Immunotherapy for endocrine tumours: a clinician's perspective.

Immunotherapy has revolutionised the treatment of oncological patients, but its application in various endocrine tumours is rather limited and is mainly used when conventional therapies have failed. Immune checkpoint inhibitors (ICIs) have been employed in progressive adrenocortical carcinoma, primarily utilizing the anti-PD-L1 agent pembrolizumab, obtaining overall response rates ranging between 14% and 23%. In contrast, the response rate in phaeochromocytoma/paraganglioma was substantially less at 9%, considering the small number of patients treated. Similarly, the response rate in advanced differentiated thyroid carcinomas treated with pembrolizumab was also low at 9%, although the combination of ICIs with tyrosine kinase inhibitors showed higher efficacy. Low response rates to ICIs have also been observed in progressive medullary thyroid cancer, except in tumours with a high mutation burden (TMB). Pembrolizumab or spartalizumab can be utilized in patients with high TMB anaplastic thyroid cancer, obtaining better response rates, particularly in patients with high PD-L1 expression. Immunotherapy has also been used in a few cases of parathyroid carcinoma, showing limited antitumour effect. Pituitary carcinomas may exhibit a more favourable response to ICIs compared to aggressive pituitary tumours, particularly corticotroph tumours. Patients with advanced neuroendocrine tumours achieve an overall response rate of 15%, which varies according to the primary tumour site of origin, degree of differentiation, and therapeutic regimen utilised. Future research is needed to evaluate the potential role of immunohistochemical biomarkers, such as programmed death 1/programmed death ligand 1 and TMB, as predictors for the response to immunotherapy. Furthermore, randomised prospective studies could provide more robust data on the efficacy and side effects of ICIs.

Comparison of perimetric 24-2 and 30-2 test patterns in detecting visual field defects in patients with tumours in the pituitary region.

PURPOSE: Automated perimetry provides a standardized method of measuring the visual field. The Humphrey Field Analyser (HFA) uses the 24-2 test pattern to cover 24 degrees centrally or the 30-2 test pattern to cover a slightly broader region of 30 degrees. The aim of this study was to determine whether the 24-2 test pattern provides comparable information to the 30-2 test pattern in detecting visual field defects in patients with tumours in the pituitary region. METHODS: A retrospective cohort study was carried out on patients with tumours in the pituitary region and radiologically confirmed compression of the visual pathway. Included patients (79 of 133) had been examined using the Humphrey 30-2 visual field test, after which the 30-2 test patterns were reduced into corresponding 24-2 test patterns. The location of visual field defects, visual acuity and the perimetric parameters mean deviation (MD) and visual field index (VFI) were also recorded. RESULTS: No patient was classified differently when evaluated with the 24-2 test pattern, compared to the 30-2 test pattern. Interestingly, although the majority of patients had visual field defects located in the temporal visual field of each eye, a significant minority did not. In addition, it was found that a large proportion of patients had normal visual acuity (≥0.8). CONCLUSIONS: The use of the HFA 24-2 test pattern reliably detected visual field defects in patients with tumours in the pituitary region. The present study indicates that MD and VFI are not reliable parameters for evaluating visual field defects due to compression.

Implications of cellular senescence in paediatric pituitary tumours.

The long-standing view of senescent cells as passive and dysfunctional biological remnants has recently shifted into a new paradigm where they are main players in the development of many diseases, including cancer. The senescence programme represents a first line of defence that prevents tumour cell growth but also leads to the secretion of multiple pro-inflammatory and pro-tumourigenic factors that fuel tumour initiation, growth, and progression. Here, we review the main molecular features and biological functions of senescent cells in cancer, including the outcomes of inducing or targeting senescence. We discuss evidence on the role of cellular senescence in pituitary tumours, with an emphasis on adamantinomatous craniopharyngioma (ACP) and pituitary adenomas. Although senescence has been proposed to be a tumour-preventing mechanism in pituitary adenomas, research in ACP has shown that senescent cells are tumour-promoting in both murine models and human tumours. Future studies characterizing the impact of targeting senescent cells may result in novel therapies against pituitary tumours.

