Bilateral Adrenocortical Adenomas Causing Adrenocorticotropic Hormone-Independent Cushing’s Syndrome

Posted on May 27, 2019 by MaryO

Adrenocorticotropic hormone (ACTH)-independent Cushing’s syndrome (CS) is mostly due to unilateral tumors, with bilateral tumors rarely reported. Its common causes include primary pigmented nodular adrenocortical disease, ACTH-independent macronodular adrenal hyperplasia, and bilateral adrenocortical adenomas (BAAs) or carcinomas. BAAs causing ACTH-independent CS are rare; up to now, fewer than 40 BAA cases have been reported. The accurate diagnosis and evaluation of BAAs are critical for determining optimal treatment options. Adrenal vein sampling (AVS) is a good way to diagnose ACTH-independent CS.

A 31-year-old woman had a typical appearance of CS. The oral glucose tolerance test showed impaired glucose tolerance and obviously increased insulin and C-peptide levels. Her baseline serum cortisol and urine free cortisol were elevated and did not show either a circadian rhythm or suppression with dexamethasone administration. The peripheral 1-deamino-8-D-arginine-vasopressin (DDVAP) stimulation test showed a delay of the peak level, which was 1.05 times as high as the baseline level. Bilateral AVS results suggested the possibility of BAAs. Abdominal computed tomography showed bilateral adrenal adenomas with atrophic adrenal glands (right: 3.1 cm × 2.0 cm × 1.9 cm; left: 2.2 cm × 1.9 cm × 2.1 cm). Magnetic resonance imaging of the pituitary gland demonstrated normal findings. A left adenomectomy by retroperitoneoscopy was performed first, followed by resection of the right-side adrenal mass 3 mo later. Biopsy results of both adenomas showed cortical tumors. Evaluations of ACTH and cortisol showed a significant decrease after left adenomectomy but could still not be suppressed, and the circadian rhythm was absent. Following bilateral adenomectomy, this patient has been administered with prednisone until now, all of her symptoms were alleviated, and she had normal blood pressure without edema in either of her lower extremities.

BAAs causing ACTH-independent CS are rare. AVS is of great significance for obtaining information on the functional state of BAAs before surgery.

World journal of clinical cases. 2019 Apr 26 [Epub]

Yu-Lin Gu, Wei-Jun Gu, Jing-Tao Dou, Zhao-Hui Lv, Jie Li, Sai-Chun Zhang, Guo-Qing Yang, Qing-Hua Guo, Jian-Ming Ba, Li Zang, Nan Jin, Jin Du, Yu Pei, Yi-Ming Mu

Department of Endocrinology, Chinese People’s Liberation Army General Hospital, Beijing 100853, China., Department of Endocrinology, Chinese People’s Liberation Army General Hospital, Beijing 100853, China. guweijun301@163.com., Department of Pathology, Chinese People’s Liberation Army General Hospital, Beijing 100853, China.

PubMed http://www.ncbi.nlm.nih.gov/pubmed/31119141

From https://www.urotoday.com/recent-abstracts/urologic-oncology/adrenal-diseases/112782-bilateral-adrenocortical-adenomas-causing-adrenocorticotropic-hormone-independent-cushing-s-syndrome-a-case-report-and-review-of-the-literature.html

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Scientists Discover Biological Reason Why Women Are More Likely to Develop Adrenal Disorders

Posted on May 25, 2019 by MaryO

Scientists have discovered a potential biological reason why women are more likely to develop adrenal disorders, including cancer. According to the researchers, the answer could lie in the increased turnover of hormone-producing cells found in the adrenal glands of females.

The adrenal gland is a hormone producing organ that sits on top of the kidneys. The outer part, or cortex, is responsible for the production of several hormones, including the stress-related hormone cortisol and the blood pressure controlling aldosterone. Adrenal cancer is relatively rare but occurs approximately three times more in women than in men. The cellular basis for this difference has not been investigated in detail but uncovering it might lead to sex-specific treatments and has huge implications for many areas of research.

Dr Andreas Schedl, from INSERM, France, who led the study said:

To our surprise we found that adrenal cells in female mice show a much more rapid turnover compared to males, which we could trace back to a different behaviour of adrenal stem cells between the two sexes. Furthermore, we could show that the observed differences are due to hormones that are produced by testes that suppress cell division, thus slowing down renewal in the male adrenal.”

The scientists studied the adrenal cortex of male and female adult mice and found that female mice replace their entire set of hormone-producing cells within 3 months, while it takes male mice an entire 9 months. Using different techniques to label cells within the adrenal cortex, they established that females not only have a higher proliferation rate of cells, but also recruit stem cells from a different part of the adrenal gland.

The research has wide reaching implications, as it demonstrates the basic mechanism underlying the increased turnover of cells within the adrenal gland, providing a possible explanation for the increased incidence of adrenal disorders in women.

Dr Schedl explained: “It is early days and many more experiments will need to be performed before our research can directly benefit patients. However, we believe that our study teaches a number of important lessons that are of immediate relevance to scientists, pharmacologists and clinicians.”

