Immunochistochemical characteristics of blood vessels in non-visualized and visualized on MRI pituitary adenoma in patients with Cushing’s disease

2016 ◽  
Vol 62 (4) ◽  
pp. 11-17
Author(s):  
Patimat M. Khandaeva ◽  
Ija А. Voronkova ◽  
Zhanna E. Belaya ◽  
Ljudmila Ya. Rozhinskaya ◽  
Aleksandr V. Vorontsov ◽  
...  
Keyword(s):  
Pituitary Adenoma ◽  
Blood Vessels ◽  
Cushing’S Disease ◽  
Pituitary Tumor ◽  
Pituitary Tumors ◽  
Average Diameter ◽  
Cushing's Disease ◽  
Retrospective Evaluation ◽  
Acth Secreting ◽  
Microvessels Density

Background. Regardless of improvements in MRI, up to 20% of ACTH-secreting pituitary tumors are only identified at surgical exploration. Aim. Тo estimate whether there is any difference in blood vessels and the subsequent ability to uptake contrast agent in visualized microadenoma as compared to non-visualized on MRI ACTH-secreting pituitary tumors.Material and methods. Retrospective evaluation of ACTH-positive pituitary tumors from patients with Cushing’s disease (n=39) with either non-visualized pituitary tumor on MRI (n=17) or pituitary tumor less then 25 mm (n=22). MRI was performed using Siemens Magnetom Harmony 1.0T with gadolinium. Selected tumors were stained with anty-СD34 antibody (clone QBEnd/10, RTU, Leica) and anty-D2-40 antibody (clone D2-40, RTU, Dako). We evaluated the microvessels density and measured the diameter of larger and smaller vessel.Results. The microvessels density were not different in subject with visualized [123 (77; 136)] and non-visualized [112 (110,0; 126,5)] pituitary adenomas as well as number of slit-shaped vessels [32 (5; 50) in visualized vs 25 (5; 50) in non-visualized pituitary adenoma]. The diameter of these vessels also did not differ: the diameter of the largest vessels in patients without visualization 53 µm (32,5; 63,5) vs 33 µm (30,0; 51,5) the average diameter of the blood vessels 15 µm (14,5—26,0) against 13 µm (12; 14).Conclusions. The diameter and microvessels density in ACTH-producing pituitary adenoma does not affect the visualization of adenoma on MRI in patients with Cushing ‘s disease.

Immunochistochemical characteristics of blood vessels in non-visualized and visualized on MRI pituitary adenoma in patients with Cushing’s disease

2016 ◽  
Vol 62 (5) ◽  
pp. 65-66
Author(s):  
Patimat M. Khandaeva ◽  
Iya A. Voronkova ◽  
Zhanna E. Belaya ◽  
Lyudmila Y. Rozhinskaya ◽  
Aleksandr V. Vorontsov ◽  
...  
Keyword(s):  
Pituitary Adenoma ◽  
Blood Vessels ◽  
Cushing’S Disease ◽  
Pituitary Tumor ◽  
Pituitary Tumors ◽  
Average Diameter ◽  
Cushing's Disease ◽  
Retrospective Evaluation ◽  
Acth Secreting ◽  
Microvessels Density

Backgraund. Regardless of improvements in MRI, up to 20% of ACTH-secreting pituitary tumors are only identified at surgical exploration.Aim: to estimate whether there is any difference in blood vessels and the subsequent ability to uptake contrast agent in visualized microadenoma as compared to non-visualized on MRI ACTH-secreting pituitary tumors.Materials and methods. retrospective evaluation of ACTH-positive pituitary tumors from patients with Cushing’s disease (n=39) with either non-visualized pituitary tumor on MRI (n=17) or pituitary tumor less then 25 mm (n=22). MRI was performed using Siemens Magnetom Harmony 1.0T with gadolinium. Selected tumors were stained with anty-СD34 antibody (clone QBEnd/10, RTU, Leica) and anty-D2-40 antibody (clone D2-40, RTU, Dako). We evaluated the microvessels density and measured the diameter of larger and smaller vessel.Results. The microvessels density were not different in subject with visualized (123 [77;136]) and non-visualized (112 [110,0;126,5]) pituitary adenomas as well as number of slit-shaped vessels (32 [5;50] in visualized vs 25 [5;50] in non-visualized pituitary adenoma). The diameter of these vessels also did not differ: the diameter of the largest vessels in patients without visualization 53 µm [32,5;63,5] vs 33 µm [30,0;51,5], the average diameter of the blood vessels 15 µm [14,5-26,0] against 13 µm [12;14].Conclusions. The diameter and microvessels density in ACTH-producing pituitary adenoma does not affect the visualization of adenoma on MRI in patients with Cushing 's disease.

scholarly journals Two Distinctive POMC Promoters Modify Gene Expression in Cushing’s Disease