Refractory Pit1 plurihormonal tumours and thyrotroph adenomas.

Pit-1 tumours are derived from neoplastic cells of either somatotroph, lactotroph or thyrotroph cell lineages, but there are also distinct mixed tumours and plurihormonal tumours within this category as described within the 2022 edition of the WHO classification of pituitary tumours. Plurihormonal tumours and thyrotroph adenomas are transcriptionally similar and grouped together to discuss in this review, although it is clear an immature type of plurihormonal tumour exists which are more commonly associated with refractory disease. Management of residual or recurrent disease should follow that of other aggressive pituitary tumours, although a trial of somatostatin analogue therapy is certainly warranted before considering temozolomide therapy.

Management of pituitary incidentalomas.

Pituitary incidentalomas are common findings with increasing use of modern neuroradiological imaging undertaken for symptoms unrelated to pituitary disease. The prevalence of these lesions is ∼10% in autopsy studies and the incidence varies from 10% to 38% on magnetic resonance imaging in the published literature. They are almost always benign in nature and most are non-functioning (non-secreting) adenomas. Although many individuals are asymptomatic at diagnosis, some with functioning (secreting) pituitary adenomas or larger non-functioning adenomas have symptoms. All identified cases should have a thorough clinical and endocrinological evaluation to help with precise management, which depends on the size of the lesion, hormonal status (functioning versus non-functioning adenoma) and the presence of visual deficits resulting from optic nerve compression by the pituitary adenoma. Here, we provide an overview of the initial assessment and management of pituitary incidentalomas for clinicians not routinely involved in the management of pituitary disease.

Pituitary tumours: molecular and genetic aspects.

'Pituitary tumours' is an umbrella term for various tumours originating from different regions of the hypothalamic-pituitary system. The vast majority of pituitary tumours are pituitary adenomas, also recently referred to as pituitary neuroendocrine tumours. The prevalence of clinically relevant pituitary adenomas is approximately 1 in 1000; other pituitary tumours such as craniopharyngioma and pituicytoma are comparatively very rare. This review addresses the molecular and genetic aspects of pituitary adenomas. We first discuss the germline genetic variants underlying familial pituitary tumours, which account for approximately 5% of all pituitary adenoma cases. This includes variants in established pituitary adenoma/hyperplasia predisposition genes (MEN1, PRKAR1A, AIP, CDKN1B, GPR101, SDHA, SDHB, SDHC, SDHD, SDHAF2) as well as emerging genetic associations. In addition, we discuss McCune-Albright syndrome which lies between the germline and somatic pituitary tumour genes as the causative GNAS mutations are postzygotic rather than being inherited, and the condition is associated with multiglandular features due to the involvement of different cell lines rather than being limited to the pituitary. By contrast, somatic GNAS mutations contribute to sporadic acromegaly. USP8 is the only other gene where somatic driver mutations have been established in sporadic pituitary tumorigenesis. However, there are now known to be a variety of other somatic genetic and molecular changes underpinning sporadic pituitary adenomas which we review here, namely: copy number variation, molecular changes in signalling and hypoxia pathways, epithelial-mesenchymal transition, DNA repair, senescence, the immune microenvironment and epigenetics.

Dopamine agonists for the treatment of pituitary tumours: From ergot extracts to next generation therapies.

