Environmental Issues and Cushing’s

Posted on December 30, 2025 by MaryO

We’ve had quite a bit of discussion on this topic on the Cushing’s Help message boards.  A few samples:

We live in a part of Ontario known as “the Chemical Valley”. We are surrounded by Dow Chemical, Imperial Oil, Dupont, British Petroleum, Shell Oil and about 12 other chemical plants.
There has been many people complaining about the high rate of cancer in our area and the government was forced to do a health study in our area but as of yet they haven’t figured out how to do the testing. My guess is they don’t want us to know how sick we really are.
We are part of the Goiter Belt which I think extends to PA. There are very few people here who do not have thyroid problems.
My 2 brothers and 2 sisters are suffering the same as I am and so are all our children! Both my parents died in their 50’s from untreated hypothyroid disease. Probably had adrenal/pituitary damage too when I think about their symptoms.
I see hypothyroid people everywhere I look and have since started checking for the hump and cushing signs.
Holy endocrine system Batman, I think we are all suffering at the hands of the Big Oil Companies. My husband works for British Petroleum!!!!

I hate to even think about it. Growing up in Buffalo – erie county new york, which is nestled between lake ontario & lake erie, I don’t believe the water is safe to drink. There are several epa areas of concern around lake ontario & lake erie. AOC’s (areas of concern) are highly polluted areas. Specificlly erie canal & buffalo river are awful. I found out some years ago that a playground that I frequented as a child was a landfill for hazardous chemicals. Now I have a pituitary tumor, coincidence? Probably not

I live near Green Bay WI, which is part of Lake Michigan. I believe our drinking water comes from the Bay. The water is polluted from the papermills (PCPs). I also did play on a heavily fertilized and treated lawn from a chemical company for at least 5 years when I was little. I had a thyroid nodule removed, hypothyroidism, and I am still in the testing phase to see if I have a pituitary tumor. My father also has hopothyroid, and seems to have kind of a hump. He has had cancer as well.
I remember the nuclear accident in the 80’s. It was really scary. I remember them saying something like it was worse than what they reported.

This is one of my future quests, I live in a town on 10,000 people and there are many cases of brain and pituitary tumors, I hear it all the time, I know of at least 3 definite pituitary cushing’s cases in my small town. My future goal when I am feeling better is to put my story in the paper, have people call me if they or someone they know has a funtioning pituitary tumor, also brain tumors and brain cancer has some large numbers too. The state sent me a letter I had to fill out when I first found out about my tumor, it was manditory, if I did not fill it out they where going to have my doctor fill it out so I did. So somewhere someone is keeping track of brain tumors in my town. I want to find out the numbers, if it is as bad as I think it is I am going to calll CDC to find out why. I also want to start a support group. But I need to feel better first because this is going to be a big undertaking.

There are many more postings on this topic.

From Wennersten: There’s something in the water

Scientists now tell us there is something in our waters that we least expected.

That “something” is a class of chemicals called endocrine disruptors, and Dr. Vicki Blazer, a fisheries biologist at the United States Geological Survey, thinks the chemicals are responsible for the high concentrations of intersex fish found in the Potomac, and other rivers in the mid-Atlantic.

The chemicals also prove a threat to human health, but a bit of explanation, first.

Our body’s endocrine system is a complex network of glands and hormones that regulate growth, development, and the operation of various organs. The endocrine glands (for example the thyroid, adrenal, pancreas, testes, ovaries and pituitary glands) release hormones that act as chemical messengers and regulate many life functions.

Endocrine disrupters are chemicals that interfere with this system, by either acting like a hormone, or blocking a hormone’s function. They can be natural, but many are man-made such as PCBs, dioxin, DDT and other pesticides, pharmaceuticals and plasticizers. They are found in many products, including plastic bottles, metal food cans, detergents, flame retardants, food, toys, cosmetics and pesticides. They enter the environment and are now commonly found in our streams, rivers, bays and oceans, where scientists are observing problems.

Then Great Lakes Area of Concerns shows a map of problem areas

Forty-three AOCs have been identified: 26 located entirely within the United States; 12 located wholly within Canada; and five that are shared by both countries. Two Canadian AOCs have been delisted and one U.S. AOC has been delisted leaving 30 AOCs remaining on the U.S. side of the border.

