‘Benign’ Adrenal Gland Tumors Might Cause Harm to Millions

Posted on January 8, 2022 by MaryO

Millions of people are at increased risk of type 2 diabetes and high blood pressure and don’t even know it, due to a hidden hormone problem in their bodies.

As many as 1 in 10 people have a non-cancerous tumor on one or both of their adrenal glands that could cause the gland to produce excess amounts of the stress hormone cortisol.

Up to now, doctors have thought that these tumors had little impact on your health.

But a new study out of Britain has found that up to half of people with these adrenal tumors are secreting enough excess cortisol to raise their risk of diabetes and high blood pressure.

Nearly 1.3 million adults in the United Kingdom alone could suffer from this disorder, which is called Mild Autonomous Cortisol Secretion (MACS), the researchers said.

Anyone found with one of these adrenal tumors should be screened to see if their health is at risk, said senior researcher Dr. Wiebke Arlt, director of the University of Birmingham Institute of Metabolism and Systems Research in England.

“People who are found to have an adrenal tumor should undergo assessment for cortisol excess and if they are found to suffer from cortisol overproduction they should be regularly screened for type 2 diabetes and hypertension and receive treatment if appropriate,” Arlt said.

These tumors are usually discovered during imaging scans of the abdomen to treat other illnesses, said Dr. André Lacroix, an endocrinologist at the University of Montreal Hospital Center, who wrote an editorial accompanying the study. Both were published Jan. 4 in the Annals of Internal Medicine.

Adrenal glands primarily produce the hormone adrenaline, but they are also responsible for the production of a number of other hormones, including cortisol, Lacroix said.

Cortisol is called the “fight-or-flight” hormone, and can cause blood sugar levels to rise and blood pressure to surge — usually in response to some perceived bodily threat.

Previous studies had indicated that about 1 in 3 adrenal tumors secrete excess cortisol, and an even lower number caused cortisol levels to rise so high that they affected health, researchers said in background notes.

But this new study of more than 1,300 people with adrenal tumors found that previous estimates were wrong.

About half of these patients had excess cortisol due to their adrenal tumors. Further, more than 15% had levels high enough to impact their health, compared to those with truly benign tumors.

MACS patients were more likely to be diagnosed with high blood pressure, and were as much as twice as likely to be on three or more blood pressure medications.

They also were more likely to have type 2 diabetes, and were twice as likely to require insulin to manage their blood sugar, the study found.

“This study clearly shows that mild cortisol production is more frequent than we thought before, and that the more cortisol you produce, the more likely to you are to have consequences such as diabetes and hypertension,” Lacroix said.

About 70% of people with MACS were women, and most were of postmenopausal age, the researchers said.

“Adrenal tumor-related cortisol excess is an important previously overlooked health issue that particularly affects women after the menopause,” Arlt said.

Lacroix agreed that guidelines should be changed so that people with adrenal tumors are regularly screened.

“Everybody who is found to have an adrenal nodule larger than 1 centimeter needs to be screened to see if they’re producing excess hormone or not,” he said. “That’s very clear.”

A number of medications can reduce cortisol overproduction or block cortisol action, if an adrenal tumor is found to be causing an excess of hormone.

People with severe cortisol excess can even have one of their two adrenal glands removed if necessary, Lacroix said.

“It is quite possible to live completely normally with one adrenal gland,” he said.

More information

The Cleveland Clinic has more about adrenal tumors.

SOURCES: Wiebke Arlt, MD, DSc, director, Institute of Metabolism and Systems Research, University of Birmingham, U.K.; André Lacroix, MD, endocrinologist, University of Montreal Hospital Center; Annals of Internal Medicine, Jan. 4, 2022

From https://consumer.healthday.com/1-4-benign-adrenal-gland-tumors-might-cause-harm-to-millions-2656172346.html

Filed under: adrenal, Diagnostic Testing, Rare Diseases | Tagged: , , , , , , , | Leave a comment »

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

Filed under: Clinical trials, Cushing, Cushing's, Diagnostic Testing | Tagged: , , , , , , , | Leave a comment »

Researchers Report Rare Case of Cushing’s Caused by Bilateral Adrenal Tumors

Posted on July 8, 2019 by MaryO

Cases of adrenocorticotropic hormone (ACTH)-independent Cushing’s syndrome are often caused by unilateral tumors in the adrenal glands, but Indian researchers have now reported a rare case where the condition was caused by tumors in both adrenal glands.

Fewer than 40 cases of bilateral tumors have been reported so far, but an accurate diagnosis is critical for adequate and prompt treatment. Sampling the veins draining the adrenal glands may be a good way to diagnose the condition, researchers said.

