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16 pages, 3104 KiB  
Article
Outcomes of the Transsphenoidal Approach for ACTH-Secreting Pituitary Tumours and the Role of Postoperative ACTH in Predicting the Late Recurrence of Cushing’s Disease: A Retrospective Analysis of 50 Cases
by Athanasios Saratziotis, Maria Baldovin, Claudia Zanotti, Sara Munari, Luca Denaro, Jiannis Hajiioannou and Enzo Emanuelli
Healthcare 2025, 13(12), 1395; https://doi.org/10.3390/healthcare13121395 - 11 Jun 2025
Viewed by 623
Abstract
Background/Objectives: The endoscopic transsphenoidal approach constitutes an excellent technique for adrenocorticotropin hormone (ACTH)-producing pituitary tumours. It is associated with subnormal postoperative serum cortisol levels, which may guide decisions regarding immediate re-operation. Methods: The authors retrospectively reviewed patients with Cushing’s disease who [...] Read more.
Background/Objectives: The endoscopic transsphenoidal approach constitutes an excellent technique for adrenocorticotropin hormone (ACTH)-producing pituitary tumours. It is associated with subnormal postoperative serum cortisol levels, which may guide decisions regarding immediate re-operation. Methods: The authors retrospectively reviewed patients with Cushing’s disease who had undergone endoscopic transsphenoidal surgery between 2013 and 2023. All operations were performed by neurosurgeons and skull-base otolaryngologists. Surgical outcomes were evaluated in combination with prognostic factors such as cortisol and ACTH levels in terms of long-term remission and late recurrence rates of Cushing’s disease. Results: Fifty patients aged between 15 and 69 (average 37.8) years were evaluated, having undergone 50 operations. The median follow-up was 76.5 months (range: 23–122 months). Major complications with a transient CSF leak resulting from the surgical approach occurred in three patients. Two patients in the series experienced minor complications, developing a deep vein thrombosis, and thirteen patients developed transient diabetes insipidus. The initial remission rate was 84% (n = 42/50). Initial non-remission occurred in eight (8) patients (16%), with three macro- and five microadenomas. A total of 3 of the 42 patients with initial remission had a late recurrence after 50 months follow-up and required repeat transsphenoidal surgery. Seven patients (16.6%) who did not exhibit early postoperative cortisol reduction subsequently achieved remission. Male gender was the only factor that was significantly associated with lower remission rates in either short- or long-term follow-up (p = 0.003 and 0.038, respectively). An immediate postoperative ACTH nadir of ≤5 pg/mL was significantly related to long-term remission (p = 0.004). In our study, a significant correlation was confirmed between remission of the disease and 24 h urinary cortisol values, both early and late (p = 0.019), and serum cortisol <138 nmol/L. In this retrospective study from a single institution specialising in pituitary tumour management, the endoscopic transsphenoidal approach was shown to be both safe and effective. Additionally, we found that the risk of relapse in patients with Cushing’s disease persisting for more than 5 years after surgery is real but low. Moreover, failure to achieve an early postoperative cortisol reduction does not preclude a subsequent remission. Conclusions: Our findings demonstrate that ACTH, postoperative serum cortisol, and urinary free cortisol are valuable predictors of relapse over a five-year period and are closely correlated to each other. Full article
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14 pages, 2588 KiB  
Article
Cushing’s Disease Manifestation in USP8-Mutated Corticotropinoma May Be Mediated by Interactions Between WNT Signaling and SST Trafficking
by Elena Nerubenko, Pavel Ryazanov, Natalia Kuritsyna, Artem Paltsev, Oksana Ivanova, Elena Grineva, Anna Kostareva, Renata Dmitrieva and Uliana Tsoy
Int. J. Mol. Sci. 2024, 25(23), 12886; https://doi.org/10.3390/ijms252312886 - 29 Nov 2024
Cited by 1 | Viewed by 1196
Abstract
In the current work, we aimed to evaluate the association of clinical data of Cushing’s disease (CD) patients with USP8 mutation status and to study USP8-related molecular mechanisms connected to the regulation of corticotropinoma growth and activity. 35 CD patients were enrolled; the [...] Read more.
