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Demographic and socioeconomic disparities of pituitary adenomas and carcinomas in the United States.Journal of Clinical Neuroscience :... Apr 2022Growth of some pituitary tumors is driven by hormones which vary in concentration along the lines of patient socioeconomic status. Thus, pituitary tumors may exhibit...
INTRODUCTION
Growth of some pituitary tumors is driven by hormones which vary in concentration along the lines of patient socioeconomic status. Thus, pituitary tumors may exhibit disparities in incidence upon stratification by socioeconomic variables. Exploring for these disparities could provide direction in tumor etiology elucidation and identification of healthcare inequalities.
METHODS
To investigate pituitary adenoma and carcinoma incidence (per 100,000) with respect to sex, age, income, residence, and race/ethnicity, we searched the largest American administrative dataset (1997-2016), the National (Nationwide) Inpatient Sample (NIS), which surveys 20% of United States (US) discharges.
RESULTS
Annual national incidence was 2.80 for adenomas and 0.046 for carcinomas. For adenomas, males had an incidence of 2.63, similar (p = 0.17) to females at 2.78; likewise, for carcinomas, males had a statistically equivalent (p = 0.24) incidence at 0.051 to females at 0.041. Amongst age groups, for adenomas incidence progressively rose, peaking 65-84 years old (6.12), before declining. For adenomas and carcinomas respectively, patients with low income had an incidence of 2.66 and 0.044, similar (p = 0.11; p = 0.72) to the 3.01 and 0.041 of middle/high income patients. Incidence was greatest for adenomas amongst urban centers (3.47), followed by rural (3.16) and suburban (3.01) communities. Examining race/ethnicity (p = 0.0000016), for adenomas, incidences amongst Blacks, Asian/Pacific Islanders, Hispanics, and Whites were as follows, respectively: 3.64, 2.57, 2.54, 2.44. Annually, incidence for adenomas was increasing (τ = 0.63, p = 0.00021), but decreasing (τ = -0.60, p = 0.00085) for carcinomas. Specifically, for carcinomas incidence was only decreasing for females and the middle/high income.
CONCLUSION
In the US, time-enduring healthcare disparities were identified for pituitary adenomas and carcinomas, against the background of sociodemographic strata. For carcinomas, annual incidence was declining only for middle/high income patients and females, which supporting prior investigations that low income patients and males are experiencing barriers to definitive treatment for pituitary adenomas. Incidence was also found to be greatest Blacks and urban residents.
Topics: Adenoma; Aged; Aged, 80 and over; Carcinoma; Ethnicity; Female; Humans; Male; Pituitary Neoplasms; Social Class; United States
PubMed: 35151063
DOI: 10.1016/j.jocn.2022.01.032 -
Neuroendocrinology 2019Dopamine agonists are usually very effective in the treatment of prolactinomas. Nonetheless, a subset of individuals does not respond satisfactorily to these agents, and... (Review)
Review
Dopamine agonists are usually very effective in the treatment of prolactinomas. Nonetheless, a subset of individuals does not respond satisfactorily to these agents, and this resistance is characterized by failure to achieve normoprolactinemia and a 30% or more reduction in maximal tumor diameter (in the case of macroprolactinoma) under maximally tolerated doses. The overall prevalence of dopamine agonist resistance is 20-30% for bromocriptine (BRC) and around 10% for cabergoline (CAB). The 2 main predictive factors are male gender and tumor invasiveness. The management of drug-resistant prolactinomas includes several options. Any BRC-resistant patient should be switched to CAB which will normalize prolactin in 80% of patients. As long as adverse effects do not develop, dose escalation of CAB is reasonable, with the expectation that subsequent dose reduction will be possible. Echocardiographic monitoring is advised in such patients because of the potential association with cardiac valvular fibrosis. Also, maintaining maximal CAB doses at 3.5 mg/week may lead to progressive hormonal control in a significant proportion of patients. Complete resistance to CAB is infrequent. In a study of 122 patients with a macroprolactinoma, only 7 (6%) could not achieve control despite maximal CAB doses for > 12 months. A large resistant prolactinoma is also an indication for transsphenoidal neurosurgery, aiming at a debulking which may improve postoperative medical control. For patients who harbor aggressive prolactinomas, radiotherapy may be considered. However, normal prolactinemia will eventually occur in only one-third of patients after many years. Finally, temozolomide may be a therapeutic option in malignant/aggressive prolactinomas.
