Pituitary最新文献

Introduction: Gender medicine focuses on disease differences between females and males regarding symptoms, treatment, prognosis, psychosocial effects and prevention. Acromegaly is a rare endocrine disorder caused by excessive growth hormone (GH) production, in the vast majority of cases due to the presence of a GH-secreting pituitary adenoma. Chronic GH elevation leads to increased insulin-like growth factor-1 (IGF-1), resulting in tissue overgrowth and a number of comorbidities. Among these, patients with acromegaly can experience various issues of the cardiovascular and metabolic system, including glucose metabolism unbalance, diabetes mellitus, arterial hypertension and cardiomyopathy.

Aim and methods: This narrative review discusses the impact of gender differences on glycometabolic and cardiovascular comorbidities in patients with acromegaly. We performed a detailed literature search, gathering scientific articles on this topic, including original research studies, case reports, reviews, systematic reviews, meta-analyses, guidelines, and consensus papers published in English from 1989 to early 2025.

Results: A diagnostic delay between females and males is reported, together with a gender-related impact of the disease on body composition, lipid and glucose metabolism; gender differences in the development and progression of acromegaly cardiomyopathy are also described. In detail, females with acromegaly exhibit greater insulin resistance, increased adiposity, and higher risk of developing overt diabetes mellitus compared to males, along with milder cardiac abnormalities, despite experiencing higher cardiovascular mortality.

Conclusion: Gender differences in metabolic and cardiovascular comorbidities of acromegaly need to be considered. Future studies should clarify the biological bases of these differences, to optimize treatment protocols and monitoring for our patients.

Background: Treatment of skeletal fragility in patients with pituitary diseases is challenging. Denosumab, an antiresorptive bone active drug, increased bone mineral density (BMD) and reduced incidence and risk of fractures in primary osteoporosis. This study aimed to evaluate the efficacy of denosumab in patients with pituitary disease-driven osteoporosis.

Methods: This retrospective study investigated the frequency of fragility fractures (FF) and the percent BMD changes at 1-, 2-, 5-, and 10-years of treatment with denosumab, in patients with osteoporosis due to secreting pituitary adenoma.

Results: Seventeen patients were included: 5 patients (29.4%) were affected by hyperprolactinemia due to PRL-secreting pituitary adenoma (PAs), six patients (35.3%) were affected by acromegaly and six patients (35.3%) by Cushing's disease. Four patients carried prevalent-FF (23.5%). A single patient with acromegaly developed FF at 2 and at 5 years of treatment with denosumab. Femoral neck BMD increased in 11 patients (64.7%) at 1 year of treatment, in 9 patients (52.9%) at 2 years of treatment, in 8 patients (47.1%) at 5 years of treatment and in 2 patients (66.7%) at 10 years of treatment. Lumbar spine BMD improved in all patients at 1 year of treatment (100%), in 16 patients at 2 years of treatment (100%), in 11 patients at 5 years of treatment (100%), and in 2 patients at 10 years of treatment (66.7%). No drug related adverse events occurred.

Conclusions: This study demonstrated for the first time that long-term treatment with denosumab is effective and safe in patients with osteoporosis due to secreting pituitary adenoma.

Purpose: Postoperative cranial nerve dysfunction remains a significant concern in endoscopic endonasal surgery for pituitary neuroendocrine tumors (PitNETs, also known as pituitary adenomas) that have invaded the cavernous sinus, but the incidence, timing, and recovery patterns vary widely across reports. This study aimed to characterize the clinical features, risk factors, and recovery patterns of patients with postoperative ophthalmoplegia following cavernous sinus exploration.

Methods: We retrospectively analyzed 127 consecutive patients who underwent endoscopic skull base surgery with cavernous sinus exploration between March 2020 and September 2024. Ophthalmoplegia onset, affected cranial nerves, and prognosis were evaluated. Risk factors were assessed using multivariable logistic regression, and recovery patterns were analyzed using Kaplan‒Meier curves.

