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Frontiers in Endocrinology 2021Up to 35% of aggressive pituitary tumors recur and significantly affect mortality and quality of life. Management can be challenging and often requires multimodal... (Review)
Review
Up to 35% of aggressive pituitary tumors recur and significantly affect mortality and quality of life. Management can be challenging and often requires multimodal treatment. Current treatment options, including surgery, conventional medical therapies such as dopamine agonists, somatostatin receptor agonists and radiotherapy, often fail to inhibit pituitary tumor growth. Recently, anti-tumor effects of chemotherapeutic drugs such as Temozolomide, Capecitabine, and Everolimus, as well as peptide receptor radionuclide therapy on aggressive pituitary tumors have been increasingly investigated and yield mixed, although sometimes promising, outcomes. The purpose of this review is to provide thorough information on non-surgical medical therapies and their efficacies and used protocols for aggressive pituitary adenomas from pre-clinical level to clinical use.
Topics: Antineoplastic Agents; Capecitabine; Combined Modality Therapy; Dopamine Agonists; Humans; Pituitary Neoplasms; Temozolomide; Treatment Outcome
PubMed: 33841328
DOI: 10.3389/fendo.2021.624686 -
Sichuan Da Xue Xue Bao. Yi Xue Ban =... Jul 2022Intracranial tumors seriously affect the physical and mental health of humans. Due to variations in the nature and the growth site of tumors, individualized and specific... (Review)
Review
Intracranial tumors seriously affect the physical and mental health of humans. Due to variations in the nature and the growth site of tumors, individualized and specific treatment of patients with intracranial tumor has become a hotspot topic of research, and targeted drug therapy of intracranial tumors, an important subspecialty of precision medicine, has become a key issue that scientists are working hard to tackle. At present, the rapid development in molecular biology and genomics has provided corresponding targets for precision therapies of tumors. However, the blood-brain barrier and blood-tumor barrier prevent drugs from reaching intracranial targets. Therefore, finding effective ways to elevate the concentration of intracranial drugs has become the key issue concerning existing targeted therapies for intracranial tumors. Herein, we reviewed the current status of targeted drug therapy for different intracranial tumors and discussed their efficacy, intending to provide new perspectives for the treatment of intracranial tumors with targeted drugs in the future.
Topics: Blood-Brain Barrier; Brain Neoplasms; Humans; Pituitary Neoplasms
PubMed: 35871724
DOI: 10.12182/20220760102 -
Frontiers in Endocrinology 2020
Topics: Adenoma; Biomarkers, Tumor; Gene Expression Regulation, Neoplastic; Gene Regulatory Networks; Humans; Molecular Targeted Therapy; Pituitary Neoplasms; Precision Medicine; Protein Interaction Maps; Signal Transduction
PubMed: 32132975
DOI: 10.3389/fendo.2020.00026 -
Neurology India 2023Primary hypophysitis is a rare condition, usually diagnosed retrospectively after surgery for a suspected pituitary adenoma. Improved awareness of the condition and... (Review)
Review
BACKGROUND
Primary hypophysitis is a rare condition, usually diagnosed retrospectively after surgery for a suspected pituitary adenoma. Improved awareness of the condition and better imaging have resulted in more patients being diagnosed without surgery.
OBJECTIVE
A retrospective chart analysis study of hypophysitis from a single secondary endocrine and neurosurgical referral center in eastern India was conducted between 1999 and 2021 to assess the diagnostic and therapeutic challenges posed by these patients.
METHODS AND MATERIAL
Fourteen patients presented to the center between 1999 and 2021. All patients had an MRI of the head with contrast and a full clinical workup. Twelve patients had headache, of whom one had progressive visual impairment. One patient had severe weakness, attributed later to hypoadrenalism and one had sixth nerve palsy.
RESULTS
Six patients had glucocorticoids as their primary treatment, four refused treatment, and one was on glucocorticoid replacement. One patient had decompressive surgery because of progressive visual loss, and two had surgery because of a presumptive diagnosis of pituitary adenoma. There was no difference between the patients who had glucocorticoids and those who did not.
CONCLUSIONS
Our data suggest that it is possible to identify most patients with hypophysitis on clinical and radiological grounds. In the largest published series on this subject and in ours, glucocorticoid treatment did not alter the outcome.