2021 ◽  
Author(s):  
Takako Araki ◽  
Yukiko Tone ◽  
Masaaki Yamamoto ◽  
Hiraku Kameda ◽  
Anat Ben-Shlomo ◽  
...  
Keyword(s):  
Cushing’S Disease ◽  
Methylation Status ◽  
Regulatory Region ◽  
Pituitary Tumors ◽  
Cushing's Disease ◽  
Human Pituitary ◽  
Ectopic Acth ◽  
Pomc Gene ◽  
Acth Secreting

Abstract Context Mechanisms underlying pituitary corticotroph adenoma ACTH production are poorly understood, yet circulating ACTH levels closely correlate with adenoma phenotype and clinical outcomes. Objective We characterized the 5’ ends of proopiomelanocortin (POMC) gene transcripts, which encode the precursor polypeptide for ACTH, in order to investigate additional regulatory mechanisms of POMC gene transcription and ACTH production. Methods We examined 11 normal human pituitary tissues, 32 ACTH-secreting tumors, as well as 6 silent pituitary corticotroph adenomas (SCA) that immunostain for but do not secrete ACTH. Results We identified a novel regulatory region located near the intron2/exon3 junction in the human POMC gene, which functions as a second promoter and an enhancer. In vitro experiments demonstrated that CREB binds the second promoter and regulates its transcriptional activity. The second promoter is highly methylated in SCA, partially demethylated in normal pituitary tissue, and highly demethylated in pituitary and ectopic ACTH-secreting tumors. In contrast, the first promoter is demethylated in all POMC-expressing cells and is highly demethylated only in pituitary ACTH-secreting tumors harboring the USP8 mutation. Demethylation patterns of the second promoter correlate with clinical phenotypes of Cushing’s disease. Conclusion We identified a second POMC promoter regulated by methylation status in ACTH-secreting pituitary tumors. Our findings open new avenues for elucidating subcellular regulation of the hypothalamic-pituitary-adrenal axis and suggest the second POMC promoter may be a target for therapeutic intervention to suppress excess ACTH production.

scholarly journals Successful long-term control of Cushing’s disease after partial resection of gigantic ACTH-secreting pituitary adenoma

2016 ◽  
Vol 2 (1) ◽  
pp. 88-93
Author(s):  
Vatroslav Čerina ◽  
◽  
Luigi Cavallo ◽  
Ivan Kruljac ◽  
Jelena Marinković Radošević ◽  
...  
Keyword(s):  
Pituitary Adenoma ◽  
Cushing’S Disease ◽  
Partial Resection ◽  
Cushing's Disease ◽  
Acth Secreting

scholarly journals Decoding the genetic basis of Cushing's disease: USP8 in the spotlight

2015 ◽  
Vol 173 (4) ◽  
pp. M73-M83 ◽  
Author(s):  
Marily Theodoropoulou ◽  
Martin Reincke ◽  
Martin Fassnacht ◽  
Masayuki Komada
Keyword(s):  
Cushing’S Disease ◽  
Growth Factor Receptor ◽  
Pituitary Tumors ◽  
Cushing's Disease ◽  
Tumor Subtypes ◽  
Important Regulator ◽  
Epidermal Growth ◽  
Acth Secreting

Cushing's disease (CD) arises from pituitary-dependent glucocorticoid excess due to an ACTH-secreting corticotroph tumor. Genetic hits in oncogenes and tumor suppressor genes that afflict other pituitary tumor subtypes are not found in corticotrophinomas. Recently, a somatic mutational hotspot was found in up to half of corticotrophinomas in the USP8 gene that encodes a protein that impairs the downregulation of the epidermal growth factor receptor (EGFR) and enables its constitutive signaling. EGF is an important regulator of corticotroph function and its receptor is highly expressed in Cushing's pituitary tumors, where it leads to increased ACTH synthesis in vitro and in vivo. The mutational hotspot found in corticotrophinomas hyper-activates USP8, enabling it to rescue EGFR from lysosomal degradation and ensure its stimulatory signaling. This review presents new developments in the study of the genetics of CD and focuses on the USP8-EGFR system as trigger and target of corticotroph tumorigenesis.

scholarly journals Cushing's disease due to an ACTH-secreting pharyngeal pituitary tumor

2001 ◽  
pp. 181-182 ◽  
Author(s):  
WY Lee ◽  
KW Oh ◽  
KH Yoon ◽  
MI Kang ◽  
BY Cha ◽  
...  
Keyword(s):  
Cushing’S Disease ◽  
Pituitary Tumor ◽  
Cushing's Disease ◽  
Acth Secreting ◽  
Pharyngeal Pituitary

A Woman with Weight Gain and Fatigue

2017 ◽  
Author(s):  
Alexandra Lovett ◽  
Whitney W. Woodmansee
Keyword(s):  
Pituitary Adenoma ◽  
Cushing’S Disease ◽  
Dexamethasone Suppression Test ◽  
Cushing's Disease ◽  
Distal Muscle ◽  
Suppression Test ◽  
Urine Cortisol ◽  
Acth Secreting ◽  
Dexamethasone Suppression ◽  
Transsphenoidal Resection