In the current work, we aimed to evaluate the association of clinical data of Cushing’s disease (CD) patients with USP8 mutation status and to study USP8-related molecular mechanisms connected to the regulation of corticotropinoma growth and activity. 35 CD patients were enrolled; the sequencing of exon 14 in USP8 revealed variants in eighteen adenomas, two of which were described for the first time in CD. USP8 variants were more common in women (94% vs. 76%; p = 0.001), and microadenomas and tumor recurrence were prevalent in the USP8-mutant group (44% vs. 29%; p = 0.04 and 44% vs. 22%; p = 0.0015). Preoperative ACTH and serum cortisol did not differ in the USP8-WT and USP8-mutant patients. All USP8-mutant adenomas were SST5-positive, and 73% of them were double-positive (SST5+/SST2+). A total of 50% of USP8-WT adenomas were double-negative (SST5−/SST2−), and 40% of them were SST5-positive. Analysis of transcriptome was performed for nine USP8-mutant and six USP8-WT adenomas and revealed the that the bidirectional dysregulation of Wnt signaling, including both the agonist RSPO2 and antagonist SFRP1, in the USP8-mutant corticotropinomas was downregulated. These alterations may indicate the existence of regulatory connections between USP8 enzyme activity, Wnt signaling, EGFR signaling and somatostatin receptors’ trafficking, which can explain, at least in part, the clinical manifestations of CD in patients with corticotropinomas harboring USP8 variants. Full article
(This article belongs to the Special Issue Advances in Molecular Biology of Pituitary Diseases)
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15 pages, 2026 KiB  
Article
A Real-World Longitudinal Study in Non-Functioning Pituitary Incidentalomas: A PRECES Micro-Adenomas Sub-Analysis
by Mihai Costachescu, Claudiu Nistor, Ana Valea, Oana-Claudia Sima, Adrian Ciuche, Mihaela Stanciu, Mara Carsote and Mihai-Lucian Ciobica
Diseases 2024, 12(10), 240; https://doi.org/10.3390/diseases12100240 - 2 Oct 2024
Viewed by 1246
Abstract
Background. Incidentalomas have an increasing incidence all over the world due to a larger access to imaging assessments, and endocrine incidentalomas make no exception in this matter, including pituitary incidentalomas (PIs). Objective. Our objective was to analyse the dynamic changes amid a second [...] Read more.
Background. Incidentalomas have an increasing incidence all over the world due to a larger access to imaging assessments, and endocrine incidentalomas make no exception in this matter, including pituitary incidentalomas (PIs). Objective. Our objective was to analyse the dynamic changes amid a second computed tomography (CT) scan after adult patients were initially confirmed with a PI (non-functioning micro-adenoma). Methods. This was a multi-centric, longitudinal, retrospective study in adults (aged between 20 and 70 y) amid real-world data collection. We excluded patients who experienced baseline pituitary hormonal excess or deficiency or those with tumours larger than 1 cm. Results. A total of 117 adults were included (94.02% females) with a mean age of 43.86 ± 11.99 years, followed between 6 and 156 months with a median (M) of 40 months (Q1 Q3: 13.50, 72.00). At the time of PI diagnosis, the transverse diameter had a mean value of 0.53 ± 0.16 cm, the longitudinal mean diameter was 0.41 ± 0.13 cm, and the largest diameter was 0.55 ± 0.16 cm. No PI became functioning during follow-up, neither associated hypopituitarism nor increased >1 cm diameter. A total of 46/117 (39.32%) patients had a larger diameter during follow-up (increase group = IG) versus a non-increase group (non-IG; N = 71, 60.68%) that included the subjects with stationary or decreased diameters. IG had lower initial transverse, longitudinal, and largest diameter versus non-IG: 0.45 ± 0.12 versus 0.57 ± 0.17 (p < 0.0001), 0.36 ± 0.11 versus 0.43 ± 0.13 (p = 0.004), respectively, 0.46 ± 0.12 versus 0.6 ± 0.16 (p < 0.0001). IG versus non-IG had a larger period of surveillance: M (Q1, Q3) of 48 (24, 84) versus 32.5 (12, 72) months (p = 0.045) and showed similar age, pituitary hormone profile, and tumour lateralisation at baseline and displayed a median diameter change of +0.14 cm versus −0.03 cm (p < 0.0001). To conclude, a rather high percent of patients might experience PI diameter increase during a longer period of follow-up, including those with a smaller initial size, while the age at diagnosis does not predict the tumour growth. This might help practitioners with further long-term surveillance protocols. Full article
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10 pages, 568 KiB  
Article
How Different Treatments for Acromegaly Modulate Sleep Quality: A Psychometric Study
by Gaspare Alfì, Danilo Menicucci, Dalì Antonia Ciampa, Vito Di Giura, Giulia Marconcini, Claudio Urbani, Fausto Bogazzi and Angelo Gemignani
Endocrines 2024, 5(3), 408-417; https://doi.org/10.3390/endocrines5030030 - 6 Sep 2024
Viewed by 2233
Abstract
Acromegaly is a rare endocrine syndrome characterized by unrestrained growth hormone (GH) secretion from a GH-secreting pituitary neuroendocrine tumor (PitNET). Data on sleep disorders are scanty and mainly linked to Obstructive Sleep Apnea Syndrome (OSAS). This study aimed to evaluate the prevalence of [...] Read more.