Topics: Humans; Glucocorticoids; Pituitary Neoplasms; Retrospective Studies; Abducens Nerve Diseases; Hypophysitis
PubMed: 36861584
DOI: 10.4103/0028-3886.370481 -
Frontiers in Endocrinology 2020Pituitary adenomas (PAs) can be classified as non-secreting adenomas, somatotroph adenomas, corticotroph adenomas, lactotroph adenomas, and thyrotroph adenomas.... (Review)
Review
Pituitary adenomas (PAs) can be classified as non-secreting adenomas, somatotroph adenomas, corticotroph adenomas, lactotroph adenomas, and thyrotroph adenomas. Substantial advances have been made in our knowledge of the pathobiology of PAs. To obtain a comprehensive understanding of the molecular biological characteristics of different types of PAs, we reviewed the important advances that have been made involving genetic and epigenetic variation, comprising genetic mutations, chromosome number variations, DNA methylation, microRNA regulation, and transcription factor regulation. Classical tumor predisposition syndromes include multiple endocrine neoplasia type 1 (MEN1) and type 4 (MEN4) syndromes, Carney complex, and X-LAG syndromes. PAs have also been described in association with succinate dehydrogenase-related familial PA, neurofibromatosis type 1, and von Hippel-Lindau, DICER1, and Lynch syndromes. Patients with aryl hydrocarbon receptor-interacting protein () mutations often present with pituitary gigantism, either in familial or sporadic adenomas. In contrast, guanine nucleotide-binding protein G(s) subunit alpha () and G protein-coupled receptor 101 () mutations can lead to excess growth hormone. Moreover, the deubiquitinase gene , , and mutations are associated with adrenocorticotropic hormone production. In this review, we describe the genetic and epigenetic landscape of PAs and summarize novel insights into the regulation of pituitary tumorigenesis.
Topics: Adenoma; Epigenesis, Genetic; Gene Expression Regulation; Genetic Markers; Genetic Predisposition to Disease; Humans; Mutation; Pituitary Neoplasms
PubMed: 33574795
DOI: 10.3389/fendo.2020.596554 -
Cell Reports Aug 2022Sporadic pituitary adenomas occur in over 10% of the population. Hormone-secreting adenomas, including those causing Cushing's disease (CD), cause severe morbidity and...
Sporadic pituitary adenomas occur in over 10% of the population. Hormone-secreting adenomas, including those causing Cushing's disease (CD), cause severe morbidity and early mortality. Mechanistic studies of CD are hindered by a lack of in vitro models and control normal human pituitary glands. Here, we surgically annotate adenomas and adjacent normal glands in 25 of 34 patients. Using single-cell RNA sequencing (RNA-seq) analysis of 27594 cells, we identify CD adenoma transcriptomic signatures compared with adjacent normal cells, with validation by bulk RNA-seq, DNA methylation, qRT-PCR, and immunohistochemistry. CD adenoma cells include a subpopulation of proliferating, terminally differentiated corticotrophs. In CD adenomas, we find recurrent promoter hypomethylation and transcriptional upregulation of PMAIP1 (encoding pro-apoptotic BH3-only bcl-2 protein noxa) but paradoxical noxa downregulation. Using primary CD adenoma cell cultures and a corticotroph-enriched mouse cell line, we find that selective proteasomal inhibition with bortezomib stabilizes noxa and induces apoptosis, indicating its utility as an anti-tumor agent.
Topics: Adenoma; Adrenocorticotropic Hormone; Animals; Apoptosis; Humans; Mice; Pituitary ACTH Hypersecretion; Pituitary Neoplasms
PubMed: 36001971
DOI: 10.1016/j.celrep.2022.111223 -
Endocrine Journal Mar 2023The majority of anterior pituitary tumors behave benignly, that is, they grow slowly and do not metastasize, and were therefore called adenomas. However, they would...
The majority of anterior pituitary tumors behave benignly, that is, they grow slowly and do not metastasize, and were therefore called adenomas. However, they would frequently invade adjacent structures, leading to recurrence. One of the misleading assumptions in their previous classification was the simplistic distinction made between adenoma and carcinoma. In the upcoming WHO 2022 classification, a new terminology will be introduced: pituitary neuroendocrine tumor (PitNET) which is consistent with that used for other neuroendocrine neoplasms. In general, aggressive PitNETs are invasive and proliferative tumors with frequent recurrences, resistant to conventional treatments, and yet virtually without metastases. At present, no single morphological or histological marker has been shown as yet to reliably predict their aggressive behavior. In terms of treatment, temozolomide (TMZ) had been considered promising and the sole therapeutic option for aggressive and malignant PitNETs following failure of standard therapies. However, recent reports have disclosed that TMZ does not provide long-term control of many aggressive PitNETs. A further multidisciplinary approach is necessary for both reliable prediction and successful management of aggressive PitNETs.
