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Pituitary Jun 2023A small subset of lactotroph adenomas is resistant to dopamine agonists (DA) and can also demonstrate aggressive or even malignant behavior. The implicated mechanisms... (Review)
Review
A small subset of lactotroph adenomas is resistant to dopamine agonists (DA) and can also demonstrate aggressive or even malignant behavior. The implicated mechanisms are not clearly defined. Management can be challenging and requires a multidisciplinary approach. In DA resistant prolactinomas, switching to another DA could be the first option to consider. Further strategies include surgery and radiotherapy used alone or in combination. In cases of aggressive or malignant prolactinomas, temozolomide could be offered. Immune checkpoint inhibitors have been also recently proposed as an alternative approach. The place of other treatments (e.g., metformin, selective estrogen modulators, somatostatin analogues, tyrosine kinase inhibitors, inhibitors of mammalian target of rapamycin and peptide radio-receptor therapy) remains to be carefully assessed.
Topics: Humans; Prolactinoma; Pituitary Neoplasms; Dopamine Agonists; Temozolomide; Somatostatin
PubMed: 36928728
DOI: 10.1007/s11102-023-01305-8 -
Journal of Neuroendocrinology Aug 2022Pituitary tumors are generally benign, although in rare cases aggressive pituitary tumors (APTs) and carcinomas present important diagnostic and therapeutic challenges... (Review)
Review
Pituitary tumors are generally benign, although in rare cases aggressive pituitary tumors (APTs) and carcinomas present important diagnostic and therapeutic challenges and are associated with a high mortality rate. Almost half of these APTs and carcinomas are corticotroph tumors, suggesting a specific prognosis. Clinical, pathological and molecular prognostic markers are limited and do not allow early management of these tumors. Temozolomide remains the first-line treatment once a diagnosis of aggressive pituitary tumor or carcinoma has been made. Novel alternative treatments exist, including immune checkpoint inhibitors, which can be used in the case of temozolomide treatment failure. The aim of this review is to present the clinical, pathological and molecular characteristics of aggressive corticotroph tumors and carcinomas, and to describe the results obtained with currently available treatments.
Topics: Adenoma; Carcinoma; Corticotrophs; Humans; Pituitary Neoplasms; Temozolomide
PubMed: 35979732
DOI: 10.1111/jne.13169 -
Pituitary Jun 2023The majority of corticotroph adenomas are benign but some are locally invasive, demonstrate high rates of recurrence, and exhibit a relatively poor response to often... (Review)
Review
The majority of corticotroph adenomas are benign but some are locally invasive, demonstrate high rates of recurrence, and exhibit a relatively poor response to often repeated surgical, medical, and radiation treatment. Herein, we summarize the currently known somatic and genetic mutations and other molecular factors that influence the pathogenesis of these tumors and discuss currently available therapies. Although recent molecular studies have advanced our understanding of the pathogenesis and behavior of these refractory corticotroph adenomas, these insights do not reliably guide treatment choices at present. Development of additional diagnostic tools and novel tumor-directed therapies that offer efficacious treatment choices for patients with refractory corticotroph adenomas are needed.
Topics: Humans; ACTH-Secreting Pituitary Adenoma; Adenoma; Pituitary Neoplasms
PubMed: 36917358
DOI: 10.1007/s11102-023-01308-5 -
Science Advances Apr 2023Despite improvements in microscopically neurosurgical techniques made in recent years, the prognosis of adamantinomatous craniopharyngioma (ACP) is still unsatisfactory....
Despite improvements in microscopically neurosurgical techniques made in recent years, the prognosis of adamantinomatous craniopharyngioma (ACP) is still unsatisfactory. Little is known about cellular atlas and biological features of ACP. Here, we carried out integrative analysis of 44,038 single-cell transcriptome profiles to characterize the landscape of intratumoral heterogeneity and tumor microenvironment (TME) in ACP. Four major neoplastic cell states with distinctive expression signatures were defined, which further revealed the histopathological features and elucidated unknown cellular atlas of ACP. Pseudotime analyses suggested potential evolutionary trajectories between specific neoplastic cell states. Notably, a distinct oligodendrocyte lineage was identified in ACP, which was associated with immunological infiltration and neural damage. In addition, we described a tumor-centric regulatory network based on intercellular communication in TME. Together, our findings represent a unique resource for deciphering tumor heterogeneity of ACP, which will improve clinical diagnosis and treatment strategies.
