-
Neuroendocrinology 2015Pituitary adenomas are common intracranial tumors that are mainly considered as benign. Rarely, these tumors can exhibit an aggressive behavior, characterized by gross... (Review)
Review
Pituitary adenomas are common intracranial tumors that are mainly considered as benign. Rarely, these tumors can exhibit an aggressive behavior, characterized by gross invasion of the surrounding tissues, resistance to conventional treatment leading to early and frequent recurrences. Even more rarely, pituitary tumors can give rise to cerebrospinal or systemic metastases qualifying as pituitary carcinomas according to the latest WHO definition. In the same classification, a subset of tumors with relatively distinct histopathological features was identified and defined as atypical adenomas designated to follow a more aggressive clinical course. This classification, although clinically useful, does not provide an accurate correlation between histopathological findings and the clinical behavior of these tumors, neither is it adequate to convey the precise features of 'aggressive' tumors. Thus, 'aggressive' pituitary adenomas need to be properly defined with clinical, radiological, histological and molecular markers in order to identify patients at increased risk of early recurrence or subsequent tumor progression. At present, no single marker or classification system of pituitary tumor aggressiveness exists, and clinically useful information in the literature is insufficient to guide diagnostic and therapeutic decisions. Treatment of patients with aggressive pituitary tumors is challenging since conventional treatments often fail, necessitating multiple surgical procedures with additional radiotherapy. Although traditional chemotherapy applied in other neuroendocrine tumors has not been shown to be efficacious, newer agents, particularly temozolomide, have shown promising results and are currently used despite the lack of data from a randomized prospective trial. Molecular targeted therapies such as mTOR and epidermal growth factor inhibitors have also been applied and might prove to be useful in the management of these patients. In the present review, we provide information regarding the epidemiology and clinical, histopathological and molecular features of aggressive pituitary tumors using recent employed definitions. In addition, we review currently employed therapeutic means providing a therapeutic algorithm and highlight the need to identify more specific disease-related and prognostic markers and the necessity for central registration of these tumors.
Topics: Adenoma; Humans; Pituitary Neoplasms
PubMed: 25571935
DOI: 10.1159/000371806 -
Minerva Endocrinologica Sep 2016Prolactinomas are pituitary tumors that originate from the adenohypophysis lactotroph cells. These tumors constitute one third of all pituitary adenomas, making them the... (Review)
Review
Prolactinomas are pituitary tumors that originate from the adenohypophysis lactotroph cells. These tumors constitute one third of all pituitary adenomas, making them the most common functional pituitary neoplasms. The signs and symptoms of patients harboring prolactin (PRL) secreting tumors may derive from hyperprolactinemia itself, as well as from direct pressure of the expanding mass on the normal pituitary gland and other surrounding tissues, in cases of invasive tumors. This review will focus on practical aspects of the medical treatment of patients with prolactinomas, and on the main differences between the treatment strategy of micro- and macroprolactinomas. Medical therapy with dopamine agonists (DA) is the preferred treatment for the vast majority of patients harboring prolactinomas. Cabergoline (CAB) is the main agent used for treating prolactinomas, achieving normoprolactinemia in 80-100% of patients with microprolactinomas, and in 75-95% of those with macroprolactinomas. Second line therapies include surgery and radiation therapy, and are indicated only in rare cases, such as patients intolerant to, or with contraindication for DAs, or patients harboring malignant or DA resistant tumors. The management principles of pregnant women with prolactinomas and of patients with suspected malignant prolactinoma are distinct from other patient populations, and are discussed separately in our review.
Topics: Dopamine Agonists; Female; Humans; Pituitary Neoplasms; Pregnancy; Pregnancy Complications, Neoplastic; Prolactinoma
PubMed: 26399371
DOI: No ID Found -
Frontiers in Endocrinology 2023Craniopharyngioma is a benign tumor originating from the sellar region. Damages in this area caused by the tumor itself, surgery, or radiotherapy may result in severe...
BACKGROUND
Craniopharyngioma is a benign tumor originating from the sellar region. Damages in this area caused by the tumor itself, surgery, or radiotherapy may result in severe hypothalamic-pituitary dysfunction (HPD) and eventually lead to a significant impairment in the long-term quality of life of patients. This study aimed to investigate the characteristics of HPD in patients with adamantinomatous craniopharyngioma (ACP) or papillary craniopharyngioma (PCP) and to identify the factors affecting HPD after surgery.
METHODS
In this single-center retrospective study, a total of 742 patients with craniopharyngioma were included. The neuroendocrine function of these patients before and after surgery was investigated. The differences in hypothalamic-pituitary function between the ACP and PCP groups were compared. The factors influencing the aggravation of HPD after surgery were identified.