Dopamine agonists are a key tool in the therapeutic arsenal of endocrinologists worldwide. They exert their effects by binding to dopamine-2 (D2) receptors expressed by pituitary tumour cells to modulate hormonal secretion and tumour size. They are the established first-line treatment for prolactinomas which express high levels of D2 receptors. Growing data support their use as an adjuvant treatment option for other pituitary tumours including growth hormone, adrenocorticotrophic hormones, thyroid hormone secreting adenomas and nonfunctional pituitary tumours, all of which have been shown to express D2 receptors as well, albeit to varying extents. For those pituitary tumours inadequately treated by dopamine agonist alone, combined agonism of D2 and somatostatin receptors represent a new frontier in clinical development. Here we review the development and role of dopamine agonist for the treatment of prolactinomas, the literature supporting their adjuvant use for the treatment of all other pituitary tumours, and recent progress in the development of the next generation of chimeric compounds that target D2 and other receptor subtypes highly expressed on pituitary tumour cells.

Coping strategies in patients undergoing surgery treatment for pituitary tumour in China: A cross-sectional survey.

AIM: To explore the coping strategies and corresponding influence factors in patients undergone surgeries for pituitary tumours. DESIGN: A cross-sectional study. METHODS: Patients diagnosed with pituitary tumours were included. The Medical Coping Questionnaire (MCMQ) and a demographic questionnaire were used for data collection. RESULTS: A total of 150 patients with pituitary tumour undergoing surgery treatment were included. Compared with the a-select sample, patients with pituitary tumours reported more avoidant coping (p < .0001) and more resigned coping (p = .031) but less confrontation coping (p = .026). Multiple regression analysis showed the regardless of recurrence or not, the type and size of pituitary tumour, education level, family income are the factors influencing the coping style (all p < .05). CONCLUSIONS: Clinical workers should pay more attention to the patients with multiplied pituitary tumour, huge adenoma, recurred tumour, low levels of education and low monthly income.

Sellar and parasellar lesions in the transition age: a retrospective Italian multi-centre study.

BACKGROUND: Sellar/parasellar lesions have been studied in the adult and paediatric age range, but during the transition age their epidemiology, clinical manifestations, management and treatment outcomes have been poorly investigated. MATERIALS AND METHODS: An Italian multicentre cohort study, in which hospital records of patients with diagnosis of sellar/parasellar lesions during the transition age and young adulthood (15-25 years), were reviewed in terms of prevalence, clinical and hormonal features at diagnosis, and outcomes where available. Both pituitary neuroendocrine tumours (pituitary tumours, Group A) and non-endocrine lesions (Group B) were included. RESULTS: Among Group A (n = 170, 46.5% macroadenomas), the most frequent were prolactin and GH-secreting tumours, with a female predominance. Among Group B (n = 28), germinomas and Rathke cells cysts were the most common. In Group A, the most frequent hormonal deficiency was gonadal dysfunction. Galactorrhoea and amenorrhoea were relatively common in female patients with prolactinomas. Pre-surgical diabetes insipidus was only seen in Group B, in which also hormone deficiencies were more frequent and numerous. Larger lesions were more likely to be seen in Group B. Patients in Group B were more frequently male, younger, and leaner than those of Group A, whereas at last follow-up they showed more obesity and dyslipidaemia. In our cohort, the percentage of patients with at least one pituitary deficiency increased slightly after surgery. CONCLUSIONS: The management of sellar/parasellar lesions is challenging in the transition age, requiring an integrated and multidisciplinary approach. Hormone and metabolic disorders can occur many years after treatment, therefore long-term follow-up is mandatory.

Prevalence, clinical presentation, management of pituitary tumour and its complications among elderly population in Mumbai, India.

Pituitary tumour is not typically thought of as an elderly patient's condition. Hence, we examined all cases of confirmed or suspected pituitary tumour diagnosed in a tertiary hospitals at Mumbai, India during May 2015 and May 2023 among patients over the age of 70 to evaluate the prevalence, clinical presentation, management, complications in elderly patients with a pituitary tumour. After the age of 70 years, 16% people having pituitary tumour were observed. The volume of fossa was statistically greater in elderly patients. The duration of follow up was statistically longer in younger controls. The visual defects observed in elderly group were greater than young patients. Pituitary adenomas in old patients can be treated with trans-sphenoidal-adenomectomy. However, the proportion is lower than younger controls. Data shows that post-operative radiotherapy was more commonly observed in old patients with pituitary adenoma than younger controls.

