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  • 1
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    Online Resource
    An unusual case of an ACTH-secreting macroadenoma with a germline variant in the aryl hydrocarbon receptor-interacting protein (AIP) gene
    Bioscientifica ; 2015
    In:  Endocrinology, Diabetes & Metabolism Case Reports Vol. 2015 ( 2015-01-1)
    Details
    In: Endocrinology, Diabetes & Metabolism Case Reports, Bioscientifica, Vol. 2015 ( 2015-01-1)
    Abstract: A patient of Cushing's disease (CD) characterized by a large tumor and only subtle symptoms of hormonal hypersecretion was examined. The patient had a germline variant in the aryl hydrocarbon receptor-interacting protein ( AIP ) gene. A 50-year-old male presenting with headache was diagnosed with a large pituitary tumor by magnetic resonance imaging (MRI). His visual fields were intact and he exhibited no features of CD. Owing to an exuberant response to synacthen, an overnight dexamethasone suppression test was performed revealing inadequate suppression of plasma cortisol (419 nmol/l). Owing to tumor growth and visual field impairment, he underwent transsphenoidal surgery and developed hypocortisolemia. The pathology specimen revealed a sparsely granulated corticotrope adenoma. Postoperative MRI showed a large tumor remnant. The patient developed skin hyperpigmentation and a synacthen test demonstrated high basal and stimulated cortisol levels; an overnight dexamethasone suppression test showed no suppression (791 nmol/l) and elevated plasma ACTH levels (135 ng/l). A transcranial operation was performed followed by radiotherapy. Two months after radiotherapy, he developed secondary adrenocortical failure. Genetic testing revealed an AIP variant of unknown significance (p.R16H) without loss of the normal AIP allele in the tumor. A literature review showed ten CD patients with AIP gene variants, of whom five (including our case) were p.R16H. CD is occasionally dominated by pituitary tumor growth rather than symptoms of hypersecretion. The particular AIP gene variant identified in our patient is shared by four other reported cases of CD. Future studies are needed to assess whether the reported AIP gene variant is more than just coincidental. Learning points CD is occasionally dominated by pituitary tumor growth rather than symptoms of hypersecretion. Resolution of both tumor remnant and hormonal hypersecretion may occur within 2 months after postoperative radiotherapy. The particular AIP gene variant identified in our patient is shared by four other reported cases of CD.
    Type of Medium: Online Resource
    ISSN: 2052-0573
    URL: Article
    DOI: 10.1530/EDM-14-0105
    Language: Unknown
    Publisher: Bioscientifica
    Publication Date: 2015
    detail.hit.zdb_id: 2785530-2
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  • 2
    Online Resource
    Online Resource
    Pituitary carcinoma: reclassification and implications in the NET schema
    Bioscientifica ; 2022
    In:  Endocrine Oncology Vol. 2, No. 1 ( 2022-04-01), p. R14-R23
    Details
    In: Endocrine Oncology, Bioscientifica, Vol. 2, No. 1 ( 2022-04-01), p. R14-R23
    Abstract: The entity known as pituitary carcinoma has been traditionally defined as a tumor of adenohypophysial cells that metastasizes systemically or craniospinally independent of the histological appearance of the lesion. Reported cases of pituitary carcinoma have clinically and histologically resembled their non-metastatic counterparts that were classified as adenomas; the majority of cases were initially diagnosed as adenomas, and with tumor progression and spread, the diagnosis was changed to carcinoma. This classification has been challenged since the definition of malignancy in most organs is not based only on metastatic spread. The extent of local invasion resulting in an inability to completely resect an adenohypophysial tumor can have serious consequences that can cause harm and are therefore not benign. To address this dilemma, it was proposed that pituitary tumors be classified as neuroendocrine tumors. This change in nomenclature is totally appropriate since these tumors are composed of classical neuroendocrine cells; as with other neuroendocrine tumors, they have variable behavior that can be indolent but can involve metastasis. With the new nomenclature, there is no requirement for a distinction between adenomas and carcinomas. Moreover, the WHO/IARC has provided an overarching classification for neuroendocrine neoplasms at all body sites; in this new classification, the term ‘neuroendocrine carcinoma’ is reserved for poorly differentiated high-grade malignancies that are clinically, morphologically and genetically distinct from well-differentiated neuroendocrine tumors. It remains to be determined if there are true pituitary neuroendocrine carcinomas.