Acromegaly is a rare endocrine syndrome characterized by unrestrained growth hormone (GH) secretion from a GH-secreting pituitary neuroendocrine tumor (PitNET). Data on sleep disorders are scanty and mainly linked to Obstructive Sleep Apnea Syndrome (OSAS). This study aimed to evaluate the prevalence of insomnia and sleep quality in a cohort of patients with a low risk of OSAS before and after therapies for acromegaly. A total of 27 naïve acromegalic patients (mean age 55.15 ± 10.53 years) were submitted to a psychometric sleep evaluation and compared to a matched control group of 24 Non-Functioning Pituitary micro-Adenoma patients (mean age 51.08 ± 11.02 years). A psychometric sleep evaluation was carried out 4 years later, after achieving acromegaly control in all patients. The role of different therapies for acromegaly (somatostatin analogues, pegvisomant, or adenomectomy) was evaluated. At the initial evaluation, most untreated acromegalic patients had a higher rate of impaired sleep quality and clinical insomnia than NFPA patients (p = 0.001 ES = 1.381, p = 0.001 ES = 1.654, respectively). Patients treated with somatostatin analogues or pituitary adenomectomy had an improvement in insomnia parameters (p = 0.046 ES = 0.777, p = 0.038 ES = 0.913, respectively). Conversely, in patients treated with pegvisomant, sleep quality and insomnia worsened (p = 0.028 ES = 1.002, p = 0.009 ES = 1.398, respectively). In summary, therapies for acromegaly seem to have divergent effects on perceived sleep disorders. Concerning sleep, somatostatin analogues and adenomectomy seem to have favorable effects on the psychometric parameters of sleep. Full article
(This article belongs to the Special Issue Feature Papers in Endocrines: 2024)
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17 pages, 581 KiB  
Article
Associations of TRAF2 (rs867186), TAB2 (rs237025), IKBKB (rs13278372) Polymorphisms and TRAF2, TAB2, IKBKB Protein Levels with Clinical and Morphological Features of Pituitary Adenomas
by Balys Remigijus Zaliunas, Greta Gedvilaite-Vaicechauskiene, Loresa Kriauciuniene, Arimantas Tamasauskas and Rasa Liutkeviciene
Cancers 2024, 16(14), 2509; https://doi.org/10.3390/cancers16142509 - 10 Jul 2024
Cited by 1 | Viewed by 1132
Abstract
Aim: The aim of this study was to determine associations of TRAF2 (rs867186), TAB2 (rs237025), IKBKB (rs13278372) gene polymorphisms and TRAF2, TAB2, IKBKB protein levels with clinical and morphological features of pituitary adenomas (PAs). Methods: This case–control study included 459 individuals [...] Read more.
Aim: The aim of this study was to determine associations of TRAF2 (rs867186), TAB2 (rs237025), IKBKB (rs13278372) gene polymorphisms and TRAF2, TAB2, IKBKB protein levels with clinical and morphological features of pituitary adenomas (PAs). Methods: This case–control study included 459 individuals divided into two groups: a control group (n = 320) and a group of individuals with PAs (n = 139). DNA from peripheral blood leukocytes was isolated using salt precipitation and column method. Real-time PCR was used for TRAF2 (rs867186), TAB2 (rs237025), and IKBKB (rs13278372) SNP genotyping, and TRAF2, TAB2, IKBKB protein concentration measurements were performed by immunoenzymatic analysis tests using a commercial ELISA kit according to the manufacturer’s recommendations. The labeling index Ki-67 was determined by immunohistochemical analysis using a monoclonal antibody (clone SP6; Spring Bioscience Corporation). Statistical data analysis was performed using the programs "IMB SPSS Statistics 29.0". Results: We found significant differences in TRAF2 (rs867186) genotypes (AA, AG, GG) between groups: 79.1%, 17.3%, 3.6% vs. 55.3%, 20.9%, 23.8% (p < 0.001). The G allele was less frequent in the PA group than in controls (12.2% vs. 34.2%, p < 0.001). The AG and GG genotypes reduced PA occurrence by 1.74-fold and 9.43-fold, respectively, compared to AA (p < 0.001). In the dominant model, GG and AG genotypes reduced PA odds by 3.07-fold, while in the recessive model, the GG genotype reduced PA odds by 8.33-fold (p < 0.001). Each G allele decreased PA odds by 2.49-fold in the additive model (p < 0.001). Microadenomas had significant genotype differences compared to controls: 81.3%, 18.8%, 0.0% vs. 55.3%, 20.9%, 23.8% (p < 0.001), with the G allele being less frequent (9.4% vs. 34.2%, p < 0.001). In macroadenomas, genotype differences were 78%, 16.5%, 5.5% vs. 55.3%, 20.9%, 23.8% (p < 0.001), and the G allele was less common (13.7% vs. 34.2%, p < 0.001). The dominant model showed that GG and AG genotypes reduced microadenoma odds by 3.5-fold (p = 0.001), and each G allele reduced microadenoma odds by 3.1-fold (p < 0.001). For macroadenomas, the GG genotype reduced odds by 6.1-fold in the codominant model (p < 0.001) and by 2.9-fold in GG and AG genotypes combined compared to AA (p < 0.001). The recessive model indicated the GG genotype reduced macroadenoma odds by 5.3-fold (p < 0.001), and each G allele reduced odds by 2.2-fold in the additive model (p < 0.001). Conclusions: The TRAF2 (rs867186) G allele and GG genotype are significantly associated with reduced odds of pituitary adenomas, including both microadenomas and macroadenomas, compared to the AA genotype. These findings suggest a protective role of the G allele against the occurrence of these tumors. Full article
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11 pages, 1823 KiB  
Article
Computed Tomographic Assessment of Pituitary Gland Dimensions in Domestic Short-Haired Cats
by Dario Costanza, Pierpaolo Coluccia, Luigi Auletta, Erica Castiello, Luigi Navas, Adelaide Greco and Leonardo Meomartino
Animals 2023, 13(12), 1935; https://doi.org/10.3390/ani13121935 - 9 Jun 2023
Cited by 2 | Viewed by 3288
Abstract
The detection of subtle changes in the pituitary dimensions has relevant clinical implications. In cats, a few studies have established the cut-off values of the pituitary gland’s dimensions using small and inhomogeneous samples. The aims of this study were: to determine by computed [...] Read more.
