Pituitary最新文献

Purpose: To assess surgical outcomes in patients with prolactinomas treated surgically with contemporary endoscopic endonasal techniques within the context of recent advances in transcavernous approaches and shifts towards surgery as a primary treatment option alongside dopamine agonists.

Methods: Surgical outcomes were retrospectively analyzed for 59 consecutive patients with prolactinomas who underwent endoscopic endonasal surgery between October 2018 and December 2024.

Results: The cohort included 42 (71%) patients with macroprolactinomas and 32 (54%) patients with cavernous sinus (CS) invasion, including 14 (24%) with isolated medial wall invasion and 18 (31%) with CS compartment invasion. Median follow-up was 19 months (interquartile range = 10-38). Overall, 82% of patients demonstrated normoprolactinemia within three days of surgery and 80% (74% macroprolactinoma, 94% microprolactinoma) achieved biochemical remission at last follow-up. Adjuvant dopamine agonist treatment and/or radiation increased the long-term remission rate to 86% overall and to 83% for macroprolactinomas. Among patients for whom total resection (vs. debulking) was the primary surgical goal, long-term biochemical remission was achieved in 84% of patients (88% with adjuvant therapy). One operative complication with no neurological sequelae occurred in a patient with a giant invasive adenoma. Permanent arginine vasopressin deficiency was observed in three patients and transient diplopia was observed in four patients.

Conclusion: The addition of endoscopic transcavernous approaches for prolactinoma resection can be safe and effective in selected patients after multidisciplinary evaluation when performed by an experienced neurosurgical team, providing further support for the wider adoption of surgery in the management of prolactinomas.

Background: Adamantinomatous craniopharyngioma (ACP) is a histologically benign yet clinically aggressive intracranial tumor characterized by high recurrence rates. Fibroblast activation protein (FAP), a marker of cancer-associated fibroblasts (CAFs), is implicated in tumor progression and microenvironment remodeling. This study evaluates the prognostic significance of FAP and develops a radiomics-based model for non-invasive preoperative risk stratification.

Methods: Immunohistochemical analysis was performed on 54 ACP cases to assess FAP expression levels. Transcriptomic data from 110 ACP cases across two external databases were analyzed for differential gene expression and pathway enrichment. Immunofluorescence was conducted to determine the spatial correlation of FAP with angiogenic markers (VEGF, CD31, CD34). A radiomics model was developed using preoperative MRI data to predict FAP expression and validated for predictive performance.

Results: High FAP expression was associated with extracellular matrix remodeling, angiogenesis, and inflammatory pathway activation. Clinically, high-FAP tumors exhibited larger volumes (P = 0.044), more severe hypothalamic dysfunction (P = 0.001), and shorter progression-free survival (P = 0.03). Multivariate analysis identified high FAP expression (HR = 9.890, P = 0.0340) as an independent predictor of recurrence. Immunofluorescence confirmed the co-localization of FAP⁺ CAFs with angiogenic markers, suggesting a role in tumor recurrence. The radiomics model integrating T1/T2-weighted MRI features demonstrated robust performance in predicting FAP expression, with AUCs of 0.742 (training set),0.822 (internal validation set) and 0.686(external validation set).

Conclusions: FAP is a prognostic biomarker in ACP, with high expression indicative of increased recurrence risk. The radiomics model offers a non-invasive approach for preoperative risk stratification, potentially guiding surgical decision-making and anti-angiogenic therapeutic strategies.

Purpose: Although endonasal endoscopic surgery (EES) is widely used to treat symptomatic Rathke's cleft cysts (RCCs), the optimal surgical strategy remains unclear. We previously proposed that the anatomical relationship between RCCs and the anterior pituitary lobe may predict recurrence. This study aimed to evaluate clinical characteristics and long-term outcomes based on anatomical classification and to assess the impact of surgical method (marsupialization vs. reconstruction) within each subtype.