    Type of Medium: Online Resource
    ISSN: 2634-4793
    URL: Article
    DOI: 10.1530/EO-22-0041
    Language: Unknown
    Publisher: Bioscientifica
    Publication Date: 2022
    detail.hit.zdb_id: 3143825-8
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  • 3
    Online Resource
    Online Resource
    Molecular profiling confirms historical immunohistochemistry in acromegaly
    Bioscientifica ; 2020
    In:  Endocrine-Related Cancer Vol. 27, No. 10 ( 2020-10), p. L1-L2
    Details
    In: Endocrine-Related Cancer, Bioscientifica, Vol. 27, No. 10 ( 2020-10), p. L1-L2
    Type of Medium: Online Resource
    ISSN: 1351-0088 , 1479-6821
    URL: Article
    DOI: 10.1530/ERC-20-0260
    Language: Unknown
    Publisher: Bioscientifica
    Publication Date: 2020
    detail.hit.zdb_id: 2010895-3
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  • 4
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    Online Resource
    Pituitary acromegaly: not one disease
    Bioscientifica ; 2017
    In:  Endocrine-Related Cancer Vol. 24, No. 3 ( 2017-03), p. C1-C4
    Details
    In: Endocrine-Related Cancer, Bioscientifica, Vol. 24, No. 3 ( 2017-03), p. C1-C4
    Abstract: Acromegaly has traditionally been regarded as a monomorphous disorder resulting from a benign pituitary adenoma. Increasing evidence, however, is highlighting that this disorder is associated with a spectrum of morphologically distinct pituitary tumors with variable clinical, biochemical and radiologic features and differing therapeutic outcomes that are attributed to different genetic and epigenetic changes. These data underscore the need for developing a more refined clinicopathological risk stratification system and implementing personalized targeted therapeutic approaches.
    Type of Medium: Online Resource
    ISSN: 1351-0088 , 1479-6821
    URL: Article
    DOI: 10.1530/ERC-16-0496
    Language: Unknown
    Publisher: Bioscientifica
    Publication Date: 2017
    detail.hit.zdb_id: 2010895-3
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  • 5
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    Online Resource
    The emerging role of the Ikaros stem cell factor in the neuroendocrine system
    Bioscientifica ; 2008
    In:  Journal of Molecular Endocrinology Vol. 41, No. 2 ( 2008-05-29), p. 45-51
    Details
    In: Journal of Molecular Endocrinology, Bioscientifica, Vol. 41, No. 2 ( 2008-05-29), p. 45-51
    Abstract: In this review, we cover the evidence implicating Ikaros as a key factor whose transcriptional actions and chromatin remodeling properties determine the fate of hypothalamic neuroendocrine and pituitary cell population expansion. We propose that the governing mechanisms involved in the regulation and action of Ikaros are of importance during developmental as well as neoplastic transitions.
    Type of Medium: Online Resource
    ISSN: 0952-5041 , 1479-6813
    URL: Article
    DOI: 10.1677/JME-08-0045
    Language: Unknown
    Publisher: Bioscientifica
    Publication Date: 2008
    detail.hit.zdb_id: 1478171-2
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  • 6
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    Online Resource
    NG2 targets tumorigenic Rb inactivation in Pit1-lineage pituitary cells
    Bioscientifica ; 2016
    In:  Endocrine-Related Cancer Vol. 23, No. 5 ( 2016-05), p. 445-456
    Details
    In: Endocrine-Related Cancer, Bioscientifica, Vol. 23, No. 5 ( 2016-05), p. 445-456
    Abstract: The proteoglycan neuron-glial antigen 2 (NG2) is expressed by oligodendrocyte progenitors, pericytes, and some cancerous cells where it is implicated in tumor development. We examined mice with NG2-driven pRb inactivation. Unexpectedly, NG2-Cre:pRb flox/flox mice developed pituitary tumors with high penetrance. Adenohypophysial neoplasms developed initially as multifocal lesions; by 1 year, large tumors showed brain invasion. Immunohistochemistry identified these as Pit1-lineage neoplasms, with variable immunoreactivity for growth hormone, prolactin, thyrotropin, and α-subunit of glycoprotein hormones. Other than modest hyperprolactinemia, circulating hormone levels were not elevated. To determine the role of NG2 in the pituitary, we investigated NG2 expression. Immunoreactivity was identified in anterior and posterior lobes but not in the intermediate lobe of the mouse pituitary; in the adenohypophysis, folliculostellate cells had the strongest NG2 immunoreactivity but showed no proliferation in response to Rb inactivation. Pit1-positive adenohypophysial cells were positive for NG2, but corticotroph and gonadotroph cells were negative. RT-PCR revealed NG2 expression in normal human pituitary and human pituitary tumors; immunohistochemistry localized NG2 in nontumorous human adenohypophysis with strongest positivity in folliculostellate cells, and in tumors of all types except corticotrophs. Functional studies in GH4 mammosomatotrophs showed that NG2 increases prolactin (PRL), reduces growth hormone (GH) expression, and enhances cell adhesion without influencing proliferation. In conclusion, NG2-driven pRb inactivation results in pituitary tumors that mimic endocrinologically inactive Pit1-lineage human pituitary tumors. This model identifies a role for NG2 in pituitary cell-type-specific functions and unmasks a protective role from Rb inactivation in folliculostellate cells; it can be used for further research, including preclinical testing of novel therapies.