Cushing’s syndrome is a descriptive term of a syndrome secondary to elevated levels of steroids or cortisol, while Cushing’s disease is hypercortisolemia that results from an adrenocorticotropic (ACTH)-secreting pituitary adenoma. Patients will present with cushingoid features on physical examination and can be myopathic with proximal rather than distal muscle weakness. Diagnosis can be obtained by multiple avenues including but not limited to checking 24 hour urine cortisol, a dexamethasone suppression test, checking ACTH levels, a CRH (corticotrophin-releasing hormone) stimulation test, and inferior petrosal sinus sampling (IPSS). Once Cushing’s disease is confirmed, treatment is via transsphenoidal resection of the pituitary adenoma.

scholarly journals Systemic Sarcoidosis Unmasked by Cushing’s Disease Surgical Treatment

2016 ◽  
Vol 2016 ◽  
pp. 1-3 ◽  
Author(s):  
Daniele Bongetta ◽  
Cesare Zoia ◽  
Francesco Lombardi ◽  
Elisabetta Lovati ◽  
Pietro Lucotti ◽  
...  
Keyword(s):  
Surgical Treatment ◽  
Pituitary Adenoma ◽  
Cushing’S Syndrome ◽  
Cushing’S Disease ◽  
Cushing's Syndrome ◽  
Cushing's Disease ◽  
Systemic Sarcoidosis ◽  
Acth Secreting ◽  
Possible Cause

Diseases responsive to glucocorticoids, like sarcoidosis, are rarely masked by Cushing’s syndrome. An ACTH secreting pituitary adenoma is a possible cause of Cushing’s syndrome and its resection can make a subclinical sarcoidosis clear. Only few cases of sarcoidosis following the treatment of hypercortisolism are reported in literature. We report a case of sarcoidosis after the resection of an ACTH secreting pituitary adenoma.

scholarly journals Progression of an Invasive ACTH Pituitary Macroadenoma with Cushing’s Disease to Pituitary Carcinoma

2015 ◽  
Vol 2015 ◽  
pp. 1-4 ◽  
Author(s):  
Clarissa Groberio Borba ◽  
Rafael Loch Batista ◽  
Nina Rosa de Castro Musolino ◽  
Vanielle Carvalho Machado ◽  
Ana Elisa Evangelista Alcantara ◽  
...  
Keyword(s):  
Pituitary Adenoma ◽  
Cushing’S Disease ◽  
Adrenocorticotropic Hormone ◽  
Pituitary Carcinoma ◽  
Cushing's Disease ◽  
Resonance Imaging ◽  
Ki 67 ◽  
P53 Expression ◽  
Acth Secreting ◽  
Pituitary Carcinomas

Pituitary carcinomas are very rare tumors that in most cases produce prolactin and adrenocorticotropic hormone (ACTH). It is a challenge to diagnosis of a pituitary carcinoma before disclosed symptomatic metastasis. We report the case of a female patient with Cushing’s disease who underwent three transsphenoidal surgeries, with pathological findings of common ACTH pituitary adenoma including Ki-67 expression <3%. She achieved hypocortisolism after the 3rd surgery although ACTH levels remained slightly elevated. The patient returned some time later with fast worsening of hypercortisolism. Magnetic resonance imaging showed clivus invasion, which led to a fourth surgery and radiation. This time, immunohistochemistry revealed strong Ki-67 (10% to 15%) and p53 expression. Liver and lumbar spine metastases were found on workup. The patient died after few months due to lung infection. Pituitary carcinomas are rare, and the transformation of an ACTH-secreting pituitary adenoma into a carcinoma is exceptional. The difficulty of defining markers for the diagnosis of carcinoma, before metastasis diagnosis, in order to change the management of the disease, is a challenge.

Cushing's Disease in a Young Woman with Anorexia Nervosa: Pathophysiological Implications

1986 ◽  
Vol 31 (9) ◽  
pp. 861-864 ◽  
Author(s):  
Jack L. Katz ◽  
Herbert Weiner ◽  
Jacob Kream ◽  
Barnett Zumoff
Keyword(s):  
Anorexia Nervosa ◽  
Pituitary Adenoma ◽  
Young Woman ◽  
Cushing’S Syndrome ◽  
Cushing’S Disease ◽  
Adrenal Glands ◽  
Cushing's Syndrome ◽  
Cushing's Disease ◽  
Sequence Of Events ◽  
Acth Secreting

This report describes a 17-year old student who was found to have Cushing's syndrome two years after she had developed anorexia nervosa (AN). The Cushing's syndrome was treated with bilateral resection of enlarged, hyperplastic, non-tumoraus adrenal glands. The diagnosis was further confirmed four years later when, two to three years after new symptoms had appeared, an ACTH secreting pituitary adenoma (that is, Cushing's disease) was found on surgery. The possible mechanism for the development of Cushing's disease in a patient with prior anorexia nervosa, a sequence of events reported once previously, is discussed. It is suggested that increased hypothalamić-pituitary corticotroph stimulation in association with the anorexia nervosa, a now well-established endocrine phenomenon, activated an occult, inactive pituitary basophil adenoma in this patient, eventually resulting in autonomous pituitary overproduction of ACTH by the tumor.

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