Methods: We retrospectively analyzed 40 patients who underwent EES for symptomatic RCCs between 2008 and 2024. RCCs were classified into four types based on displacement: type 1 (anterior-superior), type 2 (anterior-inferior), type 3 (posterior-superior), and type 4 (posterior-inferior). Clinical, imaging, and surgical outcomes were compared across subtypes.

Results: he mean follow-up duration was 112 ± 53.2 months. Recurrence occurred in 16 patients (40.0%), and 6 (15.0%) patients required reoperation. Type 2 was independently associated with a higher recurrence rate (p = 0.019), more frequent preoperative visual disturbances (p = 0.0059), and lower T1-weighted signal intensity (p = 0.027). There was no significant difference in the recurrence rate between the surgical methods within each subtype.

Conclusion: The anterior-inferior subtype is more likely to recur regardless of the surgical method. The identification of high-risk subtypes may support the use of tailored strategies, including drainage-preserving techniques, to improve long-term outcomes.

Background: Patients with Cushing's syndrome (CS) have higher weight and body mass index (BMI) compared to matched controls. We aimed to assess reversibility of weight gain (absolute weight and BMI decrease) following treatment for CS and identify predictors for weight loss.

Methods: A retrospective study using the Clalit Health Services database analyzed a cohort of patients with CS and age-, sex- and BMI-matched controls (up to five controls per case). Weight and BMI were assessed at baseline, one-year post-diagnosis and at the end of follow-up. Patients taking GLP-1 have been excluded from the analysis.

Results: The cohort included 308 CS patients (67.2% female, mean age 51.6 ± 17.4 years) and 1,020 controls (69.7% female, mean age 54.8 ± 16.9 years). After one year, CS patients who achieved remission experienced significant weight reduction from 85.1 ± 21.0 to 80.8 ± 22.7 kg and BMI decrease from 31.6 ± 7.4 to 29.9 ± 7.4 kg/m² (p < 0.01). By the end of 8.6 years of follow-up, CS patients continued to show significant reductions in both weight (85.0 ± 22.3 to 81.3 ± 22.8 kg, p < 0.01) and BMI (31.2 ± 7.6 to 29.9 ± 7.6 kg/m², p < 0.01), while controls showed slight increases in both. Among patients in remission by the end-of-follow-up, 44.0% (77/175) achieved ≥ 5% and 30.3% (53/175) achieved ≥ 10% weight loss. Patients with persistent CS exhibited no significant weight changes. Multivariate analysis identified female gender, baseline BMI ≥ 30 and a BMI decrease ≥ 1 kg/m² at one year, as predictors for ≥ 5% weight loss.

Conclusion: Approximately half of CS patients in remission achieved at least 5% decrease in BMI with long-term follow-up, and a third achieved more than 10% decrease. Disease remission, female gender, baseline BMI ≥ 30, and early BMI reduction, predicted a clinically significant weight loss.

Purpose: Double or multiple pituitary adenomas account for only 1.6-3.3% of all corticotroph tumors. We sought to better understand the underlying molecular pathogenesis of two distinct corticotroph adenomas in a 43-year-old female.

Methods: Two histopathologically confirmed corticotroph adenomas were submitted for whole-exome sequencing along with a matched blood sample. The functional effects of identified variants of uncertain significance on corticotroph tumor pro-opiomelanocortin transcription and proliferation were characterized.

Results: WES demonstrated a loss-of-function variant in the G-protein coupled receptor 162 [GPR162 (R218*)] in the right corticotroph tumor, and a novel missense variant in ubiquitin specific peptidase 8 [USP8 (P681Q)] in the left tumor. Compared to wild-type GPR162 which potently suppressed POMC transcription, the stop-gain variant (R218*) exhibited reduced inhibitory effect. The novel USP8 variant (P681Q) found in the contra-lateral tumor led to increased POMC transcription although weaker than the well characterized hotspot variant S718P, and did not affect EGFR ubiquitin. Interestingly, the patient also had a germline variant in the 21-alpha-hydroxylase gene (CYP21A2 p.A392T) though without clinical features of congenital adrenal hyperplasia.

