Pituitary最新文献

Background: The Pituitary Society established criteria to develop Pituitary Tumor Centers of Excellence (PTCOE) for optimization of patient care. These criteria were later transformed into quantitative standards based on real-life data from accredited pituitary centers worldwide. The aim of this study was to evaluate the pituitary tumor care capacity at our institute and compare it with the PTCOE criteria.

Method: We retrospectively reviewed the data of patients who underwent sellar, suprasellar, or parasellar surgery during 2021-2023 at Taipei Veterans General Hospital. Adults older than 18 years who were diagnosed with pituitary tumors were included. We collected data regarding baseline patient and tumor characteristics, the surgical method, complications, and activity volumes across involved departments. The relevant data were compared with those of the PTCOE standards.

Results: In total, 182 patients with pituitary tumors underwent surgery via the endoscopic endonasal approach during 2021-2023. Their median age was 51 (range, 20-91) years. Among them, 90.7% had macroadenomas. Functional remission rates were 55.6% for acromegaly, 69.2% for prolactinoma, and 93.3% for Cushing's disease. Our institute met the acceptable PTCOE criteria for the number of pituitary interventions, postoperative readmissions for complications, dynamic endocrine tests, neuroradiologists, and neuro-oncologists. Further, we met the preferred PTCOE criteria for mortality rate and the numbers of dedicated surgeons, endocrinologists, trained nurses, neuropathologists, and neuro-ophthalmologists.

Conclusion: Most indicators in our study met the acceptable standards for a PTCOE. During the study period, the multidisciplinary team at our institute collaborated closely to provide comprehensive care for patients with pituitary adenomas.

Purpose: Pituitary adenomas (PAs) constitute a rare pediatric diagnosis and their pathogenetic mechanisms are not clearly understood. The aim of this study was to evaluate the prevalence of genetic defects in pediatric PAs through germline and tumor testing, and to describe genotype-phenotype correlations.

Methods: Fifty-four pediatric patients with PAs and available germline and/or tumor samples were studied. Germline and/or tumor sequencing were reviewed for variants in genes previously associated with pituitary tumorigenesis.

Results: Germline genetic testing revealed a pathogenic variant in AIP gene in 2 patients with growth hormone excess (GHE) and a likely pathogenic variant in CDKN2A in a patient with Cushing's disease (CD). Somatic gene sequencing identified pathogenic variants in GNAS in 4/7 patients (57.1%) with GHE. 6/38 patients (15.8%) with CD had pathogenic variants in USP8 gene, and in one tumor pathogenic variants in PRKAR1A, TP53 and MEN1 genes were identified. Overall, pathogenic/likely pathogenic germline or somatic variants were identified in 14/54 patients (25.9%). When evaluating the genotype-phenotype correlations in patients with CD, patients with somatic USP8 pathogenic variants had larger tumors (median size: 9.5 mm [6.5, 13.3] vs. 6 mm [4.0, 7.0], p = 0.048), trend towards higher incidence of cavernous sinus invasion (50% vs. 12.5%, p = 0.06), and higher risk of non-remission after surgery (33.3% vs. 0%, p = 0.021) compared to patients without USP8 variants.

Conclusions: Somatic USP8 pathogenic variants correlate with worse tumor behavior and patient outcomes in pediatric-onset CD. Unlike GH-secreting PAs, the genetic basis of the majority of pediatric corticotroph PAs remains unclear. Further studies are needed to explore the genetic drivers of pediatric CD.

Clinicaltrials:

Gov id: NCT00001595, NCT03206099.

Background: In a resource limited setting, cabergoline remains an important part of medical management in acromegaly patients with persistent disease after surgery. Response to medical treatment may depend on the receptor expression in these tumors.

Objectives: To study the dopamine receptor subtype2 (D2R) and somatostatin receptor subtypes2&5(SSTR2&SSTR5) expression in somatotropinomas by immunohistochemistry (IHC) and real time/quantitative polymerase chain reaction(qPCR). Also, to determine the relation between density of D2R expression and remission with cabergoline therapy.

Methods: This study included 30 patients with somatotropinomas who underwent surgery and had persistent disease post-surgery treated with cabergoline. Immunostaining and qPCR for D2R, SSTR2&5 were performed on archived GH secreting pituitary adenoma specimens. The clinical, biochemical and radiological details were collected from the hospital electronic medical records.

