First report of an AIP mutation in Nelson's syndrome successfully treated with the novel multireceptor-targeted somatostatin analogue pasireotide (SOM230)

Somatic USP8 mutations are frequent events in corticotroph tumor progression causing Nelson’s tumor

“…This patient was treated with the second-generation multireceptor targeting somatostatin analog pasireotide and showed reduction in plasma ACTH and substantial improvement of symptoms after 6 months of treatment (22). This is in agreement with another study reporting good response to pasireotide treatment in patients with NS, thereby providing the rationale for their use in the management of corticotroph tumors (22,36).…”

“…We excluded three cases from subsequent statistical analyses. First, a female patient with c.2159C>A (p.Pro720Arg) mutation was also found to have the germline AIP variant c.911G>A (p.Arg304Gln) (22). This patient had a recurrent NS tumor and was operated twice.…”

“…Interestingly, in our cohort, we detected a somatic USP8 mutation in a 27-year-old patient with an associated germline AIP variant c.911G>A (p.Arg304Gln). The patient showed early manifestation and rapid progression of the disease with the NS tumor being resected twice (22). The p.Arg304Gln variant has been seen as pathogenic from a clinical point of view, but according to the in vitro studies, it is considered a variant of unknown significance (28).…”

“…This patient was treated with the second-generation multireceptor targeting somatostatin analog pasireotide and showed reduction in plasma ACTH and substantial improvement of symptoms after 6 months of treatment (22). This is in agreement with another study reporting good response to pasireotide treatment in patients with NS, thereby providing the rationale for their use in the management of corticotroph tumors (22,36). The recent report of a direct relationship between USP8 mutational status and somatostatin receptor 5 (SSTR5) expression (37) suggests that patients with USP8 mutation positive corticotroph tumors may respond favorably to pasireotide treatment.…”