Background:  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. 

Aim:  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 of all available pituitary adenomas resected at Royal North Shore Hospital from 1998 to 2012.  We initially performed SDHB and SDHA immunohistochemistry, which we have previously shown to accurately identify tumours containing SDH mutations.  SDH mutation analysis was subsequently performed in those formalin-fixed, paraffin-embedded samples exhibiting loss of SDHB and/or SDHA by immunohistochemical staining.  

Results:  One of 309 adenomas (0.3%) demonstrated an abnormal pattern of staining, a 30mm prolactin producing tumour from a 62 year old male showing loss of staining for both SDHA and SDHB.  Examination of paraffin embedded and frozen tissue from this patient confirmed the presence of two somatic SDHA mutations (c.725_736del and c.989_990insTA).  Neither of these mutations were present in the germline.

Conclusions: Although pathogenic SDH mutation may occur in sporadic pituitary adenomas, it appears to be a rare event and can occur in the absence of germline mutation.  Unless suggested by family history and physical examination it is difficult to justify screening for SDH mutations in pituitary adenomas.