Topics: Bromocriptine; Cabergoline; Dopamine Agonists; Drug Resistance; Humans; Pituitary Neoplasms; Prolactinoma
PubMed: 30481756
DOI: 10.1159/000495775 -
Clinical Endocrinology Dec 2022To profile clinically non-aggressive and aggressive pituitary adenomas (PAs)/pituitary neuroendocrine tumours (PitNETs) and pituitary carcinomas for somatic mutations... (Observational Study)
Observational Study
OBJECTIVE
To profile clinically non-aggressive and aggressive pituitary adenomas (PAs)/pituitary neuroendocrine tumours (PitNETs) and pituitary carcinomas for somatic mutations and epigenetic alterations of genes involved in cell proliferation/differentiation, microRNAs (miRNA)/long noncoding RNA (LncRNA)-post-transcriptional regulators and therapy targets.
DESIGN
Retrospective observational study.
PATIENTS AND MEASUREMENTS
A total of 64 non-aggressive and 41 aggressive PAs/PitNETs and 6 pituitary carcinomas treated by endoscopic surgery with ≥1-year follow-up were included. Somatic mutations of 17 genes and DNA methylation of 22 genes were assessed. Ten normal pituitaries were used as control.
RESULTS
We found at least one mutation in 17 tumours, including 6/64 non-aggressive, 10/41 aggressive PAs/PitNETs, and 1/6 pituitary carcinoma. AIP (N = 6) was the most frequently mutated gene, followed by NOTCH (4), and TP53 (3). Hypermethylation of PARP15, LINC00599, ZAP70 was more common in aggressive than non-aggressive PAs/PITNETs (p < .05). Lower levels of methylation of AIP, GNAS and PDCD1 were detected in aggressive PAs/PITNETs than non-aggressive ones (p < .05). For X-linked genes, males presented higher level of methylation of FLNA, UXT and MAGE family (MAGEA11, MAGEA1, MAGEC2) genes in aggressive vs. non-aggressive PAs/PITNETs (p < .05). In pituitary carcinomas, methylation of autosomal genes PARP15, LINC00599, MIR193 and ZAP70 was higher than in PAs/PITNETs, while X-linked genes methylation level was lower.
CONCLUSIONS
Somatic mutations and methylation levels of genes involved in cell proliferation/differentiation, miRNA/LncRNA-post-transcriptional regulators and targets of antineoplastic therapies are different in non-aggressive and in aggressive PAs/PitNETs. Methylation profile also varies according to gender. Combined genetic-epigenetic analysis, in association with clinico-radiological-pathological data, may be of help in predicting PA/PitNET behaviour.
Topics: Male; Humans; Pituitary Neoplasms; Epigenomics; RNA, Long Noncoding; Adenoma; Neuroendocrine Tumors; Transcription Factors; Mutation; MicroRNAs; Cell Cycle Proteins; Molecular Chaperones
PubMed: 36161330
DOI: 10.1111/cen.14827 -
BMJ Case Reports Aug 2021Pituitary apoplexy is caused by haemorrhage or infarction of the pituitary gland. Presenting signs and symptoms often include severe headache, visual disturbance,...
Pituitary apoplexy is caused by haemorrhage or infarction of the pituitary gland. Presenting signs and symptoms often include severe headache, visual disturbance, ophthalmoplegia, altered consciousness and impaired pituitary function. The management of pituitary apoplexy has very rarely been described during pregnancy and there is no existing data for further pregnancies of affected women. We present a case of a woman with a recurrent pituitary apoplexy due to haemorrhages in a pituitary adenoma in her third and fourth pregnancies. In both pregnancies, the pituitary apoplexy was managed conservatively, but due to therapy-resistant headaches, a preterm delivery was implemented.
