gms | German Medical Science

Objective: Pituitary-dependent Cushing's disease has a severe impact on the affected patient's health with a reduction of life expectancy if left untreated. Successful microsurgical resection potentially cures the patient. However, treatment of recurrent cases can be challenging. Besides repeat resections and radiotherapy, medical treatment options became available. However, a substance that achieves high rates of sustained normalization of hypercortisolemia without significant side effects has not yet been discovered. Recently, promising results have been achieved with somatostatin analogues that bind to somatostatin receptors (SSTR), which are expressed by corticotroph pituitary adenomas. The development of somatostatin analogues has been based on the analysis of SSTR subtype expression of quite small cohorts of pituitary adenomas with variable hormone production. To enable further progress with this promising treatment option, assessment of all somatostatin receptors in a larger cohort of corticotroph pituitary adenoma is paramount.

Methods: An electronic database search revealed 164 patients who suffered from Cushing’s disease and who were treated in the author’s department from October 2004 to July 2015. Paraffin-embedded tumor tissue samples of 148 cases of Cushing’s disease were available for analysis and underwent processing into tissue microarrays and immunohistochemical staining for SSTR 1, SSTR2A, SSTR3, SSTR4 and SSTR5. For comparison, 165 other pituitary adenomas were also stained and microscopically analyzed. Considering the immunostaining intensity (IS) and the area of staining positivity (ASP), an intensity distribution score (ID) was generated by the multiplication of IS and ASP.

Results: In general expression values of SSTR 2A, SSTR3 and SSTR5 were higher (mean ID score 3.68, 2.80 and 6.96, respectively) while the expression of SSTR1 and SSTR4 were lower in corticotrop adenomas (mean ID score 1.75 and 0.99, respectively). Thyrotropinomas showed the highest expression rates of SSTR1, SSTR2A and SSTR5 (mean ID score 3.00, 9.75 and 8.38, respectively).

Conclusion: There are marked differences in expression of somatostatin receptor subtypes 1 through 5 that need to be addressed when looking for other possible substances for the treatment of Cushing's disease or when planning further clinical trials. According to the expression levels, SSTR2A, SSTR3 and SSTR5 are more suitable for a targeted therapy with somatostatin analogues.