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Cancers Feb 2020Adenohypophyseal tumors, which were recently renamed pituitary neuroendocrine tumors (PitNET), are mostly benign, but may present various behaviors: invasive,... (Review)
Review
Adenohypophyseal tumors, which were recently renamed pituitary neuroendocrine tumors (PitNET), are mostly benign, but may present various behaviors: invasive, "aggressive" and malignant with metastases. They are classified into seven morphofunctional types and three lineages: lactotroph, somatotroph and thyrotroph (PIT1 lineage), corticotroph (TPIT lineage) or gonadotroph (SF1 lineage), null cell or immunonegative tumor and plurihormonal tumors. The WHO 2017 classification suggested that subtypes, such as male lactotroph, silent corticotroph and Crooke cell, sparsely granulated somatotroph, and silent plurihormonal PIT1 positive tumors, should be considered as "high risk" tumors. However, the prognostic impact of these subtypes and of each morphologic type remains controversial. In contrast, the French five-tiered classification, taking into account the invasion, the immuno-histochemical (IHC) type, and the proliferative markers (Ki-67 index, mitotic count, p53 positivity), has a prognostic value validated by statistical analysis in 4 independent cohorts. A standardized report for the diagnosis of pituitary tumors, integrating all these parameters, has been proposed by the European Pituitary Pathology Group (EPPG). In 2020, the pituitary pathologist must be considered as a member of the multidisciplinary pituitary team. The pathological diagnosis may help the clinician to adapt the post-operative management, including appropriate follow-up and early recognition and treatment of potentially aggressive forms.
PubMed: 32098443
DOI: 10.3390/cancers12020514 -
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 -
Pituitary Apr 2023Pit-1 tumours are derived from neoplastic cells of either somatotroph, lactotroph or thyrotroph cell lineages, but there are also distinct mixed tumours and... (Review)
Review
Pit-1 tumours are derived from neoplastic cells of either somatotroph, lactotroph or thyrotroph cell lineages, but there are also distinct mixed tumours and plurihormonal tumours within this category as described within the 2022 edition of the WHO classification of pituitary tumours. Plurihormonal tumours and thyrotroph adenomas are transcriptionally similar and grouped together to discuss in this review, although it is clear an immature type of plurihormonal tumour exists which are more commonly associated with refractory disease. Management of residual or recurrent disease should follow that of other aggressive pituitary tumours, although a trial of somatostatin analogue therapy is certainly warranted before considering temozolomide therapy.
Topics: Humans; Pituitary Neoplasms; Thyrotrophs; Transcription Factors; Somatotrophs; Adenoma
PubMed: 37117845
DOI: 10.1007/s11102-023-01312-9 -
Frontiers in Endocrinology 2020Pituitary adenomas (PAs) can be classified as non-secreting adenomas, somatotroph adenomas, corticotroph adenomas, lactotroph adenomas, and thyrotroph adenomas.... (Review)
Review
Pituitary adenomas (PAs) can be classified as non-secreting adenomas, somatotroph adenomas, corticotroph adenomas, lactotroph adenomas, and thyrotroph adenomas. Substantial advances have been made in our knowledge of the pathobiology of PAs. To obtain a comprehensive understanding of the molecular biological characteristics of different types of PAs, we reviewed the important advances that have been made involving genetic and epigenetic variation, comprising genetic mutations, chromosome number variations, DNA methylation, microRNA regulation, and transcription factor regulation. Classical tumor predisposition syndromes include multiple endocrine neoplasia type 1 (MEN1) and type 4 (MEN4) syndromes, Carney complex, and X-LAG syndromes. PAs have also been described in association with succinate dehydrogenase-related familial PA, neurofibromatosis type 1, and von Hippel-Lindau, DICER1, and Lynch syndromes. Patients with aryl hydrocarbon receptor-interacting protein () mutations often present with pituitary gigantism, either in familial or sporadic adenomas. In contrast, guanine nucleotide-binding protein G(s) subunit alpha () and G protein-coupled receptor 101 () mutations can lead to excess growth hormone. Moreover, the deubiquitinase gene , , and mutations are associated with adrenocorticotropic hormone production. In this review, we describe the genetic and epigenetic landscape of PAs and summarize novel insights into the regulation of pituitary tumorigenesis.
