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Endocrine Reviews Nov 2022All endocrine glands are susceptible to neoplastic growth, yet the health consequences of these neoplasms differ between endocrine tissues. Pituitary neoplasms are... (Review)
Review
All endocrine glands are susceptible to neoplastic growth, yet the health consequences of these neoplasms differ between endocrine tissues. Pituitary neoplasms are highly prevalent and overwhelmingly benign, exhibiting a spectrum of diverse behaviors and impact on health. To understand the clinical biology of these common yet often innocuous neoplasms, we review pituitary physiology and adenoma epidemiology, pathophysiology, behavior, and clinical consequences. The anterior pituitary develops in response to a range of complex brain signals integrating with intrinsic ectodermal cell transcriptional events that together determine gland growth, cell type differentiation, and hormonal production, in turn maintaining optimal endocrine health. Pituitary adenomas occur in 10% of the population; however, the overwhelming majority remain harmless during life. Triggered by somatic or germline mutations, disease-causing adenomas manifest pathogenic mechanisms that disrupt intrapituitary signaling to promote benign cell proliferation associated with chromosomal instability. Cellular senescence acts as a mechanistic buffer protecting against malignant transformation, an extremely rare event. It is estimated that fewer than one-thousandth of all pituitary adenomas cause clinically significant disease. Adenomas variably and adversely affect morbidity and mortality depending on cell type, hormone secretory activity, and growth behavior. For most clinically apparent adenomas, multimodal therapy controlling hormone secretion and adenoma growth lead to improved quality of life and normalized mortality. The clinical biology of pituitary adenomas, and particularly their benign nature, stands in marked contrast to other tumors of the endocrine system, such as thyroid and neuroendocrine tumors.
Topics: Humans; Pituitary Neoplasms; Quality of Life; Adenoma; Biology; Hormones
PubMed: 35395078
DOI: 10.1210/endrev/bnac010 -
International Journal of Molecular... Feb 2020Somatostatin analogs are an invaluable therapeutic option in the diagnosis and treatment of somatotropinomas, thyrotropinomas, and functioning and non-functioning... (Review)
Review
Somatostatin analogs are an invaluable therapeutic option in the diagnosis and treatment of somatotropinomas, thyrotropinomas, and functioning and non-functioning gastroenteropancreatic neuroendocrine tumors. They should also be considered an effective and safe therapeutic alternative to corticotropinomas, gonadotropinomas, and prolactinomas resistant to dopamine agonists. Somatostatin analogs have also shown to be useful in the treatment of other endocrine diseases (congenital hyperinsulinism, Graves' orbitopathy, diabetic retinopathy, diabetic macular edema), non-endocrine tumors (breast, colon, prostate, lung, and hepatocellular), and digestive diseases (chronic refractory diarrhea, hepatorenal polycystosis, gastrointestinal hemorrhage, dumping syndrome, and intestinal fistula).
Topics: Antineoplastic Agents, Hormonal; Diabetic Retinopathy; Graves Ophthalmopathy; Growth Hormone-Secreting Pituitary Adenoma; Humans; Intestinal Neoplasms; Macular Edema; Neuroendocrine Tumors; Pancreatic Neoplasms; Pituitary Neoplasms; Somatostatin; Stomach Neoplasms
PubMed: 32121432
DOI: 10.3390/ijms21051682 -
Head and Neck Pathology Mar 2022This review article provides a brief overview of the new WHO classification by adopting a question-answer model to highlight the spectrum of head and neck neuroendocrine... (Review)
Review
Update from the 5th Edition of the World Health Organization Classification of Head and Neck Tumors: Overview of the 2022 WHO Classification of Head and Neck Neuroendocrine Neoplasms.
This review article provides a brief overview of the new WHO classification by adopting a question-answer model to highlight the spectrum of head and neck neuroendocrine neoplasms which includes epithelial neuroendocrine neoplasms (neuroendocrine tumors and neuroendocrine carcinomas) arising from upper aerodigestive tract and salivary glands, and special neuroendocrine neoplasms including middle ear neuroendocrine tumors (MeNET), ectopic or invasive pituitary neuroendocrine tumors (PitNET; formerly known as pituitary adenoma) and Merkel cell carcinoma as well as non-epithelial neuroendocrine neoplasms (paragangliomas). The new WHO classification follows the IARC/WHO nomenclature framework and restricts the diagnostic term of neuroendocrine carcinoma to poorly differentiated epithelial neuroendocrine neoplasms. In this classification, well-differentiated epithelial neuroendocrine neoplasms are termed as neuroendocrine tumors (NET), and are graded as G1 NET (no necrosis and < 2 mitoses per 2 mm; Ki67 < 20%), G2 NET (necrosis or 2-10 mitoses per 2 mm, and Ki67 < 20%) and G3 NET (> 10 mitoses per 2 mm or Ki67 > 20%, and absence of poorly differentiated cytomorphology). Neuroendocrine carcinomas (> 10 mitoses per 2 mm, Ki67 > 20%, and often associated with a Ki67 > 55%) are further subtyped based on cytomorphological characteristics as small cell and large cell neuroendocrine carcinomas. Unlike neuroendocrine carcinomas, head and neck NETs typically show no aberrant p53 expression or loss of RB reactivity. Ectopic or invasive PitNETs are subtyped using pituitary transcription factors (PIT1, TPIT, SF1, GATA3, ER-alpha), hormones and keratins (e.g., CAM5.2). The new classification emphasizes a strict correlation of morphology and immunohistochemical findings in the accurate diagnosis of neuroendocrine neoplasms. A particular emphasis on the role of biomarkers in the confirmation of the neuroendocrine nature of a neoplasm and in the distinction of various neuroendocrine neoplasms is provided by reviewing ancillary tools that are available to pathologists in the diagnostic workup of head and neck neuroendocrine neoplasms. Furthermore, the role of molecular immunohistochemistry in the diagnostic workup of head and neck paragangliomas is discussed. The unmet needs in the field of head and neck neuroendocrine neoplasms are also discussed in this article. The new WHO classification is an important step forward to ensure accurate diagnosis that will also form the basis of ongoing research in this field.