RESULTS
The median follow-up after surgery was 15 months. Before surgery, the proportion of patients with diabetes insipidus (DI) and hyperprolactinemia in the PCP group was significantly higher than that in the ACP group (<0.01), and the proportion of patients with adrenocortical hypofunction in the PCP group was significantly lower than that in the ACP group (=0.03). Most cases of ACP originated in the sellar region, while most cases of PCP originated in the suprasellar region (<0.01). More patients experienced adenohypophyseal hypofunction, DI, and hypothalamic obesity at postoperative follow-up than at onset in both the ACP and PCP groups (both <0.01), with a higher increase observed in the ACP group (<0.01). Older age at CP onset, tumor recurrence or progression, and ACP type were risk factors for postoperative aggravation of HPD in CP patients.
CONCLUSION
Surgical treatment significantly aggravated HPD in both the ACP and PCP groups, but the specific characteristics and risk factors leading to aggravation were different between the two groups.
Topics: Humans; Craniopharyngioma; Retrospective Studies; Quality of Life; Pituitary Neoplasms; Neoplasm Recurrence, Local; Hypothalamic Diseases; Pituitary Diseases; Diabetes Insipidus
PubMed: 37324266
DOI: 10.3389/fendo.2023.1180591 -
Frontiers in Endocrinology 2023Hypothalamic-pituitary axis dysfunction is a common complication in post-operative craniopharyngioma(CP) patients, and it greatly impacts the long-term quality of life...
OBJECTIVE
Hypothalamic-pituitary axis dysfunction is a common complication in post-operative craniopharyngioma(CP) patients, and it greatly impacts the long-term quality of life of such patients. To better understand the effects of postoperative hypothalamic-pituitary dysfunction and long-term hormone replacement therapy in patients with childhood CP, we assessed approximately 200 patients with childhood-onset CP postoperatively.
METHODS
Clinical details of patients with childhood-onset CP who underwent sellar tumor resection in Beijing Children's Hospital and Beijing Tiantan Hospital from 2018 to 2019 were retrieved retrospectively. The participants were followed up to assess the effects of post-operative long-term hormone replacement therapy and assess the tumor recurrence rate.
RESULTS
The median age of admission was 8.1 (1.8, 14.3) years. Headache (45.5%), visual impairment (39.5%), and nausea (33.0%) were the most common clinical manifestations. ACP accounted for 95% of all CP cases. The incidence of central adrenal insufficiency and central hypothyroidism within the first week after surgery was 56.2% and 70.3%, respectively. At the same time 85.5% of the patients required at least one dose of desmopressin to control urine output. Total survival and tumor recurrence rates were 98.6% and 26.1%, respectively, with a median follow-up time of 29.7 (19.0, 40.3) months. During the follow-up period, 28.1% patients met the diagnostic criteria for short stature, while 54.4% fit the criteria for obesity. In addition, 94.4% of the patients were taking at least one kind of hormone substitution, and 74.7% were taking three or more. The prevalence of levothyroxine, glucocorticoid, desmopressin, and growth hormone replacement therapy was 87.3%, 77.5%, 78.9% and 31.0%, respectively. The proportion of patients treated with the substitutive combination of levothyroxine, hydrocortisone, and desmopressin was 54.9%.
CONCLUSION
This study is a large-sample systematic postoperative endocrine function evaluation of patients with childhood-onset CP. Due to the high prevalence of post-operative hypothalamic-pituitary dysfunction, patients with CP usually require long-term multiple hormone substitution therapy. Individualized management and accurate hormone replacement dosage for postoperative childhood-onset CP patients are of great importance.
Topics: Humans; Child; Craniopharyngioma; Retrospective Studies; Thyroxine; Quality of Life; Deamino Arginine Vasopressin; Neoplasm Recurrence, Local; Pituitary Neoplasms; Hypothalamic Diseases; Pituitary Diseases; Hormone Replacement Therapy; Hydrocortisone
PubMed: 38027203
DOI: 10.3389/fendo.2023.1241145 -
JPMA. the Journal of the Pakistan... Jan 2022Stereotactic radiosurgery (SRS) is a choice of treatment for pituitary adenomas (PA), particularly for residual or recurrent disease, apart from surgery. It has a... (Review)
Review
Stereotactic radiosurgery (SRS) is a choice of treatment for pituitary adenomas (PA), particularly for residual or recurrent disease, apart from surgery. It has a progression free survival and endocrine remission rate comparable to surgery, with fewer side effects, making it an ideal tool for dealing with PA. In this review, we have discussed the role of SRS for primary as well as post-operative residual/ recurrent PA, and have assessed its safety and outcomes.
Topics: Adenoma; Humans; Neoplasm Recurrence, Local; Pituitary Neoplasms; Progression-Free Survival; Radiosurgery
PubMed: 35099467
DOI: 10.47391/JPMA.22-005 -
JPMA. the Journal of the Pakistan... Nov 2022To quantify the frequency of craniopharyngiomas presenting to tertiary care neurosurgical centres, the demographics and mortality rate, and commonly presenting to...