Prognostic Biomarkers in Pituitary Tumours: A Systematic Review.

Pituitary tumours (PTs) are the second most common intracranial tumour. Although the majority show benign behaviour, they may exert aggressive behaviour and can be resistant to treatment. The aim of this review is to report the recently identified biomarkers that might have possible prognostic value. Studies evaluating potentially prognostic biomarkers or a therapeutic target in invasive/recurrent PTs compared with either non-invasive or non-recurrent PTs or normal pituitaries are included in this review. In the 28 included studies, more than 911 PTs were evaluated. A systematic search identified the expression of a number of biomarkers that may be positively correlated with disease recurrence or invasion in PT, grouped according to role: (1) insensitivity to anti-growth signals: minichromosome maintenance protein 7; (2) evasion of the immune system: cyclooxygenase 2, arginase 1, programmed cell death protein 1 (PD-1)/programmed death ligand 2, cluster of differentiation (CD) 80/CD86; (3) sustained angiogenesis: endothelial cell-specific molecule, fibroblast growth factor receptor, matrix metalloproteinase 9, pituitary tumour transforming gene; (4) self-sufficiency in growth signals: epidermal growth factor receptor; and (5) tissue invasion: matrix metalloproteinase 9, fascin protein. Biomarkers with a negative correlation with disease recurrence or invasion include: (1) insensitivity to anti-growth signals: transforming growth factor ß1, Smad proteins; (2) sustained angiogenesis: tissue inhibitor of metalloproteinase 1; (3) tissue invasion: Wnt inhibitory factor 1; and (4) miscellaneous: co-expression of glial fibrillary acidic protein and cytokeratin, and oestrogen receptors α36 and α66. PD-1/programmed cell death ligand 1 showed no clear association with invasion or recurrence, while cyclin A, cytotoxic T lymphocyte-associated protein 4, S100 protein, ephrin receptor, galectin-3 , neural cell adhesion molecule, protein tyrosine phosphatase 4A3 and steroidogenic factor 1 had no association with invasion or recurrence of PT. With the aim to develop a more personalized approach to the treatment of PT, and because of the limited number of molecular targets currently studied in the context of recurrent PT and invasion, a better understanding of the most relevant of these biomarkers by well-d esigned interventional studies will lead to a better understanding of the molecular profile of PT. This should also meet the increased need of treatable molecular targets.

Phosphorylation of ß-catenin at Serine552 correlates with invasion and recurrence of non-functioning pituitary neuroendocrine tumours.

Non-functioning pituitary tumours (NF-PitNETs) are common intracranial benign neoplasms that can exhibit aggressive behaviour by invading neighbouring structures and, in some cases, have multiple recurrences. Despite resulting in severe co-morbidities, no predictive biomarkers of recurrence have been identified for NF-PitNETs. In this study we have used high-throughput mass spectrometry-based analysis to examine the phosphorylation pattern of different subsets of NF-PitNETs. Based on histopathological, radiological, surgical and clinical features, we have grouped NF-PitNETs into non-invasive, invasive, and recurrent disease groups. Tumour recurrence was determined based on regular clinical and radiological data of patients for a mean follow-up of 10 years (SD ± 5.4 years). Phosphoproteomic analyses identified a unique phosphopeptide enrichment pattern which correlates with disease recurrence. Candidate phosphorylated proteins were validated in a large cohort of NF-PitNET patients by western blot and immunohistochemistry. We identified a cluster of 22 phosphopeptides upregulated in recurrent NF-PitNETs compared to non-invasive and invasive subgroups. We reveal significant phosphorylation of the ß-catenin at Ser552 in recurrent and invasive NF-PitNETs, compared to non-invasive/non-recurrent NF-PitNET subgroup. Moreover, ß-catenin pSer552 correlates with the recurrence free survival among 200 patients with NF-PitNET. Together, our results suggest that the phosphorylation status of ß-catenin at Ser552 could act as potential biomarker of tumour recurrence in NF-PitNETs.

