Silent corticogonadotroph adenomas: clinical and cellular characteristics and long-term outcomes.
Silent corticotrophins adenomas (SCAs) are clinically silent and non-secreting but immunostain positively for ACTH. We hypothesize that SCAs comprise both corticotroph and gonadotroph characteristics. Cohort analysis from 1994-2008 with follow-up time ranging from 1-15 years in a tertiary referral center. We compared preoperative and postoperative clinical results and tumor cytogenesis in 25 SCAs and 84 nonfunctioning adenomas in 109 consecutive patients diagnosed pre-operatively with nonfunctioning pituitary adenomas. Clinical outcomes were radiologic and hormonal measures. Pathologic outcomes were expression of relevant pituitary hormones, tissue-specific transcription factors, and electron microscopy features. Preoperative SCA presentation was similar to that observed for nonfunctioning adenomas. However, SCAs recurred postoperatively at a median of 3 years vs. 8 years for nonfunctioning adenomas (p<0.0001). Fifty-four percent of patients with SCAs had new onset postoperative hypopituitarism vs. 17% of nonfunctioning adenomas (p<0.025). SCAs (n=18) were immunopositive for ACTH, cytoplasmic and nuclear SF-1, NeuroD1, DAX-1, and alpha-gonadotropin subunit, but Tpit negative, and co-expression of tumor ACTH with either SF-1 or LH was detected. In contrast, functional corticotroph adenomas (n=11) were immunopositive for ACTH, nuclear SF-1, NeuroD1, and Tpit, but negative for DAX-1, a gonadotroph cell transcription factor. Gonadotroph adenomas (n=23) were immunonegative for ACTH and Tpit but positive for nuclear SF-1, NeuroD1, and DAX-1. SCA electron microscopy demonstrated ultrastructural features consistent with corticotroph and gonadotroph cells. As SCAs exhibit features consistent with both corticotroph and gonadotroph cytologic origin, we propose a pathologic and clinically distinct classification of SCAs as silent corticogonadotroph adenomas.
Cooper
Odelia
O
Pituitary Center, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Ben-Shlomo
Anat
A
Bonert
Vivien
V
Bannykh
Serguei
S
Mirocha
James
J
Melmed
Shlomo
S
D049913:ACTH-Secreting Pituitary Adenoma / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D000236:Adenoma / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D000328:Adult; D000368:Aged; D005260:Female; D006062:Gonadotropins / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012008:Recurrence
D006062:Gonadotropins