Prevalence of clinically silent corticotroph macroadenomas

Guttenberg, Katie B.; Mayson, Sarah E.; Sawan, Carla; Kharlip, Julia; Martinez‐Lage, Maria; Loevner, Laurie A.; Ewanichak, Jayme; Grady, M. Sean; Snyder, Peter J.

doi:10.1111/cen.13146

Cited by 19 publications

(10 citation statements)

References 30 publications

(84 reference statements)

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“…We observed that multiple microcysts appeared more often in ACTH-negative SCAs (81.8% vs. 61.5%, P = 0.022) than in ACTH-positive cases. According to the literature, more cysts were observed in SCAs (only ACTH-positive cases included) than NFPAs, with 75% of them showing multiple microcysts, which agrees with our results (61.5% of ACTH-positive SCAs and 81.8% of ACTH-negative SCAs showed multiple microcysts) ( 7 , 8 ). However, this imaging manifestation also appeared in most null cell adenomas and gonadotroph adenomas according to some series ( 8 ).…”

Section: Discussionsupporting

confidence: 92%

“…According to the literature, more cysts were observed in SCAs (only ACTH-positive cases included) than NFPAs, with 75% of them showing multiple microcysts, which agrees with our results (61.5% of ACTH-positive SCAs and 81.8% of ACTH-negative SCAs showed multiple microcysts) ( 7 , 8 ). However, this imaging manifestation also appeared in most null cell adenomas and gonadotroph adenomas according to some series ( 8 ). In other words, ACTH-negative SCAs and null cell adenomas were similar in lack of hormone secretion and imaging findings, though differ greatly in recurrence rate ( 9 ).…”

Section: Discussionsupporting

confidence: 92%

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Clinical Parameters of Silent Corticotroph Adenomas With Positive and Negative Adrenocorticotropic Hormone Immunostaining: A Large Retrospective Single-Center Study of 105 Cases

et al. 2021

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PurposeTo investigate the different clinical characteristics of silent corticotroph adenomas (SCAs) with positive and negative adrenocorticotropic hormone (ACTH) immunostaining, and to explore the value of pituitary-restricted transcription factor (Tpit) immunostaining for diagnosing SCAs.MethodsThe clinical materials of patients with SCAs who had a typical pathological feature with positive Tpit immunostaining and positive/negative ACTH immunostaining, and without clinical features and biochemical evidence for Cushing’s Syndrome in our center from April 2018 to March 2019 were analyzed retrospectively. The differences in clinical characteristics and surgical results between ACTH-positive and -negative SCAs were explored.ResultsA total of one hundred and five patients (94.3% female) with SCAs were included. There were 66 SCAs with ACTH-negative (66/105, 62.9%), and 39 SCAs with ACTH-positive (39/105, 37.1%). Cases with ACTH-negative SCAs were more likely to have lower ACTH levels (27.5 ± 24.0 vs. 54.4 ± 58.6, P = 0.011), more multiple microcysts (81.8% vs. 61.5%, P = 0.022) and lower levels of Ki-67 expression (low expression rate 90.9% vs. 74.4%, P = 0.023). No statistical significant differences were observed between patients with ACTH-positive and -negative SCAs regarding gender (97.0% vs. 89.7%, P = 0.192), age (50.3 ± 10.3 vs. 49.0 ± 11.2, P = 0.543), surgical history (16.7% vs. 23.1%, P = 0.419), suprasellar extension (66.7% vs. 74.4%, P = 0.408), sphenoid sinus extension (51.5% vs. 56.4%, P = 0.627), cavernous sinus invasion (75.8% vs. 66.7%, P = 0.314), large cyst on Magnetic Resonance Imaging (MRI) (47.0% vs. 61.5%, P = 0.149), or gross total resection rate (42.4% vs. 51.3%, P = 0.379).ConclusionsACTH-negative SCAs were observed to be more clinically silent and more likely to demonstrate multiple microcysts on MRI. The prevalence of SCAs, especially ACTH-negative SCAs, proved to be substantially underestimated and thus they should be given enough attention in consideration of the high aggressiveness of this subtype of refractory pituitary adenoma (PA).