The detection of subtle changes in the pituitary dimensions has relevant clinical implications. In cats, a few studies have established the cut-off values of the pituitary gland’s dimensions using small and inhomogeneous samples. The aims of this study were: to determine by computed tomography (CT) the pituitary linear dimensions and the pituitary-to-brain (P:B) ratio in a sample of domestic short-haired (DSH) cats; to assess the effects of sex, age, and weight on pituitary dimensions; and to evaluate the inter- and intra-observer agreement for such measurements. All skull CTs of DSH cats performed over four years using a multidetector CT and a standardized protocol were retrospectively reviewed. The exclusion criteria were: clinical, laboratory, or CT alterations of the pituitary gland, brain diseases, fractures of the neurocranium, and diabetes. The pituitary dimensions and brain area were assessed by two different observers using multiplanar reconstructions and automated segmentation tools. Fifty-one cats were included in the final sample. The intraclass correlation coefficients for intra- and inter-observer reliability were good/excellent, and moderate/good, respectively. No differences between sexes were detected, and negligible correlations were found between age and weight. According to this study, a pituitary gland with a height > 4 mm or a P:B ratio > 0.49 mm should be considered enlarged. Full article
(This article belongs to the Section Companion Animals)
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38 pages, 15560 KiB  
Review
Continuing Challenges in the Definitive Diagnosis of Cushing’s Disease: A Structured Review Focusing on Molecular Imaging and a Proposal for Diagnostic Work-Up
by Tessa N. A. Slagboom, Dirk Jan Stenvers, Elsmarieke van de Giessen, Stefan D. Roosendaal, Maartje M. L. de Win, Joseph C. J. Bot, Eleonora Aronica, René Post, Jantien Hoogmoed, Madeleine L. Drent and Alberto M. Pereira
J. Clin. Med. 2023, 12(8), 2919; https://doi.org/10.3390/jcm12082919 - 17 Apr 2023
Cited by 6 | Viewed by 3067
Abstract
The definitive diagnosis of Cushing’s disease (CD) in the presence of pituitary microadenoma remains a continuous challenge. Novel available pituitary imaging techniques are emerging. This study aimed to provide a structured analysis of the diagnostic accuracy as well as the clinical use of [...] Read more.
The definitive diagnosis of Cushing’s disease (CD) in the presence of pituitary microadenoma remains a continuous challenge. Novel available pituitary imaging techniques are emerging. This study aimed to provide a structured analysis of the diagnostic accuracy as well as the clinical use of molecular imaging in patients with ACTH-dependent Cushing’s syndrome (CS). We also discuss the role of multidisciplinary counseling in decision making. Additionally, we propose a complementary diagnostic algorithm for both de novo and recurrent or persistent CD. A structured literature search was conducted and two illustrative CD cases discussed at our Pituitary Center are presented. A total of 14 CD (n = 201) and 30 ectopic CS (n = 301) articles were included. MRI was negative or inconclusive in a quarter of CD patients. 11C-Met showed higher pituitary adenoma detection than 18F-FDG PET–CT (87% versus 49%). Up to 100% detection rates were found for 18F-FET, 68Ga-DOTA-TATE, and 68Ga-DOTA-CRH, but were based on single studies. The use of molecular imaging modalities in the detection of pituitary microadenoma in ACTH-dependent CS is of added and complementary value, serving as one of the available tools in the diagnostic work-up. In selected CD cases, it seems justified to even refrain from IPSS. Full article
(This article belongs to the Special Issue Management of Pituitary Tumors: Current and Future Treatment Options)
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14 pages, 3006 KiB  
Case Report
Pituicytoma Associated with Suspected Cushing’s Disease: Two Case Reports and a Literature Review
by Tongxin Xiao, Lian Duan, Shi Chen, Lin Lu, Yong Yao, Xinxin Mao, Huijuan Zhu and Hui Pan
J. Clin. Med. 2022, 11(16), 4805; https://doi.org/10.3390/jcm11164805 - 17 Aug 2022
Cited by 4 | Viewed by 2309
Abstract
(1) Background: Pituicytomas are rare gliomas located in the neurohypophysis or infundibulum. A misdiagnosis of pituicytoma as pituitary adenoma is common because of similar location and occasional endocrine disturbances. (2) Case presentation: We present two cases with the comorbidity of pituicytoma and Cushing’s [...] Read more.
