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Best Practice & Research. Clinical... Apr 2019Pituitary diseases are rare conditions with severe chronic multiorgan and multisystemic morbidity requiring complex multidisciplinary treatment and usually life-long... (Review)
Review
Pituitary diseases are rare conditions with severe chronic multiorgan and multisystemic morbidity requiring complex multidisciplinary treatment and usually life-long drug treatment. Most cases are caused by functioning or non-functioning pituitary adenoma. From the patient's perspective, the burden of disease is caused by the tumour itself and associated compression symptoms, interventions, hormone excess and deficiencies, systemic manifestations of these endocrine abnormalities and general psychosocial issues that can manifest in patients with a chronic condition. In this review, patient burden is classified according to classic endocrine syndromes, with burden at diagnosis and after long-term remission, and also within the framework of value-based health care and the conceptual model of wellbeing. The recently developed patient-reported outcome measurement tool that helps to evaluate burden of patients is also discussed.
Topics: Acromegaly; Adenoma; Cost of Illness; Humans; Pituitary Neoplasms; Quality of Life
PubMed: 31405752
DOI: 10.1016/j.beem.2019.101309 -
Neuroendocrinology 2019Clinically relevant pituitary adenomas are present in about 1 per 1,000 of the general population and prolactinomas are by far the most common clinical subtype of... (Review)
Review
Clinically relevant pituitary adenomas are present in about 1 per 1,000 of the general population and prolactinomas are by far the most common clinical subtype of pituitary adenomas. Usually prolactinomas affect premenopausal women and present with typical symptoms of menstrual disturbance and/or galactorrhea. They are generally managed with dopamine agonists to restore fertility and to control symptoms and tumor size. In a subset of prolactinomas, however, management remains challenging. Studies in recent years have identified the factors related to dopamine agonist resistance, such as male sex, genetic features, and aggressive tumor behavior. Certain other patient groups represent particular challenges for management, such as pediatric patients and pregnant women. Treatment with dopamine agonists is usually safe and effective, and adverse effects such as clinically relevant cardiac valvular complications and impulse control disorders may occur in isolated instances. A number of important disease characteristics of prolactinomas remain to be explained, such as the difference in sex prevalence before and after menopause, the higher prevalence of macroadenomas in older males, and the biochemical mechanisms of resistance to dopaminergic agonists.
Topics: Female; Humans; Male; Pituitary Neoplasms; Prolactinoma
PubMed: 30731464
DOI: 10.1159/000497746 -
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 -
Pituitary Apr 2018Non-functioning pituitary neuroendocrine tumors do not cause endocrine symptoms related to hypersecretion of adenohypophyseal hormones and are clinically characterized... (Review)
Review
Non-functioning pituitary neuroendocrine tumors do not cause endocrine symptoms related to hypersecretion of adenohypophyseal hormones and are clinically characterized by symptoms due to growing sellar tumor mass. Histopathological classification of this tumor group has always been challenging due to their heterogeneity, limited knowledge on their biology, and diverse methodological problems. We have searched PubMed database for data related to the histopathological classification of non-functioning pituitary tumors and methods for its application. Principles of the classification and grading presented in the recently released 4th edition of the World Health Organization classification of endocrine tumors have been summarized. Based on the expression of anterior pituitary hormones and pituitary specific transcription factors, gonadotroph tumors dominate within the group of clinically non-functioning tumors, followed by corticotroph type; however, other less common types of the non-functioning tumors can be identified. Assessment of tumor cell proliferation is important to identify "high-risk adenomas." A few subtypes of non-functioning tumors belong to the category of potentially aggressive tumors, independent of the cell proliferation rate. Here, we present up to date criteria for the classification of clinically non-functioning pituitary tumors, offer a diagnostic approach for the routine clinical use, and emphasize a need for inclusion of prognostic and predictive markers in the classification.
Topics: Animals; Humans; Immunohistochemistry; Neuroendocrine Tumors; Pituitary Neoplasms; Transcription Factors
PubMed: 29275530
DOI: 10.1007/s11102-017-0855-1 -
British Medical Journal (Clinical... Mar 1985
Topics: Humans; Hypophysectomy; Pituitary Neoplasms; Prolactin
PubMed: 3919855
DOI: 10.1136/bmj.290.6473.1002-a -
Journal of Neurosurgery Jun 2007
Topics: Child; Craniopharyngioma; Humans; Hypothalamus; Magnetic Resonance Imaging; Neurosurgical Procedures; Pituitary Neoplasms; Prognosis
PubMed: 17571327
DOI: 10.3171/ped.2007.106.6.517a -
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 -
International Journal of Molecular... Apr 2022Corticotroph cells give rise to aggressive and rare pituitary neoplasms comprising ACTH-producing adenomas resulting in Cushing disease (CD), clinically silent ACTH...
