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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 -
Veterinary Journal (London, England :... Apr 2021Pituitary tumours are common in dogs and are being increasingly recognized in cats. Pituitary tumours are usually classified as adenomas and should only be classified as... (Review)
Review
Pituitary tumours are common in dogs and are being increasingly recognized in cats. Pituitary tumours are usually classified as adenomas and should only be classified as carcinomas when there is evidence of metastatic spread of the tumour, which is rare. Despite the benign nature of most pituitary tumours, they can still compress or invade neighbouring tissues. Pituitary tumours can be functional (hormonally active) or non-functional (hormonally silent). The aim of this review was to provide an overview of the different pituitary tumour types in dogs and cats that have been reported in the literature. In dogs, the most common pituitary tumour type is the corticotroph adenoma, which can cause pituitary-dependent hypercortisolism. In cats, the most common pituitary tumour is the somatotroph adenoma, which can cause hypersomatotropism, and the second-most common is the corticotroph adenoma. A lactotroph adenoma has been described in one dog, while gonadotroph, thyrotroph and null cell adenomas have not been described in dogs or cats. Hormonally silent adenomas are likely underdiagnosed because they do not result in an endocrine syndrome. Tools used to classify pituitary tumours in humans, particularly immunohistochemistry for lineage-specific transcription factors, are likely to be useful to classify canine and feline pituitary tumours of unknown origin. Future studies are required to better understand the full range of pituitary adenoma pathology in dogs and cats and to determine whether certain adenoma subtypes behave more aggressively than others. Currently, the mechanisms that underlie pituitary tumorigenesis in dogs and cats are still largely unknown. A better understanding of the molecular background of these tumours could help to identify improved pituitary-targeted therapeutics.
Topics: ACTH-Secreting Pituitary Adenoma; Adenoma; Animals; Cat Diseases; Cats; Dog Diseases; Dogs; Growth Hormone-Secreting Pituitary Adenoma; Humans; Immunohistochemistry; Pituitary Neoplasms
PubMed: 33641809
DOI: 10.1016/j.tvjl.2021.105623 -
The Journal of Clinical Endocrinology... Jul 2019Silent pituitary adenomas are anterior pituitary tumors with hormone synthesis but without signs or symptoms of hormone hypersecretion. They have been increasingly... (Review)
Review
CONTEXT
Silent pituitary adenomas are anterior pituitary tumors with hormone synthesis but without signs or symptoms of hormone hypersecretion. They have been increasingly recognized and represent challenging diagnostic issues.
EVIDENCE ACQUISITION
A comprehensive literature search was performed using MEDLINE and EMBASE databases from January 2000 to March 2018 with the following key words: (i) pituitary adenoma/tumor and nonfunctioning; or (ii) pituitary adenoma/tumor and silent. All titles and abstracts of the retrieved articles were reviewed, and recent advances in the field of silent pituitary adenomas were summarized.
EVIDENCE SYNTHESIS
The clinical and biochemical picture of pituitary adenomas reflects a continuum between functional and silent adenomas. Although some adenomas are truly silent, others will show some evidence of biochemical hypersecretion or could have subtle clinical signs and, therefore, can be referred to as clinically silent or "whispering" adenomas. Silent tumors seem to be more aggressive than their secreting counterparts, with a greater recurrence rate. Transcription factors for pituitary cell lineages have been introduced into the 2017 World Health Organization guidelines: steroidogenic factor 1 staining for gonadotroph lineage; PIT1 (pituitary-specific positive transcription factor 1) for growth hormone, prolactin, and TSH lineage, and TPIT for the corticotroph lineage. Prospective studies applying these criteria will establish the value of the new classification.
CONCLUSIONS
A concise review of the clinical and pathological aspects of silent pituitary adenomas was conducted in view of the new World Health Organization classification of pituitary adenomas. New classifications, novel prognostics markers, and emerging imaging and therapeutic approaches need to be evaluated to better serve this unique group of patients.
Topics: Biomarkers, Tumor; Chemotherapy, Adjuvant; Humans; Magnetic Resonance Angiography; Neoplasm Recurrence, Local; Pituitary Gland, Anterior; Pituitary Hormones, Anterior; Pituitary Neoplasms; Prognosis
PubMed: 30020466
DOI: 10.1210/jc.2018-00688 -
American Family Physician Sep 2013Prolactinomas and nonfunctioning adenomas are the most common types of pituitary adenomas. Patients with pituitary adenomas may present initially with symptoms of... (Review)
Review
Prolactinomas and nonfunctioning adenomas are the most common types of pituitary adenomas. Patients with pituitary adenomas may present initially with symptoms of endocrine dysfunction such as infertility, decreased libido, and galactorrhea, or with neurologic symptoms such as headache and visual changes. The diagnosis may also be made following imaging done for an unrelated issue in an asymptomatic patient; this is termed a pituitary incidentaloma. Oversecretion of hormones from a dysfunctional pituitary gland may result in classic clinical syndromes, the most common of which are hyperprolactinemia (from oversecretion of prolactin), acromegaly (from excess growth hormone), and Cushing disease (from overproduction of adrenocorticotropic hormone). In the diagnostic approach to a suspected pituitary adenoma, it is important to evaluate complete pituitary function, because hypopituitarism is common. Therapy for pituitary adenomas depends on the specific type of tumor, and should be managed with a team approach to include endocrinology and neurosurgery when indicated. Dopamine agonists are the primary treatment for prolactinomas. Small nonfunctioning adenomas and prolactinomas in asymptomatic patients do not require immediate intervention and can be observed.
