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The Journal of Clinical Endocrinology... Aug 2023Prolactinomas are the most common pituitary tumor histotype, with microprolactinomas being prevalent in women and macroprolactinomas in men. Hyperprolactinemia is among... (Review)
Review
Prolactinomas are the most common pituitary tumor histotype, with microprolactinomas being prevalent in women and macroprolactinomas in men. Hyperprolactinemia is among the most common causes of hypogonadotropic hypogonadism in both sexes, prompting medical advice for hypogonadism (infertility, oligo-amenorrhea, impotence, osteoporosis/osteopenia) in both sexes, and for signs and symptoms of mass effects (hypopituitarism, visual loss, optic chiasm compression, cranial nerve deficits, headaches) predominantly in men. Diagnostic workup involves a single prolactin measurement and pituitary imaging, but some laboratory artifacts (ie, the "hook effect" and macroprolactin) can complicate or delay the diagnosis. The treatment of choice for prolactinomas is represented by dopamine agonists, mainly cabergoline, which are able to induce disease control, restore fertility in both sexes, and definitively cure one-third of patients, thus permitting treatment discontinuation. Pregnancy and menopause may promote spontaneous prolactin decline and anticipate cabergoline discontinuation in women. Surgery and/or radiotherapy are indicated in case of resistance to cabergoline not overcome by the increase in drug dose up to the maximally tolerated or the patient's personal choice of surgery. The evidence of resistance to cabergoline in invasive and proliferative tumors may indicate biological aggressiveness, thus requiring alternative therapeutic approaches mainly based on temozolomide use as monotherapy or combined with radiotherapy. In uncontrolled patients, new medical approaches (alternative hormonal treatments, cytotoxic drugs, peptide receptor radionuclide therapy, mTOR/Akt inhibitors, tyrosine kinase inhibitors, or immunotherapy) may be offered but the experience collected to date is still very scant. This article reviews different facets of prolactinomas and discusses approaches to the condition in more common clinical situations.
Topics: Male; Pregnancy; Humans; Female; Prolactinoma; Cabergoline; Prolactin; Ergolines; Pituitary Neoplasms; Dopamine Agonists; Hypogonadism
PubMed: 36974474
DOI: 10.1210/clinem/dgad174 -
Neuroendocrinology 2020Craniopharyngioma (CP) is a rare embryonic malformation of the sellar/parasellar region with a low histological grade. Clinical manifestations are related to... (Review)
Review
Craniopharyngioma (CP) is a rare embryonic malformation of the sellar/parasellar region with a low histological grade. Clinical manifestations are related to hypothalamic/pituitary deficiencies, visual impairment, and increased intracranial pressure. Recent insight into the molecular pathogenesis of CP opens new perspectives on targeted therapy in papillary CP harboring BRAF-V600E mutations. Further research to elucidate pathogenic mechanisms and hopefully prevent hypothalamic involvement of CP is warranted. If the tumor is favorably localized, the therapy of choice is complete resection, with care taken to preserve the optical and hypothalamic functions. In patients with unfavorable tumor localization (i.e., hypothalamic involvement), the recommended therapy is a limited hypothalamus-sparing surgical strategy followed by local irradiation. Surgical treatment strategies should be based on a multidisciplinary approach involving experienced teams. Centralizing the treatment of CP in experienced "centers of excellence" and multicenter-based networks for reference assessments should be considered to assure a high standard of treatment quality. CP recurrence and progression are frequent. Irradiation has proven effective in reducing recurrences and progression. Proton beam therapy, available in a wider range in the near future, will help to avoid radio-oncological side effects. Anatomical involvement and/or surgical lesions of posterior hypothalamic areas can result in serious sequelae that compromise quality of life (QoL), such as hypothalamic obesity and psychopathological symptoms. Novel insights into neuropsychological sequelae after CP occurrence should be the basis for the development of therapeutic neuropsychological interventions. CP should be managed as a frequently chronic disease, providing ongoing care of pediatric and adult patients' clinical and QoL consequences by experienced multidisciplinary teams.