Topics: Carcinoma, Neuroendocrine; Head and Neck Neoplasms; Humans; Ki-67 Antigen; Neuroendocrine Tumors; Paraganglioma; Pituitary Neoplasms; World Health Organization
PubMed: 35312985
DOI: 10.1007/s12105-022-01435-8 -
Neurology India 2020Pituitary adenomas are benign tumors arising in the adenohypophysis and comprise 8%-20% of all reported primary brain tumors in the west. Transsphenoidal surgery with an... (Review)
Review
Pituitary adenomas are benign tumors arising in the adenohypophysis and comprise 8%-20% of all reported primary brain tumors in the west. Transsphenoidal surgery with an aim to achieve complete tumor resection is the recommended first-line treatment for nonfunctioning as well as secretory pituitary adenoma. External beam radiation therapy (RT) has been demonstrated to be an effective treatment modality for pituitary adenoma, uncured by surgery and/or medical therapy, providing excellent long-term local control (>90%), but lower and variable rates (50%-80%) of biochemical remission in secretory tumors. The adoption of pituitary RT in the community has been limited due to concerns regarding potential late toxicity and long latency in normalization of hormonal hypersecretion. Over the years, technological advances in RT planning and delivery have resulted in progressive conformation of high doses to the target tissues while sparing adjacent neurovascular structures providing a favorable therapeutic index. The choice of RT technique should be based on size, site, and availability of infrastructure and expertise, with no significant differences between fractionated approaches and stereotactic radiosurgery (SRS). In contemporary clinical practice, the recommended dose of fractionated RT for pituitary adenoma is 45-50.4Gy in 25-28 fractions delivered over 5-6 weeks using modern high-precision techniques. The recommended dose of SRS given in a single fraction is 12-14Gy for nonfunctioning adenomas and 16-20Gy for secretory tumors. Late toxicity of pituitary RT includes hypopituitarism, neurocognitive impairment, neuropsychological dysfunction, optic neuropathy, cerebrovascular accidents, and second malignant neoplasms. Hence, RT in pituitary adenoma should be offered only to patients with residual, recurrent, progressive, or high-risk tumors with careful assessment of the benefit-risk ratio by an experienced multidisciplinary neurooncology team.
Topics: Adenoma; Humans; Pituitary Neoplasms; Radiosurgery; Radiotherapy, Conformal; Treatment Outcome
PubMed: 32611901
DOI: 10.4103/0028-3886.287678 -
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 -
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 -
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 -
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 -
Neurology India 2020Growth hormone (GH) hypersecretion from a pituitary adenoma results in acromegaly, an endocrinological disorder with multiple systemic manifestations that presents... (Review)
Review
Growth hormone (GH) hypersecretion from a pituitary adenoma results in acromegaly, an endocrinological disorder with multiple systemic manifestations that presents several unique challenges in terms of perioperative management and long term outcomes. Current guidelines provide stringent criteria for determining biochemical remission, necessitating an aggressive approach to management. Despite the development of several non-surgical therapies, transsphenoidal surgery, the endoscopic approach in particular, remains the primary line of treatment for rapid normalization of GH and Insulin-like growth factor with a low incidence of perioperative morbidity. Tumor size and invasiveness are important factors predicting surgical outcomes with better rates of postoperative remission seen in smaller and non-invasive tumors. Postoperative remission rates reported in literature with the 2020 consensus criteria vary from 30 to 85% probably reflecting varying prevalence rates of invasive tumors. Thus, a significant proportion of patients fail to achieve remission after surgery for whom treatment options for residual disease must be carefully considered. This review article discusses the surgical management of acromegaly and provides a summary of contemporary outcomes and current treatment controversies.
Topics: Acromegaly; Adenoma; Humans; Neurosurgical Procedures; Pituitary Gland; Pituitary Neoplasms; Treatment Outcome
PubMed: 32611892
DOI: 10.4103/0028-3886.287664 -
Frontiers in Endocrinology 2020
Topics: Adenoma; Biomarkers, Tumor; Gene Expression Regulation, Neoplastic; Gene Regulatory Networks; Humans; Molecular Targeted Therapy; Pituitary Neoplasms; Precision Medicine; Protein Interaction Maps; Signal Transduction
PubMed: 32132975
DOI: 10.3389/fendo.2020.00026