Topics: Adenoma; Epigenesis, Genetic; Gene Expression Regulation; Genetic Markers; Genetic Predisposition to Disease; Humans; Mutation; Pituitary Neoplasms
PubMed: 33574795
DOI: 10.3389/fendo.2020.596554 -
Orphanet Journal of Rare Diseases Oct 2016Secreting pituitary adenomas that cause acromegaly and Cushing's disease, as well as prolactinomas and thyrotroph adenomas, are uncommon, usually benign, slow-growing... (Review)
Review
Secreting pituitary adenomas that cause acromegaly and Cushing's disease, as well as prolactinomas and thyrotroph adenomas, are uncommon, usually benign, slow-growing tumours. The rarity of these conditions means that their diagnosis is not familiar to most non-specialist physicians. Consequently, pituitary adenomas may be overlooked and remain untreated, and affected individuals may develop serious comorbidities that reduce their quality of life and life expectancy. Because many signs and symptoms of pituitary adenomas overlap with those of other, more common disorders, general practitioners and non-endocrinology specialists need to be aware of the "red flags" suggestive of these conditions. A long duration of active disease in patients with secreting pituitary adenomas is associated with an increased risk of comorbidities and reduced quality of life. Appropriate treatment can lead to disease remission, and, although some symptoms may persist in some patients, treatment usually reduces the incidence and severity of comorbidities and improves quality of life. Therefore, correct, early diagnosis and characterization of a pituitary adenoma is crucial for patients, to trigger timely, appropriate treatment and to optimize outcome. This article provides an overview of the epidemiology of hormonal syndromes associated with pituitary adenomas, discusses the difficulties of and considerations for their diagnosis, and reviews the comorbidities that may develop, but can be prevented, by accurate diagnosis and appropriate treatment. We hope this review will help general practitioners and non-endocrinology specialists to suspect secreting pituitary adenomas and refer patients to an endocrinologist for confirmation of the diagnosis and treatment.
Topics: Acromegaly; Adenoma; Female; Humans; Male; Pituitary ACTH Hypersecretion; Pituitary Neoplasms; Prolactinoma; Quality of Life
PubMed: 27716353
DOI: 10.1186/s13023-016-0516-x -
Endocrine Journal Feb 2023Pituitary neuroendocrine tumors (PitNETs), which were formerly known as pituitary adenomas, are classified in 5th Edition of the WHO Classification of Endocrine and...
Pituitary neuroendocrine tumors (PitNETs), which were formerly known as pituitary adenomas, are classified in 5th Edition of the WHO Classification of Endocrine and Neuroendocrine Tumors. Since thyrotroph PitNETs are rare PitNETs, most previous studies about former thyroid stimulating hormone (TSH)-secreting pituitary adenoma have focused on a small number of cases. However, the diagnostic rate of thyrotroph PitNET has increased because of increased sensitivity of serum TSH measurement and widespread recognition that thyrotroph PitNETs are the cause of syndrome of inappropriate secretion of TSH (SITSH). Therefore, knowledge on the molecular mechanism of thyrotroph PitNET is gradually accumulating. Recently, comprehensive chromosomal, genetic, and epigenomic alterations in thyrotroph PitNET have been revealed with the availability of comprehensive gene and protein analyses, and the nature of thyrotroph PitNET is gradually being elucidated. However, further analysis is needed to determine whether the causes of these changes are directly responsible for the development of tumors.
Topics: Humans; Pituitary Neoplasms; Neuroendocrine Tumors; Thyrotrophs; Thyrotropin; Molecular Biology
PubMed: 36653153
DOI: 10.1507/endocrj.EJ22-0514 -
European Endocrinology Apr 2019Pituitary adenomas are benign tumours comprising approximately 16% of all primary cranial neoplasms. Functioning pituitary adenomas (prolactinomas, somatotroph,... (Review)
Review
Pituitary adenomas are benign tumours comprising approximately 16% of all primary cranial neoplasms. Functioning pituitary adenomas (prolactinomas, somatotroph, corticotroph, thyrotroph and rarely gonadotroph adenomas) cause complex clinical syndromes and require prompt treatment to reduce associated morbidity and mortality. Treatment approaches include transsphenoidal surgery, medical therapy and radiation. Medical therapy is the primary therapy for prolactinomas, and surgery by a skilled neurosurgeon is the first-line approach for other functioning pituitary adenomas. A multimodal treatment is frequently necessary to achieve biochemical and clinical control, especially, when surgery is not curative or when medical therapy fails. Several emerging, novel, medical treatments for acromegaly, Cushing's disease and prolactinomas are in phase II and III clinical trials and may become effective additions to the current drug armamentarium. The availability of various management options will allow an individualised treatment approach based on the unique tumour type, clinical situation and patient preference.
PubMed: 31244908
DOI: 10.17925/EE.2019.15.1.30 -
The Journal of Veterinary Medical... Jan 2009Pituitary thyrotroph hyperplasia results from prolonged primary hypothyroidism in humans, mice and rats. In dogs with Cushing's disease, many cases have low serum...
Pituitary thyrotroph hyperplasia results from prolonged primary hypothyroidism in humans, mice and rats. In dogs with Cushing's disease, many cases have low serum thyroid hormones concentrations due to euthyroid sick syndrome. A 6-year-old castrated male Beagle diagnosed with Cushing's disease had a high serum thyroid stimulating hormone (TSH) concentration that was treated by hypophysectomy. On histological examination, the resected pituitary gland contained both a corticotroph adenoma and thyrotroph hyperplasia. The TSH-positive cell ratio in this case was greater than that of healthy Beagles. In the present case, the pituitary thyrotroph hyperplasia was probably caused by primary hypothyroidism. In conclusion, this Beagle is the first histological confirmation of the coexistence of a corticotroph adenoma and thyrotroph hyperplasia.
