Objective Discordance between growth hormone (GH) and insulin-like growth factor-1 (IGF-1), where one hormone is within the age- and sex-adjusted reference and the other is not, can be observed in patients with acromegaly. The discrepancy complicates the interpretation of disease activity, thereby presenting a significant challenge in the clinical management of acromegaly. This study aimed to assess postoperative discordance prevalence and clinical correlates to clarify the implication of discordance. Methods This retrospective study describes a cohort of patients that has undergone pituitary surgery at Sahlgrenska University Hospital between 1994 and 2019 due to acromegaly. Medical records were reviewed and the group with postoperative discordant hormones was compared with the group with concordant hormones. Results In a cohort of 82 patients surgically treated for acromegaly and thereafter examined with an oral glucose tolerance test (OGTT), 16 (19.5%) exhibited biochemical discordance. Fourteen of 16 patients showed elevated IGF-1 but normal GH. The IGF-1 levels at diagnosis were significantly higher in patients with discordance compared with the controlled concordant group. However, no differences were observed between the discordant and the concordant group regarding the baseline variables at diagnosis: age, gender, invasive tumour, micro/macro-adenoma or BMI, nor hypertensive treatment at time of surgery and postoperative radiotherapy or reoperation. Conclusion The prevalence of biochemical discordance in our cohort was 19.5%. The predominant pattern was elevated IGF-1 levels with a normal nadir GH. The discordant group had higher IGF-1 at diagnosis, suggesting that greater preoperative disease activity may predispose to postoperative biochemical discordance.

BACKGROUND:Aldosterone dysregulation plays an important pathogenic role in hard-to-control hypertension. In several studies, baxdrostat, an aldosterone synthase inhibitor, reduced the seated systolic blood pressure of patients with uncontrolled or resistant hypertension. METHODS:In this phase 3, multinational, double-blind, randomized, placebo-controlled trial, we recruited patients with a seated systolic blood pressure of between 140 mm Hg and less than 170 mm Hg despite the receipt of stable treatment with two antihypertensive medications (uncontrolled hypertension) or three or more such medications (resistant hypertension), including a diuretic. After a 2-week placebo run-in period, we randomly assigned patients with a seated systolic blood pressure of 135 mm Hg or more in a 1:1:1 ratio to receive baxdrostat at a dose of 1 mg, baxdrostat at a dose of 2 mg, or placebo once daily for 12 weeks. The primary end point was the change in seated systolic blood pressure from baseline to week 12. RESULTS:A total of 796 patients underwent randomization and 794 received 1-mg baxdrostat (264 patients), 2-mg baxdrostat (266 patients), or placebo (264 patients) in addition to background therapy. At 12 weeks, the change from baseline in the least-squares mean seated systolic blood pressure was -14.5 mm Hg (95% confidence interval [CI], -16.5 to -12.5) with 1-mg baxdrostat, -15.7 mm Hg (95% CI, -17.6 to -13.7) with 2-mg baxdrostat, and -5.8 mm Hg (95% CI, -7.9 to -3.8) with placebo. The estimated difference from placebo (placebo-corrected difference) was -8.7 mm Hg (95% CI, -11.5 to -5.8) with 1-mg baxdrostat and -9.8 mm Hg (95% CI, -12.6 to -7.0) with 2-mg baxdrostat (P<0.001 for both comparisons). A potassium level of more than 6.0 mmol per liter was reported in 6 patients (2.3%) with 1-mg baxdrostat, in 8 patients (3.0%) with 2-mg baxdrostat, and in 1 patient (0.4%) with placebo. CONCLUSIONS:Among patients with uncontrolled or resistant hypertension, the addition of baxdrostat to background therapy resulted in a significantly lower seated systolic blood pressure at 12 weeks than placebo. (Funded by AstraZeneca and others; BaxHTN ClinicalTrials.gov number, NCT06034743.).