RAPs are being developed for each of these AOCs to address impairments to any one of 14 beneficial uses (e.g., restrictions on fish and wildlife consumption, dredging activities, or drinking water consumption) associated with these areas.  USEPA has assigned RAP Liaisons for AOCs.  Sediments have been identified as serious problems in many AOCs. AOC Principles and Guidelines have been finalized for formally delisting these areas as beneficial uses are restored.

What do YOU think?  Are you in one of these areas?

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Survival Probabilities in Patients with Ectopic Cushing’s Syndrome

Posted on June 9, 2025 by MaryO

Abstract

Objective

We aimed to estimate 1- and 5-year survival probabilities in patients with different forms of ectopic Cushing’s syndrome (ECS) and identify factors influencing survival.

Methods

In this systematic review and meta-analysis, we searched the online databases PubMed, Scopus and Web of Science up to October 18th, 2023, for studies reporting survival in patients with ECS. Data extraction and risk of bias assessment were performed by three independent investigators. Primary outcome was survival in patients with ECS and secondary outcome was factors influencing survival.

Results

We included 40 studies with a total of 1148 patients. The pooled mean 1-year survival probability for ECS of mixed etiologies was 78% while the mean pooled 5-year survival probability was 47%. The 5-year survival probabilities for patients with pulmonary neuroendocrine neoplasm (NEN) was 81%, occult ECS 66%, thymic NEN 50% and pancreatic NEN 40%. Only eight studies reported factors influencing survival, where total resection of the primary tumor was associated with better overall survival, and unresectable tumors, metastatic disease at diagnosis, severe hypercortisolism, hypokalemia, and new onset diabetes mellitus were associated with worse prognosis.

Conclusion

Survival in ECS varies considerably, mainly due to the underlying origin of the tumor, tumor stage and severity of the hypercortisolism. Further studies analyzing the importance of factors affecting survival are needed.

Accepted manuscripts
Accepted manuscripts are PDF versions of the author’s final manuscript, as accepted for publication by the journal but prior to copyediting or typesetting. They can be cited using the author(s), article title, journal title, year of online publication, and DOI. They will be replaced by the final typeset articles, which may therefore contain changes. The DOI will remain the same throughout.

This content is only available as a PDF.

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New Advances For Treating Complex Pituitary Tumors

Posted on May 20, 2025 by MaryO

Pituitary tumors can vary widely in severity, with some requiring surgical intervention. While certain pituitary tumors are more straightforward to remove, those that extend beyond the medial wall of the cavernous sinus (MWCS) are considered complex. A delicate region near the pituitary gland, the MWCS contains critical structures like cranial nerves and the carotid artery, which present additional surgical challenges.

Historically, surgeons avoided entering the cavernous sinus due to the risk of damaging these vital structures, but new advancements have made it possible to remove tumors more effectively and safely. Innovative surgical techniques, such as endoscopic endonasal approaches, are allowing neurosurgeons to navigate these delicate areas with greater precision and confidence than ever before.

Neurosurgeon Dr. Kaisorn Chaichana, who has performed well over 100 such procedures at Mayo Clinic in Jacksonville, Florida, says, “The latest advancements in pituitary surgery are driven by improved camera optics. Angled scopes now let us see around corners, helping us distinguish the pituitary gland from the tumor with far greater precision than traditional microscopes. Doppler and ultrasound also allow us to identify critical structures like the carotid artery, ensuring safer, more complete tumor removal.”

If a tumor that extends into the MWCS is not removed, it may continue producing excessive hormones, leaving patients with persistent symptoms. “It’s almost as if they didn’t have surgery at all because there’s still that tumor there causing that hormonal imbalance. That’s why achieving total removal is so critical for long-term success,” said Dr. Chaichana.

Although the procedure is not entirely new, widespread adoption is relatively recent, and only a few institutions perform this surgery regularly. The complexity of the procedure requires expert knowledge of the surrounding anatomy, as well as careful coordination between neurosurgeons, ear, nose, and throat (ENT) specialists, and post-operative care led by an endocrinologist. “The cavernous sinus is an area a lot of surgeons aren’t comfortable with, and that’s why we specialize in that surgery here,” added Dr. Chaichana. Mayo Clinic’s multidisciplinary approach has improved patient outcomes, allowing for safer tumor removal with reduced complications.

For patients with recurrent tumors or those initially deemed inoperable, re-evaluating surgical options at a specialized center may provide new hope. If the tumor is confined to one side of the carotid artery, surgeons can often achieve a complete resection. However, if it extends beyond this point, additional treatments such as radiation or medical therapy may be required.