Distribution of E- and N-cadherin in subgroups of non-functioning pituitary neuroendocrine tumours.

PURPOSE: Clinically non-functioning pituitary neuroendocrine tumours (NF-PitNETs) present a varying degree of aggressiveness, and reliable prognostic markers are lacking. We aimed to characterise the distribution of E- and N-cadherin in corticotroph, PIT1 and null-cell NF-PitNETs, and link it to the course of the tumours. METHODS: The distribution of E- and N-cadherin was investigated by immunohistochemistry in a retrospective cohort of 30 tumours of the less common NF-PitNETs (corticotroph (N = 18), PIT1 (N = 8) and null-cell PitNETs (N = 4)). Immunoreactive scores (IRS) were compared to previously presented cohorts of gonadotroph NF-PitNETs (N = 105) and corticotroph functioning PitNETs (N = 17). RESULTS: We found a low IRS for the extra-cellular domain of E-cadherin (median 0 (IQR 0-0, N = 135)), a medium to high IRS for the intra-cellular domain of E-cadherin (median 6 (IQR 4-9)) and a high IRS for N-cadherin (median 12 (IQR 10.5-12)) throughout the cohort of NF-PitNETs. The corticotroph NF-PitNETs presented a higher IRS for both the extra- and intra-cellular domain of E-cadherin (median 0 (IQR 0-1) and median 9 (IQR 6-12), respectively) than the gonadotroph NF-PitNETs (p < 0.001 for both comparisons). Presence of nuclear E-cadherin was associated with a weaker staining for the intra-cellular domain of E-cadherin (median 4 (IQR 0.5-6) and median 9 (IQR 9-12), for tumours with and without nuclear E-cadherin, respectively), and with a lower rate of re-intervention (p = 0.03). CONCLUSIONS: Considering our results and the benign course of NF-PitNETs, we suggest that a high N-cadherin and downregulation of membranous E-cadherin are not associated with a more aggressive tumour behaviour in these subgroups of NF-PitNETs.

Quantitative Magnetic Resonance-Derived Biomarkers as Predictors of Function and Histotype in Adenohypophyseal Tumours.

INTRODUCTION: Magnetic resonance imaging (MRI) is the main modality to diagnose adenohypophyseal tumours, while biochemical assessment of pituitary hormones allows for their functional classification. In this retrospective exploratory cohort study, we investigated if quantitative differences in tumour MR signal intensity (SI) could be utilized to predict the function and histotype. METHODS: Clinically acquired pretreatment MRI images were retrospectively analysed in 67 clinically non-functioning gonadotropinomas (NFG), 38 somatotropinomas, and 16 medically treated giant macroprolactinomas. Mean T1- and T2-weighted SI values were determined for each tumour and normalized against either centrum semiovale white matter or CSF to derive relative T1W and T2W SI values and the relative tumour T2/T1 SI ratio. Inter-group differences in quantitative MR parameters were compared, and the power of each parameter to discriminate tumour type and subtype was assessed using the area under the receiver operator characteristic curve (AUROC). In resected somatotropinomas, the relationship between tumour granulation status, relative MR SI values, and biochemical data was also compared. RESULTS: Compared to somatotropinomas, NFG and macroprolactinomas displayed higher relative T2W SI (p < 0.001) and higher relative tumour T2/T1 SI ratio values (p < 0.001, ANOVA). Compared to intermediate/densely granulated tumours, sparsely granulated somatotropinomas were larger (p = 0.006, Mann-Whitney U test), had higher relative T2W SI (p ≤ 0.005), and higher relative tumour T2/T1 SI ratios (p ≤ 0.001, 2-tailed t test). Relative tumour T2W SI values and relative tumour T2/T1 ratio values demonstrated good discriminatory power in differentiating NFG from somatotropinoma (AUROC = 0.87-0.94) and predicting somatotropinoma subtypes (AUROC = 0.87-0.95). CONCLUSION: Quantitative SI-based MR parameters derived using clinical acquisition MRI protocols may help non-invasively discriminate the functional status of adenohypophyseal tumours and the histological subtype of somatotropinomas.