Objectives To evaluate whether a person-centered care practice following surgery for pituitary tumors increased psychological well-being. Secondary aims were to study whether person-centered care would lead to better health status, less fatigue and better self-efficacy. Design and methods This study is a prospective, single-center study using a quasi-experimental design to evaluate the effect of a 12-month person-centered practice by means of a name-given nurse care manager, an interdisciplinary team and peer support against usual care. All patients (≥18 years) with a benign pituitary tumor and planned for endoscopic transsphenoidal surgery were consecutively invited to participate. Psychological well-being, self-reported health, fatigue and self-efficacy were assessed before surgery, at discharge and 3–6 and 12 months after surgery. Results In total, 86 patients in the intervention group and 68 patients in the control group were included. Psychological well-being improved 12 months following surgery in both groups to comparable levels. The intervention group had a greater improvement in anxiety compared to the control group (P = 0.02). No differences were seen between groups in self-reported health status, fatigue or self-efficacy. Patients in the intervention group with other types of pituitary tumors than non-functioning pituitary adenomas showed a greater improvement in psychological well-being than in the control group. Conclusion Our intervention did not result in major advantages in terms of health or psychological well-being. The study does, however, suggest that the intervention may reduce anxiety 12 months after surgery and that certain subgroups of patients may benefit more from a structured person-centered practice following pituitary surgery.

Acromegaly is a rare disease that can be challenging to treat due to residual pituitary adenoma after surgery or variable response to medical treatments. The primary aim of the study was to evaluate the path of treatment and long-term outcome of acromegaly after pituitary surgery. Patients with acromegaly who had undergone surgery for a growth hormone-producing pituitary neuroendocrine tumor also known as a pituitary adenoma, at Sahlgrenska University Hospital between 1994 and 2019 were included in the study. Medical records from diagnosis to the end of study (November 2022) were reviewed for surgical outcome and treatment patterns related to acromegaly. In the cohort of 103 patients, 111 surgeries were performed. Mean follow-up duration was 12.7 (range: 0–37) years. Lesions were identified as a macroadenoma in 76 (76.8

Inappropriately elevated aldosterone is a common feature of uncontrolled hypertension (uHTN) and resistant hypertension (rHTN), and is a major pathophysiological driver of adverse cardiorenal outcomes beyond elevated blood pressure (BP). Baxdrostat is a selective aldosterone synthase inhibitor that has demonstrated dose-dependent seated office systolic BP (SBP) lowering in a Phase 2 trial of patients with rHTN. Here, we report the design of the baxdrostat hypertension Phase 3 program. BaxHTN (NCT06034743), BaxAsia (NCT06344104), and Bax24 (NCT06168409) are randomized, multi-national, double-blind, placebo-controlled Phase 3 trials evaluating the efficacy and safety of baxdrostat 1 and/or 2 mg versus placebo. BaxHTN includes patients with uHTN or rHTN, BaxAsia includes patients with uHTN or rHTN primarily from Asia, and Bax24 includes patients with rHTN. Eligibility criteria include age ≥18 years, mean seated office SBP of ≥140 mmHg to <170 mmHg at screening, and ≥2 antihypertensive treatments of different classes for ≥4 weeks before screening. BaxHTN and BaxAsia have four sequential periods following placebo run-in: 12-week double-blind; 12-week open-label; 8-week randomized withdrawal; 20-week open-label. Bax24 has a placebo run-in and 12-week double-blind period. Primary endpoints are changes from baseline to Week 12 in mean seated office SBP (BaxHTN and BaxAsia) and ambulatory 24-h average SBP (Bax24). Safety and tolerability are also assessed. The Baxdrostat hypertension Phase 3 program will assess efficacy, long-term sustained effect, and safety profile in patients with hypertension across multiple geographies. The trials will evaluate the BP lowering efficacy of aldosterone synthase inhibition as a novel treatment for uHTN and rHTN.

