Pituitary最新文献

Background: Adrenocorticotropin (ACTH)-dependent Cushing's syndrome can arise from a pituitary tumour (Cushing's disease) or an ectopic ACTH-secreting tumour, making precise differentiation essential for effective treatment. Bilateral inferior petrosal sinus sampling (BIPSS) is the gold standard for this differentiation, but false-negative results can limit its accuracy. Adding prolactin (PRL) measurement to BIPSS has been proposed to improve diagnostic precision. This meta-analysis evaluates how correction for prolactin levels ('prolactin adjustment') affects the diagnostic value of BIPSS in distinguishing Cushing's disease from ectopic ACTH syndrome.

Methods: A systematic literature search was conducted in PubMed, Scopus, EMBASE, Web of Science, and Google Scholar up to July 2024. Studies were included if they provided data on BIPSS with and without PRL adjustment for ACTH-dependent Cushing's syndrome. Data extraction and quality assessment were performed, and diagnostic accuracy metrics were analysed using bivariate generalised linear mixed modelling.

Results: A total of 10 studies with 310 participants were included. The pooled sensitivity and specificity of BIPSS with PRL adjustment were 0.96 (95% CI: 0.93-0.98) and 0.68 (95% CI: 0.52-0.81), respectively. The diagnostic odds ratio (DOR) was 48.0 (95% CI: 19.0-123.0), with a positive likelihood ratio (LR) of 3.00 (95% CI: 1.9-4.7) and a negative LR of 0.06 (95% CI: 0.03-0.12). The area under the summary receiver operating characteristic (SROC) curve was 0.95 (95% CI: 0.93-0.97). For BIPSS without PRL adjustment, the pooled sensitivity was 0.90 (95% CI: 0.86-0.93) and specificity was 0.74 (95% CI: 0.59-0.85), with a DOR of 27.0 (95% CI: 13.0-59.0). The SROC curve area was 0.92 (95% CI: 0.89-0.94). Prolactin adjustment improved sensitivity (P < 0.01) without a significant change in specificity (P = 0.13).

Conclusions: Prolactin adjustment in BIPSS slightly improves sensitivity for diagnosing Cushing's disease but does not enhance specificity for ectopic ACTH syndrome. This highlights the value of PRL measurement in improving diagnostic accuracy and reducing false negatives, while BIPSS remains crucial for ruling out EAS in clinical practice.

Purpose: Rathke's cleft cysts (RCC) are present in up to 20% of autopsy studies but only a minority necessitate surgical treatment. Inflammation of RCC is thought to be significant in three processes: the development of classical symptoms, a predisposition to rupture or apoplexy, and increasing the rate of RCC recurrence. We aim to characterize clinical presentation, histological and radiological findings in patients with surgically managed RCC.

Methods: We conducted a retrospective case series of 31 RCC, which had undergone surgical management between April 2016 and April 2024. Histopathology and radiology were independently reviewed by neuropathologist and neuroradiologist, and case notes were reviewed for clinical and biochemical data.

Results: Median age was 43 years (IQR 32-63); 77% were female. 23/31 demonstrated inflammation of RCC cyst epithelium (n = 13), cyst wall (n = 20) or anterior pituitary (adenohypophysitis) (n = 12). 8 cases were not inflamed. Preoperative features included pituitary dysfunction (70%), headache (65%), visual disturbance (26%) and polyuria/polydipsia (7%). Six patients presented with features of apoplexy. Headache was more prevalent (92%) in patients with adenohypophysitis vs. those without (47%), p = 0.020, and present in all 11 cases where inflammation in the adenohypophysis was chronic. Pituitary dysfunction was not associated with inflammation overall (76% vs. 70% p = ns), nor specifically within the adenohypophysis (75 vs. 63% p = 0.69). Histological inflammation was associated with radiological loss of posterior bright spot (70% vs. 14% p = 0.024).

Conclusion: Headache but not pituitary dysfunction was associated with adenohypophyseal inflammation. A trend of increasing headache prevalence was seen with increasing degree of inflammatory infiltrate within RCC.

Purpose: Patients with Cushing's syndrome (CS) have an increased venous thromboembolism (VTE) risk with most studies focusing on the perioperative period. The purpose of this study was to assess the 5-year VTE risk and identify predictors of VTE at CS diagnosis.

Methods: A comparative nationwide retrospective cohort study of 609 patients (mean age 48.1 ± 17.2 years, 65.0% women) with CS, and 3018 age-, sex-, body mass index-, and socioeconomic status-individually matched controls. Ectopic CS and adrenal cancer were excluded. The time-to-event of pulmonary embolism (PE) or deep vein thrombosis (DVT) within 5 years of CS diagnosis was examined. VTE risk was calculated with death as competing event.