(1) Background: Pituicytomas are rare gliomas located in the neurohypophysis or infundibulum. A misdiagnosis of pituicytoma as pituitary adenoma is common because of similar location and occasional endocrine disturbances. (2) Case presentation: We present two cases with the comorbidity of pituicytoma and Cushing’s disease (CD). Case 1 is that of a 51-year-old woman, the first reported case of the comorbidity of pituicytoma, CD, and central diabetes insipidus. She received a diagnosis of CD and central diabetes insipidus. After transsphenoidal surgery, histopathology confirmed the diagnosis of pituicytoma and adrenocorticotropin-secreting microadenoma; case 2 is that of a 29-year-old man who received a biochemical diagnosis of CD, but he received a histopathological confirmation of only pituicytoma. Both patients achieved a remission of hypercortisolism without relapse during the follow-up, but they developed hypopituitarism after surgery. We also reviewed all published 18 cases with the comorbidity of pituicytoma and any pituitary adenoma. (3) Conclusions: Pituicytoma might present pituitary hyperfunction disorders such as CD or acromegaly, with or without pathologically confirmed pituitary adenoma. CD is the most common hyperpituitarism occurring concurrently with pituicytomas. The remission rate and hypopituitarism after surgery seem similar or slightly lower in CD than in common pituitary adenomas, but the long-term prognosis is unexplored. Full article
(This article belongs to the Special Issue Pituitary Tumors: Diagnosis and Treatment)
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15 pages, 1120 KiB  
Article
Extra-Pseudocapsular Transsphenoidal Surgery for Microprolactinoma in Women
by Juan Chen, Xiang Guo, Zhuangzhuang Miao, Zhuo Zhang, Shengwen Liu, Xueyan Wan, Kai Shu, Yan Yang and Ting Lei
J. Clin. Med. 2022, 11(13), 3920; https://doi.org/10.3390/jcm11133920 - 5 Jul 2022
Cited by 6 | Viewed by 2219
Abstract
A recall for histological pseudocapsule (PS) and reappraisal of transsphenoidal surgery (TSS) as a viable alternative to dopamine agonists in the treatment algorithm of prolactinomas are getting vibrant. We hope to investigate the effectiveness and risks of extra-pseudocapsular transsphenoidal surgery (EPTSS) for young [...] Read more.
A recall for histological pseudocapsule (PS) and reappraisal of transsphenoidal surgery (TSS) as a viable alternative to dopamine agonists in the treatment algorithm of prolactinomas are getting vibrant. We hope to investigate the effectiveness and risks of extra-pseudocapsular transsphenoidal surgery (EPTSS) for young women with microprolactinoma, and to look into the factors that influenced remission and recurrence, and thus to figure out the possible indication shift for primary TSS. We proposed a new classification method of microprolactinoma based on the relationship between tumor and pituitary position, which can be divided into hypo-pituitary, para-pituitary and supra-pituitary groups. We retrospectively analyzed 133 patients of women (<50 yr) with microprolactinoma (≤10 mm) who underwent EPTSS in a tertiary center. PS were identified in 113 (84.96%) microadenomas intraoperatively. The long-term surgical cure rate was 88.2%, and the comprehensive remission rate was 95.8% in total. There was no severe or permanent complication, and the surgical morbidity rate was 4.5%. The recurrence rate with over 5 years of follow-up was 9.2%, and a lot lower for the tumors in the complete PS group (0) and hypo-pituitary group (2.1%). Use of the extra-pseudocapsule dissection in microprolactinoma resulted in a good chance of increasing the surgical remission without increasing the risk of CSF leakage or endocrine deficits. First-line EPTSS may offer a greater opportunity of long-term cure for young female patients with microprolactinoma of hypo-pituitary located and Knosp grade 0-II. Full article
(This article belongs to the Special Issue Pituitary Tumors: Diagnosis and Treatment)
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14 pages, 1760 KiB  
Article
Clinical Study and Systematic Review of Pituitary Microadenomas vs. Macroadenomas in Cushing’s Disease: Does Size Matter?
by Amit Akirov, Ilan Shimon, Maria Fleseriu, Idit Dotan, Yossi Manisterski, Nirit Aviran-Barak, Varda Nadler, Sandra Alboim, Tzipora Shochat, Gloria Tsvetov and Dania Hirsch
J. Clin. Med. 2022, 11(6), 1558; https://doi.org/10.3390/jcm11061558 - 11 Mar 2022
Cited by 9 | Viewed by 3369
Abstract
Background: Reports on clinical and biochemical differences between adrenocorticotropic hormone (ACTH)-secreting pituitary microadenomas and macroadenomas are limited and inconsistent. Objective: Compare clinical and biochemical characteristics of patients with corticotroph microadenomas and macroadenomas and assess predictive factors for biochemical response to dynamic testing [...] Read more.
