The molecular mechanisms underlying the clinical differences between densely granulated (DG) and sparsely granulated (SG) somatotroph tumors remain poorly understood. To identify significant molecular differences between these subtypes, we performed quantitative mass spectrometry-based proteomic profiling followed by validation of the differentially-identified proteins. Label-free quantitative proteomic analysis was performed on SG somatotroph adenomas (SGSAs, n = 3) and DG somatotroph adenomas (DGSAs, n = 3), with each sample analyzed in technical triplicate. Key findings were subsequently validated using immunohistochemistry (IHC, n = 64), immunofluorescence (IF, n = 24), and Western blotting (WB, n = 18). Proteomic profiling identified TNFAIP3-interacting protein 1 (TNIP1) as the most significantly over-expressed protein, and coenzyme Q6 monooxygenase (COQ6) as the most significantly under-expressed protein, in SGSAs compared with DGSAs. Higher TNIP1 expression in SGSAs was significantly associated with IGF-1 [
Population-based studies describing the full clinical spectrum of pediatric sellar and parasellar lesions are scarce. Most available data derive from referral-based surgical or diagnosis-specific cohorts. We aimed to characterize presentation, lesion pathology, management, and long-term endocrine outcomes in a population-based cohort. We conducted a retrospective, population-based cohort study of patients aged 18 years or younger diagnosed with sellar or parasellar lesions between 1976 and 2021 in a multicounty region. Clinical presentation, lesion characteristics, management, and endocrine outcomes were abstracted from medical records. Associations were evaluated by lesion type, lesion size (< 10 mm vs. ≥10 mm), and management approach. Among 104 patients, endocrine abnormalities at diagnosis differed by lesion type (p = 0.0004) and were most frequent among patients with pituitary adenomas. Endocrine dysfunction at presentation was more common with lesions ≥ 10 mm than with lesions < 10 mm (74.2
There is evidence to suggest that hormonal dysregulation induced by acromegaly may affect serum cytokine levels. However, to our knowledge, no previous studies have examined the salivary cytokine profile in adults with acromegaly. The aim of this study was to identify the salivary profile of pro- and anti-inflammatory cytokines associated with acromegaly in adults. A cross-sectional study was conducted with 25 patients with acromegaly and age-, 25 age- and sex-matched controls. Demographic and general health data were collected. Saliva samples were obtained to quantify the concentrations of IL-1β, IL-4, IL-6, IL-10, IL-17A, IL-22, TGF-α, and TNF-α. Statistical analyses included the Mann-Whitney test, Spearman's correlation, and ROC curve analysis. Patients with acromegaly exhibited significantly higher salivary levels of IL-4, IL-6, IL-10, TGF-α, and TNF-α (p<0.001), as well as IL-17A (p=0.029). No significant differences were observed for isolated IL-1β and IL-22. Comparative analysis showed significantly lower IL-22/IL-4 (p<0.001), IL-1β/IL-10 (p=0.023), and IL-22/IL-10 (p=0.003) ratios in patients with acromegaly compared with controls. Given that IL-1β and IL-22 did not differ significantly between groups, whereas IL-4 and IL-10 were increased in acromegaly, these lower ratios appear to primarily reflect higher levels of the anti-inflammatory cytokines. In multivariate analysis, IL-4, IL-6, IL-17A, IL-22, and TNF-α remained statistically associated with acromegaly. The study findings suggest that patients with acromegaly exhibit a significant imbalance in the levels of pro- and anti-inflammatory cytokines in saliva, with emphasis on IL-4, IL-6, IL-17A, IL-22, and TNF-α.
To assess whether C-X-C motif chemokine receptor 4-targeted 68Ga-Pentixafor PET/MRI can localize corticotroph adenomas in patients with Cushing disease (CD), particularly when MRI is negative or inconclusive, and explore performance in newly diagnosed versus persistent/recurrent disease. In this single-center pilot study, 10 patients with newly diagnosed or persistent/recurrent CD, confirmed by inferior petrosal sinus sampling (IPSS) and/or surgical pathology, underwent 68Ga-Pentixafor PET/MRI. Clinical, biochemical, radiologic, surgical, and postoperative data were reviewed. 68Ga-Pentixafor PET/MRI were classified as positive or negative using visual and quantitative assessment, including maximum standardized uptake values (SUVmax) and target-to-background (SUVmean of the blood pool in the cavernous sinus) ratio (TBR). Participants had a mean age of 46.7 years; 9 were female. Five had newly diagnosed and 5 had persistent/recurrent CD. Two scans showed focal pituitary 68Ga-Pentixafor uptake compared to background pituitary tissue. One was confirmed by an MRI-visible lesion, positive pathology, and postoperative remission. The second occurred with an inconclusive MRI, negative pathology, and persistent postoperative disease; however, IPSS centralized. Three patients with negative scans underwent surgery and achieved remission, indicating false-negative imaging. Among 5 patients with negative scans who did not undergo subsequent surgery, 4 had persistent/recurrent CD and 1 had newly diagnosed CD treated medically. In this pilot cohort, 68Ga-Pentixafor PET/MRI showed limited and variable performance for corticotroph adenoma localization. Although it may provide complementary information in selected patients with MRI-visible or equivocal lesions, further study is needed before it can be incorporated into diagnostic algorithms or considered an alternative to IPSS.