OBJECTIVE
To quantify the frequency of craniopharyngiomas presenting to tertiary care neurosurgical centres, the demographics and mortality rate, and commonly presenting to neurosurgical practice.
METHOD
Our study was a retrospective cross-sectional analysis of patients admitted at 32 neurosurgical centres between January 1, 2019, and December 31, 2019, with brain tumour. Kruskal Wallis analysis was used to determine normality; normally distributed variables were reported as means with standard deviation, while median with interquartile range was used for non-normally distributed variables.
RESULTS
Of 2750 patients with brain tumours, 114 patients presented with craniopharyngioma. The median age at diagnosis was 18 years, with 42 (42.8%) patients below the age of 15, 40 (40.9%) patients aged 15-39, and 16 (16.3%) patients aged 40 and above. There were 70 (61.4%) males and 44 (38.6%) females in our cohort. Gross total resection was performed in 42(36.8%), 45 (39.5%) underwent subtotal resection, 9 (7.9%) underwent CSF diversion only, and 2 (1.8%) had a biopsy. Most of our patients 94(82.5%) presented to public hospitals, with 20 (17.5%) patients presenting to private hospitals (p=0.002). The overall survival at two years was 86.8% in patients with known outcomes, and only 10% of patients died within 30 days of surgery.
CONCLUSIONS
Craniopharyngiomas comprised a small portion of all brain tumours in our region. They are more common in males and in patients from the lower socioeconomic class. These patients mainly presented to public sector hospitals, and the three highest volume centres were all public sector institutions. The overall survival rate at two years in our region is lower than in other regions.
Topics: Female; Humans; Male; Brain Neoplasms; Craniopharyngioma; Cross-Sectional Studies; Pituitary Neoplasms; Retrospective Studies; Treatment Outcome
PubMed: 36591630
DOI: 10.47391/JPMA.11-S4-AKUB10 -
World Neurosurgery Sep 2018This study aimed to summarize the diagnosis, therapy, and prognosis of pituitary metastasis. (Review)
Review
OBJECTIVE
This study aimed to summarize the diagnosis, therapy, and prognosis of pituitary metastasis.
METHODS
Ten patients from the Department of Neurosurgery of the Peking Union Medical College Hospital from April 1997 to August 2014 were retrospectively analyzed.
RESULTS
The participants included 7 males (70%) and 3 females (30%), with an average age of 60.4 years. The most common initial clinical feature was visual disability (50%). The postoperative pathology reports indicated 1 case (10%) of metastatic large-cell pulmonary carcinoma, 2 cases (20%) of metastatic small cell pulmonary carcinoma, 2 cases (20%) of clear cell renal carcinoma metastasis, and 5 cases (50%) of metastasis of adenocarcinomas from different areas. All the patients underwent a thorough follow-up, and the average survival was 144 days.
CONCLUSIONS
Pituitary metastasis is a rare disease. Its diagnosis depends on the clinical manifestations and radiologic results. The primary therapeutic method is surgery and subsequent radiotherapy and chemotherapy; however, the prognosis of this disease is poor.
Topics: Adult; Aged; Female; Follow-Up Studies; Humans; Male; Middle Aged; Pituitary Neoplasms; Prognosis; Retrospective Studies
PubMed: 29883826
DOI: 10.1016/j.wneu.2018.05.205 -
Medicine Nov 2016Pituitary carcinoma (PC) is a rare type of malignant intracranial neoplasm defined as distant metastasis of pituitary adenoma (PA). Although PC incidence is low because... (Review)
Review
BACKGROUND
Pituitary carcinoma (PC) is a rare type of malignant intracranial neoplasm defined as distant metastasis of pituitary adenoma (PA). Although PC incidence is low because only 0.1% to 0.2% of PAs ultimately develop into PCs, the prognosis is poor and 66% of patients die within the first year. Existing therapeutic measures, including surgical removal, chemotherapy, and radiotherapy, have limited effectiveness. The lack of efficacy of current treatments is largely caused by the limited understanding of the molecular pathogenesis of PA and the malignant transformation to PC. Therefore, the aim of this systematic review was to summarize published research regarding gene and protein expression in PC to clarify the molecular mechanisms underlying PC genesis and development and identify new candidate diagnostic biomarkers and therapeutic targets for potential use in personalized treatment of PC.
METHODS
We followed the PRISMA guidelines to plan and conduct this systematic review. PubMed, Embase, and Web of Science databases were searched for relevant studies conducted before December 16, 2015 describing the association of PC with gene expression at the mRNA and protein levels. MeSH terms combined with free terms were used to retrieve the references.
