Pituitary最新文献

Purpose: Available stimulation tests for growth hormone (GH) deficiency are burdensome or require intravenous access, highlighting the need for accessible, oral options. Increasing plasma urea through oral ingestion may stimulate GH secretion via feedback regulation. In this analysis, we investigated the effect of oral urea on GH levels.

Methods: This is a secondary analysis of a double-blind, randomized, placebo-controlled cross-over trial in healthy adults. They received a single weight-adapted dose of oral urea (0.5 g/kg body weight; 30-45 g) or placebo in random order. Serum GH was measured at baseline, 60 and 120 min. The main outcome was the difference in absolute GH levels after placebo and urea intake.

Results: Of 22 healthy adults, 12 (55%) were female, with a median [IQR] age of 27 years [26, 32] and a body mass index of 23.3 kg/m² [21.6, 25.8]. Before urea ingestion, baseline plasma urea was 4.4 mmol/L [3.5, 5.0], peaking after 60 min at 16.8 mmol/L [14.5, 18.0]. During the placebo visit, baseline urea levels were 4.3 mmol/L [3.7, 5.6] and remained stable during observation. Upon urea ingestion, median GH at baseline was 0.83 µg/l [0.28, 5.75], maximum GH levels were observed after 120 min at 1.00 µg/l [0.71, 2.34]. GH levels during placebo testing were 0.93 µg/l [0.38, 5.34] at baseline and 0.73 µg/l [0.18, 1.59] at 120 min (p = 0.08).

Conclusion: Oral urea does not significantly stimulate GH secretion and cannot be used as a stimulation test for GH deficiency.

Purpose: Postoperative weight gain following endoscopic endonasal surgery (EES) for craniopharyngiomas remains a challenging complication. Thus, in this study, we aimed to identify risk factors for new or worsened obesity following EES and to explore age-related patterns of postoperative weight change.

Methods: We conducted a retrospective cohort study of 72 patients (26 pediatric and 46 adult) who underwent initial EES for craniopharyngioma at two academic centers. We defined obesity based on body mass index (BMI) in adults and the BMI standard deviation score in pediatric patients. The primary outcome was new or worsened obesity at follow-up. Tumor extension and hypothalamic involvement/damage were assessed using standardized classification systems. Multivariate logistic regression was used to identify independent predictors.

Results: New or worsened obesity was observed in 17 patients (23.6%). Retroinfundibular tumor extension (odds ratio [OR]: 9.81; p = 0.002) and postoperative hypothalamic damage (OR: 7.72; p = 0.016) were independently associated with new or worsened obesity. However, surgical factors, including resection and operative complexity, were not significant predictors. Subgroup analyses revealed that a subset of pediatric patients developed early-onset and persistent obesity, whereas adults (particularly young adults) experienced gradual weight gain.

Conclusion: Retroinfundibular tumor extension and hypothalamic damage are key risk factors for postoperative obesity following EES, whereas aggressive resection itself does not increase the risk. Pediatric patients may develop obesity early and persistently, whereas adults, particularly young adults, are prone to gradual weight gain. Early diagnosis and strategic treatment for high-risk individuals may improve the prognosis for patients with hypothalamic obesity.

Purpose: Crooke cell adenomas (CCAs) are rare histological subtype of corticotroph pituitary adenomas (cPAs) commonly related to worse prognosis in patients. Notable progress in understanding of the molecular background of cPAs has been made recently but biology of CCAs remains poorly recognized. Results of our previous study suggested distinct frequency of the known recurrent mutations in CCAs than in sparsely and densely granulated cPAs. Thus, the aim was to determine the prevalence of USP8, USP48, BRAF and TP53 variants in a relatively large retrospective group of patients diagnosed with CCA.

Methods: DNA was isolated from formalin-fixed and paraffin-embedded tissue of 29 CCAs (14 clinically functioning and 15 nonfunctioning). Sanger sequencing was used for the identification of USP8, USP48, BRAF hotspot variants, while semiconductor sequencing with Ion AmpliSeq TP53 Panel was used for analysis of TP53 sequence.

Results: USP8 variants were found in 2 CCA patients with Cushing's disease (CD), whereas 3 TP53 variants were identified in 1 CCA patient with CD and 2 patients with clinically nonfunctioning CCAs. USP8 variants are less frequent in clinically functioning CCAs than functioning sparsely and densely granulated corticotroph tumors (p = 0.0271). TP53 variants are more common in CCAs as compared to other histological subtypes (p = 0.0164). One BRAF V600E variant and no USP48 variant were found.

Conclusion: CCAs have slightly distinct mutational profile then other histological subtypes of cPAs. Since clinical relevance of TP53 variants in corticotroph tumors was already documented, testing toward TP53 sequence changes in patients with CCAs should be considered.

