Pituitary Gland Carcinoma

In summary, inhibiting the oncogenic miRNAs and ectopic expression of tumor-suppressive miRNAs can decrease prolactin secretion, reduce tumor invasion and migration, enhance dopamine agonist efficacy, and inhibit prolactinoma development. These findings can serve as a blueprint for future translational studies investigating miR-based therapeutics for prolactinoma.

In conclusion, we demonstrated that pituitary tumours might have mutant KRAS, and these data were not previously described probably due to lack of sensitivity of previous technologies. By identifying these variants, even at minimal levels, we open doors to a deeper understanding of the tumour microenvironment, clonal evolution and potential therapeutic targets.

68Ga-pentixafor uptake was associated with CXCR4 expression and ACTH level.

The GH level at diagnosis is the only parameter significantly associated with dura mater invasion. Lower IGF-1 levels at diagnosis are significantly associated with remission one year after surgery.

Analysis of transcriptome was performed for nine USP8-mutant and six USP8-WT adenomas and revealed the that the bidirectional dysregulation of Wnt signaling, including both the agonist RSPO2 and antagonist SFRP1, in the USP8-mutant corticotropinomas was downregulated. These alterations may indicate the existence of regulatory connections between USP8 enzyme activity, Wnt signaling, EGFR signaling and somatostatin receptors' trafficking, which can explain, at least in part, the clinical manifestations of CD in patients with corticotropinomas harboring USP8 variants.

Prolactinomas are commonly treated with dopamine receptor agonists (DAs), such as bromocriptine (BRC) and cabergoline (CAB). These findings highlight the role of p300 in regulating DRD2 transcription in DA-resistant prolactinomas. Combining Tan IIA with BRC may offer a promising strategy to overcome DA resistance.

The findings of the current study highlight the potential of PTTG genes as diagnostic biomarkers, prognostic indicators, and therapeutic targets in LUAD.

Regarding the molecular mechanism, HIF1α overexpression could down-regulated TIMP1 and up-regulated MT6-MMP expression levels but not affected EMT markers expression. Our results suggested HIF1α might contribute to the invasion of pituitary null cell adenomas through activating HIF1α/TIMP1/MT6-MMP pathway but not EMT.

P=N/A, N=70, Recruiting, Emory University | Trial completion date: Oct 2025 --> Dec 2031 | Trial primary completion date: Oct 2024 --> Dec 2030

P=N/A, N=60, Completed, Ottawa Hospital Research Institute | Recruiting --> Completed | Trial primary completion date: Nov 2023 --> Apr 2024

Surgical intervention is common, requiring meticulous precautions to avoid complications. More longitudinal studies including close follow-up with a description of outcomes are necessary to guide treatment protocols for this condition.

P2, N=22, Recruiting, National Institute of Neurological Disorders and Stroke (NINDS) | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

This study demonstrates that RACGAP1 plays a critical role in GHPA, highlighting the novel inhibitor DB07268 as a promising therapeutic approach.

Increased awareness through education targeting the multifaceted clinical presentation of acromegaly shortens the time to diagnosis and treatment. Multidisciplinary management by specialists increases the likelihood of biochemical and tumor control.

Including pituitary tumors, can also lead to the occurrence of diabetes, if the primary disease can not be well controlled in time, such secondary diabetes control is more difficult. In the process of clinical diagnosis and treatment, these factors need to be taken into account, timely detection and treatment of primary diseases, so as to reduce the possibility of clinical missed diagnosis.

The STAT4 genotypes were significantly associated with the PA occurrence, size, and relapse. Elevated serum STAT4 levels were observed in the PA patients, highlighting its potential role in PA pathogenesis.

This study demonstrates the potential of LCM-RNAseq to unlock hidden molecular diversity within archived pituitary tumor samples. By focusing on specific cell populations, we identified lncRNAs expressed at different levels within the tumors, potentially offering new insights into the complex biology of GH-secreting PitNETs. This evidence prompts further research into the role of lncRNAs in pituitary neuroendocrine tumor aggressiveness and personalized treatment strategies.

Patients with acromegaly have decreased vascular density and lower levels of Gremlin-1 independent of glucose tolerance status. Acromegaly may cause a reduction in gremlin-1 as a compensatory mechanism due to high IGF-1 levels known as an angiogenic factor, which in turn leads to the decrease in vascular density, or gremlin-1 may already have shown a decline in response to chronic inflammation and endothelial dysfunction in acromegaly resulting in a reduction in vascular density.

P=N/A, N=20, Recruiting, Shanghai Zhongshan Hospital

In contrast, SGSTs are often resistant to somatostatin analogues and instead are treated with the GH receptor antagonist pegvisomant. Differential diagnosis includes mammosomatotroph, mixed GH-/PRL-secreting, immature PIT1-lineage, and densely granulated somatotroph tumors. Studies in ER-sensitive rat tumoral mammosomatotroph cells (GH3, GH4C1) suggest that overexpression of chaperones in immature PIT1-/ER-expressing progenitors induces posttranscriptional conformational changes to tumor suppressors of the ERα and aryl hydrocarbon receptor pathways, like AIP, leading to the development of aggressive pituitary tumors like those causing fugitive acromegaly.

Patients with pituitary acrogigantism have a heavy burden of disease and a complex treatment journey; the need to control final height makes it imperative to provide a diagnosis and effective hormonal control as rapidly as possible. Multimodal therapy is often required, and this can be complicated by the need for medical therapies that are not labeled for use in the pediatric population.

Unfortunately, this classification does not fully reflect the spectrum of tumor phenotypes, does not consider the presence of drug-target receptors (i.e., somatostatin), nor molecular features that, on the contrary, have been increasingly demonstrated to influence biological behavior. Therefore, efforts of pituitary expert of the various disciplines are still necessary to reach a more comprehensive and detailed PitNET stratification to improve patient care through precision medicine.

