PNA Medical Corner: Cabergoline Research

Dr. Marvin Bergsneider

This month the PNA Medical Corner spotlights a study co-authored by Dr. Marvin Bergsneider of UCLA, a member of the PNA. The study looks a the way
Cabergoline works to target tumors. They describe for the first time the role of CD8+ T cells following CBG-treatment.
Cabergoline Targets Multiple Pathways to Inhibit PRL Secretion and Increases Stromal Fibrosis.
Dongyun Zhang 1, Willy Hugo 1, Marvin Bergsneider 2, Marilene B Wang 3, Won Kim 2, Karam Han 4, Harry V Vinters 4, Anthony P Heaney 1 2

https://pubmed.ncbi.nlm.nih.gov/38781434/                                                      

Abstract

Objective: Unravel potential mechanism(s) of the on- and off-target actions of dopamine agonist therapy in both human prolactinoma tumor and neighboring stromal and immune cells.

Design and methods: Five surgically resected prolactinomas from 3 cabergoline (CBG)-treated and 2 treatment naive patients were analyzed by single cell RNA sequencing (scRNA-seq) to compare the cellular composition and transcriptional landscape.

Results: Six major cell populations that included tumor (88.2%), immune (5.6%), stromal (4.9%), progenitor cells (0.6%), proliferating cells (0.4%), and erythrocytes (0.2%) were observed. Tumor cells from CBG-treated patients expressed lower levels of genes that regulated hormone secretion, such as SCG2, VGF, TIMP1, NNAT, and CALD1, consistent with the inhibitory effects of CBG on hormone processing and secretion. Interestingly, we also observed an increased number of CD8+ T cells in the CBG-treated tissues. These cytotoxic CD8+ T cells expressed killing granule components, such as perforin and the granzymes GZMB, GNLY and KLRD1 as well as the inflammatory cytokine CCL5. Immune cell activation of these CD8+ T cells was further analyzed in a compartment-specific manner, and increased CD25 (IL2R) expression was noted in the CD8+ T cells from CBG-treated samples. Additionally, and confirming prior reports, we noted a higher stromal cell population in CBG-treated samples.

Conclusions: Our scRNAseq studies revealed key differences in the transcriptomic features of CBG-treated and untreated PRLomas in both tumor and microenvironment
cellular constituents, and for the first time describe previously unknown activation of CD8+ T cells following CBG-treatment which may play a role in the tumoricidal actions of CBG.

Keywords: Cabergoline; Pituitary tumor; Prolactinomas; Tumor Microenvironment; scRNAseq.
© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Endocrinology.

Giant pituitary adenomas need expert treatment

Giant pituitary adenomas pose special treatment challenges. Fortunately, advances in medical technology and understanding of the disease have greatly improved the management of these rare pituitary tumors. Experience and expertise are key to achieving the best possible results.

“The treatment options for giant pituitary adenomas have expanded,” says Mayo Clinic neurosurgeon Dr. Richard W. Byrne. “Several factors should be considered when planning treatment. A major multidisciplinary center can outline the best approach for each individual.”

Giant pituitary adenomas are tumors that measure more than 4 centimeters in diameter. Their size means they are often close to important nerves and blood vessels, which complicates surgical removal. Giant pituitary adenomas are also likelier than smaller tumors to cause symptoms such as vision and hormonal problems.

Surgery is the main treatment option. The goal is to improve hormonal and other symptoms while also preserving the pituitary’s function.

The minimally invasive procedure known as endoscopic transnasal transsphenoidal surgery is increasingly applied to giant pituitary adenomas. Mayo Clinic was among the first institutions to extensively research this approach.

“Endoscopic transnasal transphenoidal surgery is associated with lower postoperative complications and a higher likelihood of preserving normal pituitary and visual function. But the surgical team’s level of experience is critical,” Dr. Byrne says. “More-experienced surgeons have a better understanding of the practicalities of tumor removal because they are farther along on the learning curve.”