Topics: Humans; Pituitary Neoplasms; Temozolomide; Adenoma; Neuroendocrine Tumors; Carcinoma
PubMed: 36858483
DOI: 10.1507/endocrj.EJ23-0007 -
Neuroendocrinology 2020The parasellar region, located around the sella turcica, is an anatomically complex area representing a crossroads for important adjacent structures. Several lesions,... (Review)
Review
The parasellar region, located around the sella turcica, is an anatomically complex area representing a crossroads for important adjacent structures. Several lesions, including tumoral, inflammatory vascular, and infectious diseases may affect this area. Although invasive pituitary tumors are the most common neoplasms encountered within the parasellar region, other tumoral (and cystic) lesions can also be detected. Craniopharyngiomas, meningiomas, as well as Rathke's cleft cysts, chordomas, and ectopic pituitary tumors can primarily originate from the parasellar region. Except for hormone-producing ectopic pituitary tumors, signs and symptoms of these lesions are usually nonspecific, due to a mass effect on the surrounding anatomical structures (i.e., headache, visual defects), while a clinically relevant impairment of endocrine function (mainly anterior hypopituitarism and/or diabetes insipidus) can be present if the pituitary gland is displaced or compressed. Differential diagnosis of parasellar lesions mainly relies on magnetic resonance imaging, which should be interpreted by neuroradiologists skilled in base skull imaging. Neurosurgery is the main treatment, alone or in combination with radiotherapy. Of note, recent studies have identified gene mutations or signaling pathway modulators that represent potential candidates for the development of targeted therapies, particularly for craniopharyngiomas and meningiomas. In summary, parasellar lesions still represent a diagnostic and therapeutic challenge. A deeper knowledge of this complex anatomical site, the improvement of imaging tools, as well as novel insights into the pathophysiology of presenting lesions are strongly needed to improve the management of parasellar lesions.
Topics: Brain Neoplasms; Cavernous Sinus; Humans; Pituitary Neoplasms; Sella Turcica
PubMed: 32126547
DOI: 10.1159/000506905 -
European Journal of Endocrinology Jul 2023The optimal approach to the surveillance of non-functioning pituitary microadenomas (micro-NFPAs) is not clearly established. Our aim was to generate evidence on the...
OBJECTIVE
The optimal approach to the surveillance of non-functioning pituitary microadenomas (micro-NFPAs) is not clearly established. Our aim was to generate evidence on the natural history of micro-NFPAs to support patient care.
DESIGN
Multi-centre, retrospective, cohort study involving 23 endocrine departments (UK NFPA consortium).
METHODS
Clinical, imaging, and hormonal data of micro-NFPA cases between January, 1, 2008 and December, 21, 2021 were analysed.
RESULTS
Data for 459 patients were retrieved [median age at detection 44 years (IQR 31-57)-152 males/307 females]. Four hundred and nineteen patients had more than two magnetic resonance imagings (MRIs) [median imaging monitoring 3.5 years (IQR 1.71-6.1)]. One case developed apoplexy. Cumulative probability of micro-NFPA growth was 7.8% (95% CI, 4.9%-8.1%) and 14.5% (95% CI, 10.2%-18.8%) at 3 and 5 years, respectively, and of reduction 14.1% (95% CI, 10.4%-17.8%) and 21.3% (95% CI, 16.4%-26.2%) at 3 and 5 years, respectively. Median tumour enlargement was 2 mm (IQR 1-3) and 49% of micro-NFPAs that grew became macroadenomas (nearly all >5 mm at detection). Eight (1.9%) patients received surgery (only one had visual compromise with surgery required >3 years after micro-NFPA detection). Sex, age, and size at baseline were not predictors of enlargement/reduction. At the time of detection, 7.2%, 1.7%, and 1.5% patients had secondary hypogonadism, hypothyroidism, and hypoadrenalism, respectively. Two (0.6%) developed hypopituitarism during follow-up (after progression to macroadenoma).
CONCLUSIONS
Probability of micro-NFPA growth is low, and the development of new hypopituitarism is rare. Delaying the first follow-up MRI to 3 years and avoiding hormonal re-evaluation in the absence of tumour growth or clinical manifestations is a safe approach for micro-NFPA surveillance.
Topics: Male; Female; Humans; Adult; Middle Aged; Pituitary Neoplasms; Retrospective Studies; Cohort Studies; Adenoma; Hypopituitarism; United Kingdom
PubMed: 37345849
DOI: 10.1093/ejendo/lvad070 -
The Ulster Medical Journal Sep 2021The pituitary gland is an unusual site for metastatic spread and has been associated with a poor prognosis. Clinical presentation is variable but can include visual... (Review)
Review
The pituitary gland is an unusual site for metastatic spread and has been associated with a poor prognosis. Clinical presentation is variable but can include visual field defects, cranial nerve palsies, anterior pituitary dysfunction and/ or diabetes insipidus. Management options include surgery or radiotherapy, chemotherapy/immunotherapy or a conservative approach. The pituitary should not be overlooked as a site for metastasis in patients with known cancer and can be the first presentation of neoplastic disease in some patients. Given that patients are now living longer with cancer, clinicians should be alert to the varied presentation of pituitary metastasis. We provide a clinical overview of pituitary metastasis with the aid of illustrative clinical cases.
Topics: Diabetes Insipidus; Humans; Pituitary Neoplasms
PubMed: 34815592
DOI: No ID Found