Pituitary最新文献

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.

Purpose: This systematic review aims to evaluate tumor control outcomes associated with antineoplastic drug therapies used for aggressive pituitary tumors (APTs) and pituitary carcinomas (PCs).

Methods: We included studies on patients with PC or APT who received one of the following therapies: temozolomide (TMZ), peptide receptor radionuclide therapy (PRRT), everolimus, immune checkpoint inhibitors (ICIs), lapatinib, bevacizumab, capecitabine plus temozolomide (CAPTEM). Search strategies were applied to MEDLINE, EMBASE, LILACS and CENTRAL. Two independent reviewers selected studies, assessed the risk of bias, and extracted data. Proportional meta-analyses were used to calculate overall frequencies of complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD).

Results: Seventy eight studies were included. TMZ was the most commonly used therapy, followed by ICIs, bevacizumab, PRRT, CAPTEM, lapatinib, and everolimus. Among 434 patients treated with TMZ in studies involving three or more participants, CR occurred in 4% (95% confidence interval [95% CI], 1-13), PR in 33% (95% CI, 28-37), SD in 32% (95% CI, 28-36), and PD in 29% (95% CI, 25-34). For ICIs, PR occurred in 24% (95% CI, 11-44), SD in 12% (95% CI, 4-31), and PD in 67% (95% CI, 24-93).

Conclusion: TMZ was the most frequently reported therapy, with PR as the predominant outcome. However, the limited data on ICIs, PRRT, bevacizumab, lapatinib, and everolimus yielded imprecise results, highlighting the need for further research with the aim of gaining more insights into treatment effects of antineoplastic drug therapies for APTs and PCs.