New way to study pituitary tumors holds potential for better diagnoses and treatments

Posted on February 8, 2020 by MaryO

Houston Methodist neurosurgeons and neuroscientists are looking at a new way to classify pituitary tumors that could lead to more precise and accurate diagnosing for patients in the future.

Found in up to 10% of the population, pituitary tumors, also called adenomas, are noncancerous growths on the pituitary gland and very common. Although these pituitary tumors are benign in nature, they pose a major health challenge in patients.

The new tests being investigated at Houston Methodist not only have the potential to lead to better diagnoses for patients with pituitary adenomas, but also for many other types of brain tumors in the future. The findings, which were published Jan. 28 in Scientific Reports, an online journal from Nature Publishing Group, describe a new way being looked at to study the blood of patients with pituitary tumors to determine exactly what tumor type they have and whether they might respond to medical treatment rather than surgery.

“Often called the ‘master gland,’ the pituitary gland controls the entire endocrine system and regulates various body functions by secreting hormones into the bloodstream to control such things as metabolism, growth and development, reproduction and sleep,” said corresponding author Kumar Pichumani, Ph.D., a research physicist at the Houston Methodist Research Institute. “When pituitary adenomas occur, they may secrete too much of one or more hormones that could lead to a variety of issues, ranging from infertility and sexual dysfunction to vision problems and osteoporosis, among many other health problems.”

Neurosurgeon David S. Baskin, M.D., director of the Kenneth R. Peak Center for Brain and Pituitary Tumor Treatment and Research in the Department of Neurosurgery at Houston Methodist Hospital, collaborated with Pichumani on this study. He said some pituitary tumors can be treated with medication rather than surgery, but a precise diagnosis of the type of tumor someone has and what  it’s secreting is essential for proper treatment. This is sometimes very difficult to do based on standard endocrine hormone testing.

“To guide our decisions on diagnosis and treatment, we currently rely on a blood-based hormone panel test that measures the levels of hormones in the blood to determine which hormones are overproducing in the tumor,” Baskin said. “However, some tumors secrete too much of more than one hormone, making this test ambiguous for diagnosis.”

Led by Pichumani and Baskin, a team of researchers from the Peak Brain and Pituitary Tumor Treatment and Research Center and Houston Methodist Neurological Institute studied 47 pituitary adenoma patients of different subtypes by collecting blood during surgery to remove their tumors. They confirmed that elevated blood levels of a non-hormonal compound called betahydroxybutyrate, also known as BHB, was found only in patients with the prolactinoma subtype of noncancerous pituitary gland brain tumor that overproduces the hormone prolactin. This compound is known to supply energy to the brain during starvation, which led the researchers to speculate that BHB might be providing non-hormonal energy to these prolactinoma tumors causing them to grow and spread. The discovery could be further developed into a diagnostic lab test.

This study is part of a developing field called metabolomics in which researchers study small molecules in tumors to see what’s unique about their metabolism and how they’re used as nutrients to supply energy. This contributes to better diagnoses and discovering new ways to kill tumors by poisoning the specific energy they use without causing damage to normal cells.

The researchers are now enrolling more patients in a larger study currently underway to validate the results of their pilot study. If successful, they say BHB could be used as a non-hormonal metabolic biomarker for prolactinoma pituitary tumor diagnosis and prognosis to supplement the current hormone panel tests. They’re also looking for biological reasons why only prolactin-secreting tumors have elevated BHB blood levels to inform therapeutic intervention.

From https://medicalxpress.com/news/2020-02-pituitary-tumors-potential-treatments.html

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Fluorescent Metabolite Might Help Surgeons Remove Pituitary Tumors

Posted on April 14, 2018 by MaryO

The resection of microadenomas — small, benign tumors in the pituitary gland underlying Cushing’s disease — could be aided by a fluorescent marker that is naturally produced by the tumor, a new study shows.

The findings were presented recently at the 2018 George Washington Research Days in a poster titled, “Enhanced 5-ALA Induced Fluorescence in Hormone Secreting Pituitary Adenomas.”

Cushing’s disease is characterized by high cortisol levels that cause debilitating physical, mental, and hormonal symptoms. The excess cortisol is caused by tiny benign tumors in the pituitary gland, called microadenomas, with a size of less than 10 millimeters.

On account of their small size, these microadenomas pose imaging challenges to physicians. Up to 40 percent of microadenomas remain undetected in the gold-standard magnetic resonance imaging (MRI).

Pituitary adenomas, however, have a characteristic that distinguishes them from the surrounding healthy tissue. They process (metabolize) a natural haemoglobin metabolite, called 5-aminolevulinic acid (5-ALA), into protoporphyrin IX (PpIX) at much higher rates — up to 20 to 50 times higher — than normal tissues.

Importantly, PpIX emits red fluorescence when excited with blue light.

This means that exogenous 5-ALA is taken up by the adenoma cells and rapidly metabolized into the fluorescent metabolite, PpIX, which may establish its use for fluorescence-guided resection of pituitary adenomas.

To test this, researchers incubated human-derived corticotropinoma, as well as the adjacent normal gland cells with 5-ALA. They did the same with mouse model normal pituitary cells and a mouse model pituitary tumor cell line, called AtT20.

They then analyzed the cells’ fluorescence profile by microscopy and with a technique called flow cytometry.

The analysis showed that compared to normal pituitary tissue, human-derived adenomatous cells had a significant increase of tenfold in 5-ALA-induced PpIX fluorescence intensity.

Similarly, mouse pituitary tumor cells (AtT20 cell line) fluoresced seven times more intensely than normal murine pituitary tissue.

The microscopy analysis revealed that the 5-ALA localized in subcellular organelles called mitochondria.

