Outcome prediction after Gamma Knife radiosurgery (GKRS) for pituitary adenomas remains guided by tumor anatomy, functional status, prior treatment, optic-apparatus proximity, and physician experience rather than individualized estimates of tumor response, biochemical remission, and endocrine morbidity. We developed THINKERS-PA, a mixture-of-experts (MoE) framework for outcome prediction and prescription-dose simulation after GKRS. We performed a retrospective study of 125 patients with pituitary adenomas treated with GKRS. Variables available at treatment planning were used to train a three-expert MoE neural network integrating clinical and endocrine history, tumor anatomy and imaging, and radiosurgical dosimetry. Discrete-time survival heads estimated tumor progression, biochemical remission in functioning adenomas, and new hypopituitarism. Secondary endpoints include a favorable composite outcome, visual deterioration, and need for additional treatment. Validation used repeated nested 5-fold cross-validation. A dose-sweeping module evaluated treatment doses. The cohort included 72 functioning and 53 nonfunctioning adenomas. Tumor progression occurred in 14.4
Population-based studies overall report no excess mortality among patients with prolactinoma compared with the general population. However, since prolactinomas are clinically heterogeneous, mortality may not be uniform across data-driven patient profiles. We analyzed 3,378 adult prolactinoma cases (26,118 person-years) from the Surveillance, Epidemiology, and End Results database (2004–2022). Standardized mortality ratios (SMRs) were calculated using US life tables matched by age, sex, calendar year, race/ethnicity, and geography. Among 2,481 patients with available tumor size (18,097 person-years), unsupervised clustering (Fuzzy C-Means) based on age, tumor size, and sex defined patient profiles. Excess mortality ratios (EMRs) compared observed-to-expected mortality across profiles, adjusting for race, calendar year, surgery, and radiotherapy. Prolactinoma was associated with significant excess all-cause mortality (SMR 1.21, 95
Craniopharyngiomas are benign tumors that develop in the hypothalamic-pituitary region. Their treatment mainly involves surgery, sometimes combined with radiotherapy. The hypothalamus plays an essential role in hormonal balance and energy regulation, but also in cognition through connectivity circuits. The cognitive impact of craniopharyngioma treatment is poorly understood and has mainly been studied in children. We report the neuropsychological assessments of 22 adult patients treated for craniopharyngioma with a follow-up of at least 5 years, 16 of whom were diagnosed while being adults. All assessments were performed by a neuropsychologist using validated tests. More than 65
DNA methylation profiling identifies clinically relevant subgroups of non-functioning pituitary adenomas (NFPAs), but requires tumour tissue and is unavailable preoperatively. We investigated whether reported outcome-associated methylation-defined NFPA phenotypes are associated with preoperative MRI radiomic features. We performed a single-centre retrospective radiogenomic analysis nested within a previously published, outcome-characterised NFPA methylation cohort. Seventy-four patients with preoperative gadolinium-enhanced T1-weighted MRI were included. Tumours were automatically segmented using a fine-tuned U-Net. The primary analysis tested binary discrimination between the outcome-associated low-risk (k1/k2) and high-risk (k3/k4/k5) methylation strata using a prespecified L1-penalised logistic-regression model with leakage-controlled repeated stratified cross-validation, 0.632 + bootstrap optimism correction, and 1000-shuffle whole-pipeline permutation testing. Seven radiomic features were false-discovery-rate significant and four survived Bonferroni correction, predominantly LoG-filtered first-order intensity features. The prespecified model separated high-risk from low-risk tumours with balanced accuracy 0.69 (95