Topics: Adenoma; Female; Headache; Humans; Magnetic Resonance Imaging; Pituitary Apoplexy; Pituitary Gland; Pituitary Neoplasms; Pregnancy
PubMed: 34380676
DOI: 10.1136/bcr-2021-242353 -
Annales D'endocrinologie Jul 2015Prevalence of pituitary incidentaloma is variable: between 1.4% and 27% at autopsy, and between 3.7% and 37% on imaging. Pituitary microincidentalomas (serendipitously... (Review)
Review
Prevalence of pituitary incidentaloma is variable: between 1.4% and 27% at autopsy, and between 3.7% and 37% on imaging. Pituitary microincidentalomas (serendipitously discovered adenoma <1cm in diameter) may increase in size, but only 5% exceed 10mm. Pituitary macroincidentalomas (serendipitously discovered adenoma>1cm in diameter) show increased size in 20-24% and 34-40% of cases at respectively 4 and 8years' follow-up. Radiologic differential diagnosis requires MRI centered on the pituitary gland. Initial assessment of nonfunctioning (NF) microincidentaloma is firstly clinical, the endocrinologist looking for signs of hypersecretion (signs of hyperprolactinemia, acromegaly or Cushing's syndrome), followed up by systematic prolactin and IGF-1 assay. Initial assessment of NF macroincidentaloma is clinical, the endocrinologist looking for signs of hormonal hypersecretion or hypopituitarism, followed up by hormonal assay to screen for hypersecretion or hormonal deficiency and by ophthalmologic assessment (visual acuity and visual field) if and only if the lesion is near the optic chiasm (OC). NF microincidentaloma of less than 5mm requires no surveillance; those of≥5mm are not operated on but rather monitored on MRI at 6months and then 2years. Macroincidentaloma remote from the OC is monitored on MRI at 1year, with hormonal exploration (for anterior pituitary deficiency), then every 2years. When macroincidentaloma located near the OC is managed by surveillance rather than surgery, MRI is recommended at 6months, with hormonal and visual exploration, then annual MRI and hormonal and visual assessment every 6months. Surgery is indicated in the following cases: evolutive NF microincidentaloma, NF macroincidentaloma associated with hypopituitarism or showing progression, incidentaloma compressing the OC, possible malignancy, non-compliant patient, pregnancy desired in the short-term, or context at risk of apoplexy.
Topics: Consensus; Humans; Pituitary Neoplasms; Prevalence
PubMed: 26054868
DOI: 10.1016/j.ando.2015.04.004 -
European Neurology 2022Pituitary adenomas (PAs) account for the top three primary intracranial tumors in terms of total incidence rate. PAs can cause severe endocrine disorders and even... (Review)
Review
Pituitary adenomas (PAs) account for the top three primary intracranial tumors in terms of total incidence rate. PAs can cause severe endocrine disorders and even malignant features, such as invasion, metastasis, and recurrence. Therefore, the early diagnosis and accurate prognosis would be greatly beneficial for clinical treatment of PAs. MicroRNAs (miRNAs) are small, protein-noncoding RNAs that regulate gene expression posttranscriptionally. They regulate essential physiological processes, including proliferation, growth, and apoptosis, and also they involve in the invasion and metastasis of malignant tumors. At the tissue level, differential miRNA expression in endocrine malignancies including PAs has been reported. When miRNAs have been successfully detected in various biofluids and cell-free environments, their important roles as potential screening or prognostic biomarkers have been extensively investigated. The current work reviews recent studies on the emerging roles of miRNAs in PAs and the clinical significance.
