis conducted immediately after the surgical removal of adrenal incidentalomas — adrenal tumors discovered by chance in imaging tests — could identify patients in need of glucocorticoid replacement before discharge. Using this approach, they found that most subclinical patients did not require treatment with hydrocortisone, a glucocorticoid taken to compensate for low levels of cortisol in the body, after surgery. The study, “Alterations in hypothalamic-pituitary-adrenal function immediately after resection of adrenal adenomas in patients with Cushing’s syndrome and others with incidentalomas and subclinical hypercortisolism,” was published in Endocrine. The HPA axis is the body’s central stress response system. The hypothalamus releases corticotropin-releasing hormone (CRH) that acts on the pituitary gland to release adrenocorticotropic hormone (ACTH), leading the adrenal gland to produce cortisol. As the body’s defense mechanism to avoid excessive cortisol secretion, high cortisol levels alert the hypothalamus to stop producing CRH and the pituitary gland to stop making ACTH. Therefore, in diseases associated with chronically elevated cortisol levels, such as Cushing’s syndrome and adrenal incidentalomas, there’s suppression of the HPA axis. After an adrenalectomy, which is the surgical removal of one or both adrenal glands, patients often have low cortisol levels (hypocortisolism) and require glucocorticoid replacement therapy. “Most studies addressing the peri-operative management of patients with adrenal hypercortisolism have reported that irrespective of how mild the hypercortisolism was, such patients were given glucocorticoids before, during and after adrenalectomy,” the researchers wrote. Evidence also shows that, after surgery, glucocorticoid therapy is administered for months before attempting to test for recovery of HPA function. For the past 30 years, researchers at the University Hospitals Cleveland Medical Center have withheld glucocorticoid therapy in the postoperative management of patients with ACTH-secreting pituitary adenomas until there’s proof of hypocortisolism. “The approach offered us the opportunity to examine peri-operative hormonal alterations and demonstrate their importance in predicting need for replacement therapy, as well as future recurrences,” they said. In this prospective observational study, the investigators extended their approach to patients with subclinical hypercortisolism. “The primary goal of the study was to examine rapid alteration in HPA function in patients with presumably suppressed axis and appreciate the modulating impact of surgical stress in that setting,” they wrote. Collected data was used to decide whether to start glucocorticoid therapy. The analysis included 14 patients with Cushing’s syndrome and 19 individuals with subclinical hypercortisolism and an adrenal incidentaloma. All participants had undergone surgical removal of a cortisol-secreting adrenal tumor. “None of the patients received exogenous glucocorticoids during the year preceding their evaluation nor were they taking medications or had other illnesses that could inﬂuence HPA function or serum cortisol measurements,” the researchers noted. Glucocorticoid therapy was not administered before or during surgery. To evaluate HPA function, the clinical team took blood samples before and at one, two, four, six, and eight hours after the adrenalectomy to determine levels of plasma ACTH, serum cortisol, and dehydroepiandrosterone sulfate (DHEA-S) — a hormone produced by the adrenal glands. Pre-surgery assessment of both groups showed that patients with an incidentaloma plus subclinical hypercortisolism had larger adrenal masses, higher ACTH, and DHEA-S levels, but less serum cortisol after adrenal function suppression testing with dexamethasone. Dexamethasone is a man-made version of cortisol that, in a normal setting, makes the body produce less cortisol. But in patients with a suppressed HPA axis, cortisol levels remain high. After the adrenalectomy, the ACTH concentrations in both groups of patients increased. This was found to be negatively correlated with pre-operative dexamethasone-suppressed cortisol levels. Investigators reported that “serum DHEA-S levels in patients with Cushing’s syndrome declined further after adrenalectomy and were undetectable by the 8th postoperative hour,” while incidentaloma patients’ DHEA-S concentrations remained unchanged for the eight-hour postoperative period. Eight hours after surgery, all Cushing’s syndrome patients had serum cortisol levels of less than 2 ug/dL, indicating suppressed HPA function. As a result, all of these patients required glucocorticoid therapy for several months to make up for HPA axis suppression. “The decline in serum cortisol