Downregulation of miR-216a-5p and miR-652-3p is associated with growth and invasion by targeting JAK2 and PRRX1 in GH-producing pituitary tumours.

Expression of aberrant microRNA (miRNA) is associated with tumour formation, migration, and invasion. However, there is limited information about the epigenetics of pituitary tumorigenesis. This study investigated the role of miRNA expression during the tumorigenesis of growth hormone (GH)-secreting pituitary tumours. miRNA profiling and real-time PCR were used to analyse the mRNA expression profile in sequential pituitary tissues of a unique animal model with a GH-producing pituitary tumour. Selected miRNAs were further validated in GH-producing cell lines and human pituitary tumour samples. The expression of significantly altered miRNAs and their predicted targets, as detected by microarray, was evaluated by real-time PCR, Western blotting, and immunohistochemistry using samples from mouse models and human pituitary tumours. The effect of miRNAs on tumour proliferation and invasion was examined in GH3 cells using the MTS and Matrigel invasion assays. Among the 14 miRNAs whose expression was significantly changed, miR-216a-5p (fold change = -5.638, P -value = 0.014) and miR-652-3p (fold change = -3.482, P -value = 0.010) were constantly and significantly downregulated. Transfection with mimics of miR-216a-5p and miR-652-3p inhibited GH3 proliferation and invasion, whereas inhibitors promoted them. The direct target genes of miR-216a-5p and miR-652-3p were Jak2 and Prrx1, respectively, which were downregulated in GH3 cells transfected with mimics and in serial pituitary gland tissues, including hyperplasic tissues and tumours of acromegalic animal models and pituitary tumour tissues of acromegalic patients. Downregulated miR-216a-5p and miR-652-3p expression may contribute to tumour progression by targeting JAK2 and PRRX1 on GH-producing pituitary tumours.

The effect of exposure to radiofrequency fields on cancer risk in the general and working population: A protocol for a systematic review of human observational studies.

BACKGROUND: The World Health Organization (WHO) has an ongoing project to assess potential health effects of exposure to radiofrequency electromagnetic fields (RF-EMF) in the general and working population. Here we present the protocol for a systematic review of the scientific literature on cancer hazards from exposure to RF-EMF in humans, commissioned by the WHO as part of that project. OBJECTIVE: To assess the quality and strength of the evidence provided by human observational studies for a causal association between exposure to RF-EMF and risk of neoplastic diseases. ELIGIBILITY CRITERIA: We will include cohort and case-control studies investigating neoplasia risks in relation to three types of exposure to RF-EMF: near-field, head-localized, exposure from wireless phone use (SR-A); far-field, whole body, environmental exposure from fixed-site transmitters (SR-B); near/far-field occupational exposures from use of handheld transceivers or RF-emitting equipment in the workplace (SR-C). While no restriction on tumour type will be applied, we will focus on selected neoplasms of the central nervous system (brain, meninges, pituitary gland, acoustic nerve) and salivary gland tumours (SR-A); brain tumours and leukaemias (SR-B, SR-C). INFORMATION SOURCES: Eligible studies will be identified through Medline, Embase, and EMF-Portal. RISK-OF-BIAS ASSESSMENT: We will use a tailored version of the OHAT's tool to evaluate the study's internal validity. DATA SYNTHESIS: We will consider separately studies on different tumours, neoplasm-specific risks from different exposure sources, and a given exposure-outcome pair in adults and children. When a quantitative synthesis of findings can be envisaged, the main aims of the meta-analysis will be to assess the strength of association and the shape of the exposure-response relationship; to quantify the degree of heterogeneity across studies; and explore the sources of inconsistency (if any). When a meta-analysis is judged inappropriate, we will perform a narrative synthesis, complemented by a structured tabulation of results and appropriate visual displays. EVIDENCE ASSESSMENT: Confidence in evidence will be assessed in line with the GRADE approach. FUNDING: This project is supported by the World Health Organization. Co-financing was provided by the New Zealand Ministry of Health; the Istituto Superiore di Sanità in its capacity as a WHO Collaborating Centre for Radiation and Health; ARPANSA as a WHO Collaborating Centre for Radiation Protection. REGISTRATION: PROSPERO CRD42021236798.