Conclusion: We report, for the first time, the genetic profiles of a patient with dual pituitary corticotroph tumors, identifying a stop-gain variant in GPR162 in one tumor and a novel USP8 variant (S718P) in the other. While both somatic variants increased POMC expression, only GPR162 R218* affected proliferation. We hypothesize that alterations in adrenal steroidogenesis due to the CYP21A1 mutation may have reduced negative feedback on corticotroph cells and acted in a permissive way to facilitate corticotroph tumorigenesis.

Purpose: Biochemical remission is the primary treatment goal in acromegaly. However, some patients experience biochemical discordance between growth hormone (GH) and insulin-like growth factor-I (IGF-I) levels following multimodal therapy, complicating disease assessment and management. This study aims to identify predictive factors associated with post-therapeutic biochemical discrepancy.

Methods: We conducted a retrospective monocentric analysis of 156 patients with GH-producing pituitary adenomas (PAs) who underwent transsphenoidal surgery between 1984 and 2017. Biochemical outcomes were classified into four groups: group 1 (biochemical remission), group 2 (isolated GH normalization), group 3 (isolated IGF-I normalization), and group 4 (persistent acromegaly). Predictive factors for biochemical discrepancy were assessed, including demographic data, tumor characteristics, medication, irradiation, follow up duration, and disease recurrence.

Results: The median age of the cohort was 48.2 years, with a female predominance (61.5%). Most PAs were macroadenomas (79.6%) and invasive (53.9%). Biochemical remission was achieved in 69.9%, while 19.2% exhibited biochemical discrepancy. Univariate analysis identified overall medication (pre- and/or postoperative), irradiation, and invasive PAs as significant factors associated with biochemical discordance. Logistic regression confirmed medication as the most influential predictor, with irradiation as a potential contributing factor. Disease recurrence was the only distinguishing factor between persistent acromegaly and biochemical discrepancy.

Conclusion: Overall medication use is the strongest predictor of biochemical discrepancy, with irradiation potentially contributing. No clear distinguishing factors between biochemical discordance and persistent acromegaly were identified, except from disease recurrence. Managing patients with biochemical discrepancy similarly to those with persistent acromegaly may be advisable. Further research is needed to refine treatment strategies.

Purpose: To evaluate the prevalence and the timing of gonadal axis restoration in men with hypogonadism secondary to hyperprolactinemia after prolactin (PRL) normalization, and to identify factors associated with testosterone (TT) recovery to normal values.

Methods: We retrospectively analyzed clinical records of male patients with central hypogonadism and successfully treated isolated hyperprolactinemia. Data on PRL, TT, gonadotropins levels were retrieved for different time points: diagnosis, PRL normalization, gonadal axis restoration (if achieved) and last follow-up. Testosterone replacement therapy within 6 months of PRL normalization was an exclusion criterion.

Results: Twenty-nine patients, median age 50 years (IQR 41-58), were included. The etiology of hyperprolactinemia included: prolactinoma (n = 23, 79%), non-functioning pituitary adenoma causing stalk effect (n = 5, 17%) and idiopathic cause (n = 1, 4%). After successful treatment of hyperprolactinemia, 20 patients (69%) spontaneously recovered the gonadal axis, achieving normal TT levels. Ten patients normalized PRL and TT values concurrently, while the other 10 exhibited a median delay of 6.5 months (4-9.25) after PRL normalization; the former group showed lower baseline PRL levels at diagnosis compared to the latter (p = 0.007). Patients who recovered the gonadal axis had higher baseline TT values compared to those with persistent hypogonadism (p = 0.02). At ROC curve analysis, baseline TT was a good predictor of spontaneous gonadal axis recovery after PRL normalization (AUC 0.869, p = 0.002).

Conclusion: In patients with hypogonadism secondary to isolated hyperprolactinemia, gonadal axis recovery occurs frequently, particularly in those with higher baseline TT. Lower PRL levels at diagnosis are associated with a faster recovery of gonadal axis.