Patients facing pituitary surgery should seek a neurosurgeon with experience in endoscopic techniques at a specialized facility with extensive expertise in pituitary tumor treatment.

Choosing the right surgical team can significantly impact outcomes, particularly for complex cases. While not all tumors require MWCS resection, for those that do, this approach offers a path to better surgical success and long-term remission. With ongoing advancements in pituitary surgery, more patients than ever have access to safer, more effective treatment options.

For more information or to request an appointment, please visit Pituitary Tumor Care – Mayo Clinic

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Sparrow Pharmaceuticals Hopes To Change The Future Of Endocrinology

Posted on November 5, 2021 by MaryO

By Ed Miseta, Chief Editor, Clinical Leader
Follow Me On Twitter @EdClinical

Go ahead and continuously improvement iStock-1295289697

Sparrow Pharmaceuticals is an emerging biopharma company on a mission to help patients suffering from an excess of corticosteroids, with a focus on Cushing’s syndrome, autonomous cortisol secretion (ACS), and polymyalgia rheumatica (PMR).

Cushing’s and ACS are both caused by an excess of cortisol produced by tumors. Patients with Cushing’s can present physically with a fatty hump between their shoulders, a rounded face, and pink or purple stretch marks on their skin. Cushing’s syndrome and ACS can both result in high blood pressure, bone loss, type 2 diabetes, weight gain, and mood, cognition, and sleep disorders. Any of those symptoms may be side effects for patients with conditions such as PMR who rely on long-term treatment with corticosteroid medications such as prednisone.

“Cushing’s syndrome impacts around 20,000 patients in the U.S. alone,” says David Katz, Chief Scientific Officer for Sparrow. “Approximately 50% of those patients can be cured by surgery, but some will develop another tumor years later. ACS is an under-recognized condition, but it may affect up to 3 million patients in the U.S. There are also around 2 million people in the U.S. who rely on long-term use of corticosteroid medications to control autoimmune diseases and other conditions.”

The treatments being developed by Sparrow are based on recognition that cortisol and corticosteroid medications are activated in certain tissues such as the liver, bone, fat, and brain, where in excess they act to cause toxicity. The company’s investigational drugs inhibit HSD-1, the enzyme responsible for that activation.

Sparrow is about to launch a Phase 2 trial for Cushing’s syndrome. In early 2022 the company will also begin two additional Phase 2 trials for ACS and PMR, a common autoimmune disease in elderly patients. PMR is an arthritic syndrome characterized by a phenomenon known as claudication, which means the more you use a limb, the more it hurts and the harder it is to use. “For example, the more a PMR patient walks, the more painful and stiff their legs will become,” says Katz. “If they’re trying to do anything with their arms, the arms will get stiffer and more painful. The disease is pretty debilitating in terms of physical function. The only approved treatment for PMR is steroids, which have side effects such as diabetes, hypertension, osteoporosis, and fractures.”

Unknown Clinical Challenges

Katz is excited about the clinical trials for ACS and PMR because no sizable interventional trials have been reported in either of those conditions.

“We’re going into a completely new area, and we don’t know what we’re going to encounter in terms of patient recruitment and retention,” says Katz. “There is also no strong precedent for how to get approval for a drug in these conditions. The only treatment indicated for PMR is steroids, and that came without any efficacy clinical trials. There are no drugs approved for ACS. It’s hard to anticipate the challenges we will face when we are in an area that is very new.”

Patient centricity is a topic that is very important to Katz, and he spends a lot of time thinking about how to make trials a more pleasant experience for patients by limiting the burden placed on them. He notes that can sometimes be a difficult trade-off because of the procedures that must be performed to meet regulatory standards.

“In Cushing’s syndrome clinical care and clinical trials, the standard way for someone’s cortisol level to be measured is a 24-hour urine collection,” states Katz. “That involves looking at the amount of cortisol in the urine over a 24-hour period. That collection is inconvenient and burdensome, and the patient must then carry it somewhere to be analyzed.”

Sparrow hopes to shift that collection to a spot urine sample, like what patients would experience during a physical. The patient would urinate into a cup and hand it off to a clinic employee for analysis. The process would be much simpler and less burdensome for the patient. Sparrow will first need to prove that in a clinical trial the spot sample will work as well or better than the 24-hour collection. Subjects in the initial clinical trials will have to contribute the 24-hour collections so that Sparrow can demonstrate that future patients will not need to do so.