Results: D2R was the predominantly expressed receptor followed by SSTR2 and SSTR5. The median(range) duration of cabergoline therapy was 20(6-72) months. 23% (7/30) of patients achieved normalization of IGF-I or GH < 1ng/ml (random/post glucose suppression) with cabergoline. Subjects with baseline IGF-1 < 1.5 times the upper limit of normal were more likely to achieve remission with cabergoline. D2R mRNA expression was significantly higher in patients in remission. On ROC curve analysis, a D2R ^ΔΔ CT of 19.2 (19-fold higher expression compared to normal tissue) predicted remission with cabergoline with a sensitivity of 71% and specificity of 74% (AUC 0.745).

Conclusion: D2 receptor profiling of growth hormone secreting pituitary tumors and post-operative IGF-1 level at 3 months are helpful to predict response to medical treatment with cabergoline.

Purpose: This study aimed to develop a core outcome set (COS) for pituitary surgery to enhance the quality, efficiency and effectiveness of future pituitary adenoma surgery research.

Methods: Thirty-three outcomes were identified through a systematic review of pituitary adenoma surgery outcomes and a study on patient-reported measures. These were presented in an online survey to healthcare professionals (HCPs), patients and caregivers. In the first round, participants scored each outcome's importance on a 5-point scale (1-strongly disagree; 5-strongly agree) and could also suggest additional outcomes, which were reviewed and, if appropriate, added to existing domains. In the second round, participants re-scored the updated the list, considering group median and interquartile range scores from the previous round. Outcomes with a median score of 5 were included in the COS. A final live online consensus meeting discussed and voted on borderline outcomes (median scores 3-4).

Results: The first round received 95 responses (52% HCPs, 48% patients/caregivers). Of the 33 outcomes, 16 received a median score of 5 (strongly agree), three received 4.5 and 14 received 4 (agree). Round two received 87 responses (52% HCPs, 48% patients and caregivers). Of the 33 outcomes, 14 received a median ranking of 5, two received 4.5, 15 received 4 and two received 3 (neutral). The live meeting (attended by 12 participants: 5 HCPs, 6 patients, 1 caregiver), reached consensus on the final COS, which includes 7 domains: short-term surgical outcomes; nasal outcomes; ophthalmic outcomes; endocrine outcomes; quality of life and psychological outcomes; other short-term outcomes; and disease control outcomes.

Conclusion: We advocate for use of the COS in future pituitary surgery research.

Introduction: X-linked acrogigantism (X-LAG; OMIM: 300942) is a rare X-linked dominant, fully penetrant form of infancy-onset pituitary gigantism caused by Xq26.3 tandem duplications involving the GPR101 gene. All previously reported X-LAG-associated duplications disrupt the integrity of the resident topologically associating domain (TAD). This creates a neo-TAD, permitting ectopic chromatin interactions between GPR101 and centromeric pituitary enhancers postulated to lie between RBMX and VGLL1, and culminating in pituitary GPR101 misexpression and growth hormone excess. Conversely, none of the few previously reported cases of Xq26.3 duplications in unaffected individuals include the tissue-invariant TAD border that shields GPR101 from its centromeric enhancers. Preservation of this boundary has thus been considered synonymous with non-penetrance of X-LAG.

Methods: We examined a series of four family members from the same kindred with an incidentally detected GPR101-containing Xq26.3 duplication involving the invariant TAD border.

Results: Chromosome microarray demonstrated an interstitial chromosome Xq26.3 duplication: arr[GRCh37] Xq26.3(135,954,223 - 136,224,319)x2, including GPR101, the TAD invariant border and RBMX, but not VGLL1. None of the relatives with the Xq26.3 duplication exhibited evidence of growth hormone excess, making this the first unaffected family with a GPR101-containing Xq26.3 duplication involving the invariant TAD border. The predicted neo-TAD in this kindred excludes the VGLL1 region, which is present in all previously described X-LAG patients and absent in all previously described unaffected individuals with Xq26.3 duplications.

Conclusion: Our clinical findings suggest that TAD border involvement is not sufficient for X-LAG to develop, and implicates the VGLL1 region as likely the sole pituitary enhancer responsible for GPR101 misexpression and the X-LAG phenotype. Pending corroborative studies, this new insight into X-LAG pathogenesis may guide interpretation of future Xq26.3 duplications and counselling of families in whom such duplications are found.