Abstract
The development of somatostatin analogs for the treatment of pituitary Cushing's disease has been based on somatostatin receptor expression analyses of small cohorts of pituitary adenomas. Additionally, the classification of pituitary adenomas has recently changed. To enable progress with this treatment option, we assessed somatostatin receptors in a large cohort of corticotroph and other pituitary adenomas according to the new WHO classification of endocrine tumors. Paraffin-embedded tumor samples of 88 corticotroph pituitary adenomas and 30 nonadenomatous pituitary biopsies were analyzed after processing into tissue microarrays and immunohistochemical staining for SSTR 1, SSTR2A, SSTR3, SSTR4, and SSTR5. For comparison, 159 other noncorticotroph pituitary adenomas were analyzed. SSTR3 expression was higher in corticotroph adenomas compared to PIT-1-positive, gonadotroph, and nonfunctioning pituitary adenomas (p < 0.0001, p = 0.0280, and p < 0.0001, respectively). This was also the case for the expression of SSTR5 (p = 0.0003, p < 0.0001, and p < 0.0001, respectively). SSTR2A expression was higher compared to gonadotroph and nonfunctioning pituitary adenomas (p = 0.0217 and 0.0126, respectively) while PIT-1-positive adenomas showed even higher SSTR2A expression (p < 0.0001). SSTR2A and SSTR5 were both expressed higher in nonadenomatous pituitary biopsies than in pituitary adenomas (p = 0.0126 and p = 0.0008, respectively). There are marked expression differences of SSTR1-5 as well as changes in expression in recurrent disease that need to be addressed when looking for other possible substances for the treatment of Cushing's disease. SSTR2A, SSTR3, and SSTR5 seem to be most suitable biomarkers for a targeted therapy with somatostatin analogs.
Highlights
Cushing’s disease (CD) is caused by an overproduction of the adrenocorticotroph hormone (ACTH) from the adenomatous tissue of the pituitary gland leading to hypercotisolism and the typical clinical and morphological changes [1, 2]
In thirty additional cases of CD, no adenoma was identified in the obtained pituitary tissue biopsies
The findings described by van der Hoek et al indicate that SSTR5-specific substances may be less susceptible to this mechanism [31]
Summary
Cushing’s disease (CD) is caused by an overproduction of the adrenocorticotroph hormone (ACTH) from the adenomatous tissue of the pituitary gland leading to hypercotisolism and the typical clinical and morphological changes [1, 2]. 15% of all pituitary adenomas are corticotroph adenomas arising from TPIT-lineage adenohypophyseal cells (TPIT = T-box protein 19) with a peak incidence in patients of 30-50 years [3]. 20% of the corticotroph adenomas lack ACTH excess but these silent adenomas may cause neurological or ophthalmological symptoms as macroadenomas. Corticotroph adenomas are classified either as densely or sparsely granulated or as Crooke cell adenomas depending on their ACTH expression pattern [4]. Consequences of untreated chronic glucocorticoid excess are increased mortality, mainly caused by cardiovascular. If successful treatment leads to a remission of the hypercortisolism, the mortality rate may return to a normal level [5, 6]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