Topics: ACTH-Secreting Pituitary Adenoma; Adenoma; Animals; Dog Diseases; Dogs; Hyperplasia; Immunohistochemistry; Male; Pituitary ACTH Hypersecretion; Thyrotrophs
PubMed: 19194082
DOI: 10.1292/jvms.71.93 -
Veterinary Pathology Mar 2021Pituitary glands from 141 feline autopsy cases were reviewed histologically. Adenoma and hyperplasia were the most common lesions at 13 cases each. Pituitary adenoma was...
Pituitary glands from 141 feline autopsy cases were reviewed histologically. Adenoma and hyperplasia were the most common lesions at 13 cases each. Pituitary adenoma was more likely than hyperplasia to be associated with clinical evidence of endocrinopathy or an intracranial mass ( < .001). A histochemical and immunohistochemical panel was applied to 44 autopsy- or hypophysectomy-derived pituitary adenomas in 43 cats from 2 diagnostic laboratories. Adenomas were differentiated from hyperplasia by the presence of disrupted reticulin fibers. One cat had a double (somatotroph and melanotroph) adenoma. Twenty somatotroph adenomas consisted of periodic acid-Schiff (PAS)-negative acidophils that expressed growth hormone; 16/20 had hypersomatotropism; 17/20 had diabetes mellitus. Eleven melanotroph adenomas consisted of PAS-positive basophils or chromophobes that expressed melanocyte-stimulating and adrenocorticotrophic hormones; 5/11 had hypercortisolism; 6/11 had diabetes mellitus. Eleven gonadotroph adenomas consisted of PAS-negative chromophobes that expressed follicle-stimulating and/or luteinizing hormones. Two thyrotroph adenomas consisted of PAS-negative basophils or chromophobes that expressed thyroid-stimulating hormone. Pituitary-dependent disease was not recognized in cats with gonadotroph or thyrotroph adenomas. The Ki-67 proliferation index in hypophysectomy specimens was lower in somatotroph than in melanotroph adenomas. Fourteen cats with hypophysectomy-treated somatotroph or melanotroph adenoma had an 899-day median survival time versus 173 days in 17 nonsurgical cases. After adjusting for age, adenoma size and type, hypophysectomized cats had an overall better survival time than nonsurgical cases ( = .029). The study results underscore the value of hypophysectomy and trophic hormone immunohistochemistry in the treatment and classification of feline pituitary adenomas.
Topics: Acromegaly; Adenoma; Animals; Cat Diseases; Cats; Hypophysectomy; Luteinizing Hormone; Pituitary Neoplasms
PubMed: 33280571
DOI: 10.1177/0300985820978309 -
Frontiers in Endocrinology 2021Thyrotropin-secreting adenoma (TSH-oma) is a very rare kind of functional pituitary adenoma, especially that which occurs in adolescents. However, its potential clinical...
BACKGROUND
Thyrotropin-secreting adenoma (TSH-oma) is a very rare kind of functional pituitary adenoma, especially that which occurs in adolescents. However, its potential clinical and therapeutic characteristics are still unknown.
OBJECTIVES
The study was aimed to summarize the clinical and therapeutic characteristics of patients with adolescent-onset TSH-oma.
METHODS
We retrospectively analyzed six (4.1%) adolescent-onset TSH-oma cases from 148 patients who were diagnosed with TSH-oma at our hospital between January 2012 and October 2020. A literature review was performed on the PubMed online database, and 14 adolescent-onset TSH-oma cases were retrieved. Then, the characteristics of clinical manifestations, treatment outcomes, and follow-ups were analyzed and compared to the adult TSH-oma patients.
RESULTS
Altogether, 20 adolescent-onset cases were included in this study having mean onset age of 13.4 ± 3.3 years. Males were found to be slightly predominant (M: F = 1.5:1) in our study. The median baseline levels of TSH, FT3, and FT4 in adolescent-onset cases were found to be 6.30 [interquartile range (IQR) 9.82] µIU/ml, 9.18 (IQR 11.61) pg/ml, and 3.22 (IQR 1.90) ng/dl, respectively, which were all significantly higher than the adult patients of our hospital. Also, the adolescent-onset cases showed more large tumor ratio (36.8% vs. 9.3%, p = 0.007) compared to the adult patients. Compared to the patients of all ages in the literature, the biochemical remission rate of SSAs (57.1%) and remission rate of TSS (38.9%) were found to be considerably lower in adolescent-onset patients, while the recurrence rate (44.4%) was found to be considerably higher.
CONCLUSIONS
Adolescent-onset TSH-oma patients showed higher TSH and thyroid hormone levels, more large tumors, and worse treatment outcomes than adult cases. Hence, early diagnosis, multidisciplinary therapy, and close follow-up should be highlighted to improve the prognosis.
Topics: Adenoma; Adolescent; Child; Female; Humans; Magnetic Resonance Imaging; Male; Pituitary Neoplasms; Retrospective Studies; Thyrotrophs; Treatment Outcome
PubMed: 35002961
DOI: 10.3389/fendo.2021.771673