Results: VTE occurred in 16 cases (2.6%), compared to 17 (0.56%) controls (hazard ratio [HR] 4.71, 95% CI, 2.38-9.33). The 5-year HRs for PE and DVT were 7.47 (95% CI, 2.66-20.98) and 3.32 (95% CI, 1.36-8.12), respectively. After excluding patients and controls with current or prior malignancy the risk for VTE was 7.57 (95% CI, 2.98-19.20). Patients with CS ≥ 60 years at diagnosis (HR, 3.49; 95% CI, 1.30-9.35), with hypertension (HR, 5.53; 95% CI, 1.26-24.27), ischemic heart disease (HR, 3.60; 95% CI, 1.25-10.36), kidney disease (HR, 4.85; 95% CI, 1.39-16.90), or VTE event prior to CS diagnosis (HR, 33.65; 95% CI, 10.07-112.42) had an increased risk of VTE within five years.

Conclusions: In this large cohort of patients with CS, the 5-year VTE risk was 5 times higher compared with matched controls. Key baseline predictors included age ≥ 60, hypertension, heart/kidney disease, and prior VTE.

Purpose: Craniopharyngiomas (CPs) often lead to growth hormone deficiency (GHD) in children. Growth hormone replacement therapy (GHRT) is essential for managing GHD but its impact on body mass index (BMI) and metabolic outcomes is controversial. Concerns exist that GHRT might contribute to tumor recurrence, with guidelines varying on when to start therapy post-surgery. This updated systematic review and meta-analysis explores the effects and timing of GHRT in children post-craniopharyngioma surgery.

Methods: We systematically searched PubMed, Embase, and Cochrane Library databases. Included studies compared the effects of GHRT in childhood-onset craniopharyngioma patients who received GHRT versus those who did not. Random-effects meta-analyses were used to pool relative risk (RR) or mean difference (MD) for each outcome. Heterogeneity was assessed using the I² statistic. This study is registered with PROSPERO (CRD42024498082).

Results: We included 11 studies in the meta-analysis. No differences in tumor progression/recurrence were found between the GHRT and no GHRT groups (RR 0.77, 95% CI 0.56-1.05, p = 0.10). The impact of timing of GHRT is less clear because of limited data and high heterogeneity. There were no differences in BMI between the GHRT and no GHRT (MD -0.94, 95% CI -1.88,0.00, p = 0.05). Two studies reported that GHRT might improve lipid profiles.

Conclusion: Our study suggests that GHRT does not increase the risk of tumor progression/recurrence in CP patients. GHRT can improve linear growth, but its effects on the BMI and lipid profiles remain inconclusive, requiring further studies.

Purpose: Acromegaly patients occasionally achieve either of the remission criterion of IGF-1 or GH level postoperatively; however, treatment for patients with discordant IGF-1 and GH levels remains unclear. This study aimed to clarify the clinical courses and features of postoperative patients with normal IGF-1 and high GH levels and support their management.

Methods: Overall, 110 acromegaly patients underwent initial surgery and a 75-g oral glucose tolerance test (OGTT) 3 months postoperatively. Of the 110, 23 patients with normal IGF-1 and nadir GH levels of ≥ 0.4 µg/L on OGTT (high-GH group) were categorized into three subtypes based on their repeated examinations thereafter: late-remission type (nadir GH level on OGTT of < 0.4 µg/L later), recurrence type (elevated IGF-1 and GH levels later), and persistent type (normal IGF-1 levels and constantly high nadir GH levels on OGTTs).

Results: Proportion of patients in the high-GH group was 23.6%, and they were distributed as follows: late-remission type (n = 10), recurrence type (n = 5), and persistent type (n = 8). There were significantly more women (P = 0.0178) than men in the late-remission type, and patients in the persistent type had significantly larger tumors (P = 0.0110) and higher preoperative GH levels (P = 0.0018) than those that achieved complete remission 3 months postoperatively.

Conclusion: Careful monitoring without additional medications is recommended at first in acromegaly patients with normal IGF-1 and high GH levels considering the possibility of recurrence in the future.

Introduction: First-generation somatostatin receptor ligands (fg-SRLs) are the cornerstone of acromegaly treatment. Additional benefits were shown using high dose (HD) or high frequency (HF), relatively short-term regimens. Although several predictors of response to standard dose (SD)-fg-SRLs were reported, outcome biomarkers for HF administration are not yet available. Here, we aimed to identify predictors of response to long-term HF-fg-SRLs.

