Related Experiment Video

Updated: Jul 26, 2026

Fecal Glucocorticoid Analysis: Non-invasive Adrenal Monitoring in Equids
08:02

Fecal Glucocorticoid Analysis: Non-invasive Adrenal Monitoring in Equids

Published on: April 25, 2016

Why don't corticotroph tumors always produce Cushing's disease?

A García-Martínez1, D A Cano2, A Flores-Martínez2

  • 1Research Laboratory, Alicante General University Hospital-Institute for Health and Biomedical Research (ISABIAL), Alicante, Spain.

European Journal of Endocrinology
|July 19, 2019
PubMed
Abstract

Insights

Silent corticotroph tumors lack secretory activity due to impaired pro-opiomelanocortin (POMC) processing and increased adrenocorticotropic hormone (ACTH) degradation. This study investigated the molecular basis of this silencing in pituitary tumors.

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Oncology

Background:

  • Silent corticotroph tumors are a subtype of pituitary neuroendocrine tumors.
  • Their lack of clinical manifestation, unlike Cushing's disease, is not fully understood.
  • Understanding the molecular mechanisms behind tumor silencing is crucial for diagnosis and treatment.

Purpose of the Study:

  • To investigate the post-transcriptional and post-translational regulation of POMC/ACTH in silent and functioning corticotroph tumors.
  • To identify molecular factors contributing to the lack of secretory activity in silent tumors.
  • To compare molecular profiles between silent, functioning, and gonadotroph tumors.

Main Methods:

  • Analysis of 24 silent corticotroph, 23 functioning corticotroph, and 25 silent gonadotroph tumors.
  • Sanger sequencing for genetic alterations in POMC.
  • Quantitative real-time PCR and Western blot for gene and protein expression analysis of key processing enzymes and POMC/ACTH.

Main Results:

  • Identified POMC gene polymorphisms, some linked to pro-opiomelanocortin deficiency.
  • Silent corticotroph tumors exhibited lower PC1/3 gene and protein expression compared to functioning tumors.
  • Positive correlation between PC2 and CPE expression in silent tumors was observed.

Conclusions:

  • The lack of secretory activity in silent corticotroph tumors is associated with impaired POMC processing and enhanced ACTH degradation.
  • Macro-functioning corticotroph tumors represent an intermediate state between micro-functioning and silent tumors.
  • These findings provide insights into the molecular basis of pituitary tumor dormancy.

More Related Videos

A Novel Method: Super-selective Adrenal Venous Sampling06:08

A Novel Method: Super-selective Adrenal Venous Sampling

Published on: September 15, 2017

Endoscopic Endonasal Trans-sphenoidal Approach: Minimally Invasive Surgery for Pituitary Adenomas07:43

Endoscopic Endonasal Trans-sphenoidal Approach: Minimally Invasive Surgery for Pituitary Adenomas

Published on: January 17, 2018

Related Concept Videos

Hypothalamic-Pituitary Axis01:37

Hypothalamic-Pituitary Axis

The response to stress—be it physical or psychological, acute or chronic—involves activation of the Hypothalamic-Pituitary-Adrenal (HPA) axis. The HPA axis is part of the neuroendocrine system because it involves both neuronal and hormonal communication. Its function is to regulate homeostatic systems—metabolic, cardiovascular, and immune—providing the necessary means to respond to a stressor.
Adrenal Gland Disorders01:27

Adrenal Gland Disorders

Adrenal gland disorders manifest when the production of adrenal hormones deviates from the norm, resulting in either excessive or insufficient concentrations.
Adrenal insufficiency, characterized by insufficient cortisol and aldosterone production, leads to conditions like Addison's disease. This disorder, affecting the adrenal cortex, exhibits symptoms such as skin bronzing, dehydration, low blood pressure, fatigue, and weight loss. Congenital adrenal hyperplasia, a genetic ailment causing...
Hyperthyroidism I: Introduction01:25

Hyperthyroidism I: Introduction

Hyperthyroidism is a type of thyrotoxicosis characterized by the thyroid gland's overproduction of the thyroid hormones triiodothyronine (T3) and thyroxine (T4). This hormone excess increases the basal metabolic rate and enhances sensitivity to catecholamines.DiagnosisDiagnosis is based on clinical features and biochemical testing. It typically shows suppressed thyroid-stimulating hormone (TSH) levels below 0.4 mIU/L, with elevated free T3 and/or T4. Additional tests, including thyroid...
Hyperthyroidism II: Pathophysiology01:27

Hyperthyroidism II: Pathophysiology

Hyperthyroidism is a hypermetabolic state caused by elevated levels of thyroid hormones, triiodothyronine (T3) and thyroxine (T4). It results from dysregulation at the thyroid, pituitary, or immune system level and affects multiple organ systems.PathophysiologyThe most common cause of hyperthyroidism is Graves’ disease, an autoimmune disorder in which antibodies, specifically thyroid-stimulating antibodies (TSAb), a subtype of TSH receptor antibodies (TRAb), bind to and activate TSH receptors...
Cushing Syndrome I: Introduction01:26

Cushing Syndrome I: Introduction

Cushing syndrome refers to the collection of clinical manifestations that arise when tissues are exposed to excessive amounts of cortisol or cortisol-like medications over an extended period. Cortisol, a glucocorticoid produced by the adrenal cortex, regulates metabolism, immune responses, and the body’s adaptation to stress. When its concentration remains chronically elevated, these physiological pathways become dysregulated, resulting in the characteristic features of the syndrome.Exogenous...
Cushing Syndrome II: Pathophysiology01:19

Cushing Syndrome II: Pathophysiology

Cortisol production is normally governed by the hypothalamic–pituitary–adrenal (HPA) axis, which maintains hormonal balance through tightly regulated feedback mechanisms. Disruption of this regulatory system is central to the development of Cushing syndrome, whether the excess cortisol originates from external medications or internal pathology. Persistent cortisol elevation alters metabolism, immune function, and endocrine signaling, producing the characteristic clinical features of the...