Topics: Adenoma; Humans; MicroRNAs; Pituitary Neoplasms; Prognosis
PubMed: 35034033
DOI: 10.1159/000521388 -
Frontiers in Endocrinology 2020Most pituitary adenomas (PAs) are considered benign tumors, but approximately 0.2% can present metastasis and are classified as pituitary carcinomas (PCs). Refractory... (Review)
Review
Most pituitary adenomas (PAs) are considered benign tumors, but approximately 0.2% can present metastasis and are classified as pituitary carcinomas (PCs). Refractory PAs lie between benign adenomas and true malignant PC and are defined as aggressive-invasive PAs characterized by a high Ki-67 index, rapid growth, frequent recurrence, and resistance to conventional treatments, including temozolomide. It is notoriously difficult to manage refractory PAs and PC because of the limited therapeutic options. As a promising therapeutic approach, cancer immunotherapy has been experimentally used for the treatment of many tumors, including pituitary tumors. The purpose of this review is to report the progress of immunotherapy in pituitary tumors, including refractory PAs and PCs. The tumor immune microenvironment has been recognized as a key contributor to tumorigenesis, progression, and prognosis. One study indicated that the number of CD68+ macrophages was positively correlated with tumor size and Knosp classification grade for tumor invasiveness. The infiltration of CD4+ and CD8+ T cells was relatively scant in these adenomas, but pituitary growth hormone (GH) adenomas exhibited significantly more CD4+ and CD8+ T cells than non-GH adenomas. These results suggest an association of CD68+ macrophage infiltration with an increase in pituitary tumor size and invasiveness. Another study suggested that a lower number of CD8+ lymphocytes is associated with cavernous sinus invasion and resistance to treatment with first-generation somatostatin analogs in acromegaly patients, highlighting a potential role of the tumor immune microenvironment in determining the prognosis of somatotroph pituitary tumors. Preclinical studies have indicated that widely varying degrees of programmed death-ligand 1 (PD-L1) expression and tumor-infiltrating lymphocytes (TILs) are found among different subtypes. Functional PAs and aggressive PAs express significantly higher levels of PD-L1 and TILs than other subtypes, indicating that PD-1 blockade might be a promising alternative therapy for patients with aggressive PAs. PD-L1 transcript and protein levels were found to be significantly increased in functioning (GH and prolactin-expressing) pituitary tumors compared to nonfunctioning (null cell and silent gonadotroph) adenomas. Moreover, primary pituitary tumors harbored higher levels of PD-L1 mRNA than recurrent tumors. These findings suggest the possibility of considering checkpoint blockade immunotherapy for functioning pituitary tumors refractory to conventional management. Animal models of Cushing's disease also demonstrated PD-L1 and TIL expression in cultured tumors and murine models, as well as the effectiveness of checkpoint blockade therapy in reducing the tumor mass, decreasing hormone secretion, and increasing the survival rate. Clinical studies show that immunotherapy may be an effective treatment in patients with pituitary tumors. One corticotroph carcinoma patient showed a significant reduction in hormone levels and shrinkage of the tumor size of primary and metastatic lesions immediately after investigational treatment with ipilimumab and nivolumab. However, another patient with corticotroph adenoma progressed rapidly after four cycles of anti-PD-1 (pembrolizumab) treatment. To date, there are two registered clinical trials of immunotherapy for pituitary tumors. One of them is the phase II clinical trial of nivolumab combined with ipilimumab for patients with aggressive pituitary tumors (NCT04042753). The other one is also a phase II clinical trial of the combination of nivolumab and ipilimumab for rare tumors, including pituitary tumors (NCT02834013). Both clinical trials are in the stage of recruiting patients and have not been completed. In summary, the results from preclinical research and clinical studies indicated that immunotherapy might be a promising alternative therapy for PCs and refractory PAs resistant to conventional treatments. The combination of immunotherapy and radiotherapy or temozolomide may have synergistic effects compared to a single treatment. More preclinical and clinical studies are needed to further indicate the exact efficacy of immunotherapy in pituitary tumors.