On June 6, 2017, the U.S. Food and Drug Administration approved the use of 5-ALA (under the brand name Gleolan) as an optical imaging agent for patients with gliomas (brain tumors), as an add-on compound to assist surgeons in identifying the malignant tissue during surgery.

Now, these findings suggest that 5-ALA also may be used for fluorescence-guided surgery of microadenomas in Cushing’s disease.

“The supraphysiological levels of glucocorticoids, as seen in CD [Cushing’s disease], may enhance the 5-ALA fluorescence in corticotropinomas,” researchers wrote.

From https://cushingsdiseasenews.com/2018/04/13/fluorescent-metabolite-might-help-surgeons-removepituitary-tumors/

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Pituitary tumors require collaborative care for best treatment results

Posted on September 28, 2017 by MaryO

A statement released by the Pituitary Society outlines criteria for developing pituitary tumor centers of excellence and asserts that the best care for patients comes from a collaboration of endocrinologists and experienced pituitary surgeons.

“Such a core team needs to be supported by a collaborative environment of specialists in other areas, such as neuroradiology, neuropathology, radiation oncology, neuro-ophthalmology, otorhinolaryngology, plus trained nursing,” the authors wrote.

Felipe F. Casanueva, MD, PhD, professor of medicine in the department of medicine, endocrine division at Santiago de Compostela University in Spain, and nine other experts served as a task force to develop the statement.

The authors wrote that goals of the collaborative team should include the following:

  • detecting the tumor early;
  • diagnosing the tumor;
  • determining the most suitable treatment, whether observation, surgical, medical or radiotherapy;
  • removing the pituitary mass and preserving normal pituitary tissue, if surgical treatment is needed;
  • using treatments that eliminate hormonal hypersecretion and/or its effects;
  • preventing tumor recurrence; and
  • recognizing and caring for delayed complications.

“The final goal is the elimination or at least reduction of the excess morbidity and mortality associated with the tumor and hypersecretion syndrome as well as treatment of accompanying pituitary hormone insufficiencies,” the authors wrote. “For many patients, this requires a program of care, including medical therapy, surgery and radiation therapy, in addition with long-term follow-up.”

Further, pituitary tumor centers of excellence should be patient-centered and focus on engagement activity, family impact, educational platforms and digital infrastructure to facilitate care across specialties.

“In the last few decades, a considerable body of evidence supports the concept that patients with pituitary tumors would receive the best care from units of excellence composed of expert neurosurgeons performing pituitary surgery by transsphenoidal and other approaches, plus experienced neuroendocrinologists devoted to these types of tumors,” the authors wrote. “These experts, working in liaison with supporting units, would form a center of excellence for pituitary tumors (PTCOE). Such a center would be the optimal organization for patients, the most cost-effective for health administrators, and a more suitable structure to allow for derivation and presentation of results, and advancement of pituitary science.” – by Amber Cox

Disclosures: Casanueva reports he is a consultant and receives lecture fees from Novo Nordisk, Orexigen and Pronokal and is a member of the board of directors of the Pituitary Society. Please see the study for all other authors’ relevant financial disclosures.

From https://www.healio.com/endocrinology/neuroendocrinology/news/in-the-journals/%7B94d60bd1-9b48-4da4-b54f-fce7fea5b7df%7D/pituitary-tumors-require-collaborative-care-for-best-treatment-results

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Cushing Syndrome in Children: Growth after Surgical Cure

Posted on October 22, 2014 by MaryO

Cushing syndrome (CS) occurs only rarely in children, but when it does, it causes weight gain and stunting. In young children, adrenal tumors are usually the cause while in adolescents, pituitary tumors are more likely.

The September 2014 issue of Endocrine-Related Cancer examines growth patterns in 19 pediatric patients with ACTH-dependent CS (CD) and 18 patients with a form of ACTH-independent CS, micronodular adrenal hyperplasia (MAH). The researchers gathered data at the time of surgery and also followed up one year later.

Patients in the CD and the MAH groups had similar demographic characteristics, baseline heights and BMI scores before surgery. All patients experienced significant improvements in height and BMI after surgery. Patients with MAH, however, fared significantly better than those with CD and had better post-operative growth.

The researchers propose several reasons:

  • When ACTH-secreting pituitary adenoma requires extensive surgical exploration, remaining pituitary cells often lose some of their function.
  • CD patients tend to be older and have consistent and increased glucocorticoid exposure; they develop vertebral fractures more often leading to compromised skeletal and overall growth potential. MAH patients often have cyclical CS, with intermittent hypercortisolism and an overall milder CS.
  • CD patients often need a longer-than-expected course of therapy with steroids after surgery, which alters metabolism and growth.
  • CD patients have been shown to have advance bone age because of ACTH-induced metabolic changes.

The authors indicate that CS patients are often considered for growth hormone therapy once the underlying problem is corrected. They remind clinicians that MAH patients are less likely to need growth hormone. They recommend close monitoring for CD patients, and early intervention with growth hormone if growth does not meet expectation. –

See more at: http://www.hcplive.com/articles/Cushing-Syndrome-in-Children-Growth-after-Surgical-Cure

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

Cushing’s Awareness Challenge, Day 3: Symptoms

Posted on April 3, 2014 by MaryO

robin-symptoms

 

Robin has made another excellent graphic of some of the symptoms of Cushing’s.  There are far too many to be listed in any image, as shown by the list at http://www.cushings-help.com/toc.htm#symptoms

 

Just to be silly, a few years ago, I did my own version of Cushing’s symptoms:

 

The Seven Dwarves of Cushing's

Filed under: Cushing's, Cushing's Awareness Challenge 2014, FAQ, pituitary, Rare Diseases | Tagged: , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , | Leave a comment »

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