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 92%

Clinical Parameters of Silent Corticotroph Adenomas With Positive and Negative Adrenocorticotropic Hormone Immunostaining: A Large Retrospective Single-Center Study of 105 Cases

et al. 2021

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“…In some cases, corticotroph tumors are discovered during examination or analyses in patients showing no clinical signs of Cushing's disease and these are termed silent corticotroph tumors. Diagnosis of such tumors arises because of symptoms related to tumor mass, symptoms of hyperprolactinemia or pituitary deficiency, and they are often classified as non-functioning pituitary tumors (4,5). Treatment of Cushing's disease is obligatory in order to control cortisol excess and to prevent morbi-mortality.…”

Section: Introductionmentioning

confidence: 99%

SST5 expression and USP8 mutation in functioning and silent corticotroph pituitary tumors

Castellnou

Vasiljevic

Lapras

et al. 2020

Endocrine Connections

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Objective Somatostatin receptor type 5 (SST5) is inconsistently expressed by corticotroph tumors, with higher expression found in corticotropinomas having ubiquitin-specific protease 8 (USP8) mutations. Aims were to study the correlation between characteristics of corticotropinomas and SST5 expression/USP8 mutation status and to describe the response to pasireotide in five patients. Design Retrospective cohort study. Methods Clinico-biochemical, radiological and pathological data of 62 patients, operated for a functioning or silent corticotropinoma between 2013 and 2017, were collected. SST5 expression was measured by immunohistochemistry (clone UMB-4, Abcam, IRS > 1 being considered positive), and Sanger sequencing was performed on 50 tumors to screen for USP8 mutations. Results SST5 expression was positive in 26/62 pituitary tumors. A moderate or strong IRS was found in 15/58 corticotropinomas and in 13/35 functioning corticotropinomas. Among functioning tumors, those expressing SST5 were more frequent in women (22/24 vs 9/15, P = 0.04) and had a lower grade (P = 0.04) compared to others. USP8 mutations were identified in 13/50 pituitary tumors and were more frequent in functioning compared to silent tumors (11/30 vs 2/20, P = 0.05). SST5 expression was more frequent in USP8mut vs USP8wt tumors (10/11 vs 7/19, P = 0.007). Among treated patients, normal urinary free cortisol levels were obtained in three patients (IRS 0, 2 and 6), while a four-fold decrease was observed in one patient (IRS 4). Conclusion SST5 expression appears to be associated with functioning, USP8mut and lower grade corticotropinomas. A correlation between SST5 expression or USP8mut and response to pasireotide remains to be confirmed.

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“…When a macro‐adenoma is not compressing the chiasm, the decision to operate is less clear‐cut as the small risks of surgery might arguably be greater than the risk of clinical harm from the untreated adenoma. Whether to send postoperative patients with residual tumour for repeat surgery or radiotherapy (RT) is also not clear‐cut and depends on tumour factors (such as size of residuum, presensce of immuno‐staining for ACTH, and extrasellar extension) and patient factors (such as age, comorbidity and patient preference). The management is also influenced by whether the clinical team is more interventionist or conservative by nature.…”

Section: Introductionmentioning

confidence: 99%

Long‐term follow‐up of a large prospective cohort of patients with nonfunctioning pituitary adenomas: The outcome of a conservative management policy

Levy

Robertson

Khalk

et al. 2018

Clinical Endocrinology

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Prevalence of clinically silent corticotroph macroadenomas

Cited by 19 publications

References 30 publications

Clinical Parameters of Silent Corticotroph Adenomas With Positive and Negative Adrenocorticotropic Hormone Immunostaining: A Large Retrospective Single-Center Study of 105 Cases

Clinical Parameters of Silent Corticotroph Adenomas With Positive and Negative Adrenocorticotropic Hormone Immunostaining: A Large Retrospective Single-Center Study of 105 Cases

SST5 expression and USP8 mutation in functioning and silent corticotroph pituitary tumors

Long‐term follow‐up of a large prospective cohort of patients with nonfunctioning pituitary adenomas: The outcome of a conservative management policy

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