Double pituitary adenomas are rare with a reported incidence of 1%. The majority are concomitant growth hormone (GH)-secreting and prolactin (PRL)-secreting tumours1. We describe a case of acromegaly with dual adenomas found to be AIP R304X mutation positive with two histologically and genetically distinct GH-secreting tumours.
A 25-year-old male with classic acromegaly was found on MRI to have two lesions: a large left-sided hypoenhancing tumour (Tumour A); and an additional right-sided 8mm hypoenhancing nodule (Tumour B). At initial transphenoidal surgery the larger tumour A was resected. Due to only partial biochemical remission (IGF-1 93 nmol/l, GH 9 mIU/L), he returned for surgery one year later and achieved complete biochemical remission after removal of tumour B.
Histopathologic analysis of tumour A revealed a sparsely granulated GH-secreting pituitary adenoma with Ki67 <1%. Tumour B was a densely granulated GH-secreting adenoma with an elevated Ki67 (5%). He was found to carry an AIP germline mutation (c.910 C>T, pR304X). RNA expression analysis on both tumours demonstrated 6767 differentially expressed genes (>2 logFC). Neuronatin (NNAT) was the most highly differentially expressed gene (-8.5 logFC) with higher expression in the atypical densely granulated subtype. There was significant differential expression in SSTR2 and SSTR5, although higher expressions of both were seen in the sparsely granulated tumour. Gene set enrichment analysis (GSEA) demonstrated significant differences in expression of genes involved in epithelial-mesenchymal transition and KRAS signaling. Next generation sequencing analysis utilising a custom 300 gene panel yielded distinct somatic gene variants between tumours and 13 germline rare variants.
Herein we demonstrate the finding of double GH-secreting adenomas in an AIP-positive R304X gentleman. These tumours are genetically and histologically distinct, but arise from an underlying germline predisposition to pituitary tumour formation. Individuals with familial pituitary tumour syndromes may be at increased risk of multiple pituitary adenomas.