Background: Reports on clinical and biochemical differences between adrenocorticotropic hormone (ACTH)-secreting pituitary microadenomas and macroadenomas are limited and inconsistent. Objective: Compare clinical and biochemical characteristics of patients with corticotroph microadenomas and macroadenomas and assess predictive factors for biochemical response to dynamic testing for Cushing’s disease (CD) in a clinical trial and a systematic review. A second aim was to evaluate differences between macroadenomas with and without cavernous and sphenoid sinus invasion. Methods: Retrospective charts review of patients with CD, treated at Rabin Medical Center between 2000 and 2020 or at Maccabi Healthcare Services in Israel between 2005 and 2017. Clinical and biochemical factors were compared between patients with corticotroph microadenomas and macroadenomas. We have also performed a systematic review of all studies (PRISMA guidelines) comparing corticotroph microadenomas with macroadenomas up to 31 November 2021. Results: The cohort included 105 patients (82 women, 78%; mean age, 41.5 ± 14.5 years), including 80 microadenomas (mean size, 5.2 ± 2.2 mm) and 25 macroadenomas (mean size, 18.0 ± 7.7 mm). Other baseline characteristics were similar between groups. Most common presentation suggestive for hypercortisolemia among patients with both micro- and macroadenomas were weight gain (46.3% vs. 48.0%, p = NS) and Cushingoid features (27.5% vs. 20.0%, p = NS). Mean 24 h urinary free cortisol (5.2 ± 5.4 × ULN vs. 7.8 ± 8.7 × ULN) and serum cortisol following low-dose dexamethasone (372.0 ± 324.5 vs. 487.6 ± 329.8 nmol/L), though higher for macroadenomas, were not significant. Levels of ACTH were greater for macroadenomas (1.9 ± 1.2 × ULN vs. 1.3 ± 0.8 × ULN, respectively, p = 0.01). Rates of recurrent/persistent disease were similar, as were rates of post-operative adrenal insufficiency and duration of post-operative glucocorticoid replacement. Macroadenomas with sphenoid or cavernous sinus invasion were associated with higher ACTH, 24 h free urinary cortisol, and serum cortisol following low-dose dexamethasone, compared with suprasellar or intrasellar macroadenomas. Conclusions: While ACTH-secreting macroadenomas exhibit higher plasma ACTH than microadenomas, there was no association between tumor size with cortisol hypersecretion or clinical features of hypercortisolemia. Though overall rare, increased awareness is needed for patients with CD with tumor extension in the cavernous or sphenoid sinus, which displays increased biochemical burden, highlighting that extent/location of the adenoma may be more important than size per se. Our systematic review, the first on this topic, highlights differences and similarities with our study. Full article
(This article belongs to the Special Issue Management of Pituitary Tumors: Current and Future Treatment Options)
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16 pages, 3907 KiB  
Article
MRI Protocol for Pituitary Assessment in Children with Growth or Puberty Disorders—Is Gadolinium Contrast Administration Actually Needed?
by Marta Michali-Stolarska, Andrzej Tukiendorf, Anna Zacharzewska-Gondek, Jagoda Jacków-Nowicka, Joanna Chrzanowska, Grzegorz Trybek and Joanna Bladowska
J. Clin. Med. 2021, 10(19), 4598; https://doi.org/10.3390/jcm10194598 - 6 Oct 2021
Cited by 2 | Viewed by 3857
Abstract
The aim of this study was to assess the diagnostic value of non-contrast pituitary MRI in children with growth or puberty disorders (GPDs) and to determine the criteria indicating the necessity to perform post-contrast examination. A retrospective study included re-analysis of 567 contrast-enhanced [...] Read more.
