“Take care of your body. It’s the only place you have to live in.”

 

 

— Jim Rohn

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.”

Featured News and Updates

News Articles April 2025

Pituitary journey: woman learns to slow down while facing melanoma, pituitary inflammation

Blogger Amanda Goodwin is a hard-charging businesswoman, who was forced to slow down and “embrace the sick” as she battled melanoma in her lungs, liver and brain, and suffered from inflammation of the pituitary. Read more here: https://substack.com/home/post/p-156259244?utm_campaign=post&utm_medium=web

 

Study: Cushing’s patients develop cataracts at younger ages

An article in Cushing’s Disease News examines a study published in Graefe’s Archive for Clinical and Experimental Ophthalmology, that finds that Cushing’s patients are at higher risk of developing cataracts at a younger age compared to non-Cushing’s patients.  They developed them at an average age of 48.1. Patients with Cushing’s Syndrome “being 34% more likely to develop cataracts than the general population. For those with Cushing’s disease, the risk was 39% higher.” Read more: https://cushingsdiseasenews.com/news/cushings-patients-higher-risk-developing-cataracts-younger-age/

 

Pituitary Journey: British celebrity astrologer recounts battle with pituitary tumor

Russell Grant, a celebrity astrologer in the U.K. who competed on the show “Strictly Come Dancing” recounts his battle with a pituitary tumor, diabetes, and now vision issues. Read more: https://tinyurl.com/44zujvkm

Houston Hospital gets $2 million in donations for pituitary research

Houston Methodist hospital announced it has commitments to receive 2 million dollars to support its Kenneth R. Peak Brain & Pituitary Treatment Center. $1.5 million comes from the Henry J.N. Taub Foundation and is paired with an anonymous $500,000 donation. Read more: https://philanthropynewsdigest.org/news/houston-methodist-receives-1.5-million-for-brain-pituitary-research

Research Articles

April 2025 Research Articles

Pituitary Surgery

Indocyanine green fluorescence in endoscopic transsphenoidal resection of pituitary neuroendocrine tumors: a systematic review.

Olesrud I, Halvorsen IJ, Storaker MA, Heck A, Dahlberg D, Wiedmann MKH.Acta Neurochir (Wien). 2025 Mar 28;167(1):92. doi: 10.1007/s00701-025-06500-z.


Extended endoscopic endonasal approach for solid or predominantly solid third ventricle craniopharyngiomas complicated with obstructive hydrocephalus: a single-center experience of 27 patients.

Qiao N, Li C, Liu X, Song Y, Liang L, Zou Y, Lu P, Zhang Y, Gui S.Neurosurg Rev. 2025 Mar 26;48(1):325. doi: 10.1007/s10143-025-03486-1.

 

Transsphenoidal Surgery for Pituitary Neuroendocrine Tumours (PiTNETs) in a Tertiary Hospital: Are There Differences Between Young and Elderly Patients?

Borrego-Soriano I, Parra-Ramírez P, Martín-Rojas-Marcos P, Pérez-López C, García-Feijoo P, Álvarez-Escolá C.Clin Endocrinol (Oxf). 2025 Mar 24. doi: 10.1111/cen.15242. Online ahead of print.PMID: 40129236

 

Pituitary Tumors


Fungal Sinusitis Spreading to the Sellar Region Mimicking a Pituitary Tumor: Case Report and Literature Review.

Pekic Djurdjevic S, Arsic Arsenijevic V.J Fungi (Basel). 2025 Mar 19;11(3):233. doi: 10.3390/jof11030233.

 

Functional Transformation of a Corticotroph Pituitary Neuroendocrine Tumor 128 Months Following Primary Excision ? A Case Report.

Goyal-Honavar A, Abraham AP, Asha HS, Chacko G, Chacko AG.Turk Neurosurg. 2025;35(2):355-359. doi: 10.5137/1019-5149.JTN.44912-23.2

 

Genetic Characterization of Turkish Patients with Pituitary Neuroendocrine Tumors.

Alavanda C, Sonmez O, Geckinli BB, Bayrakli F, Guney AI.Turk Neurosurg. 2025;35(2):319-320. doi: 10.5137/1019-5149.JTN.45761-23.2.

 

 

Empty Sella

 

Relationship Between Radiological Features of Primary Empty or Primary Partial Empty Sella and Pituitary Hormone Levels.

Kałuża B, Furmanek M, Domański J, Żuk-Łapan A, Babula E, Poprawa I, Walecki J, Franek E.Biomedicines. 2025 Mar 15;13(3):722. doi: 10.3390/biomedicines13030722.

 

Acromegaly

 

Copeptin and Mid-Regional Proadrenomedullin Are Not Useful Biomarkers of Cardiometabolic Disease in Patients with Acromegaly-A Preliminary Study.

Strzelec M, Kubicka E, Kuliczkowska-Płaksej J, Kolačkov K, Janek Ł, Bolanowski M, Jawiarczyk-Przybyłowska A.Biomedicines. 2025 Mar 8;13(3):666. doi: 10.3390/biomedicines13030666.

 

Hypopituitarism


Identification of POU1F1 Variants in Vietnamese Patients with Combined Pituitary Hormone Deficiency.

Nguyen HT, Nguyen KN, Dien TM, Can TBN, Nguyen TTN, Lien NTK, Tung NV, Xuan NT, Tao NT, Nguyen NL, Tran VK, Mai TTC, Tran VA, Nguyen HH, Vu CD.Int J Mol Sci. 2025 Mar 7;26(6):2406. doi: 10.3390/ijms26062406.


Hypopituitarism: genetic, developmental, and acquired etiologies with a focus on the emerging concept of autoimmune hypophysitis.

Bando H, Urai S, Kanie K, Yamamoto M.Endocr J. 2025 Mar 27. doi: 10.1507/endocrj.EJ25-0035. Online ahead of print.

 

Hormonal Health

A Novel Missense Variant in LHX4 in Three Children with Multiple Pituitary Hormone Deficiency Belonging to Two Unrelated Families and Contribution of Additional GLI2 and IGFR1 Variant.

Santoro C, Aiello F, Farina A, Miraglia Del Giudice E, Pascarella F, Licenziati MR, Improda N, Piluso G, Torella A, Del Vecchio Blanco F, Cirillo M, Nigro V, Grandone A.Children (Basel). 2025 Mar 14;12(3):364. doi: 10.3390/children12030364.

 

Hyperprolactinemia is associated with height attainment within or above target height in adult patients with pituitary stalk interruption syndrome.

Wang Y, Mao J, Wang X, Nie M, Zhang J, Zhang W, Liu H, Xu Z, Wu X.Endocr Pract. 2025 Mar 25:S1530-891X(25)00095-3. doi: 10.1016/j.eprac.2025.03.010. Online ahead of print.

 

Multiple Endocrine Neoplasia Type 1 (MEN1) Syndrome Clinical Presentation and the Role of Newer Functional Imaging in the Diagnosis and Management: A Case Report.

Singh R, Goel SA, Singh JS, John DR, Suthar PP.Cureus. 2025 Feb 24;17(2):e79580. doi: 10.7759/cureus.79580. eCollection 2025 Feb.

 

 

 

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)

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