Topics: Craniopharyngioma; Humans; Pituitary Neoplasms
PubMed: 31678973
DOI: 10.1159/000504512 -
Frontiers in Bioscience (Landmark... Dec 2022Craniopharyngiomas (CP) are rare noncancerous brain tumors located in the skull base. To date, CP remain challenging-to-resect tumors, owing to their difficult location... (Review)
Review
Craniopharyngiomas (CP) are rare noncancerous brain tumors located in the skull base. To date, CP remain challenging-to-resect tumors, owing to their difficult location and invasive potential, with profound adverse effects for the patient if left to grow. Indeed, gross total resection may also be accompanied by unwelcome sequalae, underscoring the need for continued investigation. In the present work, we provide a scoping review of current CP management, with emphasis on our knowledge of their genesis, available treatment options, post-intervention clinical outcomes. Leading theories of CP development are (1) the embryonic theory, explaining the development of adamantinomatous CP from epithelial remnants of Rathke's pouch and (2) the metaplastic theory, which describes papillary CP development as a result of adenohypophyseal cell metaplasia. Treatment may include surgery, intracystic therapy, or irradiation depending on tumor size, history and location. However, whether a single ideal approach and timing for CP intervention exists remains debated. We appraise and critique these areas with priority for emerging basic results and innovation.
Topics: Humans; Craniopharyngioma; Pituitary Neoplasms
PubMed: 36624954
DOI: 10.31083/j.fbl2712328 -
Endocrine Practice : Official Journal... Jan 2023Pituitary Incidentalomas (PI) are pituitary lesions serendipitously identified on imaging. PIs have become common in clinical practice because of increased use of... (Review)
Review
Pituitary Incidentalomas (PI) are pituitary lesions serendipitously identified on imaging. PIs have become common in clinical practice because of increased use of imaging and radiologic advances. The most frequently incidentally detected lesions in adults are pituitary adenomas, followed by cystic lesions, and rarely other types of tumors and infiltrative and inflammatory disorders. Biochemical screening for hyperprolactinemia and acromegaly is needed in all patients with PI, whereas testing for hyposecretion is recommended for lesions larger than 6.0 mm. Most PIs are small nonfunctioning adenomas or cysts, which can be conservatively managed. For larger lesions, a multidisciplinary approach including endocrinology, neurosurgery, and neuro-ophthalmology is required. For incidentally detected lactotroph, somatotroph, and corticotroph adenomas, disease-specific management guidelines apply. Prospective studies are needed to enhance our understanding of the long-term course and response to treatment.
Topics: Adult; Humans; Pituitary Neoplasms; Adenoma; Pituitary Gland; ACTH-Secreting Pituitary Adenoma; Acromegaly
PubMed: 36270609
DOI: 10.1016/j.eprac.2022.10.004 -
Neurology India 2020Pituitary apoplexy (PA) is a rare, usually vision-threatening and occasionally life-threatening entity. The exact incidence of PA in large series of pituitary adenomas... (Review)
Review
Pituitary apoplexy (PA) is a rare, usually vision-threatening and occasionally life-threatening entity. The exact incidence of PA in large series of pituitary adenomas is variable; however, it is more common in macroadenomas and nonfunctioning adenomas though it has been reported rarely in microadenomas. There are several well-known precipitating factors for PA including the use of anticoagulants, surgery, head trauma, pregnancy, etc. The typical clinical presentation is characterized by the near universal presence of headache with or without the following: visual disturbances, extraocular palsies, altered sensorium. MRI is the imaging modality of choice. Most patients have hormonal and/or electrolyte disturbances at the time of presentation which needs to be quickly corrected. Both conservative and surgical treatment modalities have been advised for the management of this condition. However, on the basis of the evidence available in the literature, the treatment should be individualized for each patient with PA. If conservative management is chosen, close clinical monitoring is necessary for early identification of deterioration. Surgery generally is through the trans-sphenoidal route. Most patients have a good recovery in visual function and extraocular palsy. There is some evidence in the literature that surgical intervention, when necessary, should be undertaken early as it is associated with better visual outcome. The majority of the patients will have residual hormonal deficits which will require prolonged hormone replacement therapy. There is a small but significant risk of recurrent PA in patients with residual tumors, especially, in those with large tumor residues. There is also a small risk of tumor recurrence following PA and hence all patients should undergo surveillance imaging periodically to detect the possible recurrence of tumor. In recent years, the mortality from PA has decreased significantly. A high index of suspicion and prompt multidisciplinary management will often lead to an overall good outcome.
