Objective:  Mutations in genes encoding succinate dehydrogenase (SDHA, SDHB, SDHC and SDHD) have been well established as playing a role in hereditary phaeochromocytoma, paraganglioma, renal cell carcinoma and gastrointestinal stromal tumours.  Recently, the spectrum of tumours associated with SDH mutations (at least for SDHA, SDHC and SDHD) has been expanded to include pituitary adenomas.  Although pituitary adenomas appear rare among patients carrying SDH mutations, they may have been under-recognised due to the low penetrance of disease and lack of systematic surveillance.  The aim of this study was to determine the prevalence of SDH mutations in a large pituitary adenoma cohort.   

Methods: We constructed a tissue microarray (TMA) of all pituitary adenomas resected at Royal North Shore Hospital from 1998 to 2012 for which tissue was available (n=346).  We initially performed SDHB and SDHA immunohistochemistry, which we have previously shown to accurately identify tumours containing SDH mutations.  SDH mutation analysis is subsequently being performed in those formalin-fixed, paraffin-embedded samples exhibiting complete or reduced expression of SDHB and/or SDHA by immunohistochemical staining.  

Results:  One of 346 pituitary adenomas (0.3%) showed complete loss of SDHB and SDHA staining by immunohistochemistry.  Nine additional pituitary adenomas showed weak but positive staining for SDHB and SDHA by immunohistochemistry.  The remaining 336 adenomas demonstrated diffusely strongly positive staining making SDH mutation unlikely.  SDH mutation analysis is pending.

Conclusions: Our findings suggest that SDH mutation is a rare cause of sporadic pituitary adenomas.  However, discovery of an SDH-deficient pituitary adenoma may have important implications both for the patient (screening for associated tumours, such as phaeochromocytoma, paraganglioma, renal cell carcinoma and gastrointestinal stromal tumours) and family.