The Future of Endocrinology

Katz has a positive outlook on the future of endocrinology. Sparrow’s leading drug candidate, SPI-62, is an oral, small-molecule HSD-1 inhibitor. In four clinical trials, it demonstrated potent targeting of HSD-1 in both the brain and liver, and significantly lowered cortisol levels in the liver. The studies also showed a favorable safety and tolerability profile.

“If we are successful at developing SPI-62, I believe it will change the field of endocrinology,” says Katz. “We aim to shift the focus in Cushing’s syndrome to intracellular cortisol as the main driver of symptoms. What I mean by that is if we find that SPI-62 substantially reduces symptoms and that the degree of inhibition of our target HSD-1 correlates well with clinical improvement, then we can get to a new standard of care. We can potentially get rid of the 24-hour urine collections, which will be a big relief to patients. Additionally, many of today’s drugs have a side effect called adrenal insufficiency, which results when the drugs either reduce cortisol too much or completely block activity. Many of today’s drugs also require frequent monitoring and dose titration to prevent adrenal insufficiency. We believe that with HSD-1 inhibition we might avoid adrenal insufficiency as well.”

Katz is hopeful patients treated with SPI-62 will not require monitoring and dose titration. That proof will take years and lots of clinical trials. Sparrow may also produce the first targeted therapy for ACS. That could improve the recognition of ACS as a prevalent form of hypercortisolism and a substantial cause of morbidity and mortality.

“ACS is probably the most under-recognized condition in endocrinology based on recent epidemiological studies,” adds Katz. “It’s possible that as few as 3% of patients who have ACS actually have a diagnosis.  That is shocking for a condition that is associated with a lot of cardiometabolic and bone morbidity, negative effects on mood and cognition, sleep, and muscle strength, and is associated with excess mortality. We want to bring attention to this condition by bringing out a targeted therapy to treat a spectrum of symptoms by getting to the root cause of them.”

From https://www.clinicalleader.com/doc/sparrow-pharmaceuticals-hopes-to-change-the-future-of-endocrinology-0001

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Cushing Death Rate ‘Unacceptable,’ Triple That of General Population

Posted on April 15, 2021 by MaryO

Excess mortality among people with endogenous Cushing syndrome (CS) has declined in the past 20 years yet remains three times higher than in the general population, new research finds.

Among more than 90,000 individuals with endogenous CS, the overall proportion of mortality ― defined as the ratio of the number of deaths from CS divided by the total number of CS patients ― was 0.05, and the standardized mortality rate was an “unacceptable” three times that of the general population, Padiporn Limumpornpetch, MD, reported on March 20 at ENDO 2021: The Endocrine Society Annual Meeting.

Excess deaths were higher among those with adrenal CS compared to those with Cushing disease. The most common causes of death among those with CS were cardiovascular diseases, cerebrovascular accident, infection, and malignancy, noted Limumpornpetch, of Songkla University, Hat Yai, Thailand, who is also a PhD student at the University of Leeds, Leeds, United Kingdom.

“While mortality has improved since 2000, it is still significantly compromised compared to the background population…. The causes of death highlight the need for aggressive management of cardiovascular risk, prevention of thromboembolism, infection control, and a normalized cortisol level,” she said.

Asked to comment, Maria Fleseriu, MD, told Medscape Medical News that the new data show “we are making improvements in the care of patients with CS and thus outcomes, but we are not there yet…. This meta-analysis highlights the whole spectrum of acute and life-threatening complications in CS and their high prevalence, even before disease diagnosis and after successful surgery.”

She noted that although she wasn’t surprised by the overall results, “the improvement over time was indeed lower than I expected. However, interestingly here, the risk of mortality in adrenal Cushing was unexpectedly high despite patients with adrenal cancer being excluded.”

Fleseriu, who is director of the Pituitary Center at Oregon Health and Science University, Portland, Oregon, advised, “Management of hyperglycemia and diabetes, hypertension, hypokalemia, hyperlipidemia, and other cardiovascular risk factors is generally undertaken in accordance with standard of clinical care.

“But we should focus more on optimizing more aggressively this care in addition to the specific Cushing treatment,” she stressed.

In addition, she noted, “Medical therapy for CS may be needed even prior to surgery in severe and/or prolonged hypercortisolism to decrease complications…. We definitely need a multidisciplinary approach to address complications and etiologic treatment as well as the reduced long-term quality of life in patients with CS.”

