Clinical, hormonal and molecular differences in pituitary ACTH adenomas without (silent corticotroph adenomas) or with Cushing's disease
Gérald Raverot1,2, Anne Wierinckx1,3, Emmanuel Jouanneau1,4, Françoise Borson-Chazot2, Joël Lachuer1,3, Michel Pugeat2 & Jacqueline Trouillas1,5
Objective: Silent corticotroph adenomas (SCA) are rare pituitary tumours immunoreactive for ACTH but without clinical evidence of Cushings disease. They have been compared to non functioning pituitary adenomas or ACTH adenomas with Cushings disease, but no distinction has been made between micro and macro ACTH-adenomas. We characterize SCA on clinical, hormonal and molecular data and compared the characteristic of these tumours with those of macro (MCA) and micro ACTH-adenomas (mCA) with Cushings disease.
Methods: Twenty-one ACTH adenomas (9 SCA, 7 MCA, 5mCA) with complete clinical, radiological and biochemical data and frozen tumoural samples were selected. Quantification by qRT-PCR of the mRNA expression of genes associated with corticotroph differentiation or function (T-Pit, POMC, GRα, PC1/3, galectin 3) was performed.
Results: Despite an absence of clinical hypercortisolism, elevated plasma ACTH levels similar to mCA was observed in SCA. Cortisol/ACTH ratio was similar in SCA and MCA and lower compare to mCA (P<0.05). This dissociation could be explained by a lower expression of PC1/3 in SCA and MCA compared to in mCA (P<0.05). Cytological and immunocytochemical analyses as well as mRNA expression levels of T-pit, POMC and GRα confirmed corticotroph differentiation in both mCA and MCA and in half of the SCA, with a strong correlation between t-Pit and POMC mRNA expression (R2: 0.72, P<0.01) in SCA and MCA (R2=0.65, P<0.05).
Conclusions: SCA are macroACTH tumours showing hormonal and molecular similarities to macroACTH tumours with Cushings disease, suggesting common pathological pathways which are distinct to those involved in microACTH tumours.