This research might lead to sex-specific treatment options for diseases like adrenal cancer and, according to Dr Schedl, could have implications on a far wider field of disorders: “Importantly, while our study concentrated on the adrenals, we are convinced that similar differences may also be found in other organ systems.”

Dr Helen Rippon, Chief Executive of the charity Worldwide Cancer Research, whose supporters helped fund the study, said: “Sex differences are not necessarily the first thing that comes to mind when thinking about cancer research or treatments. But this study has shown that it is crucial to consider potential differences between male and female when trying to understand the basis of cancer biology. Most importantly, these findings could have implications for treatment options further down the line and highlight the importance of early-stage, discovery research. We are delighted to fund this kind of research, as we believe that these innovative approaches are ultimately going to lead to a world where no life is cut short by cancer.”

Worldwide Cancer Research, La Ligue Contre le Cancer and the ANR supported this research. The research was published in Cell Stem Cell.

Source:

Worldwide Cancer Research

Journal reference:

Grabek, A. et al. (2019) The Adult Adrenal Cortex Undergoes Rapid Tissue Renewal in a Sex-Specific Manner. Cell Stem Cell. doi.org/10.1016/j.stem.2019.04.012.

From https://www.news-medical.net/news/20190522/Scientists-discover-biological-reason-why-women-are-more-likely-to-develop-adrenal-disorders.aspx

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Even in Remission, Cushing’s Patients Have Excess Mortality

Posted on March 11, 2019 by MaryO

Cushing’s disease patients in Sweden have a higher risk of death than the general Swedish population, particularly of cardiovascular complications, and that increased risk persists even in patients in remission, a large nationwide study shows.

The study, “Overall and disease-specific mortality in patients with Cushing’s disease: a Swedish nationwide study,” was published in the Journal of Clinical Endocrinology and Metabolism.

The outcomes of Cushing’s disease patients have improved with the introduction of several therapeutic approaches, such as minimally invasive surgery and cortisol-lowering therapies. However, mortality is still high, especially among those who do not achieve remission.

While currently patients in remission are thought to have a better prognosis, it is still unclear whether these patients still have a higher mortality than the general population. Understanding whether these patients are more likely to die and what risk factors are associated with increased mortality is critical to reduce death rates among Cushing’s patients.

A team of Swedish researchers thus performed a retrospective study that included patients diagnosed with Cushing’s disease who were part of the Swedish National Patient Registry between 1987 and 2013.

A total of 502 patients with Cushing’s disease were included in the study, 419 of whom were confirmed to be in remission. Most patients (77%) were women; the mean age at diagnosis was 43 years, and the median follow-up time was 13 years.

During the follow-up, 133 Cushing’s patients died, compared to 54 expected deaths in the general population — a mortality rate 2.5 times higher, researchers said.

The most common causes of death among Cushing’s patients were cardiovascular diseases, particularly ischemic heart disease and cerebral infarctions. However, infectious and respiratory diseases (including pneumonia), as well as diseases of the digestive system, also contributed to the increased mortality among Cushing’s patients.

Of those in remission, 21% died, compared to 55% among those not in remission. While these patients had a lower risk of death, their mortality rate was still 90% higher than that of the general population. For patients who did not achieve remission, the mortality rate was 6.9 times higher.

The mortality associated with cardiovascular diseases was increased for both patients in remission and not in remission. Also, older age at the start of the study and time in remission were associated with mortality risk.

“A more aggressive treatment of hypertension, dyslipidemia [abnormal amount of fat in the blood], and other cardiovascular risk factors might be warranted in patients with CS in remission,” researchers said.

Of the 419 patients in remission, 315 had undergone pituitary surgery, 102 had had their adrenal glands removed, and 116 had received radiation therapy.

Surgical removal of the adrenal glands and chronic glucocorticoid replacement therapy were associated with a worse prognosis. In fact, glucocorticoid replacement therapy more than twice increased the mortality risk. Growth hormone replacement was linked with better outcomes.

In remission patients, a diagnosis of diabetes mellitus or high blood pressure had no impact on mortality risk.

Overall, “this large nationwide study shows that patients with [Cushing’s disease] continue to have excess mortality even after remission,” researchers stated. The highest mortality rates, however, were seen in “patients with persistent disease, those who were treated with bilateral adrenalectomy and those who required glucocorticoid replacement.”

“Further studies need to focus on identifying best approaches to obtaining remission, active surveillance, adequate hormone replacement and long-term management of cardiovascular and mental health in these patients,” the study concluded.

From https://cushingsdiseasenews.com/2019/02/28/even-in-remission-cushings-patients-have-excess-mortality-swedish-study-says/

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Laparoscopic Removal of Adrenal Glands Safe for Obese Cushing’s Patients

Posted on March 9, 2019 by MaryO

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/

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Cushing’s Syndrome Patients at More Risk of Blood-clotting Problems After Adrenal Surgery

Posted on February 16, 2019 by MaryO

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/

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