RESULTS
In total, 207 records were obtained by primary search, and 32 were included in the systematic review. Compared with normal pituitary gland and/or PA, 30 and 18 genes were found to have higher or lower expression, respectively, in PCs using different analytical methods. Among them, we selected 9 upregulated and 7 downregulated genes for further analysis based on their identification as candidate treatment targets in other cancers, potential clinical application, or further research value.
CONCLUSION
Previous studies demonstrated that many genes promote PC malignant transformation, angiogenesis, invasion, metastasis, and recurrence. Although most of these genes and proteins have not been fully analyzed with regard to their downstream mechanisms or potential diagnostic and therapeutic application, they have the potential to become candidate PC biomarkers and/or molecular targets for guiding personalized treatment. Modern advanced technologies should be utilized in future research to identify more candidate genes for PC pathogenesis, as precisely targeted gene therapies against PC are urgently required.
Topics: Biomarkers, Tumor; Carcinoma; Gene Expression; Humans; Pituitary Neoplasms; Precision Medicine
PubMed: 27893664
DOI: 10.1097/MD.0000000000005268 -
Hormone Research in Paediatrics 2014Pituitary adenomas, although rare in the paediatric age range and mostly benign, represent very challenging disorders for diagnosis and management. The recent... (Review)
Review
Pituitary adenomas, although rare in the paediatric age range and mostly benign, represent very challenging disorders for diagnosis and management. The recent identification of genetic alterations in young individuals with pituitary adenomas has broadened the scope of molecular investigations and contributed to the understanding of mechanisms of tumorigenesis. Recent identification of causative mutations of genes such as GNAS, PRKAR1A, MEN1 and AIP has introduced the concept of molecular screening of young apparently healthy family members. Population-based studies have reported a significantly higher number of affected subjects and genetic variations than expected. Radiological techniques have advanced, yet many microadenomas remain undetectable on scanning. However, experience with transsphenoidal and endoscopic pituitary surgery has led to higher rates of cure. Prolactinomas, corticotroph and somatotroph adenomas remain the most prevalent, with each diagnosis presenting its own challenges. As paediatric pituitary adenomas occur very infrequently within the paediatric age range, paediatric endocrine units cannot provide expert management in isolation. Consequently, close co-operation with adult endocrinology colleagues with experience of pituitary disease is strongly recommended.
Topics: Adolescent; Child; Child, Preschool; Endoscopy; Female; Humans; Infant; Male; Mutation; Neoplasm Proteins; Pituitary Neoplasms; Prevalence
PubMed: 24525527
DOI: 10.1159/000357673 -
The Journal of Clinical Endocrinology... Mar 2021Aggressive pituitary tumors (APTs) are characterized by unusually rapid growth and lack of response to standard treatment. About 1% to 2% develop metastases being...
CONTEXT
Aggressive pituitary tumors (APTs) are characterized by unusually rapid growth and lack of response to standard treatment. About 1% to 2% develop metastases being classified as pituitary carcinomas (PCs). For unknown reasons, the corticotroph tumors are overrepresented among APTs and PCs. Mutations in the alpha thalassemia/mental retardation syndrome X-linked (ATRX) gene, regulating chromatin remodeling and telomere maintenance, have been implicated in the development of several cancer types, including neuroendocrine tumors.
OBJECTIVE
To study ATRX protein expression and mutational status of the ATRX gene in APTs and PCs.
DESIGN
We investigated ATRX protein expression by using immunohistochemistry in 30 APTs and 18 PCs, mostly of Pit-1 and T-Pit cell lineage. In tumors lacking ATRX immunolabeling, mutational status of the ATRX gene was explored.
RESULTS
Nine of the 48 tumors (19%) demonstrated lack of ATRX immunolabelling with a higher proportion in patients with PCs (5/18; 28%) than in those with APTs (4/30;13%). Lack of ATRX was most common in the corticotroph tumors, 7/22 (32%), versus tumors of the Pit-1 lineage, 2/24 (8%). Loss-of-function ATRX mutations were found in all 9 ATRX immunonegative cases: nonsense mutations (n = 4), frameshift deletions (n = 4), and large deletions affecting 22-28 of the 36 exons (n = 3). More than 1 ATRX gene defect was identified in 2 PCs.
CONCLUSION
ATRX mutations occur in a subset of APTs and are more common in corticotroph tumors. The findings provide a rationale for performing ATRX immunohistochemistry to identify patients at risk of developing aggressive and potentially metastatic pituitary tumors.
Topics: ACTH-Secreting Pituitary Adenoma; Adenoma; Adolescent; Adult; Aged; Carcinoma; Cohort Studies; Corticotrophs; Europe; Female; Gene Frequency; Genetic Predisposition to Disease; Humans; Male; Middle Aged; Mutation; Neoplasm Invasiveness; Pituitary Neoplasms; X-linked Nuclear Protein; Young Adult
PubMed: 33106857
DOI: 10.1210/clinem/dgaa749