Topics: Adenoma; Animals; Carcinoma; Humans; Immunotherapy; Pituitary Neoplasms
PubMed: 33362722
DOI: 10.3389/fendo.2020.608422 -
Annales D'endocrinologie Jul 2015Non-functioning pituitary adenoma may lead to blindness and causes visual impairment in 58% of cases and, more rarely, ocular motor disorder. Patients are slow to become... (Review)
Review
Non-functioning pituitary adenoma may lead to blindness and causes visual impairment in 58% of cases and, more rarely, ocular motor disorder. Patients are slow to become aware of their visual dysfunction, vision in one eye compensating the deficit in the other. Assessment of visual function, comprising visual acuity and visual field evaluation and fundus examination, should be performed regularly according to the severity of impairment. Optic nerve optical coherence tomography (OCT) can quantify optic atrophy reproducibly, and is of prognostic value for postoperative visual recovery. Diplopia most often involves decompensation of heterophoria, visual field fusion being hampered by the visual field defect; such diplopia without ocular motor deficit is known as "hemifield slide". Diplopia associated with ocular motor palsy is caused by tumoral invasion of the cavernous sinus (IIIrd, IVth or VIth nerve palsy); in large impairment, restricted eye movement is easily observed; milder palsies require neuro-ophthalmologic assessment and/or Lancaster test. Pituitary apoplexy induces ocular motor impairment in 70% of cases, strongly guiding diagnosis. Visual impairment is associated in 75% of cases. The degree of neuro-ophthalmologic (visual and ocular motor) impairment is one of the main criteria guiding treatment of pituitary apoplexy (conservative medical and/or surgical treatment) and follow-up.
Topics: Adenoma; Humans; Neurologic Examination; Oculomotor Nerve Diseases; Pituitary Apoplexy; Pituitary Neoplasms; Vision Tests; Visual Field Tests
PubMed: 26070465
DOI: 10.1016/j.ando.2015.04.006 -
Frontiers in Endocrinology 2024Prolactinomas (PRLomas) constitute approximately half of all pituitary adenomas and approximately one-fifth of them are diagnosed in males. The clinical presentation of... (Review)
Review
Prolactinomas (PRLomas) constitute approximately half of all pituitary adenomas and approximately one-fifth of them are diagnosed in males. The clinical presentation of PRLomas results from direct prolactin (PRL) action, duration and severity of hyperprolactinemia, and tumor mass effect. Male PRLomas, compared to females, tend to be larger and more invasive, are associated with higher PRL concentration at diagnosis, present higher proliferative potential, are more frequently resistant to standard pharmacotherapy, and thus may require multimodal approach, including surgical resection, radiotherapy, and alternative medical agents. Therefore, the management of PRLomas in men is challenging in many cases. Additionally, hyperprolactinemia is associated with a significant negative impact on men's health, including sexual function and fertility potential, bone health, cardiovascular and metabolic complications, leading to decreased quality of life. In this review, we highlight the differences in pathogenesis, clinical presentation and treatment of PRLomas concerning the male sex.
Topics: Female; Male; Humans; Prolactinoma; Hyperprolactinemia; Quality of Life; Pituitary Neoplasms; Adenoma
PubMed: 38370355
DOI: 10.3389/fendo.2024.1338345 -
Endocrinology and Metabolism (Seoul,... Dec 2023Pituitary neuroendocrine tumors (PitNETs) are the third most frequently diagnosed intracranial tumors, with nonfunctioning PitNETs (nfPitNETs) accounting for 30% of all... (Review)
Review
Pituitary neuroendocrine tumors (PitNETs) are the third most frequently diagnosed intracranial tumors, with nonfunctioning PitNETs (nfPitNETs) accounting for 30% of all pituitary tumors and representing the most common type of macroPitNETs. NfPitNETs are usually benign tumors with no evidence of hormone oversecretion except for hyperprolactinemia secondary to pituitary stalk compression. Due to this, they do not typically present with clinical syndromes like acromegaly, Cushing's disease or hyperthyroidism and instead are identified incidentally on imaging or from symptoms of mass effects (headache, vision changes, apoplexy). With the lack of effective medical interventions, first-line treatment is transsphenoidal surgical resection, however, nfPitNETs often have supra- or parasellar extension, and total resection of the tumor is often not possible, resulting in residual tumor regrowth or reoccurrence. While functional PitNETs can be easily followed for recurrence using hormonal biomarkers, there is no similar parameter to predict recurrence in nfPitNETs, hence delaying early recognition and timely management. Therefore, there is a need to identify prognostic biomarkers that can be used for patient surveillance and as therapeutic targets. This review focuses on summarizing the current evidence on nfPitNETs, with a special focus on potential new biomarkers and therapeutics.
Topics: Humans; Pituitary Neoplasms; Neuroendocrine Tumors; Adenoma; Acromegaly; Biomarkers
PubMed: 37964483
DOI: 10.3803/EnM.2023.1838