Hyperprolactinemia has been associated with adverse cardiometabolic alterations, whereas the metabolic consequences of treatment-induced hypoprolactinemia remain uncertain. We aimed to evaluate longitudinal cardiometabolic changes across sequential prolactin states in dopamine agonist–treated prolactinoma patients. We conducted a retrospective multicentre longitudinal cohort study including 47 prolactinoma patients from 19 tertiary hospitals in Spain. All patients sequentially transitioned from hyperprolactinemia (HyperPRL) to normoprolactinemia (NormoPRL) and subsequently to hypoprolactinemia (HypoPRL) during cabergoline therapy. Longitudinal changes in anthropometric, hemodynamic, and metabolic parameters were assessed using repeated-measures analyses and generalized estimating equation (GEE) models. Correlation and multivariable regression analyses were performed to evaluate associations between prolactin reduction and metabolic changes. Transition from HyperPRL to NormoPRL was associated with significant reductions in body weight (80.4 ± 23.6 vs. 78.7 ± 22.8 kg; p = 0.009), body mass index (29.3 ± 7.4 vs. 28.4 ± 7.3 kg/m²; p = 0.034), and total cholesterol (194.3 ± 36.5 vs. 178.7 ± 34.8 mg/dL; p = 0.006). Triglyceride concentrations showed a trend toward reduction across prolactin states, with a significant decrease observed between HyperPRL and NormoPRL. No additional cardiometabolic improvements were detected after transition from NormoPRL to HypoPRL. GEE analyses confirmed significant longitudinal reductions in body weight and total cholesterol after adjustment for age, sex, and initial cabergoline dose, and results remained unchanged in sensitivity analyses additionally accounting for treatment duration. Although percentage prolactin reduction showed a weak inverse association with body weight change in exploratory analyses, no independent associations were identified after multivariable adjustment. Normalization of prolactin concentrations was associated with significant improvements in body weight, BMI, and total cholesterol concentrations. In contrast, no significant cardiometabolic improvements were detected following the subsequent development of treatment-induced hypoprolactinemia. Furthermore, the magnitude of prolactin reduction was not independently associated with changes in anthropometric or metabolic parameters after multivariable adjustment. These findings suggest that the main cardiometabolic changes occur during the transition from hyperprolactinemia to normoprolactinemia. However, the specific cardiometabolic effects of treatment-induced hypoprolactinemia require confirmation in larger prospective studies.
Acquired hypothalamic obesity (AHO) is a complex neuroendocrine disorder characterized by rapid weight gain and multisystem dysfunction following hypothalamic damage. AHO represents the weight-related manifestation of the broader hypothalamic syndrome (HS), a heterogeneous spectrum of dysfunctions that can also encompass disturbances in pituitary function, energy expenditure, sleep, behavior, and thermoregulation, with obesity itself absent in some affected individuals. This narrative review provides an updated and integrative overview of AHO pathophysiology, clinical characterization, and current and emerging approaches to diagnosis, prevention, and treatment, with the aim of proposing a multidimensional framework to improve patient care. The literature, including seminal studies, recent systematic reviews, clinical trials, and expert consensus statements, was critically appraised with emphasis on clinical applicability and existing knowledge gaps. Current evidence highlights the limitations of BMI-based assessment and supports a multidomain clinical approach. In this context, a three-layer diagnostic model is proposed, integrating etiological factors, longitudinal anthropometric and metabolic assessment, and domain-specific clinical evaluation. Preventive strategies remain underexplored, although hypothalamus-sparing interventions, early monitoring of weight trajectory, and management in specialized Pituitary Tumor Centers of Excellence in surgical cases appear critical. Therapeutic options are limited, with modest evidence for conventional treatments; however, emerging therapies targeting the melanocortin pathway, including MC4R agonists, showed promising results. Overall, AHO requires a paradigm shift toward early identification, multidimensional assessment, and coordinated multidisciplinary care, with future research prioritizing preventive strategies and robust clinical trials to improve outcomes.