BACKGROUND:Wilms tumors (WT) are the most common kidney tumors in children, with excellent survival rates (90%). However, late adverse effects warrant attention. Limited data exist on musculoskeletal sequelae in WT survivors. We aimed to assess the prevalence and determinants of impaired bone mineral density (BMD) and fractures in a national cohort of Dutch WT survivors. METHOD:This cross-sectional study includes WT survivors treated between 1963 and 2002, recruited as part of the DCCSS-LATER cohort between 2016 and 2020. Dual-energy X-ray absorptiometry (DXA) scans were used to assess BMD. Low BMD was defined as a Z-score ≤ 1. From 5 years after diagnosis, fracture prevalence was assessed by questionnaires. Univariable logistic regression was used to analyze associations between impaired BMD as well as fractures with independent variables like patient characteristics, treatments, comorbidities, and lifestyle-related factors. RESULTS:Of 437 invited kidney tumor survivors, 233 WT survivors participated (median age 32.1 years, median follow-up 27.8 years). DXA scans and fracture data were available for 173 and 221 WT survivors, respectively. Low BMD at any site was observed in 26% (n = 46/173) of survivors and was significantly associated with treatment including ≥ 4 drugs (OR 2.76; 95% CI = 1.13-6.70). Abdominal radiotherapy doses > 30 Gy (OR 4.84; 95% CI = 1.06-22.2) were significantly associated with low lumbar spine BMD. The prevalence of fragility fractures was 16.3% (n = 36/221). The standardized incidence ratio (SIR) of any first fracture was 2.34 for males and 5.38 for females. CONCLUSION:Wilms tumor survivors treated with ≥ 4 drugs or abdominal radiotherapy (> 30 Gy) seem to be at increased risk of impaired BMD; this could indicate the need for surveillance for this subset of Wilms tumor survivors exposed to these treatment regimens in the past.

PURPOSE:The aim of this prospective longitudinal study was to evaluate cognitive function and fatigue before and 12 months after transsphenoidal surgery (TSS) for a pituitary adenoma. METHODS:This study was part of the Gothenburg Pituitary Tumour Study, which consecutively includes patients undergoing TSS at Sahlgrenska University Hospital. Adult patients with a pituitary adenoma were recruited between October 2016 and May 2021. Cognitive function and fatigue were evaluated using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the Multidimensional Fatigue Inventory (MFI-20). Paired comparisons were made for total and subscale scores before and after TSS. Based on normative data, individual scores were classified into one of three categories for symptom severity (normal, moderate, or severe) before and after TSS. RESULTS:Fifty-nine patients (31 females) were included. Among them, 42 had non-functioning pituitary adenomas (NFPA) and 17 had a functioning pituitary adenoma. There were no differences in RBANS total or domain indices before and 12 months after surgery except for the attention index which improved. Total MFI-20 and all subscale scores improved. The improvement was more pronounced in patients with functioning pituitary adenoma, who reported worse fatigue before surgery compared to patients with NFPA. Individual differences between pre- and postoperative scores that also changed category of symptom severity were seen for 37% of all patients regarding cognition and for 35% regarding fatigue. Improvements accounted for the majority of these changes. CONCLUSION:Cognitive function remained largely unchanged from before to 12 months after TSS, while self-reported fatigue improved.

Various factors may affect cognition in patients with pituitary adenoma, including size and extension of the tumor, degree of pituitary hormone deficiencies, and treatment of the tumor, most often being transsphenoidal surgery (TSS). The aim of this cross-sectional study was to evaluate cognitive function in patients with clinically significant pituitary adenoma and to identify factors influencing cognition. Sixty-eight patients with pituitary adenoma were included. Of these, 31 patients were evaluated before TSS and 37 patients 12 months following TSS. Cognitive function was evaluated by using the Repeatable Battery for the Assessment of Neuropsychological Status. Patients had lower mean scores on cognitive assessment compared to age-adjusted normative data. Variability in cognition, analyzed by linear regression analysis, was explained by sex, educational level, and self-perceived fatigue, but not by pituitary hormone deficiencies, diabetes insipidus, or surgical treatment. Our results are in line with previous findings, namely that pituitary adenoma affects cognition. To better evaluate the factors affecting cognition, longitudinal studies are recommended. Such studies would allow for within-individual comparisons, effectively controlling for the considerable influence of sex and education on test results.

Objective: Aldosterone is a key driver of cardiorenal disease as well as hard-to-treat hypertension. Highly selective aldosterone synthase inhibitors (ASI) are a new class of anti-hypertensive therapy that hold great promise for management of blood pressure (BP), having demonstrated BP lowering in a proof-of-concept study. The rationale for and design of a phase 3 trial with the novel ASI baxdrostat are described here. Design and method: The international, multicenter, randomized, double-blind, placebo-controlled phase 3 BaxHTN trial (NCT06034743) will enroll approximately 720 adults with uncontrolled or resistant hypertension defined as seated office systolic BP greater than/equal to 135 mmHg despite 2+ antihypertensives including a diuretic, serum potassium 3.5-5.0 mmol/L, and eGFR greater than/equal to 45mL/min/1.73m2. Given the need to address long-term efficacy but limit placebo use due to the risks of uncontrolled hypertension, the study will have 4 sequential parts following placebo run-in: 1) 12-week double-blind period, 1:1:1 randomization to baxdrostat 2 mg, baxdrostat 1 mg, or placebo; 2) 12-week open label period, re-randomization of the placebo and 1 mg arms to 2 mg or standard-of-care; 3) 8-week randomized withdrawal period to 2 mg or placebo; and 4) 20-week open label period. The primary endpoint will be the change in office systolic BP from baseline to 12 weeks. Adverse events will be evaluated under independent data monitoring committee supervision. Results: Results are expected in late 2025. Conclusions: The phase 3 BaxHTN trial design will allow assessing the safety of baxdrostat and its effect on BP in patients with uncontrolled or resistant hypertension. Results are expected in late 2025.