levels was slower and less steep [in the incidentaloma group] when compared to that observed in patients with Cushing’s syndrome. At the 6th–8th postoperative hours only 5/19 patients [26%] with subclinical hypercortisolism had serum cortisol levels at ≤3ug/dL and these 5 were started on hydrocortisone therapy,” the researchers wrote. Replacement therapy in the subclinical hypercortisolism group was continued for up to four weeks. Results suggest that patients with an incidentaloma plus subclinical hypercortisolism did not have an entirely suppressed HPA axis, as they were able to recover its function much faster than the CS group after surgical stress. From https://cushingsdiseasenews.com/2018/10/11/most-subclinical-cushings-patients-dont-need-glucocorticoids-post-surgery-study/?utm_source=Cushing%27s+Disease+News&utm_campaign=a881a1593b-RSS_WEEKLY_EMAIL_CAMPAIGN&utm_medium=email&utm_term=0_ad0d802c5b-a881a1593b-72451321
All patients who undergo removal of one adrenal gland due to Cushing’s syndrome (CS) or adrenal incidentaloma (AI, adrenal tumors discovered incidentally) should receive a steroid substitutive therapy, a new study shows. The study, “Predictability of hypoadrenalism occurrence and duration after adrenalectomy for ACTH‐independent hypercortisolism,” was published in the Journal of Endocrinological Investigation. CS is a rare disease, but subclinical hypercortisolism, an asymptomatic condition characterized by mild cortisol excess, has a much higher prevalence. In fact, subclinical hypercortisolism, is present in up to 20 percent of patients with AI. The hypothalamic-pituitary-adrenal axis (HPA axis) is composed of the hypothalamus, which releases corticotropin-releasing hormone (CRH) that acts on the pituitary to release adrenocorticotropic hormone (ACTH), that in turn acts on the adrenal gland to release cortisol. To avoid excess cortisol production, high cortisol levels tell the hypothalamus and the pituitary to stop producing CRH and ACTH, respectively. Therefore, as CS and AI are characterized by high levels of cortisol, there is suppression of the HPA axis. As the adrenal gland is responsible for the production of cortisol, patients might need steroid substitutive therapy after surgical removal of AI. Indeed, because of HPA axis suppression, some patients have low cortisol levels after such surgeries – clinically known as post-surgical hypocortisolism (PSH), which can be damaging to the patient. While some researchers suggest that steroid replacement therapy should be given only to some patients, others recommend it should be given to all who undergo adrenalectomy (surgical removal of the adrenal gland). Some studies have shown that the severity of hypercortisolism, as well as the degree of HPA axis suppression and treatment with ketoconazole pre-surgery in CS patients, are associated with a longer duration of PSH. Until now, however, there have been only a few studies to guide in predicting the occurrence and duration of PSH. Therefore, researchers conducted a study to determine whether HPA axis activity, determined by levels of ACTH and cortisol, could predict the occurrence and duration of PSH in patients who undergo an adrenalectomy. Researchers studied 80 patients who underwent adrenalectomy for either CS or AI. Prior to the surgery, researchers measured levels of ACTH, urinary free cortisol (UFC), and serum cortisol after 1 mg dexamethasone suppression test (1 mg-DST). After the surgery, all patients were placed on steroid replacement therapy and PSH was determined after two months. For those with PSH, levels of cortisol were determined every six months for at least four years. Results showed that PSH occurred in 82.4 percent of CS patients and 46 percent of AI patients. PSH lasted for longer than 18 months in 50 percent of CS and 30 percent of AI patients. Furthermore, it lasted longer than 36 months for 35.7 percent of CS patients. In all patients, PSH was predicted by pre-surgery cortisol levels after the 1 mg-DST, but with less than 70 percent accuracy. In AI patients, a shorter-than-12-month duration of PSH was not predicted by any HPA parameter, but was significantly predicted by an absence of pre-surgery diagnosis of subclinical hypercortisolism. So, this study did not find any parameters that could significantly predict with high sensitivity and specificity the development or duration of PSH in all patients undergoing adrenalectomy. Consequently, the authors concluded that “the PSH occurrence and its duration are hardly predictable before surgery. All patients undergoing unilateral adrenalectomy should receive a steroid substitutive therapy.” From https://cushieblog.com/2017/12/14/patients-undergoing-adrenalectomy-should-receive-steroid-substitutive-therapy/