Purpose: Craniopharyngiomas (CPs) cause hypopituitarism in most patients, with growth hormone deficiency (GHD) being the most prevalent form. Growth hormone replacement therapy (GHRT) is the standard treatment for GHD, but the impact of this therapy on CP recurrence remains unclear. This study aimed to evaluate the effect of GHRT on CP recurrence in both pediatric and adult populations.

Methods: The PubMed, Cochrane Library, Web of Science, Embase and ClinicalTrials.gov databases were systematically searched in accordance with the 2020 PRISMA guidelines. Original studies comparing the impact of GHRT and non-GHRT on CP recurrence were included. Among the 817 initially identified records, 12 studies met the inclusion criteria. Two independent investigators extracted the data and assessed the quality of the included studies.

Results: The meta-analysis revealed that GHRT significantly reduced the risk of recurrence (OR = 0.56, 95% CI 0.41-0.77). Subgroup analyses revealed that GHRT had a more significant effect among patients with a follow-up period of more than five years. Initiating GHRT within 12 months after CP treatment significantly reduced the recurrence rate (OR = 0.32, 95% CI 0.16-0.62). Sensitivity analyses and publication bias tests revealed that the results were robust.

Conclusions: The meta-analysis shows that GHRT does not increase the risk of recurrence in CP, even when initiated within 12 months postoperatively. GHRT should be considered an essential treatment for CP patients with GHD.

Objective: We aimed to evaluate the neurocognitive functions of patients with non-functioning pituitary adenoma (NFPA).

Methods: Eighty patients with NFPA and 80 control subjects matched for age, sex, body mass index (BMI) and educational status were included. The Beck Depression Inventory (BDI) for depression, the Cognitive Failures Questionnaire (CFQ), the Prospective and Retrospective Memory Questionnaire (PRMQ) and the Memory Functioning Questionnaire (MFQ) for assessing cognitive functions were administered.

Results: NFPA patients had significantly higher CFQ and PRMQ scores than controls (p < 0.05), reflecting greater cognitive failure and memory impairment. MFQ subscales revealed increased general forgetfulness, severity of forgetting, and impaired retrospective function in NFPA patients (p < 0.05). Name recall was worse among those who underwent surgery or received radiotherapy/gamma-knife treatment. Social dysfunction was more common in patients with secondary adrenal insufficiency (p = 0.038), higher corticosteroid doses (p < 0.05), and greater concentration problems (p = 0.036). Hypogonadism was associated with impaired name recall (p = 0.040) and social failure (p = 0.024). Name recall declined as postoperative time increased (p = 0.029). Low IGF-1 levels were linked to worse prospective memory, more frequent forgetfulness, and greater social dysfunction (p = 0.042).

Conclusion: Our findings suggest that the cognitive impairments observed in patients with NFPA may result not only from pituitary dysfunction but also from treatment approaches such as reoperations, gamma-knife or radiotherapy. These results highlight the importance of comprehensive neurocognitive assessment and long-term follow-up in the management of NFPA patients, particularly those with hormonal deficiencies or who undergo repeated interventions.

Objective: According to existing epidemiological evidence, whether proton therapy is more efficacious and safe than photon therapy in the treatment of craniopharyngioma (CP) remains controversial. This study aimed to evaluate whether proton therapy exhibits better efficacy and safety in terms of survival outcomes and toxic effects than photon therapy.

Methods: An extensive search of pertinent articles published between 1990 and February 2025 was performed in the following four databases: PubMed, Web of Science, Embase, and the Cochrane Library. Original studies investigating the efficacy and safety of proton or photon therapy in patients with CP were included. This meta-analysis is reported following the PRISMA reporting guidelines, and data were pooled using a random effects model.

Results: A total of 43 studies on 2784 patients were included in the meta-analysis. The pooled analysis favored proton therapy over photon therapy in terms of 3-year progression-free survival, 5-year progression-free survival, 5-year overall survival, 3-year local control and 5-year local control but not 3-year overall survival. In the safety analysis, compared with photon therapy, proton therapy was associated with reduced probabilities of visual, neurological, cognitive, and other miscellaneous toxicities, whereas the opposite trend was observed for endocrine toxicity. Subgroup analysis indicated that conventional radiation therapy had superior survival outcomes than stereotactic radiosurgery.

Conclusions: Compared with photon therapy, proton therapy may be associated with improved survival outcomes and reduced incidence of toxic effects in CP patients. Conventional radiation therapy appears to be more effective than stereotactic radiosurgery.

Purpose: Langerhans cell histiocytosis (LCH) is a rare disease involving multiple organs, including the endocrine system. This multicenter study aimed to characterize patients with hypothalamic- pituitary involvement in LCH.

Methods: The Hypopituitarism European NeuroEndocrine Association (ENEA) Rare Etiologies Observational Study (HEROS) platform invited ENEA members to include patients with rare pituitary diseases like LCH. Demographic data, presenting symptoms, hormonal profile, imaging tests, treatment, and prognosis were retrieved.