Patients with adrenal insufficiency (AI) have excess morbidity and mortality related to infectious disorders. Whether patients with AI have increased morbidity and mortality from COVID-19 is unknown. In this linked Swedish national register-based cohort study, patients with primary and secondary AI diagnosis were identified and followed from 1 January 2020 to 28 February 2021. They were compared with a control cohort from the general population matched 10:1 for age and sex. The following COVID-19 outcomes were studied: incidence of COVID-19 infection, rates of hospitalization, intensive care admission and death. Hazard ratios (HR) with 95% confidence intervals (95% CI) adjusted for socioeconomic factors and comorbidities were estimated using Cox regression analysis. We identified 5430 patients with AI and 54,300 matched controls: There were 47.6% women, mean age was 57.1 (standard deviation 18.1) years, and the frequency of COVID-19 infection was similar, but the frequency of hospitalization (2.1% vs. 0.8%), intensive care (0.3% vs. 0.1%) and death (0.8% vs. 0.2%) for COVID-19 was higher in AI patients than matched controls. After adjustment for socioeconomic factors and comorbidities, the HR (95% CI) was increased for hospitalization (1.96, 1.59–2.43), intensive care admission (2.76, 1.49–5.09) and death (2.29, 1.60–3.28). Patients with AI have a similar incidence of COVID-19 infection to a matched control population, but a more than twofold increased risk of developing a severe infection or a fatal outcome. They should therefore be prioritized for vaccination, antiviral therapy and other appropriate treatment to mitigate hospitalization and death.

Context Women with hypopituitarism remain at increased risk of morbidity and mortality. Insufficient replacement of sex steroids has been suggested as a contributing factor, but sex steroid levels in women with hypopituitarism have not been comprehensively mapped. Objective To quantify sex steroids in women with hypopituitarism by a high-sensitivity assay. Methods Using a combination of clinical and biochemical criteria, women with hypopituitarism (n = 104) who started GH replacement in 1995 to 2014 at a single center were categorized as eugonadal or having hypogonadotropic hypogonadism (HH). A population-based cohort of women (n = 288) served as controls. Eugonadal women and controls were categorized as pre-/postmenopausal and HH women as younger/older (≤ or >52 years). Dehydroepiandrosterone (DHEA), androstenedione, testosterone, dihydrotestosterone, progesterone, 17αOH-progesterone, estradiol, and estrone were analyzed by a validated liquid chromatography-tandem mass spectrometry assay. Results Among both premenopausal/younger and postmenopausal/older women, women with HH had lower levels of sex steroid precursors (DHEA, androstenedione) and androgens (testosterone and dihydrotestosterone) than controls. Progesterone, 17αOH-progesterone, estrone, and estradiol showed similar patterns. Women with HH and ACTH deficiency had markedly lower concentrations of all sex hormones than those without ACTH deficiency. Conclusion This study demonstrates for the first time a broad and severe sex steroid deficiency in both younger and older women with HH, particularly in those with combined gonadotropin and ACTH deficiency. The health impact of low sex steroid levels in women with hypopituitarism requires further study, and women with combined gonadotropin and ACTH deficiency should be a prioritized group for intervention studies with sex hormone replacement.