Topics: Adenoma; Humans; Magnetic Resonance Imaging; Neurosurgical Procedures; Pituitary Apoplexy; Pituitary Neoplasms
PubMed: 32611895
DOI: 10.4103/0028-3886.287669 -
Frontiers in Endocrinology 2022The hypothalamus is the centre of neuroendocrine regulation of energy homeostasis and appetite. Maldevelopment of, or damage to, the key hypothalamic nuclei disrupts the... (Review)
Review
The hypothalamus is the centre of neuroendocrine regulation of energy homeostasis and appetite. Maldevelopment of, or damage to, the key hypothalamic nuclei disrupts the coordinated balance between energy intake and expenditure leading, to rapid and excessive weight gain. Hypothalamic obesity is compounded by a disruption of the hypothalamic-pituitary axis, sleep disruption, visual compromise, and neurological and vascular sequalae. Amongst suprasellar tumors, craniopharyngioma is the most common cause of acquired hypothalamic obesity, either directly or following surgical or radiotherapeutic intervention. At present, therapy is limited to strategies to manage obesity but with a modest and variable impact. Current approaches include optimizing pituitary hormone replacement, calorie restriction, increased energy expenditure through physical activity, behavioral interventions, pharmacotherapy and bariatric surgery. Current pharmacotherapeutic approaches include stimulants that increase energy consumption, anti-diabetic agents, hypothalamic-pituitary substitution therapy, octreotide, and methionine aminopeptidase 2 (MetAP2) inhibitors. Some pharmacological studies of hypothalamic obesity report weight loss or stabilization but reported intervention periods are short, and others report no effect. The impact of bariatric surgery on weight loss in hypothalamic obesity again is variable. Novel or combined approaches to manage hypothalamic obesity are thus required to achieve credible and sustained weight loss. Identifying etiological factors contributing hypothalamic obesity may lead to multi-faceted interventions targeting hyperphagia, insulin resistance, decreased energy expenditure, sleep disturbance, hypopituitarism and psychosocial morbidity. Placebo-controlled trials using current single, or combination therapies are required to determine the impact of therapeutic agents. A well-defined approach to defining the location of hypothalamic damage may support the use of future targeted therapies. Intranasal oxytocin is currently being investigated as an anorexogenic agent. Novel agents including those targeting pro-opimelanocortin-C and AgRP/NPY expressing neurons and the MC4 receptor may result in better outcomes. This article discusses the current challenges in the management of hypothalamic obesity in children and young people and future therapeutic approaches to increasing weight loss and quality of life in these patients.
Topics: Adolescent; Child; Craniopharyngioma; Humans; Pediatric Obesity; Pituitary Neoplasms; Quality of Life; Weight Loss
PubMed: 35464063
DOI: 10.3389/fendo.2022.846880 -
Brain Pathology (Zurich, Switzerland) Jul 2022Ependymal neoplasms occur at all ages and encompass multiple tumor types and subtypes that develop in the supratentorial compartment, the posterior fossa, or the spinal... (Review)
Review
Ependymal neoplasms occur at all ages and encompass multiple tumor types and subtypes that develop in the supratentorial compartment, the posterior fossa, or the spinal cord. Clinically, ependymomas represent a very heterogeneous group of tumors from rather benign subependymomas to very aggressive and often deadly childhood ependymomas of the posterior fossa. Newly identified biological markers and classification schemes, e. g. based on global DNA methylation profiling, have led to the definition of 10 types of ependymal tumors and an improved prediction of patients' outcome by applying the new classification system. While the exact genetic basis for several ependymoma types still remains unclear, the knowledge about ependymoma driving events has significantly increased within the last decade and contributed to a classification based on molecular characteristics and localization rather than histological features alone. Convincing evidence is now pointing towards gene fusions involving ZFTA or YAP1 causing the development of supratentorial ependymomas. Also, H3, EZHIP, or TERT mutations have been detected in a fraction of infratentorial ependymal tumors. Finally, MYCN amplifications have recently been identified in spinal ependymomas, in addition to the previously known mutations in NF2. This review summarizes how recent findings regarding biology, molecular tumor typing, and clinical outcome have impacted the classification of ependymomas as suggested by the updated 2021 WHO CNS tumor classification system. We focus on changes compared to the previous classification of 2016 and discuss how a formal grading could evolve in the future and guide clinicians to treat ependymoma patients.
Topics: Brain Neoplasms; Child; Ependymoma; Humans; Infratentorial Neoplasms; Supratentorial Neoplasms; World Health Organization
PubMed: 35307892
DOI: 10.1111/bpa.13068 -
Journal of Clinical Oncology : Official... Mar 2023Clinical outcomes of patients with CNS lymphomas (CNSLs) are remarkably heterogeneous, yet identification of patients at high risk for treatment failure is challenging....
PURPOSE
Clinical outcomes of patients with CNS lymphomas (CNSLs) are remarkably heterogeneous, yet identification of patients at high risk for treatment failure is challenging. Furthermore, CNSL diagnosis often remains unconfirmed because of contraindications for invasive stereotactic biopsies. Therefore, improved biomarkers are needed to better stratify patients into risk groups, predict treatment response, and noninvasively identify CNSL.