Results: The overall gross total resection rate was 74.8% (96.9% for functioning adenomas), with 96.9% biochemical remission in functioning PitNETs at 3-month follow-up. New cranial nerve dysfunction occurred in 13.6% (17/125), manifesting exclusively as ophthalmoplegia. The abducen nerve was most frequently affected nerve (52.9%), followed by the oculomotor (41.2%) and trochlear nerves (11.8%). Early onset (≤ 3 days) occurred in 29.4%, while delayed onset (> 3 days) occurred in 70.6% of cases (mean onset: 9 days). Extensive hemostatic agent use (≥ 3 applications) (OR 15.57, p < 0.001) and lateral compartment involvement (OR 9.00, p = 0.011) were significant risk factors. Complete resolution occurred in 94.1% with median duration of 20 days.

Conclusions: Postoperative ophthalmoplegia following cavernous sinus exploration occurs more frequently than previously reported but follows a benign course with near-complete resolution. The distinct temporal patterns and risk factors suggest different pathophysiological mechanisms for early- versus delayed-onset ophthalmoplegia, guiding surgical decisions and patient counseling.

Purpose: Immunosenescence is a gradual decline in immune function, leading to increased susceptibility to infections and autoimmune conditions. Growth hormone (GH) has been shown to have an effect on both immune function and aging. In fact, the absence of GH-induced intracellular signaling can slow the aging process, as demonstrated by the longest-lived laboratory mouse (GH receptor gene disrupted or GHR-/- mice). Because GH receptors (GHR) are expressed in B and T cells, and these cells undergo age-related changes that impact immune function, we hypothesized that decreased GH action protects from immunosenescence. To validate this hypothesis, this study aimed to characterize differences in B cell and T cell populations within the lymphoid organs of aged female GHR-/- mice (24 months of age) compared to wild-type controls.

Methods: B and T cell populations in mouse blood, spleen, thymus, and bone marrow (BM) were analyzed by multicolor flow cytometry.

Results: The current study showed significantly higher levels of anti-inflammatory follicular (FO) B cells in spleens and BM and lower levels of pro-inflammatory aging-associated B cells (ABC) in the spleens, BM, and blood of aged GHR-/- mice compared to WT mice. In addition, T cell populations in aged GHR-/- mice showed higher levels of naïve T cells and lower levels of memory T cells in the thymus, BM, spleen, and blood.

Conclusion: Female GHR-/- mice are protected from age-related shifts in lymphocyte populations, suggesting that the absence of GH action mitigates immunosenescence. These results offer novel insights into mechanisms and therapeutic strategies to preserve immune balance and combat age-related immune dysfunction.

Purpose: To evaluate the diagnostic contribution of MRI-based morphological and signal features-particularly T2-weighted signal intensity-for differentiating the etiology of pituitary stalk thickening (PST), and to develop imaging-based models for predicting inflammatory and neoplastic pathologies.

Methods: This retrospective study included 41 adult (51.2%) and pediatric (48.8%) patients with confirmed PST who underwent contrast-enhanced pituitary MRI between 2012 and 2021. Etiologies were classified as congenital/idiopathic, inflammatory/infectious, or neoplastic based on clinical, radiological, or histopathological criteria. Imaging findings including enhancement pattern and T2 signal intensity were assessed in consensus by two neuroradiologists blinded to clinical data. Statistical analyses included univariate and multivariate logistic regression and receiver operating characteristic (ROC) curve analysis.

Results: Neoplastic lesions were associated with significantly greater stalk thickness (median: 5.9 mm) compared to non-neoplastic lesions (median: 3.83 mm; p = 0.012). T2-weighted hyperintensity was present in 70% of neoplastic lesions, while hypointensity was more frequent in inflammatory/infectious lesions (p = 0.017). A multivariable model incorporating stalk thickness, non-T2 hypointensity and V-shaped enhancement patterns yielded excellent diagnostic performance for neoplastic pathologies (AUC: 0.848; 95% CI: 0.713-0.982). A second model using stalk thickness and T2 hypointensity predicted inflammatory lesions with an AUC of 0.836 (95% CI: 0.715-0.957).