    Type of Medium: Online Resource
    ISSN: 1351-0088 , 1479-6821
    URL: Article
    DOI: 10.1530/ERC-16-0013
    Language: Unknown
    Publisher: Bioscientifica
    Publication Date: 2016
    detail.hit.zdb_id: 2010895-3
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  • 7
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    Online Resource
    The PI3K/AKT/mTOR pathway in the pathophysiology and treatment of pituitary adenomas
    Bioscientifica ; 2014
    In:  Endocrine-Related Cancer Vol. 21, No. 4 ( 2014-08), p. R331-R344
    Details
    In: Endocrine-Related Cancer, Bioscientifica, Vol. 21, No. 4 ( 2014-08), p. R331-R344
    Abstract: Pituitary adenomas are common intracranial neoplasms. Patients with these tumors exhibit a wide range of clinically challenging problems, stemming either from results of sellar mass effect in pituitary macroadenoma or the diverse effects of aberrant hormone production by adenoma cells. While some patients are cured/controlled by surgical resection and/or medical therapy, a proportion of patients exhibit tumors that are refractory to current modalities. New therapeutic approaches are needed for these patients. Activation of the AKT/phophotidylinositide-3-kinase pathway, including mTOR activation, is common in human neoplasia, and a number of therapeutic approaches are being employed to neutralize activation of this pathway in human cancer. This review examines the role of this pathway in pituitary tumors with respect to tumor biology and its potential role as a therapeutic target.
    Type of Medium: Online Resource
    ISSN: 1351-0088 , 1479-6821
    URL: Article
    DOI: 10.1530/ERC-14-0188
    Language: Unknown
    Publisher: Bioscientifica
    Publication Date: 2014
    detail.hit.zdb_id: 2010895-3
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  • 8
    Online Resource
    Online Resource
    Expression of the melanoma-associated antigen is associated with progression of human thyroid cancer
    Bioscientifica ; 2009
    In:  Endocrine-Related Cancer Vol. 16, No. 2 ( 2009-06), p. 455-466
    Details
    In: Endocrine-Related Cancer, Bioscientifica, Vol. 16, No. 2 ( 2009-06), p. 455-466
    Abstract: Thyroid cancer exhibits a spectrum from relatively indolent tumors to tumors that are invasive, metastatic, or progress to poorly differentiated carcinoma. Microarray expression analysis of thyroid cancer cell lines has implicated a member of the melanoma-associated (MAGE) family of cancer–testis antigens in thyroid cancer development and progression. We performed this study to validate the role of MAGE in human thyroid cancers. A tissue microarray (TMA) of samples from 375 patients with thyroid cancer was analyzed with immunohistochemistry (IHC) to localize MAGE. Western blotting of fractionated proteins from MAGE-transfected cells was used to confirm intracellular localization of proteins. Automated analysis of TMA samples was evaluated and subjected to statistical analysis. MAGE immunoreactivity was identified in nuclear and cytoplasmic compartments of normal and malignant tissues. Specificity of staining was proved by fractionation studies that confirmed MAGE expression in nucleus and cytoplasm. Normal thyroid tissue exhibited weak cytoplasmic and strong nuclear MAGE reactivity. Tumors exhibited an increase in cytoplasmic MAGE scores that correlated with clinical behavior: larger tumors had higher MAGE scores, and there was a positive and significant correlation between MAGE cytoplasmic score and the number of histologically proven lymph node metastases. There was a statistically significant negative correlation between cytoplasmic MAGE and the percentage of p53-positive nuclei. Our data confirm gene-profiling evidence that members of the MAGE family play a role in thyroid cancer progression. The use of TMA analyses identifies IHC techniques that are translatable to the clinical setting for prognostic assessment of patients with thyroid cancer.