PATIENTS AND METHODS
We explored the value of circulating tumor DNA (ctDNA) for early outcome prediction, measurable residual disease monitoring, and surgery-free CNSL identification by applying ultrasensitive targeted next-generation sequencing to a total of 306 tumor, plasma, and CSF specimens from 136 patients with brain cancers, including 92 patients with CNSL.
RESULTS
Before therapy, ctDNA was detectable in 78% of plasma and 100% of CSF samples. Patients with positive ctDNA in pretreatment plasma had significantly shorter progression-free survival (PFS, < .0001, log-rank test) and overall survival (OS, = .0001, log-rank test). In multivariate analyses including established clinical and radiographic risk factors, pretreatment plasma ctDNA concentrations were independently prognostic of clinical outcomes (PFS HR, 1.4; 95% CI, 1.0 to 1.9; = .03; OS HR, 1.6; 95% CI, 1.1 to 2.2; = .006). Moreover, measurable residual disease detection by plasma ctDNA monitoring during treatment identified patients with particularly poor prognosis following curative-intent immunochemotherapy (PFS, = .0002; OS, = .004, log-rank test). Finally, we developed a proof-of-principle machine learning approach for biopsy-free CNSL identification from ctDNA, showing sensitivities of 59% (CSF) and 25% (plasma) with high positive predictive value.
CONCLUSION
We demonstrate robust and ultrasensitive detection of ctDNA at various disease milestones in CNSL. Our findings highlight the role of ctDNA as a noninvasive biomarker and its potential value for personalized risk stratification and treatment guidance in patients with CNSL.
UNLABELLED
[Media: see text].
Topics: Humans; Circulating Tumor DNA; Prognosis; Lymphoma, Non-Hodgkin; Supratentorial Neoplasms; Risk Assessment; Brain; Biomarkers, Tumor; Mutation
PubMed: 36542815
DOI: 10.1200/JCO.22.00826 -
Cell Reports. Medicine Feb 2023Pituitary neuroendocrine tumor (PitNET) is one of the most common intracranial tumors with variable recurrence rate. Currently, the recurrence prediction is unsatisfying...
Pituitary neuroendocrine tumor (PitNET) is one of the most common intracranial tumors with variable recurrence rate. Currently, the recurrence prediction is unsatisfying and can be improved by understanding the cellular origins and differentiation status. Here, to comprehensively reveal the origin of PitNET, we perform comparative analysis of single-cell RNA sequencing data from 3 anterior pituitary glands and 21 PitNETs. We identify distinct genes representing major subtypes of well and poorly differentiated PitNETs in each lineage. To further verify the predictive value of differentiation biomarkers, we include an independent cohort of 800 patients with an average follow-up of 7.2 years. In both PIT1 and TPIT lineages, poorly differentiated groups show significantly higher recurrence rates while well-differentiated groups show higher recurrence rates in SF1 lineage. Our findings reveal the possible origin and differentiation status of PitNET based on which new differentiation classification is proposed and verified to predict tumor recurrence.
Topics: Humans; Neoplasm Recurrence, Local; Pituitary Neoplasms; Pituitary Gland; Cell Differentiation; Neuroendocrine Tumors
PubMed: 36754052
DOI: 10.1016/j.xcrm.2023.100934 -
Science Advances Apr 2023Despite improvements in microscopically neurosurgical techniques made in recent years, the prognosis of adamantinomatous craniopharyngioma (ACP) is still unsatisfactory....
Despite improvements in microscopically neurosurgical techniques made in recent years, the prognosis of adamantinomatous craniopharyngioma (ACP) is still unsatisfactory. Little is known about cellular atlas and biological features of ACP. Here, we carried out integrative analysis of 44,038 single-cell transcriptome profiles to characterize the landscape of intratumoral heterogeneity and tumor microenvironment (TME) in ACP. Four major neoplastic cell states with distinctive expression signatures were defined, which further revealed the histopathological features and elucidated unknown cellular atlas of ACP. Pseudotime analyses suggested potential evolutionary trajectories between specific neoplastic cell states. Notably, a distinct oligodendrocyte lineage was identified in ACP, which was associated with immunological infiltration and neural damage. In addition, we described a tumor-centric regulatory network based on intercellular communication in TME. Together, our findings represent a unique resource for deciphering tumor heterogeneity of ACP, which will improve clinical diagnosis and treatment strategies.
Topics: Humans; Craniopharyngioma; Pituitary Neoplasms; Transcriptome; Cell Communication; Sequence Analysis, RNA; Tumor Microenvironment
PubMed: 37043580
DOI: 10.1126/sciadv.adc8933