Topics: Humans; Craniopharyngioma; Pituitary Neoplasms; Transcriptome; Cell Communication; Sequence Analysis, RNA; Tumor Microenvironment
PubMed: 37043580
DOI: 10.1126/sciadv.adc8933 -
Medicina (Kaunas, Lithuania) Apr 2023Pituitary neuroendocrine tumors (PitNETs), the third most common intracranial tumor, are mostly benign. However, some of them may display a more aggressive behavior,... (Review)
Review
Pituitary neuroendocrine tumors (PitNETs), the third most common intracranial tumor, are mostly benign. However, some of them may display a more aggressive behavior, invading into the surrounding structures. While they may rarely metastasize, they may resist different treatment modalities. Several major advances in molecular biology in the past few years led to the discovery of the possible mechanisms involved in pituitary tumorigenesis with a possible therapeutic implication. The mutations in the different proteins involved in the Gsa/protein kinase A/c AMP signaling pathway are well-known and are responsible for many PitNETS, such as somatotropinomas and, in the context of syndromes, as the McCune-Albright syndrome, Carney complex, familiar isolated pituitary adenoma (FIPA), and X-linked acrogigantism (XLAG). The other pathways involved are the MAPK/ERK, PI3K/Akt, Wnt, and the most recently studied HIPPO pathways. Moreover, the mutations in several other tumor suppressor genes, such as and , are responsible for the MEN1 and MEN4 syndromes and succinate dehydrogenase (SDHx) in the context of the 3PAs syndrome. Furthermore, the pituitary stem cells and miRNAs hold an essential role in pituitary tumorigenesis and may represent new molecular targets for their diagnosis and treatment. This review aims to summarize the different cell signaling pathways and genes involved in pituitary tumorigenesis in an attempt to clarify their implications for diagnosis and management.
Topics: Humans; Syndrome; Phosphatidylinositol 3-Kinases; Pituitary Gland; Pituitary Neoplasms; Carcinogenesis; Cell Transformation, Neoplastic
PubMed: 37109772
DOI: 10.3390/medicina59040812 -
The Ulster Medical Journal Sep 2021The pituitary gland is an unusual site for metastatic spread and has been associated with a poor prognosis. Clinical presentation is variable but can include visual... (Review)
Review
The pituitary gland is an unusual site for metastatic spread and has been associated with a poor prognosis. Clinical presentation is variable but can include visual field defects, cranial nerve palsies, anterior pituitary dysfunction and/ or diabetes insipidus. Management options include surgery or radiotherapy, chemotherapy/immunotherapy or a conservative approach. The pituitary should not be overlooked as a site for metastasis in patients with known cancer and can be the first presentation of neoplastic disease in some patients. Given that patients are now living longer with cancer, clinicians should be alert to the varied presentation of pituitary metastasis. We provide a clinical overview of pituitary metastasis with the aid of illustrative clinical cases.
Topics: Diabetes Insipidus; Humans; Pituitary Neoplasms
PubMed: 34815592
DOI: No ID Found -
Otolaryngologic Clinics of North America Apr 2022Cushing disease is a disorder of hypercortisolemia caused by hypersecretion of adrenocorticotropic hormone by a pituitary adenoma and is a rare diagnosis. Cushing... (Review)
Review
Cushing disease is a disorder of hypercortisolemia caused by hypersecretion of adrenocorticotropic hormone by a pituitary adenoma and is a rare diagnosis. Cushing disease presents with characteristic clinical signs and symptoms associated with excess cortisol, but diagnosis is difficult and often relies on repeated and varied endocrinologic assays and neuroradiologic investigations. Gold standard treatment is surgical resection of adrenocorticotropic hormone-secreting pituitary adenoma, which is curative. Patients require close endocrinologic follow-up for maintenance of associated neuroendocrine deficiencies and surveillance for potential recurrence. Medications, radiation therapy, and bilateral adrenalectomy are alternative treatments for residual or recurrent disease.