The aim of this study was to assess the diagnostic value of non-contrast pituitary MRI in children with growth or puberty disorders (GPDs) and to determine the criteria indicating the necessity to perform post-contrast examination. A retrospective study included re-analysis of 567 contrast-enhanced pituitary MRIs of children treated in a tertiary reference center. Two sets of sequences were created from each MRI examination: Set 1, including common sequences without contrast administration, and Set 2, which included common pre- and post-contrast sequences (conventional MRI examination). The differences in the visibility of pituitary lesions between pairs of sets were statistically analyzed. The overall frequency of Rathke’s cleft cysts was 11.6%, ectopic posterior pituitary 3.5%, and microadenomas 0.9%. Lesions visible without contrast administration accounted for 85% of cases. Lesions not visible before and diagnosed only after contrast injection accounted for only 0.18% of all patients. Statistical analysis showed the advantage of the antero-posterior (AP) pituitary dimension over the other criteria in determining the appropriateness of using contrast in pituitary MRIs. The AP dimension was the most significant factor in logistic regression analysis: OR = 2.23, 95% CI, 1.35–3.71, p-value = 0.002, and in ROC analysis: AUC: 72.9% with a cut-off value of 7.5 mm, with sensitivity/specificity rates of 69.2%/73.5%. In most cases, the use of gadolinium-based contrast agent (GBCA) in pituitary MRI in children with GPD is unnecessary. The advantages of GBCA omission include shortening the time of MRI examination and of general anesthesia; saving time for other examinations, thus increasing the availability of MRI for waiting children; and acceleration in their further clinical management. Full article
(This article belongs to the Section Endocrinology & Metabolism)
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10 pages, 418 KiB  
Article
Reappraising the Role of Trans-Sphenoidal Surgery in Prolactin-Secreting Pituitary Tumors
by Pier Paolo Mattogno, Quintino Giorgio D’Alessandris, Sabrina Chiloiro, Antonio Bianchi, Antonella Giampietro, Alfredo Pontecorvi, Laura De Marinis, Alessandro Olivi, Carmelo Anile and Liverana Lauretti
Cancers 2021, 13(13), 3252; https://doi.org/10.3390/cancers13133252 - 29 Jun 2021
Cited by 16 | Viewed by 1909
Abstract
Background: Prolactinomas represent a unique challenge for endocrinologists and neurosurgeons. Considering recent innovations in surgical practice, the authors aimed to investigate the best management for prolactinomas. Methods: A retrospective, cross-sectional and monocentric study was designed. Consecutive patients affected by prolactinomas were enrolled if [...] Read more.
Background: Prolactinomas represent a unique challenge for endocrinologists and neurosurgeons. Considering recent innovations in surgical practice, the authors aimed to investigate the best management for prolactinomas. Methods: A retrospective, cross-sectional and monocentric study was designed. Consecutive patients affected by prolactinomas were enrolled if treated with a first-line treatment with a dopamine agonist (DA) or trans-sphenoidal surgery (TSS). Patients carried giant prolactinomas, and those with a follow-up <12 months were excluded. Results: Two hundred and fifty-nine patients were enrolled. The first treatment was DA for 140 patients and TS for 119 cases. One hundred and forty-six of 249 patients (58.6%) needed a second therapy. The mean follow-up was 102.2 months (12–438 months). Surgery highly impacted on the cure rate—in particular, in females (p = 0.0021) and in microprolactinomas (p = 0.0020). Considering the multivariate analysis, the female gender and surgical treatment in the course of the clinical history were the only independent positive predictors of a cure at the end of 5 years follow-up (p = 0.0016, p = 0.0005). The evaluation of serum prolactin (24 hours after TSS) revealed that 86.4% of patients with postoperative prolactin (PRL) ≤10 ng/mL were cured at the end of the follow-up (p < 0.0001). Conclusions: According to our experience, surgery allows a high cure rate of prolactinomas, particularly in females with microadenoma, with a good safety profile. TSS for prolactinomas should be considered as a concrete option, during the multidisciplinary evaluation, in centers of reference for pituitary diseases. Full article
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9 pages, 1286 KiB  
Article
Findings of Brain Magnetic Resonance Imaging in Girls with Central Precocious Puberty Compared with Girls with Chronic or Recurrent Headache
by Shin-Hee Kim, Moon Bae Ahn, Won Kyoung Cho, Kyoung Soon Cho, Min Ho Jung and Byung-Kyu Suh
J. Clin. Med. 2021, 10(10), 2206; https://doi.org/10.3390/jcm10102206 - 19 May 2021
Cited by 4 | Viewed by 3000
Abstract
In the present study, the results of brain magnetic resonance imaging (MRI) in girls with central precocious puberty (CPP) were compared those in with girls evaluated for headaches. A total of 295 girls with CPP who underwent sellar MRI were enrolled. A total [...] Read more.