To study the long-term effect of transsphenoidal surgery (TSS) on headache in patients with non-functioning pituitary adenoma (NFPA) and identify factors predicting headache relief following TSS. We evaluated headache in 101 consecutive patients with NFPA who underwent TSS from September 2015 to December 2021, preoperatively and 12-months post-surgery, by using the Migraine Disability Assessment (MIDAS) questionnaire. Health-related quality of life (QoL) was assessed using the EQ-5D visual analogue scale (EQ-VAS). Of 101 patients, 27 (27

Objectives While glucocorticoid (GC) treatment initiated for COVID-19 reduces mortality, it is unclear whether GC treatment prior to COVID-19 affects mortality. Long-term GC use raises infection and thromboembolic risks. We investigated if patients with oral GC use prior to COVID-19 had increased mortality overall and by selected causes.Design Population-based observational cohort study.Settings Population-based register data in Sweden.Participants All patients infected with COVID-19 in Sweden from January 2020 to November 2021 (n=1 200 153).Outcome measures Any prior oral GC use was defined as ≥1 GC prescription during 12 months before index. High exposure was defined as ≥2 GC prescriptions with a cumulative prednisolone dose ≥750 mg or equivalent during 6 months before index. GC users were compared with COVID-19 patients who had not received GCs within 12 months before index. We used Cox proportional hazard models and 1:2 propensity score matching to estimate HRs and 95% CIs, controlling for the same confounders in all analyses.Results 3378 deaths occurred in subjects with any prior GC exposure (n=48 806; 6.9%) and 14 850 among non-exposed (n=1 151 347; 1.3%). Both high (HR 1.98, 95% CI 1.87 to 2.09) and any exposure (1.58, 1.52 to 1.65) to GCs were associated with overall death. Deaths from pulmonary embolism, sepsis and COVID-19 were associated with high GC exposure and, similarly but weaker, with any exposure. High exposure to GCs was associated with increased deaths caused by stroke and myocardial infarction.Conclusion Patients on oral GC treatment prior to COVID-19 have increased mortality, particularly from pulmonary embolism, sepsis and COVID-19.

OBJECTIVE:Acromegaly is associated with increased morbidity and mortality if left untreated. The therapeutic options include surgery, medical treatment, and radiotherapy. Several guidelines and recommendations on treatment algorithms and follow-up exist. However, not all recommendations are strictly evidence-based. To evaluate consensus on the treatment and follow-up of patients with acromegaly in the Nordic countries. METHODS:A Delphi process was used to map the landscape of acromegaly management in Denmark, Sweden, Norway, Finland, and Iceland. An expert panel developed 37 statements on the treatment and follow-up of patients with acromegaly. Dedicated endocrinologists (n = 47) from the Nordic countries were invited to rate their extent of agreement with the statements, using a Likert-type scale (1-7). Consensus was defined as ≥80% of panelists rating their agreement as ≥5 or ≤3 on the Likert-type scale. RESULTS:Consensus was reached in 41% (15/37) of the statements. Panelists agreed that pituitary surgery remains first line treatment. There was general agreement to recommend first-generation somatostatin analog (SSA) treatment after failed surgery and to consider repeat surgery. In addition, there was agreement to recommend combination therapy with first-generation SSA and pegvisomant as second- or third-line treatment. In more than 50% of the statements, consensus was not achieved. Considerable disagreement existed regarding pegvisomant monotherapy, and treatment with pasireotide and dopamine agonists. CONCLUSION:This consensus exploration study on the management of patients with acromegaly in the Nordic countries revealed a relatively large degree of disagreement among experts, which mirrors the complexity of the disease and the shortage of evidence-based data.

CONTEXT:There is a lack of reliable biomarkers capable of predicting postoperative tumor progression of nonfunctioning pituitary adenomas (NFPAs). OBJECTIVE:To discover proteomic profiles associated with postoperative tumor progression in patients with NFPAs. This was a case-controlled exploratory study at a tertiary university hospital. Tissue samples were obtained from 46 patients with residual tumor following surgery for NFPAs of gonadotroph lineage. Two patient groups were compared: patients requiring reintervention due to residual tumor progression (cases; reintervention group, n = 29) and patients with a residual tumor showing no progression for a minimum of 5 years (controls; radiologically stable group, n = 17). Differentially expressed proteins (DEPs) between patient groups were measured. RESULTS:Global quantitative proteomic analysis identified 4074 proteins, of which 550 were differentially expressed between the 2 groups (fold change >80%, false discovery rate-adjusted P ≤ .05). Principal component analysis showed good separation between the 2 groups. Functional enrichment analysis of the DEPs indicated processes involving translation, ROBO-receptor signaling, energy metabolism, mRNA metabolism, and RNA splicing. Several upregulated proteins in the reintervention group, including SNRPD1, SRSF10, SWAP-70, and PSMB1, are associated with tumor progression in other cancer types. CONCLUSION:This is the first exploratory study analyzing proteomic profiles as markers of postoperative tumor progression in NFPAs. The findings clearly showed different profiles between tumors with indolent postoperative behavior and those with postoperative tumor progression. Both enriched pathways involving DEPs and specific upregulated proteins have previously been associated with tumor aggressiveness. These results suggest the value of proteomic profiling for predicting tumor progression in patients with NFPAs.