    Type of Medium: Online Resource
    ISSN: 1351-0088 , 1479-6821
    URL: Article
    DOI: 10.1677/ERC-09-0002
    Language: Unknown
    Publisher: Bioscientifica
    Publication Date: 2009
    detail.hit.zdb_id: 2010895-3
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  • 9
    Online Resource
    Online Resource
    Ectopic Cushing’s syndrome from a corticotropin-releasing hormone-secreting medullary thyroid carcinoma: a rare pitfall of inferior petrosal sinus sampling
    Bioscientifica ; 2023
    In:  Endocrinology, Diabetes & Metabolism Case Reports Vol. 2023, No. 3 ( 2023-07-01)
    Details
    In: Endocrinology, Diabetes & Metabolism Case Reports, Bioscientifica, Vol. 2023, No. 3 ( 2023-07-01)
    Abstract: This case report describes a rare presentation of ectopic Cushing’s syndrome (CS) due to ectopic corticotropin-releasing hormone (CRH) production from a medullary thyroid carcinoma (MTC). The patient, a 69-year-old man, presented with symptoms of muscle weakness, facial plethora, and easy bruising. An inferior petrosal sinus sampling test (IPSS) demonstrated pituitary adrenocorticotrophic hormone (ACTH) secretion, but a whole-body somatostatin receptor scintigraphy ( 68 Ga-DOTATOC PET/CT) revealed enhanced uptake in the right thyroid lobe which, in addition to a grossly elevated serum calcitonin level, was indicative of an MTC. A 18 F-DOPA PET/CT scan supported the diagnosis, and histology confirmed the presence of MTC with perinodal growth and regional lymph node metastasis. On immunohistochemical analysis, the tumor cell stained positively for calcitonin and CRH but negatively for ACTH. Distinctly elevated plasma CRH levels were documented. The patient therefore underwent thyroidectomy and bilateral adrenalectomy. This case shows that CS caused by ectopic CRH secretion may masquerade as CS due to a false positive IPSS test. It also highlights the importance of considering rare causes of CS when diagnostic test results are ambiguous. Learning points Medullary thyroid carcinoma may secrete CRH and cause ectopic CS. Ectopic CRH secretion entails a rare pitfall of inferior petrosal sinus sampling yielding a false positive test. Plasma CRH measurements can be useful in selected cases.
    Type of Medium: Online Resource
    ISSN: 2052-0573
    URL: Article
    DOI: 10.1530/EDM-23-0057
    Language: Unknown
    Publisher: Bioscientifica
    Publication Date: 2023
    detail.hit.zdb_id: 2785530-2
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  • 10
    Online Resource
    Online Resource
    Biomarkers of aggressive pituitary adenomas
    Bioscientifica ; 2012
    In:  Journal of Molecular Endocrinology Vol. 49, No. 2 ( 2012-07-19), p. R69-R78
    Details
    In: Journal of Molecular Endocrinology, Bioscientifica, Vol. 49, No. 2 ( 2012-07-19), p. R69-R78
    Abstract: Pituitary adenomas exhibit a wide range of behaviors. The prediction of aggressive or malignant behavior in pituitary adenomas remains challenging; however, the utility of biomarkers is rapidly evolving. In this review, we discuss potential biomarkers as they relate to aggressive behavior in pituitary adenomas. While detailed histological subtyping remains the best independent predictor of aggressive behavior in the majority of cases, evidence suggests that the additional analyses of FGFR4, MMP, PTTG, Ki-67, p53, and deletions in chromosome 11 may contribute to decisions concerning management of aggressive pituitary adenomas.
    Type of Medium: Online Resource
    ISSN: 0952-5041 , 1479-6813
    URL: Article
    DOI: 10.1530/JME-12-0113
    Language: Unknown
    Publisher: Bioscientifica
    Publication Date: 2012
    detail.hit.zdb_id: 1478171-2
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