Tumors extending into certain brain regions generally require open surgery, or craniotomy. “There are several techniques for these open procedures, each of which has advantages and disadvantages,” Dr. Byrne says. Sometimes, open surgery is performed in combination with an endoscopic approach.

Some giant pituitary adenomas can be treated with medication. “A thorough presurgical evaluation can identify patients who might be able to avoid surgery,” Dr. Byrne says. “But it’s important to note that giant pituitary adenomas treated only with medication might need prolonged, annual imaging to detect recurrences.”

Due to their location, some giant pituitary adenomas are difficult to completely remove with surgery. Radiation therapy can be used to treat the remaining tumor. There are several options, including stereotactic radiosurgery, external beam radiation, intensity-modulated radiation therapy and proton beam therapy.

Identifying the best treatment for each individual requires a multidisciplinary team. “Collaboration among neurosurgeons, endocrinologists, and radiation oncologists is crucial for optimal patient care,” Dr. Byrne says.

Choosing the best approach for managing pituitary tumors

Some pituitary tumors don’t need treatment. They aren’t cancer, so if they don’t cause symptoms, monitoring them over time with regular imaging might be a good approach. But some pituitary tumors cause significant problems and require surgical removal.

“Surgery is usually needed if the tumor is pressing on the optic nerves and limiting eyesight, if it’s causing headache or facial pain, or if it’s affecting hormone production,” explains Mayo Clinic neurosurgeon Dr. Chandan Krishna.

The best surgical approach depends on factors such as the tumor’s size, location and growth over time. It’s important to ask your health care provider which surgery is right for you, and to talk about the possible complications, risks and side effects. Surgical options include endoscopic transnasal transsphenoidal surgery, and craniotomy.

“With a transnasal endoscopic approach, we place a surgical instrument through the nostril to access the tumor. We then remove the tumor through the nose and sinuses,” Dr. Krishna says. “The surgery doesn’t need an incision and doesn’t affect other parts of the brain.” Mayo Clinic was among the first institutions to extensively research the endoscopic through-the-nose approach. Now standard practice, the procedure lowers discomfort and usually requires only an overnight stay in the hospital. At Mayo Clinic, ENT/head and neck surgeons work alongside neurosurgeons during these procedures.

Large pituitary tumors might be hard to remove through the nose — especially if the tumor has spread to nearby nerves, blood vessels or other parts of the brain. In those cases, a surgeon generally performs a craniotomy. A small cut is placed in the scalp, and the tumor is removed through the upper part of the skull.

“Both approaches to pituitary tumor removal are generally safe procedures,” Dr. Krishna says. “Complications are uncommon.”

Radiation therapy might be recommended if surgery isn’t feasible. Radiation therapy also might be used if a tumor isn’t completely removed with surgery or if a tumor comes back after surgery. There are several options, including stereotactic radiosurgery, external beam radiation, intensity-modulated radiation therapy and proton beam therapy.

Getting a second opinion or care at a major pituitary center helps ensure the best treatment for each individual. “No two patients are alike. No two pituitary tumors are alike,” Dr. Krishna says. “Experience and expertise in the full range of treatment approaches goes a long way towards providing the best outcomes.”

Count on your Xeris CareConnection™ Team for unparalleled Cushing’s Support

Cushing’s can be challenging, but there is support so patients can feel like themselves again. The main goal of treating Cushing’s is to get cortisol levels back to normal. This Pituitary Awareness Month, Xeris Pharmaceuticals® is highlighting the importance of one-on-one support for patients living with Cushing’s Syndrome and support for HCPs treating Cushing’s Syndrome.