Acromegaly is a rare endocrine disorder characterized by delayed diagnosis and substantial multisystem morbidity. Nurses play an important role in early recognition and multidisciplinary management of the disease; however, evidence regarding their knowledge of acromegaly is limited. This study aimed to assess the knowledge and awareness of nurses regarding acromegaly and to identify factors associated with knowledge level. A descriptive cross-sectional study was conducted between December 2024 and March 2025 at Ankara Bilkent City Hospital, Türkiye. A total of 884 nurses participated voluntarily. Data were collected using a researcher-developed, content-validated Acromegaly Experience and Knowledge Questionnaire (Cronbach's α = 0.852). Binary logistic regression analysis was performed to identify independent predictors of knowledge level. The mean age of participants was 29.8 ± 6.3 years; 84.8
Pediatric gigantism associated with somatotropinomas is exceedingly rare. Although transsphenoidal surgery (TSS) constitutes first-line management, tumor recurrence is common. However, it remains unclear how surgical cure rates differ between transsphenoidal microsurgery (TMS) and the more contemporary endoscopic endonasal approach (EEA). Three children with somatotropinoma-induced gigantism who underwent EEA between December 2010 and October 2021 were identified via retrospective chart review. Primary outcomes collected included complications, length of stay (LOS), and rates of postoperative biochemical remission according to the 2010 Acromegaly Consensus Group criteria. A literature review compiled surgical cure rates for pediatric gigantism, stratified by TSS technique (TMS vs EEA). Three children (2F, 1 M) presented with clinical signs of gigantism at an average age of 12 years [range: 10-14y]. Two patients failed prior somatostatin analogue therapy and one underwent attempted but incomplete EEA at an outside institution. Mean tumor diameter was 0.9 ± 0.2 cm. EEA was performed without complications and a mean LOS of 4.6 days [range: 3-7d]. Biochemical remission was achieved in all patients without adjuvant therapy during follow-up [range: 1-11y]. Nineteen historical studies report surgical outcomes for 325 total pediatric patients with gigantism. Overall surgical cure rates are estimated at 24.7
Personalized therapy in acromegaly is limited by interindividual variability in drug responses and the lack of robust markers predicting tumor shrinkage, rather than biochemical control alone. To test whether ex vivo drug-induced viability changes in patient-derived 3D cultures (Pd3D) of GH–secreting pituitary adenomas reflect tumor cell-intrinsic pharmacological sensitivity and align with established clinical predictors. Spheroid-based Pd3D cultures were established from 27 patients with acromegaly. Cultures were exposed to octreotide, cabergoline, pasireotide, or vehicle control. We assessed cell viability changes; sample-level responder status (viability reduction vs vehicle, p < 0.05); and associations between responder status and known predictive markers, including clinical characteristics, MRI findings, dynamic drug tests, and pathological features. In 6 cases, AI-based digital image analysis quantified pre- and post-treatment SSTR2 expression in liquid-based cytology (LBC). All agents modestly reduced median cell viability (84–86
Dopamine agonists, particularly cabergoline, are the first-line treatment for prolactinomas, but have been associated with impulse control disorders (ICDs). However, data on impulsivity and related behaviors in this population remain limited and inconsistent. To evaluate impulsivity and ICDs in patients with prolactinoma treated with cabergoline and to compare these findings with healthy controls. This case–control study included 131 patients with prolactinoma receiving cabergoline and 131 healthy controls. Impulsivity was assessed using the Barratt Impulsiveness Scale (BIS-11), and ICDs were evaluated using specific questionnaires addressing hypersexuality, gambling, compulsive shopping, and punding. Multivariable analyses were performed to assess independent associations. Patients treated with cabergoline exhibited higher overall impulsivity, reflected by increased BIS-11 scores and a higher proportion of individuals with increased impulsivity (BIS-11 ≥ 60). Attentional impulsivity remained significantly higher in patients after multivariable adjustment. Patients also had more than fourfold higher odds of compulsive shopping compared with controls, whereas no significant differences were observed for other ICDs. Lower educational level was also associated with higher impulsivity across all BIS-11 domains and with compulsive shopping. Patients with prolactinoma treated with cabergoline exhibit increased impulsivity, particularly in the attentional domain, along with higher odds of compulsive shopping. These results highlight the role of dopaminergic modulation and the influence of sociodemographic factors, supporting the importance of actively assessing impulsivity during clinical follow-up.