Largest Study in Scale and Scope of Cushing Syndrome Mortality

Endogenous Cushing syndrome occurs when the body overproduces cortisol. The most common cause of the latter is a tumor of the pituitary gland (Cushing disease), but another cause is a usually benign tumor of the adrenal glands (adrenal Cushing syndrome). Surgery is the mainstay of initial treatment of Cushing syndrome. If an operation to remove the tumor fails to cause remission, medications are available.

Prior to this new meta-analysis, there had been limited data on mortality among patients with endogenous CS. Research has mostly been limited to single-cohort studies. A previous systematic review/meta-analysis comprised only seven articles with 780 patients. All the studies were conducted prior to 2012, and most were limited to Cushing disease.

“In 2021, we lacked a detailed understanding of patient outcomes and mortality because of the rarity of Cushing syndrome,” Limumpornpetch noted.

The current meta-analysis included 91 articles that reported mortality among patients with endogenous CS. There was a total of 19,181 patients from 92 study cohorts, including 49 studies on CD (n = 14,971), 24 studies on adrenal CS (n = 2304), and 19 studies that included both CS types (n = 1906).

Among 21 studies that reported standardized mortality rate (SMR) data, including 13 CD studies (n = 2160) and seven on adrenal CS (n = 1531), the overall increase in mortality compared to the background population was a significant 3.00 (range, 1.15 – 7.84).

This SMR was higher among patients with adrenal Cushing syndrome (3.3) vs Cushing disease (2.8) (P = .003) and among patients who had active disease (5.7) vs those whose disease was in remission (2.3) (P < .001).

The SMR also was worse among patients with Cushing disease with larger tumors (macroadenomas), at 7.4, than among patients with very small tumors (microadenomas), at 1.9 (P = .004).

The proportion of death was 0.05 for CS overall, with 0.04 for CD and 0.02 for adrenal adenomas.

Compared to studies published prior to the year 2000, more recent studies seem to reflect advances in treatment and care. The overall proportion of death for all CS cohorts dropped from 0.10 to 0.03 (P < .001); for all CD cohorts, it dropped from 0.14 to 0.03; and for adrenal CS cohorts, it dropped from 0.09 to 0.03 (P = .04).

Causes of death were cardiovascular diseases (29.5% of cases), cerebrovascular accident (11.5%), infection (10.5%), and malignancy (10.1%). Less common causes of death were gastrointestinal bleeding and acute pancreatitis (3.7%), active CS (3.5%), adrenal insufficiency (2.5%), suicide (2.5%), and surgery (1.6%).

Overall, in the CS groups, the proportion of deaths within 30 days of surgery dropped from 0.04 prior to 2000 to 0.01 since (P = .07). For CD, the proportion dropped from 0.02 to 0.01 (P = .25).

Preventing Perioperative Mortality: Consider Thromboprophylaxis

Fleseriu told Medscape Medical News that she believes hypercoagulability is “the least recognized complication with a big role in mortality.” Because most of the perioperative mortality is due to venous thromboembolism and infections, “thromboprophylaxis should be considered for CS patients with severe hypercortisolism and/or postoperatively, based on individual risk factors of thromboembolism and bleeding.”

Recently, Fleseriu’s group showed in a single retrospective study that the risk for arterial and venous thromboembolic events among patients with CS was approximately 20%. Many patients experienced more than one event. Risk was higher 30 to 60 days postoperatively.

The odds ratio of venous thromoboembolism among patients with CS was 18 times higher than in the normal population.

“Due to the additional thrombotic risk of surgery or any invasive procedure, anticoagulation prophylaxis should be at least considered in all patients with Cushing syndrome and balanced with individual bleeding risk,” Fleseriu advised.

A recent Pituitary Society workshop discussed the management of complications of CS at length; proceedings will be published soon, she noted.

Limumpornpetch commented, “We look forward to the day when our interdisciplinary approach to managing these challenging patients can deliver outcomes similar to the background population.”

Limumpornpetch has disclosed no relevant financial relationships. Fleseriu has been a scientific consultant to Recordati, Sparrow, and Strongbridge and has received grants (inst) from Novartis and Strongbridge.

ENDO 2021: The Endocrine Society Annual Meeting: Presented March 20, 2021

Miriam E. Tucker is a freelance journalist based in the Washington, DC, area. She is a regular contributor to Medscape. Other work of hers has appeared in the Washington Post, NPR’s Shots blog, and Diabetes Forecast magazine. She can be found on Twitter @MiriamETucker.

From https://www.medscape.com/viewarticle/949257

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