Novelties in the field of medical treatment in acromegaly can be summarized as follows: (a) new protocols applied to existing medications; (b) new devices to administer old drugs; (c) new formulations, and (d) new drugs. In this review, we aim at summarizing the current protocols and drugs to treat acromegaly (standard of care), and presenting the new pharmacological options including those drugs that are still being tested and could be released in the market in the next few years.

We found a causal relationship between T2DM and glioblastoma, fasting glucose and spinal cord tumours, glycated haemoglobin and spinal cord tumours, and insulin-like growth factor-1 and spinal cord tumours, pituitary tumours, and craniopharyngiomas. These results clarify the relationship between T2DM, glucose-related factors, and common CNS tumours, and they provide valuable insight into further clinical and basic research on CNS tumours, as well as new ideas for their diagnosis and treatment.

Irrespective of functional status of a PitNET, routine application of pituitary transcription factors is warranted to identify these tumors. Data on the molecular correlates and clinical significance are still needed for these rare multilineage PitNETs.

P=N/A, N=15, Not yet recruiting, Imperial College London

4 pts received TT at recurrence, within clinical trials: one with grade 3 meningioma and ALK rearrangement treated with alectinib, one with PTCH1 mutant medulloblastoma treated with vismodegib, and two with high TMB treated with nivolumab/ipilumumab. The incidence of targettable molecular alterations in adult CNS tumor patients was lower than in GBM. Nevertheless, in a few selected cases TT have the potential to increase treatment options at recurrence and improve outcomes.

Although further research is needed to firmly establish a possible association, this case also highlights the necessity of exploring genetic backgrounds when patients present with clinical manifestations not readily explained by a single endocrine disorder. Investigating potential genetic associations is crucial since a positive genetic test allows for the testing of relatives, genetic counseling, and proper surveillance of individuals at risk.

GNAS mutations are prevalent among Chinese acromegaly patients, correlating with reduced pituitary tumor sizes and enhanced GH secretion functions. Our findings underscore the influence of gender on the clinical manifestations of GNAS mutations. Accordingly, we recommend that future clinical and foundational researches on acromegaly give heightened consideration to gender-specific differences.

Pasireotide long-acting release (PAS-LAR) is a second-generation somatostatin receptor ligand (SRL) approved for acromegaly treatment. These findings suggest that PAS-LAR is an effective option for acromegaly patients resistant to fgSRL, but careful monitoring of glucose levels is essential. The high heterogeneity observed across studies emphasizes the need for identifying PAS-LAR response biomarkers to set-up individualized treatment approaches for optimizing patient outcomes.

Our findings point to a pivotal role of PANX1 in promoting PA invasion, which indicated a potential therapeutic target for invasive PA.

TRIM21 may represent a therapeutic target for tumors, and inhibiting TRIM21 could be a potential strategy for tumor treatment.

P=N/A, N=500, Not yet recruiting, Beijing Tiantan Hospital, Capital Medical University; Beijing Tiantan Hospital, Capital Medical University

P4, N=290, Not yet recruiting, Beijing Tian Tan Hospital, Capital Medical University; Beijing Tian Tan Hospital, Capital Medical University

P4, N=882, Not yet recruiting, Beijing Tiantan Hospital

sPitNETs fall into three relevant cytogenetic groups: highly aneuploid tumors characterized by known prognostically favorable features and low aneuploidy tumors including specific subtype with chromosome 11 loss.

Importantly, B2R-D2R complexes were detected in human prolactinomas and nonfunctioning pituitary adenomas (NFPA), but not in mixed (prolactin + growth hormone) secreting adenomas. These results suggest that overexpression of B2R in resistant prolactinomas may promote the formation of B2R-D2R complexes, with B2R precluding D2R signaling, thus generating resistance to D2R agonists.

Microscopic trans-sphenoidal resection is associated with a lower risk of under-treatment. Postoperative outcomes and clinical benefits of curative surgeries are based on the complete type of surgical removal and size of the pituitary adenomas mass (Level of Evidence: 3; Technical Efficacy Stage: 4).

In this specific setting, treatment with somatostatin receptor ligands seems to have a protective role on fracture risk. Based on this evidence, a comprehensive osteometabolic evaluation should be performed in all patients with TSHoma, including assessment of BTM, measurement of BMD, and morphometric evaluation of VFs, both at diagnosis and then during follow-up, particularly in patients at high risk for fragility fractures.

Urinary free cortisol measurement was 21-fold the upper limit of the reference range (3,614.0 nmol/24 h), and cortisol concentration did not decrease after 1mg-dexamethasone suppression test (1,812 nmol/L for an expected value <50 nmol/L), confirming the ACTH-dependent CS...Hypercortisolism symptoms were effectively managed with an adrenal enzyme inhibitor (ketoconazole) in combination with somatostatin analogs...This redifferentiation phenomenon in neuroendocrine tumors should be further investigated as patients might be, under certain conditions, eligible for PRRT. Therefore, we suggest that newly occurring paraneoplastic syndromes in patients with NEC should always be evaluated using 68Ga-DOTATATE PET/CT.

Although many different scoring systems for SST2 immunohistochemistry showing correlation with SRL response have been reported, among which the immunoreactivity score (IRS) has been the most consistently used, a universally validated immunohistochemical technique and scoring scheme is lacking. Efforts should be made on collaborative multicenter studies aiming at validating homogeneous immunostaining protocols and a scoring system for SST2 and SST5 expression, to help clinicians to define the optimal therapeutic strategy for the patients with somatotroph tumors.

P=N/A, N=200, Active, not recruiting, Huashan Hospital