Even in Remission, Cushing’s Patients Have Excess Mortality

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/

Rare Disease Day 2019

rare disease day

 

Each and every day since 1987,  I tell anyone who will listen about Cushing’s.  I pass out a LOT Cushing’s business cards. My husband also passes out cards and brochures.

Adding to websites, blogs and more which I have maintained continuously since 2000 – at mostly my own expense.

Posting on the Cushing’s Help message boards about Rare Disease Day.  I post there most every day.

Tweeting/retweeting info about Cushing’s and Rare Disease Day today.

Adding info to one of my blogs about Cushing’s and Rare Disease Day.

Adding new and Golden Oldies bios to another blog, again most every day.

Thinking about getting the next Cushing’s Awareness Blogging Challenge set up for April…and will anyone else participate?

And updating https://www.facebook.com/CushingsInfo with a bunch of info today (and every day!)

~~~

Today is Rare Disease Day.

I had Cushing’s Disease due to a pituitary tumor. I was told to diet, told to take antidepressants and told that it was all my fault that I was so fat. My pituitary surgery in 1987 was a “success” but I still deal with the aftereffects of Cushing’s and of the surgery itself.

I also had another Rare Disease – Kidney Cancer, rare in younger, non-smoking women.

And then, there’s the secondary adrenal insufficiency…and growth hormone deficiency

If you’re interested, you can read my bio here: https://cushingsbios.com/2018/10/28/maryo-pituitary-bio/

What are YOU doing for Rare Disease Day?

 

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Cushing’s Disease Patients with USP8 Mutations More Likely to Achieve Remission After Surgery

Cushing’s disease patients whose pituitary tumors carry a USP8 mutation are more likely to achieve remission after surgery than those without such mutations, a retrospective Italian study found.

The study, “Clinical characteristics and surgical outcome in USP8-mutated human adrenocorticotropic hormone-secreting pituitary adenomas,” was published in the journal Endocrine.

Cushing’s disease is a condition where a tumor on the pituitary gland produces too much of the adrenocorticotropin hormone (ACTH), which will act on the adrenal gland to make cortisol in excess.

While rare, the condition can be life-threatening, as excess cortisol is linked to an increased risk of infections and cardiovascular complications, along with an increased likelihood of obesity and diabetes.

The reasons some patients develop these pituitary adenomas are far from understood, but researchers recently found that some of these patients show mutations in the USP8 gene. These appear to increase EGFR signaling which, in turn, has a stimulatory role for the synthesis of ACTH.

But more than influencing the development of Cushing’s disease, researchers believe the USP8 mutations may also determine response to treatment.

Thus, a team in Italy examined whether patients with USP8 mutations presented different clinical features and responded differently to the standard surgical procedure, called transsphenoidal pituitary surgery.

The study included 92 patients with ACTH-secreting pituitary tumors who received surgery at the neurosurgical department of the Istituto Scientifico San Raffaele in Milan between 1996 and 2016.

“All surgical procedures were performed by the same experienced neurosurgeon, which is one of the most important factors affecting early and late surgical outcome of pituitary adenomas,” researchers explained.

Among study participants, 22 (23.9%) had mutations in the USP8 gene, but these mutations were significantly more common in women than in men — 28.7% vs. 5.3%. Researchers think estrogens — a female sex hormone — may have a role in the development of mutated pituitary tumors.

Overall, the two groups had similar tumor size and aggressiveness and similar ACTH and cortisol levels before surgery. But among those with microadenomas — tumors smaller then 10 mm in diameter — USP8-mutated patients had significantly larger tumor diameters.

After receiving surgery, 81.5% of patients achieved surgical remission — deemed as low cortisol levels requiring glucocorticoid replacement therapy, normal cortisol levels in urine, and normal response to a dexamethasone-suppression test.

But remission rates were significantly higher among those with USP8 mutations — 100% vs. 75.7%. Also, USP8 mutation carriers required steroid replacement therapy for shorter periods, despite ACTH and cortisol levels being similar among the two groups after surgery.

Among patients who entered remission, 12 (16%) saw their disease return. While more patients with USP8 mutations experienced a recurrence — 22.7% vs. 13.2% — this difference was not significant. After five years, 73.8% of UPS8-mutated patients remained alive and recurrence-free, which researchers consider comparable to the 88.5% seen in patients without the mutation.

Researchers also tested sex, age at surgery, and post-surgical ACTH and cortisol levels as possible predictors of disease recurrence, but none of these factors was associated with this outcome.

“ACTH-secreting pituitary adenomas carrying somatic USP8 mutations are associated with a greater likelihood of surgical remission in patients operated on by a single neurosurgeon. Recurrence rates are not related with USP8-variant status,” researchers concluded.

From https://cushingsdiseasenews.com/2018/10/23/cushings-disease-patients-usp8-mutations-more-likely-achieve-remission-after-surgery/

Finding Ways to Deal with Post-surgery Anxieties

Post-traumatic stress disorder (PTSD) following Cushing’s disease is a real issue many of us face. However, we don’t have to let it control our lives — there are ways to cope.

Cushing’s changes us both mentally and physically. We become forgetful. We lose strength. We become someone we don’t recognize in the mirror. We lose hair on our heads and gain it everywhere else. We’re always in pain, and we’re always sick, with no end in sight (or at least it feels that way).