The study, “Bilateral adrenocortical adenomas causing adrenocorticotropic hormone-independent Cushing’s syndrome: A case report and review of the literature,” was published in the World Journal of Clinical Cases.

Cushing’s syndrome, a condition characterized by excess cortisol in circulation, can be divided into two main forms, depending on ACTH status. Some patients have tumors that increase the amount of ACTH in the body, and this hormone will act on the adrenal glands to produce cortisol in excess. Others have tumors in the adrenal glands, which produce excess cortisol by themselves, without requiring ACTH activation. This is known as ACTH-independent Cushing’s syndrome.

Among the latter, the disease is mostly caused by unilateral tumors — in one adrenal gland only —  with cases of bilateral tumors being extremely rare in this population.

Now, researchers reported the case of a 31-year-old Indian woman who developed ACTH-independent Cushing’s syndrome because of tumors in both adrenal glands.

The patient complained of weight gain, red face, moon face, bruising, and menstrual irregularity for the past two years. She recently had been diagnosed with high blood pressure and had started treatment the month prior to the presentation.

A physical examination confirmed obesity in her torso, moon face, buffalo hump, thin skin, excessive hair growth, acne, swollen legs and feet, and skin striae on her abdomen, arms, and legs.

Laboratory examinations showed that the woman had an impaired tolerance to glucose, excess insulin, and elevated cortisol in both the blood and urine. Consistent with features of Cushing’s syndrome, cortisol levels had no circadian rhythm and were non-responsive to a dexamethasone test, which in normal circumstances lowers cortisol production.

Because ACTH levels were within normal levels, researchers suspected an adrenal tumor, which led them to conduct imaging scans.

An abdominal computed tomography (CT) scan showed adrenal adenomas in both adrenal glands (right: 3.1 cm × 2.0 cm × 1.9 cm; left: 2.2 cm × 1.9 cm × 2.1 cm). A magnetic resonance imaging (MRI) scan showed that the pituitary gland (which normally produces ACTH) was normal.

To determine whether both adrenal tumors were producing cortisol, researchers sampled the adrenal veins and compared their cortisol levels to those of peripheral veins. They found that the left adrenal gland was producing higher amounts of cortisol, thought the right adrenal gland was also producing cortisol in excess.

“Our case indicates that adrenal vein [blood] sampling might be useful for obtaining differential diagnoses” in cases of Cushing’s syndrome, researchers stated. Also, they may help design a surgical plan that makes much more sense.”

The tumors were surgically removed — first the left, and three months later the right — which alleviated many of her symptoms. She also started prednisolone treatment, which helped resolve many disease symptoms.

“Bilateral cortisol-secreting tumors are a rare cause of Cushing’s syndrome,” researchers said. So when patients present bilateral adrenal lesions, “it is crucial to make a definitive diagnosis before operation since various treatments are prescribed for different causes,” they said.

The team recommends that in such cases the two tumors should not be removed at the same time, as this approach may cause adrenal insufficiency and the need for glucocorticoid replacement therapy.

From https://cushingsdiseasenews.com/2019/06/27/rare-case-of-cs-due-to-bilateral-tumors-in-the-adrenal-glands/

Filed under: adrenal, Cushing's, Rare Diseases, symptoms | Tagged: , , , , , , , , , , , , , | Leave a comment »

Post-traumatic Stress Symptoms Common in Cushing’s Patients Before Surgery

Posted on June 29, 2019 by MaryO

Patients with Cushing’s disease may develop post-traumatic stress symptoms, which are generally resolved once they undergo surgery to remove the tumor, but can persist in some cases, a study shows.

The study, “Posttraumatic stress symptoms (PTSS) in patients with Cushing’s disease before and after surgery: A prospective study,” was published in the Journal of Clinical Neuroscience.

Cushing’s disease is an endocrine disorder characterized by excess secretion of the adrenocorticotropic hormone (ACTH) by a pituitary adenoma (tumor of the pituitary gland). This leads to high levels of cortisol, a condition known as hypercortisolism.

Chronic hypercortisolism is associated with symptoms such as central obesity, buffalo hump, body bruising, muscle weakness, high blood pressure, high blood sugar, and weak bones.

Additionally, patients can develop psychiatric disorders including depression, anxiety, and cognitive dysfunction, all of which contribute considerably to a lower health-related quality of life.

Depression and anxiety rates are particularly high in Cushing’s disease patients, with 54% of them experiencing major depression and 79% having anxiety.

Due to the significant impact of psychological factors in these patients, they may be susceptible to post-traumatic stress symptoms (PTSS). But more information on this phenomenon in these patients is still needed.

To address this lack of data, a group of Chinese researchers conducted a prospective study to investigate the occurrence, correlated factors, and prognosis of PTSS in patients with Cushing’s disease.