BACKGROUND Patients with adrenal insufficiency (AI) have excess morbidity and mortality related to infectious disorders. Whether patients with AI have increased morbidity and mortality from COVID-19 is unknown. METHODS In this linked Swedish national register-based cohort study, patients with primary and secondary AI diagnosis were identified and followed from 1 January 2020 to 28 February 2021. They were compared with a control cohort from the general population matched 10:1 for age and sex. The following COVID-19 outcomes were studied: incidence of COVID-19 infection, rates of hospitalization, intensive care admission and death. Hazard ratios (HR) with 95% confidence intervals (95% CI) adjusted for socioeconomic factors and comorbidities were estimated using Cox regression analysis. RESULTS We identified 5430 patients with AI and 54,300 matched controls: There were 47.6% women, mean age was 57.1 (standard deviation 18.1) years, and the frequency of COVID-19 infection was similar, but the frequency of hospitalization (2.1% vs. 0.8%), intensive care (0.3% vs. 0.1%) and death (0.8% vs. 0.2%) for COVID-19 was higher in AI patients than matched controls. After adjustment for socioeconomic factors and comorbidities, the HR (95% CI) was increased for hospitalization (1.96, 1.59-2.43), intensive care admission (2.76, 1.49-5.09) and death (2.29, 1.60-3.28). CONCLUSION Patients with AI have a similar incidence of COVID-19 infection to a matched control population, but a more than twofold increased risk of developing a severe infection or a fatal outcome. They should therefore be prioritized for vaccination, antiviral therapy and other appropriate treatment to mitigate hospitalization and death.

Objective Data on pre- and postoperative pituitary function in nonfunctioning pituitary adenomas (NFPA) are not consistent. We aimed to investigate pituitary function before and up to 5 years after transsphenoidal surgery with emphasis on the hypothalamic-pituitary-adrenal axis (HPA). Design and methods Data from the Swedish Pituitary Register was used to analyze anterior pituitary function in 838 patients with NFPA diagnosed between 1991 and 2014. Patients who were reoperated or had received radiotherapy were excluded. Results Preoperative ACTH, TSH, LH/FSH, and GH deficiencies were reported in 31% (236/755), 39% (300/769), 51% (378/742), and 28% (170/604) of the patients, respectively. Preoperative median tumor volume was 5.0 (2.4-9.0) cm(3). Among patients with preoperative, 1 year and 5 years postoperative data on the HPA axis (n = 428), 125 (29%) were ACTH-deficient preoperatively. One year postoperatively, 26% (32/125) of them had recovered ACTH function while 23% (70/303) patients had developed new ACTH deficiency. Thus, 1 year postoperatively, 163 (38%) patients were ACTH-deficient (P < .001 vs. preoperatively). No further increase was seen 5 years postoperatively (36%, P = .096). At 1 year postoperatively, recoveries in the TSH and LH/FSH axes were reported in 14% (33/241) and 15% (46/310), respectively, and new deficiencies in 22% (88/403) and 29% (83/288), respectively. Conclusions Adrenocorticotrophic hormone deficiency increased significantly at 1 year postoperatively. Even though not significant, some patients recovered from or developed new deficiency between 1 and 5 years postoperatively. This pattern was seen in all axes. Our study emphasizes that continuous individual evaluations are needed during longer follow-up of patients operated for NFPA.

