Chapter 7 - The 3PAs syndrome and succinate dehydrogenase deficiency in pituitary tumors

Abstract

The 3PAs association describes the coexistence of pituitary adenoma, pheochromocytoma (PHEO), and paraganglioma (PGL). There are 90 3PAs cases reported in the literature (with and without genetic mutations/variants) since 1952. Most cases carry SDHx defects, whereas MEN1 and MAX are the second and third most common genes involved. Overall, pituitary adenomas in 3PAs with genetic defects are significantly more common among familial cases, more frequently macroadenomas secreting PRL or growth hormone; they often lead to multiple phenotypes within the same family and require multiple treatment modalities. A distinctive pathologic feature of SDHx-mutated pituitary adenomas is an extensive vacuolization of the cytoplasm. Utilizing the Sdhb+/− mouse model, we found increased HIF-1 expression in adenohypophyseal cells and mitochondrial and nuclear abnormalities. Patients presenting with 3PAs should be initially screened for SDHx mutations, particularly if there is a history of PHEOs/PGLs in other family members. If family history is negative, screening for SDHx, MEN1, and MAX mutations may be considered.