To quantify the severity, frequency of symptom exacerbations, and associated life impact of acromegaly symptoms in patients treated with injected depot somatostatin receptor ligands (SRLs). Patients receiving depot SRLs completed daily 24-hour recall surveys for 3 months. The daily surveys assessed the severity of 7 core symptoms and 2 additional symptoms on numeric scales (0–10). Symptom exacerbation was defined as a ≥ 2-point increase in any symptom score, comparing the current 2-day average with the prior 2-day average. Patients completed a final survey assessing 3-month recall of symptom severity and daily functioning, treatment satisfaction, and healthcare resource utilization (HCRU). The analysis population included 31 patients: mean (SD) age was 53.4 (13.6) years; 24 (77.4
In adults with hypothalamic–pituitary disease, the presence of at least three additional pituitary hormone deficiencies, with or without markedly reduced IGF-I levels, is considered diagnostic of growth hormone deficiency (GHD) without the need for stimulation testing. In all other cases, dynamic testing is required despite its well-recognized limitations. To date, no formal strategy has been proposed to exclude GHD without performing stimulation tests. This study aims to develop a probabilistic model to estimate the likelihood of GHD in adults with hypothalamic–pituitary disease but no additional pituitary hormone deficiencies, based on IGF-I standard deviation scores (SDS). We combined literature-derived data on: (1) the probability of an impaired GH response to stimulation tests in patients with hypothalamic–pituitary disease and preserved anterior pituitary function; and (2) the probability that adults with isolated GHD present IGF-I SDS values ≥ 0, ≥ 0.5, or ≥ 1. A Bayesian approach was applied to estimate the post-test probability of GHD in patients meeting these criteria. Across all models, the estimated probability of adult-onset GHD ranged from 6.5
To evaluate the hypothesis that breakthrough acromegaly symptom exacerbation frequency would be reduced after switching biochemically controlled patients from depot somatostatin receptor ligand (SRL) injections to once-daily oral paltusotine. Biochemical disease control (insulin-like growth factor 1 [IGF-I]) and Acromegaly Symptom Diary (ASD) data were analyzed from PATHFNDR-1, a 36-week, randomized, placebo-controlled, double-blind, phase 3 trial of paltusotine in patients with acromegaly biochemically controlled (IGF-I ≤ 1.0× ULN) with SRLs. The ASD measured the daily severity of 7 core and 2 exploratory acromegaly symptoms, each rated on a scale from 0 to 10 based on 24-hour recall. Breakthrough acromegaly symptom exacerbations were defined as ≥ 2-point increases for any individual symptom score, comparing a 2-day average with the prior 2-day average. Despite no significant changes in IGF-I levels or overall core symptom severity scores, mean (SE) symptom exacerbation frequencies declined progressively after switching to paltusotine, from 30.2
Differentiating prolactinomas from non-functional pituitary adenomas (NFPAs) with stalk effect relies on biochemical thresholds that assume a linear relationship between tumor size and prolactin secretion. We applied a pathology-informed Prolactin Secretory Efficiency (PSE) framework to characterize diagnostic overlap between prolactinomas and NFPAs and evaluate the limitations of current prolactin thresholds. Retrospective study of 425 patients undergoing first-time surgery for pituitary adenomas: 115 pathology-confirmed lactotroph adenomas, 291 NFPAs, and 19 mammosomatotrophs. Patients with clinical or biochemical evidence of ACTH- or GH-secreting tumors were excluded. PSE was calculated as the serum prolactin-to-tumor volume ratio (ng/mL∙ mm^3 ). Primary outcomes included PSE-based group separation and diagnostic accuracy of the 200 ng/mL threshold. While no NFPA exceeded 200 ng/mL, 42
To evaluate bone mineral density (BMD) in postmenopausal women with prolactinoma diagnosed during the premenopausal period and to compare skeletal outcomes according to prolactin status during drug-free follow-up. This retrospective cross-sectional single-center study included 42 postmenopausal women with prolactinoma. Patients were classified as hyperprolactinemic or normoprolactinemic based on serum prolactin levels at the last follow-up visit. BMD was assessed by dual-energy X-ray absorptiometry at the lumbar spine and femoral neck. Clinical variables were compared between groups. Correlation analysis, receiver operating characteristic (ROC) analysis, and multivariable logistic regression were performed. Lumbar spine BMD was significantly lower in hyperprolactinemic patients than in normoprolactinemic patients (0.861 ± 0.124 vs. 0.960 ± 0.129 g/cm², p = 0.022), whereas femoral neck BMD did not differ. Patients with hyperprolactinemia had longer cumulative exposure to hyperprolactinemia and required longer and higher-dose cabergoline treatment. Baseline prolactin levels were higher in patients with osteoporosis and showed potential discriminatory value for identifying osteoporosis (AUC = 0.861). Lumbar spine BMD and T-scores were inversely correlated with prolactin levels. In multivariable analysis, baseline prolactin level remained independently associated with low BMD. Persistent hyperprolactinemia is associated with lower lumbar spine BMD in postmenopausal women with prolactinoma. Baseline prolactin level and cumulative exposure to prolactin excess appear to be important contributors to skeletal deterioration, supporting the need for routine bone health assessment during long-term follow-up.