In the present study, the results of brain magnetic resonance imaging (MRI) in girls with central precocious puberty (CPP) were compared those in with girls evaluated for headaches. A total of 295 girls with CPP who underwent sellar MRI were enrolled. A total of 205 age-matched girls with chronic or recurrent headaches without neurological abnormality who had brain MRI were included as controls. The positive MRI findings were categorized as incidental non-hypothalamic–pituitary (H–P), incidental H–P, or pathological. Positive MRI findings were observed in 39 girls (13.2%) with CPP; 8 (2.7%) were classified as incidental non-H–P lesions, 30 (10.2%) as incidental H–P lesions, and 1 (0.3%) as a pathological lesion (tuber cinereum hamartoma). The prevalence of positive MRI findings in girls with CPP did not differ from girls with headaches (13.2% vs. 12.2%, p = 0.74). The prevalence of incidental H–P lesions in girls with CPP <6 years of age, 6–6.9 years of age, and 7–7.9 years of age was 21.2%, 13.5%, and 9.6%, respectively (p = 0.21). Known pathological lesions were detected in only one (3.0%) girl with CPP aged <6 years and in no girls with CPP aged 6–7.9 years. Microadenomas were detected in no girls with CPP aged <6 years and in 5 (1.9%) girls with CPP aged of 6–7.9 years. Our findings call into question the routine use of brain MRI in girls with CPP, especially in girls 6 years or older. Current guidelines recommend a follow-up MRI in cases of microadenoma, but few data exist to support this recommendation for children. Full article
(This article belongs to the Section Clinical Neurology)
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16 pages, 688 KiB  
Review
Pancreatic Neuroendocrine Neoplasms in Multiple Endocrine Neoplasia Type 1
by Francesca Marini, Francesca Giusti, Francesco Tonelli and Maria Luisa Brandi
Int. J. Mol. Sci. 2021, 22(8), 4041; https://doi.org/10.3390/ijms22084041 - 14 Apr 2021
Cited by 29 | Viewed by 4625
Abstract
Pancreatic neuroendocrine tumors (pNETs) are a rare group of cancers accounting for about 1–2% of all pancreatic neoplasms. About 10% of pNETs arise within endocrine tumor syndromes, such as Multiple Endocrine Neoplasia type 1 (MEN1). pNETs affect 30–80% of MEN1 patients, manifesting prevalently [...] Read more.
Pancreatic neuroendocrine tumors (pNETs) are a rare group of cancers accounting for about 1–2% of all pancreatic neoplasms. About 10% of pNETs arise within endocrine tumor syndromes, such as Multiple Endocrine Neoplasia type 1 (MEN1). pNETs affect 30–80% of MEN1 patients, manifesting prevalently as multiple microadenomas. pNETs in patients with MEN1 are particularly difficult to treat due to differences in their growth potential, their multiplicity, the frequent requirement of extensive surgery, the high rate of post-operative recurrences, and the concomitant development of other tumors. MEN1 syndrome is caused by germinal heterozygote inactivating mutation of the MEN1 gene, encoding the menin tumor suppressor protein. MEN1-related pNETs develop following the complete loss of function of wild-type menin. Menin is a key regulator of endocrine cell plasticity and its loss in these cells is sufficient for tumor initiation. Somatic biallelic loss of wild-type menin in the neuroendocrine pancreas presumably alters the epigenetic control of gene expression, mediated by histone modifications and DNA hypermethylation, as a driver of MEN1-associated pNET tumorigenesis. In this light, epigenetic-based therapies aimed to correct the altered DNA methylation, and/or histone modifications might be a possible therapeutic strategy for MEN1 pNETs, for whom standard treatments fail. Full article
(This article belongs to the Special Issue Pancreatic Cancer: From Molecular Basis to Therapy)
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17 pages, 3267 KiB  
Article
Novel Protein-Based Vaccine against Self-Antigen Reduces the Formation of Sporadic Colon Adenomas in Mice
by Elodie Belnoue, Alyssa A. Leystra, Susanna Carboni, Harry S. Cooper, Rodrigo T. Macedo, Kristen N. Harvey, Kimberly B. Colby, Kerry S. Campbell, Lisa A. Vanderveer, Margie L. Clapper and Madiha Derouazi
Cancers 2021, 13(4), 845; https://doi.org/10.3390/cancers13040845 - 17 Feb 2021
Cited by 16 | Viewed by 4530
Abstract
Novel immunopreventive strategies are emerging that show great promise for conferring long-term protection to individuals at high risk of developing colorectal cancer. The KISIMA vaccine platform utilizes a chimeric protein comprising: (1) a selected tumor antigen; (2) a cell-penetrating peptide to improve antigen [...] Read more.
Novel immunopreventive strategies are emerging that show great promise for conferring long-term protection to individuals at high risk of developing colorectal cancer. The KISIMA vaccine platform utilizes a chimeric protein comprising: (1) a selected tumor antigen; (2) a cell-penetrating peptide to improve antigen delivery and epitope presentation, and (3) a TLR2/4 agonist to serve as a self-adjuvant. This study examines the ability of a KISIMA vaccine against achaete-scute family bHLH transcription factor 2 (Ascl2), an early colon cancer antigen, to reduce colon tumor formation by stimulating an anti-tumor immune response. Vaccine administrations were well-tolerated and led to circulating antibodies and antigen-specific T cells in a mouse model of colorectal cancer. To assess preventive efficacy, the vaccine was administered to mice either alone or in combination with the immune checkpoint inhibitor anti-PD-1. When delivered to animals prior to colon tumor formation, the combination strategy significantly reduced the development of colon microadenomas and adenomas, as compared to vehicle-treated controls. This response was accompanied by an increase in the intraepithelial density of CD3+ T lymphocytes. Together, these data indicate that the KISIMA-Ascl2 vaccine shows great potential to be a safe and potent immunopreventive intervention for individuals at high risk of developing colorectal cancer. Full article
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