Patients and methods: A retrospective study was performed on 102 patients, treated with Lanreotide. Patients not controlled at 12 months of SD-Lanreotide (120 mg/28 days) were switched to HF-Lanreotide (120 mg/21 days) for additional 12 months.

Results: Twenty-eight patients were controlled at 6 months of SD-Lanreotide (27.4%); 35 patients were controlled at 12 months of treatment (34.3%). Out of 67 patients treated with HF- Lanreotide, 18 (26.9%) were controlled at 6 months of treatment and remained controlled until 12 months. Both during SD and HF-Lanreotide administrations, IGF-I levels were reduced during the first six months of treatment (p < 0.001), without further significant reduction between 6 and 12 months of therapy. Response at 12 months of SD-Lanreotide was predicted by IGF-I reached at six months of SD-Lanreotide (p = 0.024). Response at 12 months of HF-Lanreotide treatment was predicted by IGF-I levels reached at six months of SD-Lanreotide treatment (p = 0.04) and six months of HF-Lanreotide treatment (p = 0.01).

Conclusion: Our results demonstrated that initial IGF-I levels during SD-Lanreotide predicted the biochemical outcome after 12 months of HF-Lanreotide. Patients in whom HF-Lanreotide did not normalize IGF-I after 6 months of treatment remained uncontrolled 12 months after starting this regimen.

Background: Human adamantinomatous craniopharyngioma (ACP) is a brain tumor that originates at the base of the skull and shows aggressive local behavior, invading sensitive structures such as the optic pathways and hypothalamus. The conventional treatment of the tumor has been surgery and radiotherapy with the consequent development of serious sequelae. It is well known that Substance P (SP) peptide and Neurokinin-1 receptor (NK-1R) are involved in inflammation and cancer progression and its blockage with NK-1R antagonists has been shown to effectively counteract tumor development in preclinical trials. The oncogenic mechanism underlying ACP is based on a secretory phenotype associated with the production of paracrine biomarkers that establish an inflammatory and angiogenic microenvironment for the progression of ACP.

Methods: With the aim of describing the existence and distribution of SP/NK-1R in the ACP, we studied by immunohistochemistry the expression of SP and NK-1R in 43 human ACP and compared with healthy pituitary gland samples.

Results: SP and the NK-1R were overexpressed in all ACP more than in pituitary glands samples. SP expression is found widespread the ACP and is preferentially localized in the nucleus than in cytoplasm of tumor cells. Likewise, areas of glial reaction and endothelial cells also express SP preferentially in the cell nuclei. NK-1R is expressed mainly in the glial reaction, especially in the nuclei and membranes of its inflammatory cells and less prominently in the cytoplasm. In ACP neovessels, NK-1R is expressed in endothelial cells and fibroblasts that constitute their basement membranes. Tumor cells did not show significant NK-1R expression.

Conclusions: These findings, reported here for the first time, suggest a role for SP and NK-1R in pituitary gland and ACP and opens the door to future clinical trials on treatment with NK-1R antagonist drugs in ACP patients.

Purpose: The objective of this study was to characterize the clinical characteristics and factors predictive of biochemical remission in patients with symptomatic acromegaly undergoing transsphenoidal surgery (TSS) at an academic tertiary care center, as defined by the 2022 Acromegaly Consensus Conference guidelines.

Methods: In this single institution, longitudinal, retrospective study, a large cohort of 158 patients with a preoperative diagnosis of acromegaly undergoing surgery at a large, academic, tertiary care center were examined. We excluded 38 patients as IGF-1 testing was performed less than 12 weeks postoperatively.

Results: The majority of tumors were intrasellar macroadenomas (75%), receiving endoscopic surgery (98.3%). Patients who failed remission appeared to have higher raw IGF-1 levels preoperatively (732 ± 313 ng/mL) compared to those who attained remission (278 ± 313 ng/mL), and trended towards higher rates of GH hypersecretion (93.1% vs. 78.4%). Patients failing remission had higher GH levels and IGF-1 levels postoperatively and experienced a lower percentage reduction in raw IGF-1 levels. Multivariable logistic regression demonstrated that the magnitude of preoperative IGF-1 (OR: 1.001, 95% CI: 1.00, 1.003) and the percentage change in IGF-1 (OR: 1.021, 95% CI: 1.01, 1.04) were predictive of remission failure. Radiographic characteristics such as tumor size, suprasellar extension, and location were not necessarily predictive of worse postoperative outcomes.

Conclusions: Lesions which failed to achieve biochemical remission appeared to display distinctive preoperative endocrinological characteristics, with preoperative IGF-1 levels and percentage changes in IGF-1 levels being predictive of biochemical remission status.