Corticotroph cells give rise to aggressive and rare pituitary neoplasms comprising ACTH-producing adenomas resulting in Cushing disease (CD), clinically silent ACTH adenomas (SCA), Crooke cell adenomas (CCA) and ACTH-producing carcinomas (CA). The molecular pathogenesis of these tumors is still poorly understood. To better understand the genomic landscape of all the lesions of the corticotroph lineage, we sequenced the whole exome of three SCA, one CCA, four ACTH-secreting PA causing CD, one corticotrophinoma occurring in a CD patient who developed Nelson syndrome after adrenalectomy and one patient with an ACTH-producing CA. The ACTH-producing CA was the lesion with the highest number of single nucleotide variants (SNV) in genes such as , and . The variant was found only in the ACTH-CA and in the corticotrophinoma occurring in a patient with Nelson syndrome. In CCA, SNV in and SNV were present. and SNVs were present in all three SCA, whereas in two of these tumors SNV in and were found. None of the analyzed tumors showed SNV in or . The amplification of 17q12 was found in all tumors, except for the ACTH-producing carcinoma. The four clinically functioning ACTH adenomas and the ACTH-CA shared the amplification of 10q11.22 and showed more copy-number variation (CNV) gains and single-nucleotide variations than the nonfunctioning tumors.
Topics: ACTH-Secreting Pituitary Adenoma; Adenoma; Adrenocorticotropic Hormone; Aurora Kinase A; Carcinoma; Corticotrophs; ErbB Receptors; Genomics; Humans; Melanocortins; Multienzyme Complexes; Nelson Syndrome; Nucleotides; Pituitary Neoplasms
PubMed: 35563252
DOI: 10.3390/ijms23094861 -
European Journal of Endocrinology Aug 2023Data on pre- and postoperative pituitary function in nonfunctioning pituitary adenomas (NFPA) are not consistent. We aimed to investigate pituitary function before and...
OBJECTIVE
Data on pre- and postoperative pituitary function in nonfunctioning pituitary adenomas (NFPA) are not consistent. We aimed to investigate pituitary function before and up to 5 years after transsphenoidal surgery with emphasis on the hypothalamic-pituitary-adrenal axis (HPA).
DESIGN AND METHODS
Data from the Swedish Pituitary Register was used to analyze anterior pituitary function in 838 patients with NFPA diagnosed between 1991 and 2014. Patients who were reoperated or had received radiotherapy were excluded.
RESULTS
Preoperative ACTH, TSH, LH/FSH, and GH deficiencies were reported in 31% (236/755), 39% (300/769), 51% (378/742), and 28% (170/604) of the patients, respectively. Preoperative median tumor volume was 5.0 (2.4-9.0) cm3. Among patients with preoperative, 1 year and 5 years postoperative data on the HPA axis (n = 428), 125 (29%) were ACTH-deficient preoperatively. One year postoperatively, 26% (32/125) of them had recovered ACTH function while 23% (70/303) patients had developed new ACTH deficiency. Thus, 1 year postoperatively, 163 (38%) patients were ACTH-deficient (P < .001 vs. preoperatively). No further increase was seen 5 years postoperatively (36%, P = .096). At 1 year postoperatively, recoveries in the TSH and LH/FSH axes were reported in 14% (33/241) and 15% (46/310), respectively, and new deficiencies in 22% (88/403) and 29% (83/288), respectively.
CONCLUSIONS
Adrenocorticotrophic hormone deficiency increased significantly at 1 year postoperatively. Even though not significant, some patients recovered from or developed new deficiency between 1 and 5 years postoperatively. This pattern was seen in all axes. Our study emphasizes that continuous individual evaluations are needed during longer follow-up of patients operated for NFPA.
Topics: Humans; Pituitary Neoplasms; Hypothalamo-Hypophyseal System; Sweden; Pituitary-Adrenal System; Follicle Stimulating Hormone; Adrenocorticotropic Hormone; Thyrotropin
PubMed: 37551511
DOI: 10.1093/ejendo/lvad104