Results: Forty-eight patients (58% males) were included. Age at diagnosis was 22 ± 16.1 years, with 58% diagnosed as adults (> 18 years). The mean follow-up was 15.8 ± 10.6 years, 46% of the patients initially presented with bone lesions, 42% with lung involvement, and five were incidentally diagnosed. At diagnosis, 69% of the patients had arginine vasopressin deficiency (AVD), 42% had central hypogonadism, 25% hypothyroidism, and 12.5% hypocortisolism. Magnetic resonance imaging (MRI) was available in 41 patients, 73% of whom had pathology of the posterior pituitary/pituitary stalk. Visual disturbances were reported in only one patient. Diagnosis was histopathologically confirmed in all patients, mainly from extra-pituitary lesions. Transcranial biopsy was performed in five patients, and two underwent transsphenoidal intervention. During follow-up, 27% of the patients developed new AVD and five acquired new anterior pituitary hormone deficiency. There was no disease-related mortality during follow-up.

Conclusions: Patients with LCH and hypothalamic-pituitary involvement remained clinically stable during long-term follow-up. However, new hormonal deficits may develop years after diagnosis, with most patients ultimately experiencing AVD.

Background: Nelson syndrome (NS), or corticotroph tumor progression after bilateral adrenalectomy (CTP-BADX/NS), is a serious complication in patients with Cushing disease (CD) following BADX. Surgical tumor removal is the recommended treatment, though adjuvant therapies may be necessary.

Aim of the study: To evaluate clinical, radiological, and hormonal features of CD patients after BADX, identify risk factors for CTP-BADX/NS and assessed treatment outcome and cardio-metabolic complications.

Methods: Retrospective study of 30 patients (male/female: 9/21; median age at CD diagnosis: 33 years, IQR 27-42) who underwent BADX and had a minimum follow-up of 18 months. Data were collected at diagnosis and during follow-up (6, 24 months and last visit).

Results: Over a median follow-up of 135 months, 9/30 patients (30%) developed NS, median 60 months after BADX. NS patients had earlier CD diagnosis and higher ACTH levels two years post-BADX [458 ng/L (IQR 245-723) vs. 146 ng/L (61-247), p = 0.020]. They also took lower fludrocortisone [0.05 mg/day vs. 0.1 mg/day, p = 0.001] and tended to use less hydrocortisone [20 mg/day [20-25] vs. 30 [25-30], p = 0.06]. Pre-BADX stereotactic radiosurgery (SRS) was more frequent in non-NS patients (52% vs. 22%, p = 0.11). Hypertension was more common in NS patients (78% vs 43%), but diabetes less so (33% vs 48%). In the CTP-BADX group, 6/9 required pituitary surgery and/or radiotherapy; medical therapy was used in 5 patients with varied results.

Conclusion: CTP-BADX/NS occurred in 30% of cases in our cohort. Higher ACTH post-BADX and younger age at CD onset may predict NS. No hormonal or radiological markers reliably predicted tumor progression. SRS before BADX and higher hydrocortisone doses might offer protection. Tumor control often needed a multimodal approach, with limited success from medical therapy alone.

Purpose: To evaluate the clinical characteristics, surgical outcomes, and endocrinological follow-up findings of pediatric patients who underwent surgical treatment for sellar and parasellar masses.

Methods: Forty-seven patients who underwent surgical treatment for sellar and parasellar masses between January 2021 and January 2025 were retrospectively analyzed. All patients were followed up in the pediatric endocrinology clinic. Demographic characteristics, clinical findings, surgical approaches, histopathological diagnoses, and postoperative outcomes were evaluated. Endocrinological assessments were performed using standardized hormone assays with age- and sex-specific reference ranges.

Results: Twenty-eight (59.6%) patients were female, with a median age of 10.1 years (range: 2.5-17.5). The most common presenting complaint was headache (46.8%), followed by visual impairment (27.7%) and short stature (14.9%). Histopathological examination revealed non-pituitary masses in 35 (74.5%) patients, with craniopharyngioma being the most frequent (44.7%). An endoscopic approach was used in 42 (89.4%) patients, and total resection was achieved in 30 (63.8%) patients. Panhypopituitarism developed in 27 (57.4%) patients postoperatively, representing a significant increase from preoperative rates (10.6%, p < 0.001). During a median follow-up of 2.5 years, recurrence occurred in 10 (21.3%) patients and mortality in 11 (23.4%) patients. Patients with non-pituitary tumors had significantly higher rates of re-operation (37.1% vs. 0%, p = 0.012) and mortality (31.4% vs. 0%, p = 0.024) compared to those with pituitary tumors.

Conclusions: Surgical management of pediatric sellar and parasellar masses carries significant risk of endocrinological complications, particularly panhypopituitarism. A multidisciplinary approach combining appropriate surgical technique selection, comprehensive endocrinological evaluation, and long-term follow-up is essential for optimal patient outcomes. Non-pituitary masses, especially craniopharyngioma, are associated with higher morbidity and mortality rates.