A total of 49 patients newly diagnosed with Cushing’s disease who underwent transsphenoidal removal of the tumor as their first-line treatment were asked to participate in this study. Another group of 49 age- and sex-matched healthy individuals were included as controls.

PTSS was measured using the Impact of Event Scale-Revised (IES-R), depression/anxiety were measured using the Hospital Anxiety and Depression scale (HADS), and quality of life was measured using the 36-item short-form (SF-36). These parameters were measured before surgery, and then at six and 12 months after the procedure.

Before surgery, 15 patients (30.6%) had PTSS. These patients also had higher cortisol levels, worse levels of depression/anxiety, and worse quality of life scores than those without PTSS.

While most of the patients recovered after the operation, there were five (33.3%) for whom PTSS persisted for more than a year.

Additionally, one patient who had a recurrence of Cushing’s disease developed PTSS between six and 12 months after the first surgery.

PTSS severity showed consistent improvement after surgery, which was correlated with better depression/anxiety scores and psychological aspects of the SF-36. However, Cushing’s disease patients in remission still performed worse than healthy individuals concerning their physical and mental health.

Therefore, “patients with [Cushing’s disease] can develop PTSS, and they may persist for over a year even after successful surgery. Combined psychological intervention is advised for these patients,” the researchers concluded.

From https://cushingsdiseasenews.com/2019/06/25/cushings-patients-often-have-post-traumatic-stress-symptoms

Filed under: Cushing's, symptoms, Treatments | Tagged: , , , , , , , , , , , , , , , | Leave a comment »

Temozolomide Effective Against Cushing’s Caused by Aggressive Tumors

Posted on June 29, 2019 by MaryO

The oral chemotherapy temozolomide might be an effective treatment for Cushing’s disease caused by aggressive tumors in the pituitary gland that continue to grow after surgery and taking other medications, a case report suggests.

The study, “Successful reduction of ACTH secretion in a case of intractable Cushing’s disease with pituitary Crooke’s cell adenoma by combined modality therapy including temozolomide,” was published in the journal J-Stage.

Cushing’s disease is often caused by a tumor in the pituitary gland that secretes high levels of adrenocorticotropic hormone (ACTH), leading to high levels of cortisol and other symptoms.

Macroadenomas are aggressive, fast-growing tumors that reach sizes larger than 10 millimeters. Crooke’s cell adenoma is a type of macroadenoma that does not respond to conventional therapies, but has deficient mechanisms of DNA repair. That is why chemotherapeutic agents that damage the DNA, such as temozolomide, might be potential treatments.

Researchers in Japan reported the case of a 56-year-old woman with Cushing’s disease caused by a Crooke’s cell adenoma in the pituitary gland who responded positively to temozolomide.

The patient was diagnosed with Cushing’s disease at age 39 when she went to the hospital complaining of continuous weight gain. She also had excessive production of urine and a loss of vision in the right eye.

The lab tests showed high levels of cortisol and ACTH, and the MRI detected a tumor of 4.5 centimeters in the pituitary gland. The doctors removed a part of the tumor surgically, which initially reduced the levels of ACTH and cortisol.

However, the hormone levels and the size of the residual tumor started to increase gradually after the surgery, despite treatment with several medications.

By the time the patient was 56 years old, she went to the hospital complaining of general fatigue, leg edema (swelling from fluid), high blood pressure, and central obesity (belly fat).

Further examination showed a 5.7 cm tumor, identified as a Crooke’s cell macroadenoma. The patient underwent a second surgery to remove as much tumor as possible, but the levels of ACTH remained high. She took temozolomide for nine months, which normalized the levels of ACTH and cortisol. After the treatment, the patient no longer had high blood pressure or leg edema.

The tumor shrunk considerably in the year following temozolomide treatment. The patient started radiation therapy to control tumor growth. The levels of cortisol and ACHT remained normal, and the tumor did not grow in the seven years following temozolomide treatment.

“These clinical findings suggest that [temozolomide] treatment to patients with Crooke’s cell adenoma accompanied with elevated ACTH may be a good indication to induce lowering ACTH levels and tumor shrinkage,” researchers wrote.

Other cases of Cushing’s disease caused by aggressive macroadenomas showed positive results, such as reduction of tumor size and decrease in plasma ACTH, after temozolomide treatment. However, more studies are needed to establish the ideal course of chemotherapy to treat these tumors, the researchers noted.

From https://cushingsdiseasenews.com/2019/06/18/temozolomide-effective-cushings-disease-aggressive-tumors-case-report/

Filed under: Cushing's, Treatments | Tagged: , , , , , , , , | Leave a comment »

« Previous Page — Next Page »