Abstract Disclosure: G. Johannsson: None. M. Persson: None. S. Schlaffer: None. A. Fehr: None. C. Örndal: Employee; Self; Unilabs AB. W. Seager: None. M. Buchfelder: None. G. Stenman: None. D.S. Olsson: Consulting Fee; Self; Ipsen, Novo Nordisk, Sandoz. Grant Recipient; Self; Pfizer Global R&D. Employee; Self; AstraZeneca. Background: Residual tumors are common after primary surgery in patients with non-functioning pituitary adenoma (NFPA), 30-50% of these will experience tumor progression. Tumor control is of vital importance for patient outcome since tumor progression is strongly associated with excess morbidity and mortality. The aim of the study was to explore new potential biomarkers of tumor progression by studying the DNA copy number profiles of NFPAs with either a stable residual tumor behavior or marked tumor progression. Methods: In this case-controlled study, 72 patients operated for NFPA were selected. The progression group (n = 39) included patients [age at diagnosis (mean ± SD) 41.3±14.0 years] with marked tumor progression (30 patients required ≥3 surgical procedures). The stable group (n = 33; 61.1±10.2 years) had either a stable residual tumor without evidence of tumor progression during follow-up (n = 25) or no recurrence during follow-up (n = 8). The mean follow-up time in the stable group was 6.2 years (range 3.6-15 years). ArrayCGH analysis was performed on DNAs isolated from fresh frozen tumor tissue using the Human Genome CGH Microarray 244K and 180K oligonucleotide arrays. Copy number alterations (CNAs) were validated using FISH on formalin-fixed paraffin-embedded sections. Results: CNAs were identified in 29 tumors (40%). A total of 183 CNAs were detected in the 72 tumors, including 75 segmental alterations and 108 gains and losses of whole chromosomes and chromosome arms. The average number of CNAs per tumor was 2.5 (SD 5.9). CNAs were more common in the progression group compared to the stable group (Mean no. of CNAs 3.7 vs 1.2; P = 0.060). Twenty-four tumors (72%) in the stable group had normal profiles whereas only 19 (49%) in the progression group lacked CNAs. Eighteen CNAs were recurrent, defined as minimal common regions of deletion or gain in ≥4 tumors. The most frequently lost region was 11q21-q23.3 (n = 10). Deletions involving 10q23.21-q23.3 were seen in both the progression group (n = 5) and the stable group (n = 2) and included an approximately 2.8 Mb minimal common region harboring the tumor suppressor gene PTEN. The most frequent gains involved whole chromosomes 5 (n = 8), 7 (n = 10) and 12 (n = 7). Recurrent CNAs involving 10q (PTEN probe), 11q (MAML2 probe), and chromosomes 5 and 7 were confirmed using FISH. Conclusion: In this explorative study, we found a higher number of CNAs in NFPAs with marked tumor progression compared to stable adenomas without the need for reintervention during the long-term follow-up. Interestingly, segmental losses of chromosome 10q23.21-q23.3, including the tumor suppressor gene PTEN, were overrepresented in patients with marked tumor progression. Presentation: Thursday, June 15, 2023

BACKGROUND:Patients undergoing pituitary surgery may experience short- and long-term postoperative morbidity. Intraoperative factors such as hypotension might be a contributing factor. Our aim was to investigate the association between intraoperative hypotension and postoperative plasma levels of tau, neurofilament light (NfL), and glial fibrillary acidic protein (GFAP) as markers of perioperative brain injury. METHODS:Between June 2016 and October 2017, 35 patients from the Gothenburg Pituitary Tumor Study were included. For tau, NfL, and GFAP, concentrations were measured in plasma samples collected before and immediately following surgery, and on postoperative days 1 and 5. The difference between the highest postoperative value and the value before surgery was used for analysis (∆taupeak , ∆NfLpeak , ∆GFAPpeak ). Intraoperative hypotension was defined as the area under the curve of an absolute threshold below 70 mmHg (AUC70) and a relative threshold below 20% (AUC20%) of the baseline mean arterial blood pressure. RESULTS:Plasma tau and GFAP were highest immediately following surgery and on day 1, while NfL was highest on day 5. There was a positive correlation between AUC20% and both ∆taupeak (r2  = .20, p < .001) and ∆NfLpeak (r2  = .26, p < .001). No association was found between AUC20% and GFAP or between AUC70 and ∆taupeak , ∆NfLpeak or ∆GFAPpeak . CONCLUSION:Intraoperative relative, but not absolute, hypotension was associated with increased postoperative plasma tau and NfL concentrations. Patients undergoing pituitary surgery may be vulnerable to relative hypotension, but this needs to be validated in future prospective studies.