Topics: ACTH-Secreting Pituitary Adenoma; Adenoma; Humans; Pituitary ACTH Hypersecretion; Pituitary Neoplasms
PubMed: 35256173
DOI: 10.1016/j.otc.2021.12.006 -
Frontiers in Endocrinology 2022Acromegaly is a disease that occurs secondary to high levels of GH, most often from a hormone-secreting pituitary adenoma, with multisystem adverse effects. Diagnosis... (Review)
Review
Acromegaly is a disease that occurs secondary to high levels of GH, most often from a hormone-secreting pituitary adenoma, with multisystem adverse effects. Diagnosis includes serum GH and IGF-1 levels, and obtaining an MRI pituitary protocol to assess for a functional pituitary adenoma. Attempted gross total resection of the GH-secreting adenoma is the gold standard in treatment for patients with acromegaly for a goal of biochemical remission. Medical and radiation therapies are available when patients do not achieve biochemical cure after surgical therapy.
Topics: Acromegaly; Adenoma; Goals; Growth Hormone-Secreting Pituitary Adenoma; Humans; Pituitary Neoplasms
PubMed: 35992136
DOI: 10.3389/fendo.2022.924589 -
Neuroendocrinology 2020The pituitary fossa is an uncommon site for metastatic tumor spread. Metastatic lesions to the sellar area derived mostly from breast, lung, renal, prostate, and colon... (Review)
Review
The pituitary fossa is an uncommon site for metastatic tumor spread. Metastatic lesions to the sellar area derived mostly from breast, lung, renal, prostate, and colon cancers, and rarely from other solid and hematologic malignancies. Almost every cancer has been reported as a source of pituitary metastasis. Pituitary metastasis can involve both the anterior and posterior lobes, but the neuro-hypophysis is mainly involved. Clinical manifestations include diabetes insipidus, hypopituitarism, headache, visual disturbances, ophthalmoplegia, and also compression of adjacent structures by aggressive tumor masses. Metastatic spread to the pituitary from a distant primary malignancy is commonly associated with metastases to other tissues and poor prognosis, unless efficient systemic targeted medical treatment is available for the primary cancer (melanoma, lymphoma).
Topics: Humans; Pituitary Neoplasms
PubMed: 32101869
DOI: 10.1159/000506810 -
Neuroendocrinology 2020The parasellar region, located around the sella turcica, is an anatomically complex area representing a crossroads for important adjacent structures. Several lesions,... (Review)
Review
The parasellar region, located around the sella turcica, is an anatomically complex area representing a crossroads for important adjacent structures. Several lesions, including tumoral, inflammatory vascular, and infectious diseases may affect this area. Although invasive pituitary tumors are the most common neoplasms encountered within the parasellar region, other tumoral (and cystic) lesions can also be detected. Craniopharyngiomas, meningiomas, as well as Rathke's cleft cysts, chordomas, and ectopic pituitary tumors can primarily originate from the parasellar region. Except for hormone-producing ectopic pituitary tumors, signs and symptoms of these lesions are usually nonspecific, due to a mass effect on the surrounding anatomical structures (i.e., headache, visual defects), while a clinically relevant impairment of endocrine function (mainly anterior hypopituitarism and/or diabetes insipidus) can be present if the pituitary gland is displaced or compressed. Differential diagnosis of parasellar lesions mainly relies on magnetic resonance imaging, which should be interpreted by neuroradiologists skilled in base skull imaging. Neurosurgery is the main treatment, alone or in combination with radiotherapy. Of note, recent studies have identified gene mutations or signaling pathway modulators that represent potential candidates for the development of targeted therapies, particularly for craniopharyngiomas and meningiomas. In summary, parasellar lesions still represent a diagnostic and therapeutic challenge. A deeper knowledge of this complex anatomical site, the improvement of imaging tools, as well as novel insights into the pathophysiology of presenting lesions are strongly needed to improve the management of parasellar lesions.
Topics: Brain Neoplasms; Cavernous Sinus; Humans; Pituitary Neoplasms; Sella Turcica
PubMed: 32126547
DOI: 10.1159/000506905