Resistance to first-generation somatostatin receptor ligands does not impair the results of gamma knife radiosurgery in acromegaly.

OBJECTIVE: Gamma knife radiosurgery (GKRS) has proven to be an effective adjuvant treatment for patients with acromegaly. We performed the present study to investigate, which would be the outcome of GKRS, independently on the response to somatostatin receptor ligand (SRL). DESIGN: Retrospective, observational study. PATIENTS: Ninety-six patients with active acromegaly were included. MEASUREMENTS: The cumulative probability of normalisation of insulin-like growth factor 1 (IGF-1) levels after GKRS was assessed by the Kaplan-Meier method. The association of several clinical characteristics with GKRS outcomes was explored with the use of a Cox proportional-hazard model with the relative hazard ratio and 95% confidence interval (CI). RESULTS: Resistance to SRL occurred in 39 of the 96 patients (40.6%). After GKRS, patients resistant to SRL had a 5- and 10-year probability of remission of 40.7% (95% CI: 23.7%-57.7%) and 75.9% (95% CI: 57.9%-93.9%), respectively. Patients responding to SRL had a 5- and 10-year probability of remission of 46.8% (95% CI: 32.2%-61.4%) and 58.1% (95% CI: 41.5%-74.7%), respectively. The difference was not significant (p = .48 by the log-rank test). Multivariate Cox analysis confirmed that the only independent variables associated with GKRS outcome were basal growth hormone (GH; p = .001) and IGF-1 multiple of the upper limit of normal levels before GKRS (p = .013). CONCLUSION: We demonstrate for the first time that the responsiveness to SRL has no effect on the probability to obtain remission of acromegaly after GKRS. The remission of disease occurred more frequently in patients who had lower GH and IGF-1 levels before GKRS.

Surgically treated acromegaly patients have a similar quality of life whether controlled by surgery or requiring additional medical therapy (QuaLAT Study).

PURPOSE: There is no consensus on quality of life (QOL) in patients with acromegaly requiring medical treatment after surgery compared with those achieving remission by surgery alone. METHODS: QuaLAT is a cross-sectional study comparing QOL in surgery-only treated acromegaly patients versus those requiring medical treatment post-surgery. Patients attending clinics were identified and divided into-Group 1: patients who had surgery only and were in biochemical remission, Group 2: all patients on medical treatment post-surgery, Group 3: patients from Group 2 with biochemical control. Participants were asked to fill three questionnaires; Acromegaly Quality of Life Questionnaire (ACROQOL), 36-Item Short Form Survey (SF36), and Fatigue Severity Scale (FSS). RESULTS: There were 32 patients in Group 1 and 25 in Group 2. There was no difference in QOL scores between groups 1 and 2, as measured by ACROQOL (mean difference [MD] = - 2.5, 95% CI - 16.6 to 11.6; p = 0.72), SF36v2 [Physical component score (PCS) MD = - 4.9, 95% CI - 10.9 to 1.2; p = 0.12; mental component score MD = - 3.0, 95% CI - 10.5 to 4.4; p = 0.44], or FSS (MD = - 0.004, 95% CI - 1.14 to 1.33; p = 0.1). Comparison between groups 1 and 3 however showed that PCS (and 3 subdomains) was significantly better in group 3 (MD = - 8.3, 95% CI - 14.8 to -1.8; p = 0.01). All three QOL scores were lower when compared with healthy controls. CONCLUSIONS: Medical treatment not only achieves a QOL comparable to surgery, it may also be associated with better QOL in physical subdomains. When compared with healthy controls, QOL remains worse in treated acromegaly patients compared to controls.