Topics: Adenoma; Hormones; Humans; Pituitary Neoplasms
PubMed: 24010395
DOI: No ID Found -
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 -
Cancer Cell Jan 2020Pituitary neuroendocrine tumors (PitNETs) are common, with five main histological subtypes: lactotroph, somatotroph, and thyrotroph (POU1F1/PIT1 lineage); corticotroph...
Pituitary neuroendocrine tumors (PitNETs) are common, with five main histological subtypes: lactotroph, somatotroph, and thyrotroph (POU1F1/PIT1 lineage); corticotroph (TBX19/TPIT lineage); and gonadotroph (NR5A1/SF1 lineage). We report a comprehensive pangenomic classification of PitNETs. PitNETs from POU1F1/PIT1 lineage showed an epigenetic signature of diffuse DNA hypomethylation, with transposable elements expression and chromosomal instability (except for GNAS-mutated somatotrophs). In TPIT lineage, corticotrophs were divided into three classes: the USP8-mutated with overt secretion, the USP8-wild-type with increased invasiveness and increased epithelial-mesenchymal transition, and the large silent tumors with gonadotroph transdifferentiation. Unexpected expression of gonadotroph markers was also found in GNAS-wild-type somatotrophs (SF1 expression), challenging the current definition of SF1/gonadotroph lineage. This classification improves our understanding and affects the clinical stratification of patients with PitNETs.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cell Lineage; Chromosome Aberrations; DNA Methylation; Endopeptidases; Endosomal Sorting Complexes Required for Transport; Epigenesis, Genetic; Epigenome; Exome; Female; Humans; Male; Middle Aged; Mutation; Neoplasm Invasiveness; Neuroendocrine Tumors; Pituitary Gland; Pituitary Neoplasms; Prognosis; Transcriptome; Ubiquitin Thiolesterase; Young Adult
PubMed: 31883967
DOI: 10.1016/j.ccell.2019.11.002 -
Neuroendocrinology 2019
Topics: Humans; Hyperprolactinemia; Pituitary Neoplasms; Prolactinoma
PubMed: 31167201
DOI: 10.1159/000500723 -
Neuroendocrinology 2019Prolactin-secreting adenomas (prolactinomas) are the most common secreting adenomas of the pituitary. Microprolactinomas (diameter <10 mm) are frequently diagnosed in... (Review)
Review
Prolactin-secreting adenomas (prolactinomas) are the most common secreting adenomas of the pituitary. Microprolactinomas (diameter <10 mm) are frequently diagnosed in women, whereas macroprolactinomas (maximum diameter ≥10 mm) are generally seen in men. Most macroprolactinomas measure between 10 and 40 mm. Giant prolactinomas, measuring >40 mm, are rare, accounting for only 1-5% of all prolactinomas. Although generally benign, giant prolactinomas are aggressive and invasive, extending into the suprasellar region and also involving the cavernous sinuses. The optic chiasm is frequently involved, which leads to visual damage, and patients occasionally suffer from ophthalmoplegia. Long-term (usually lifetime) therapy with high-dose dopamine agonists (cabergoline or bromocriptine), together with pituitary surgery in some cases and radiotherapy if required, can achieve biochemical remission, tumor control, and clinical improvement in most patients.
Topics: Female; Humans; Male; Pituitary Neoplasms; Prolactinoma
PubMed: 30404098
DOI: 10.1159/000495184 -
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 -
Endocrinology and Metabolism Clinics of... Mar 2015Pituitary tumors are commonly encountered intracranial neoplasms that are invariably benign. Classic oncogene mutations are not encountered in these tumors, and... (Review)
Review
Pituitary tumors are commonly encountered intracranial neoplasms that are invariably benign. Classic oncogene mutations are not encountered in these tumors, and disrupted cell cycle control and growth factor signaling likely contribute to pathogenesis and natural history. They have unique clinical features that are determined by the secreted hormone gene product.
Topics: Animals; Humans; Pituitary Neoplasms
PubMed: 25732636
DOI: 10.1016/j.ecl.2014.11.004