Sign up to get dedicated support:

Patients: Sign up for support | Recorlev® (levoketoconazole)

HCP’s: Connect with Xeris support | RECORLEV® (levoketoconazole)

Have more questions? Call for more support at 1-844-444-RCLV (7258)

PNA Medical Corner: Age and progression-free survival with nonfunctioning pituitary adenomas

Dr. John Atkinson

Dr. Jamie Van Gompel

Dr. Maria Peris Celda

This month the PNA Medical Corner focuses on a study coauthored by three members of the PNA: Drs. John Atkinson, Jamie Van Gompel and Maria Peris Celda. They conclude that older patients with nonfunctioning pituitary tumors had better progression-free survival rates, even when they underwent aggressive surgery.

https://pubmed.ncbi.nlm.nih.gov/38669710/

Correlation of older age with better progression-free survival despite less aggressive resection in nonfunctioning pituitary adenomas

Yuki Shinya ^1 2, John L D Atkinson ¹, Dana Erickson ³, Irina Bancos ³, Carlos D Pinheiro Neto ⁴, Caroline J Davidge-Pitts ³, Maria Peris Celda ¹, Justine S Herndon ³, Sukwoo Hong ^1 2, Jamie J Van Gompel ¹

Abstract

Objective: Nonfunctioning pituitary adenomas (NFPAs) present at a wide range of ages; it is possible that variable

outcomes are based on patient age at presentation. This study aimed to explore long-term outcomes of patients with NFPAs following endonasal transsphenoidal surgery (ETS), considering age stratification.

Methods: This retrospective study included 228 patients with NFPAs who underwent ETS, with a median follow-up period of 63 months. The outcomes included progression-free survival (PFS) rates and neurological and endocrinological outcomes. Age-stratified Kaplan-Meier and Cox proportional hazards analyses were performed. Patients were classified into four age groups: ≤ 49, 50-59, 60-69, and ≥ 70 years.

Results: Age-stratified analysis showed a significant correlation between age and PFS in NFPAs (5-year PFS rates: 63.0% in those ≤ 49 years, 76.7% in those 50-59 years, 85.0% in those 60-69 years, and 88.1% in those ≥ 70 years; p = 0.001, log-rank test). Bivariate (HR 1.03, 95% CI 1.01-1.05; p = 0.001) and multivariable (HR 1.03, 95% CI 1.02-1.05; p = 0.001) analyses demonstrated that older age was significantly associated with longer PFS. Multivariable analysis also demonstrated that smaller maximum tumor diameter (HR 0.77, 95% CI 0.60-0.99; p = 0.036) and gross-total resection (HR 8.55, 95% CI 3.90-18.75; p = 0.001) were significantly associated with longer PFS. Multivariable logistic regression analysis demonstrated that only younger age was associated with postoperative improvement of male hypogonadism (HR 0.91, 95% CI 0.84-0.99; p = 0.019). Other postoperative neurological and endocrinological outcomes were not significantly associated with age.

Conclusions: Older patients with NFPAs treated with ETS demonstrated a longer PFS. Of endocrinological outcomes studied, only male hypogonadism improvement was associated with younger patient age.

Keywords: age-dependent outcome; endonasal transsphenoidal surgery; nonfunctioning pituitary adenomas; pituitary surgery

The FDA has approved NGENLA (somatrogon-ghla)

The FDA has approved NGENLA (somatrogon-ghla), a once-weekly, human growth hormone analog indicated for treatment of pediatric patients aged three years and older who have growth failure due to an inadequate secretion of endogenous growth hormone.

See the Press Release here>

Count on your Xeris CareConnection™ Team for unparalleled Cushing’s Support

Cushing’s can be challenging, but there is support so patients can feel like themselves again. The main goal of treating Cushing’s is to get cortisol levels back to normal. This Pituitary Awareness Month, Xeris Pharmaceuticals® is highlighting the importance of one-on-one support for patients living with Cushing’s Syndrome and support for HCPs treating Cushing’s Syndrome.

Sign up to get dedicated support:

Patients: Sign up for support | Recorlev® (levoketoconazole)

HCP’s: Connect with Xeris support | RECORLEV® (levoketoconazole)

Have more questions? Call for more support at 1-844-444-RCLV (7258)