Some days will be trying and seem as if nothing seems to work, no matter what you do. I promise that you’re not alone, and you will make it through those days.

Following are a list of ways to deal with post-surgery scares:

  • Therapy/counseling: If you can afford it, talk with a professional about your health worries and how your anxiety affects you. It takes the burden off your caregivers who don’t like to see you suffer because they care so much.
  • Journaling: Journaling is a therapeutic and inexpensive way to let out your worries. Documenting your anxieties can help you keep track of how your thought processes are changing. Writing out your stresses is cathartic. Give it a try — if you haven’t already.
  • Yoga or any light exercise: If you’re in the early stages of recovery, you shouldn’t go straight back to the gym — working out is a stressor on the body. Light yoga, such as restorative yoga, in which you practice stretching, deep breathing, and relaxation, will help your mind and body to recover. Light walks are amazing for the brain and body post-surgery.
  • Delve into things you enjoy: Read, cook, go for walks, sit outside, etc. Do whatever feeds your soul and keeps your mind free from negative thoughts. Feeding your soul is one sure way to keep your mind and body happy and healthy.
  • Other ideas from the CushieWiki
  • Please share your ideas in the comments on this post or on the message boards

Adapted from https://cushingsdiseasenews.com/2018/10/19/cushings-post-surgery-anxieties-ptsd-post-traumatic-stress-disorder-journaling-yoga-therapy/

Transsphenoidal Surgery Is Safe and Effective Treatment for Cushing’s Disease

Transsphenoidal surgery, a minimally invasive surgery to remove tumors in the pituitary gland, is safe and effective to treat Cushing’s disease, a 20-year history of cases in a Belgian hospital shows.

The surgery resulted in high remission rates (83%) in patients. It was also found to be safe, rarely leading to insufficient functioning of the pituitary gland.

The study, “Outcome of transsphenoidal surgery for Cushing’s Disease: a single-center experience over 20 years,” was published in the journal World Neurosurgery.

Surgical removal of tumors in the pituitary gland of the brain remains the gold standard for Cushing’s disease treatment.

Transsphenoidal surgery (TSS) usually leads to good remission rates ranging from 68-95%, depending on the location and type of tumor, the neurosurgeon’s expertise, follow-up period, and the definition of remission.

Today, TSS consists of surgery directed through the nose to get to the bottom of the skull, where the pituitary gland is located. The tumor is reached via the nasal cavity with no need for incisions on the face.

To address the safety and effectiveness of this type of surgery for treating Cushing’s, researchers retrospectively reviewed the outcome of 71 patients who received their first TSS at Saint-Luc Hospital, Belgium, between 1996 and 2017. Patients were followed for an average of 6.8 years (82 months).

Surgeons used a type of TSS that is image-guided with the help of a microscope which magnifies the surgeon’s vision.

Remission was defined as normal fasting cortisol level, normal 24-hour urinary-free cortisol, or prolonged need for hydrocortisone replacement for one year after surgery.

Replacement therapies are sometimes needed when the pituitary is not producing enough cortisol after surgery.

Patients were mostly women, ages 15 to 84. Some of them, 32%, required multiple surgeries.

In total, 46 patients out of 71 were in remission after the first surgery, 11 after the second surgery, one after the third, and one after the fourth intervention.

A successful first surgery, resulting in a one-year remission, was a positive indicator for patients, as it was associated with high final remission rates (95%).

However, if the first surgery failed, only 36% of patients achieved a final remission.

“Obtaining a lasting remission after a first TSS could be an interesting parameter to influence future therapeutic decisions [like] performing repeated surgery rather than choosing second-line therapies,” researchers wrote.

Overall, remission was achieved in 83% of patients who underwent a single or multiple TSS intervention, a recurrence rate comparable to previous reports.

Surgery was particularly successful for curing patients with macroadenomas — tumors larger than 10 mm — leading to a 92% remission rate.

Small tumors that were not visible on magnetic resonance imaging (MRI) scans were more difficult to treat, with only 71% of patients being cured. Still, such a remission rate was better than what is commonly reported for MRI-negative tumors. This is likely explained by a higher level of expertise by the surgeon.

Levels of cortisol one day after TSS were significantly lower in patients with long-term remission. However, high levels were still observed in a few patients, especially those who had Cushing’s disease for many years.

“Therefore, high cortisol levels in the postoperative early days do not always indicate persistent disease and later [cortisol] evaluation is warranted,” the researchers wrote.

Most complications from surgery were minor and transient, except for seven patients who developed diabetes. Only 8.8% of patients developed long-term failure of the pituitary gland, likely because physicians favored a less aggressive intervention plan to leave the pituitary gland as intact as possible.

However, such an approach may also explain why some patients had to undergo multiple surgeries to completely remove the tumor.

In addition, a longer duration of Cushing’s disease symptoms and higher cortisol levels before surgery could significantly predict a poorer likelihood of being cured by TSS.

“Neuronavigation-guided microscopic TSS is a safe and effective primary treatment for [Cushing’s disease], allowing high remission rates,” the researchers wrote.

From https://cushingsdiseasenews.com/2018/07/26/transsphenoidal-surgery-safe-effective-treatment-cushings-disease/

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