Conclusion: To our knowledge, this is the first study to propose MRI-based models using stalk morphology and signal features to predict PST etiology. These non-invasive models, developed without clinical input, demonstrate promising diagnostic accuracy and may aid in differential diagnosis. Further validation in larger cohorts is needed.

Purpose: Prolactinomas are often treated initially with dopamine agonists (DA). For patients subsequently treated with surgery, the effect of cabergoline (CAB) on tumor fibrosis and its potential impact on surgical outcomes is largely unexplored.

Methods: Records of patients with prolactinoma treated by a single surgeon between 2006 and 2024 were examined. Analyses considered relationships among duration and cumulative dose of presurgical DA (DA + vs. DA-), extent of fibrosis measured quantitatively by collagen volume fraction (CVF) and qualitatively by surgeon assessment, and remission status at last follow-up.

Results: Of 59 patients, 22 were DA- and 37 were DA+, including 29 treated only with CAB and 8 treated with CAB and bromocriptine. There were 44 macroadenomas, 13 microadenomas, and 2 giant adenomas; 28 had cavernous sinus invasion (Knosp grade 3-4) 52.5% were in remission at last follow-up. Median cumulative CAB dose was 79.3 mg (range, 5.4-6711), used for a median duration of 570 days (range, 16-7830). Neither CAB dose nor duration correlated with CVF (r² < 0.01, p = NS). Both surgeon fibrosis assessment and CVF were higher in DA + patients, but neither independently predicted remission. Cumulative CAB dose and duration also did not predict remission. On univariable analysis, cavernous sinus invasion (OR 10.3, p < 0.001) and tumor size (OR 6.6, p = 0.02) predicted remission, but in multivariable analysis no single factor remained significant.

Conclusion: Duration and cumulative dose of presurgical CAB use do not correlate with quantitative measures of tumor fibrosis and do not reliably predict the degree of fibrosis at surgery or the likelihood of surgical remission.

Background: Hypoglycaemia stimulates growth hormone (GH) secretion, whereas hyperglycaemia suppresses it. However, the underlying mechanisms are not fully understood, particularly the potential role of gut-derived hormones released in response to oral glucose.

Aim: To investigate whether GH suppression is modulated by the route of glucose administration.

Methods: A two-day intervention study in healthy volunteers. GH, insulin, glucagon-like peptide-1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP) responses during a 2-h oral glucose tolerance test (OGTT) were compared with those during a 2-h isoglycaemic intravenous (IV) glucose infusion. GH levels were analyzed using paired t-test of GH concentrations at every blood sample time point. The effect of intervention on all measured hormones were also assessed by paired t-test of Area Under the Curve (AUC).

Results: 12 healthy volunteers (6 females, mean age 47.9 ± 5.4 years) were included. In 9 of the 12 subjects, IV glucose induced an early peak in plasma-GH followed by a decrease. At 20 min after glucose intake GH levels increased by 46% during IV glucose compared to a decrease of 17% during oral glucose. The biggest numerically difference in GH between oral vs IV glucose was seen at 45 min (median [range], 0.30 [0.05-1.13] vs. 0.46 [0.05-9.82] µg/l, p = 0.072). There was no difference between AUC of GH levels (p = 0.381). During IV glucose, two subjects did not reach the threshold for excluding acromegaly. Oral glucose showed significant increases compared to IV glucose for insulin (p < 0.001), GLP-1 (p = 0.002) and GIP (p < 0.001) when using paired t-test of AUC.

Conclusions: Route of glucose exposure might influence the suppressive effect of glucose on GH secretion. This finding suggests that stimulation of other hormone systems may play a contributing role on the regulation of GH. The potential mechanism behind remains elusive but changes in gut-derived hormones might be of importance.