Purpose Non-functioning pituitary adenomas (NFPA) are one of the most frequent pituitary adenoma subtypes, yet dedicated management guidelines do not exist. This study aimed to characterise real-world clinical decision-making across the spectrum of NFPA presentations and to identify areas of practice conformity versus heterogeneity within and between specialty groups.Methods A cross-sectional, anonymous electronic survey was administered to endocrinologists, neurosurgeons, ENT surgeons, and radiation oncologists involved in pituitary adenoma care in Australia and New Zealand between January and April 2025. Three clinical scenarios were presented: an incidental microadenoma, an incidental asymptomatic macroadenoma, and a symptomatic macroadenoma with visual compromise. Concordance was defined as greater than 70% agreement on a single response within any group.Results A total of 145 clinicians completed the survey (99 endocrinologists, 31 surgeons, 15 radiation oncologists). Areas of conformity included broad anterior pituitary hormonal evaluation, conservative management of incidental asymptomatic macroadenomas, and active intervention for symptomatic disease with visual loss. Significant heterogeneity was identified in ophthalmological assessment, repeat imaging intervals, post-operative MRI and visual field timing, and multidisciplinary team (MDT) meeting referral rates. Compared to general endocrinologists, pituitary subspecialty endocrinologists were significantly more likely to refer patients for MDT discussion and know the caseload of the surgeon to whom they were referring, and less likely to measure serum cortisol immediately post-operatively.Conclusion This survey identifies clinically important variation in NFPA management, concentrated in domains lacking guideline recommendations. These findings highlight the need for dedicated NFPA guidelines spanning the full spectrum of NFPA presentations.
Low prolactin levels are associated with an increased risk of vascular and metabolic diseases. Women with prolactin deficiency appear to have attenuated responses to lipid-lowering and insulin-sensitizing medications. This study aimed to evaluate the impact of hypoprolactinemia on the cardiometabolic effects of rosuvastatin in men. Three groups of men with indications for statin therapy were included. Group 1 comprised 16 individuals with prolactin levels below 3 ng/mL, while groups 2 (n = 23) and 3 (n = 37) included patients with levels between 3 and 20 ng/mL. Participants in groups 1 and 2 were chronically treated with cabergoline. Throughout the six-month study period, all patients received rosuvastatin. In addition to lipid profile and prolactin levels, assessed parameters included high-sensitivity C-reactive protein (hs-CRP), fibrinogen, homocysteine, uric acid, urinary albumin-to-creatinine ratio (UACR), carbohydrate metabolism markers, testosterone, and carotid intima-media thickness (CIMT). At baseline, men with hypoprolactinemia showed higher hs-CRP, fibrinogen, homocysteine, UACR, HbA1c, and HOMA-IR, and lower testosterone than those with normal prolactin levels. Rosuvastatin reduced total and LDL cholesterol in all groups, with a greater effect in groups 2 and 3. Reductions in hs-CRP, fibrinogen, uric acid, homocysteine, and UACR occurred only in groups with normal prolactin. Group 1 exhibited increases in HbA1c and HOMA-IR. At study end, CIMT was greater in group 1 than in groups 2 and 3, whereas the latter two groups had comparable values. In men with hypoprolactinemia, the effects of rosuvastatin on total and LDL cholesterol, hs-CRP, fibrinogen, uric acid, homocysteine, UACR, HbA1c, HOMA-IR, and CIMT correlated with baseline and posttreatment prolactin concentrations. These findings suggest that hypoprolactinemia may worsen cardiometabolic outcomes in men receiving rosuvastatin therapy.