Posterior pituitary tumours: patient outcomes and determinants of disease recurrence or persistence.

OBJECTIVE: Posterior pituitary tumours (PPTs) are rare neoplasms with the four recognised subtypes unified by thyroid transcription factor -1 (TTF-1) expression, according to the 2017 WHO classification. Though traditionally defined as low-grade neoplasms, a substantial proportion of them show recurrence/persistence following surgery. METHODS: We selected patients with PPTs in our cohort of 1760 patients operated for pituitary tumours over the past 10 years (2010-2019). The clinical, radiological, hormonal, histopathological profiles and long-term outcomes of the three cases identified (two pituicytomas and one spindle cell oncocytoma, SCO) were analysed. Following a literature review, data of all published cases with documented TTF-1 positive pituicytomas and SCOs were analysed to determine the predictors of recurrence/persistence in these tumours. RESULTS: Patients presented with compressive features or hypogonadism. Two had sellar-suprasellar masses. One had a purely suprasellar mass with a pre-operative radiological suspicion of pituicytoma. Two were operated by transsphenoidal surgery and one transcranially guided by neuronavigation. Histopathology confirmed spindle cells in a storiform arrangement and low Ki67 index. Immunohistochemistry showed positive TTF-1, S-100 expression and variable positivity for EMA, vimentin and GFAP. Re-evaluation showed recurrence/persistence in two patients. A literature review of recurrent/persistent pituicytoma (n = 17) and SCO (n = 9) cases revealed clinical clues (headache for pituicytomas, male gender for SCO), baseline tumour size (≥20.5 mm with sensitivity exceeding 80%) and longer follow-up duration as determinants of recurrence/persistence. CONCLUSION: PPTs are rare sellar masses with quintessential TTF-1 positivity. Recurrent/persistent disease following surgery is determined by greater tumour size at baseline and duration of follow-up. This warrants intensive and long-term surveillance in these patients.

Targeting the TR4 nuclear receptor with antagonist bexarotene can suppress the proopiomelanocortin signalling in AtT-20 cells.

Drug options for the life-threatening Cushing's disease are limited, and surgical resection or radiation therapy is not invariably effective. Testicular receptor 4 (TR4) has been identified as a novel drug target to treat Cushing's disease. We built the structure model of TR4 and searched the TR4 antagonist candidate via in silico virtual screening. Bexarotene was identified as an antagonist of TR4 that can directly interact with TR4 ligand binding domain (TR4-LBD) and induces a conformational change in the secondary structure of TR4-LBD. Bexarotene suppressed AtT-20 cell growth, proopiomelanocortin (POMC) expression and adrenocorticotropin (ACTH) secretion. Mechanism dissection revealed that bexarotene could suppress TR4-increased POMC expression via promoting the TR4 translocation from the nucleus to the cytoplasm. This TR4 translocation might then result in reducing the TR4 binding to the TR4 response element (TR4RE) on the 5' promoter region of POMC. Results from in vivo mouse model also revealed that oral bexarotene administration markedly suppressed ACTH-secreting tumour growth, adrenal enlargement and the secretion of ACTH and corticosterone in mice with already established tumours. Together, these results suggest that bexarotene may be developed as a potential novel therapeutic drug to better suppress Cushing's disease.