Abstract

Simple SummaryThe 2017 World Health Organization classification of endocrine tumors defines pituitary adenomas based on their cell lineages. T-PIT can serve as a complimentary tool for further identification of silent corticotroph adenomas (SCAs). Unlike functioning corticotroph adenomas in patients with Cushing’s disease, SCAs present no clinical and biochemical features of Cushing’s syndrome. SCAs have been shown to exhibit a more aggressive course characterized by a higher probability of recurrence and resistance to conventional treatment due to their intrinsic histological features. The aim of our review is to offer an update on the diagnosis, mechanisms, clinical features and management of SCAs. Studies of the molecular mechanisms of SCA pathogenesis will provide new directions for the diagnosis and management of SCAs.With the introduction of 2017 World Health Organization (WHO) classification of endocrine tumors, T-PIT can serve as a complementary tool for identification of silent corticotroph adenomas (SCAs) in some cases if the tumor is not classifiable by pituitary hormone expression in pathological tissue samples. An increase of the proportion of SCAs among the non-functioning pituitary adenomas (NFPAs) has been witnessed under the new rule with the detection of T-PIT-positive ACTH-negative SCAs. Studies of molecular mechanisms related to SCA pathogenesis will provide new directions for the diagnosis and management of SCAs. A precise pathological diagnosis can help clinicians better identify SCAs. Understanding clinical features in the context of the pathophysiology of SCAs is critical for optimal management. It could provide information on appropriate follow-up time and aid in early recognition and treatment of potentially aggressive forms. Management approaches include surgical, radiation, and/or medical therapies.

Highlights

  • Silent corticotroph adenomas (SCAs) are a subtype of non-functioning pituitary adenomas (NFPAs)

  • If an adenoma, for NFPA, is still not classifiable by pituitary hormone expression according to a cell lineage, assessment of transcription factors may serve as a second-step complimentary tool for further classification, e.g., T-PIT in the case of silent corticotroph adenomas (SCAs)

  • This review provides an update on the SCA diagnostic approach; novel molecular mechanisms related to SCA pathogenesis, which are implicated in adrenocorticotropic hormone (ACTH) silence, growth, invasion, and aggressive behavior; and a summary of the clinical characteristics of SCAs and their management

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Summary

Introduction

Silent corticotroph adenomas (SCAs) are a subtype of non-functioning pituitary adenomas (NFPAs). If an adenoma, for NFPA, is still not classifiable by pituitary hormone expression according to a cell lineage, assessment of transcription factors may serve as a second-step complimentary tool for further classification, e.g., T-PIT in the case of SCAs. SCAs are reportedly highly proliferative and invasive [3,9,10,11,12]. SCAs are reportedly highly proliferative and invasive [3,9,10,11,12] They have been shown to exhibit a more aggressive course characterized by a higher probability of recurrence and resistance to conventional treatment and are classified as “high-risk” tumors according to the 2017 WHO classification system [6,7,13]. This review provides an update on the SCA diagnostic approach; novel molecular mechanisms related to SCA pathogenesis, which are implicated in ACTH silence, growth, invasion, and aggressive behavior; and a summary of the clinical characteristics of SCAs and their management

Identification of SCAs
Why Silent?
SCAs Could Represent Silent Cortico-Gonadotroph Adenomas?
Progression and Growth
Clinical Manifestations
Preoperative Diagnosis
Radiologic Characteristics
Postoperative Hypopituitarism
Recurrence
Recurrence Prediction
Transformation into CD
Management and Prognosis
Radiotherapy
Targeted Therapies
Chemotherapy
Findings
Conclusions
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