Silent corticotroph staining pituitary adenoma (SCA) represents an uncommon subset of Non-Functioning adenomas (NFAs), hypothesized to be more locally aggressive. In this retrospective multicenter study, we investigate the safety and effectiveness of Stereotactic Radiosurgery (SRS) in patients with SCA compared with other non-SCA NFA's. Eight centers participating in the International Gamma-Knife Research Foundation (IGKRF) contributed to this study. Outcomes of 50 patients with confirmed SCAs and 307 patients with confirmed non-SCA NFA's treated with SRS were evaluated. Groups were matched. SCA was characterized by a lack of clinical evidence of Cushing disease, yet with positive immunostaining for corticotroph. Median age was 55.2 years (13.7-87). All patients underwent at least one trans-sphenoidal tumor resection prior to SRS. SRS parameters were comparable as well. Median follow-up 40 months (6-163). Overall tumor control rate (TCR) 91.2% (n = 280). In the SCA group, TCR were 82% (n = 41) versus 94.1% (n = 289) for the control-NFA (p = 0.0065). The SCA group showed a significantly higher incidence of new post-SRS visual deficit (p < 0.0001) assigned to tumor progression and growth, and post-SRS weakness and fatigue (p < 0.0001). In univariate and multivariate analysis, only the status of silent corticotroph staining (p = 0.005, p = 0.009 respectively) and margin dose (p < 0.0005, p = 0.0037 respectively) significantly influenced progression rate. A margin dose of ≥17 Gy was noted to influence the adenoma progression rate in the entire cohort (p = 0.003). Silent corticotroph staining represents an independent factor for adenoma progression and hypopituitarism after SRS. A higher margin dose may convey a greater chance of TCR.

Department of Anesthesiology West Virginia University Morgantown WV USA

Department of Neurological Surgery University of Virginia Charlottesville VA 22908 USA

Department of Neurosurgery Centre de Recherche Clinique Étienne LeBel University of Sherbrooke Sherbrooke QC Canada

Department of Neurosurgery Neurological Institute Taipei Veteran General Hospital Taipei Taiwan Republic of China

Department of Neurosurgery New York University Langone Medical Center New York NY USA

Department of Neurosurgery University of Pittsburgh Pittsburgh PA USA

Department of Neurosurgery University of Virginia Charlottesville VA USA

Department of Neurosurgery West Virginia University Morgantown WV USA

Department of Radiation Oncology Beaumont Health System Royal Oak MI USA

Department of Radiology Taipei Veteran General Hospital Taipei Taiwan Republic of China

Department of Stereotactic and Radiation Neurosurgery Na Homolce Hospital Prague Czech Republic

National Yang Ming University Taipei Taiwan Republic of China

Rose Ella Burkhardt Brain Tumor and Neuro oncology Center Cleveland Clinic Cleveland OH USA

See more in PubMed

Dekkers OM, Pereira AM, Romijn JA. Treatment and follow-up of clinically nonfunctioning pituitary macroadenomas. J Clin Endocrinol Metab. 2008;93:3717–3726. PubMed

Melmed S. Medical progress: acromegaly. N Engl J Med. 2006;355:2558–2573. PubMed

Vance ML. Treatment of patients with a pituitary adenoma: one clinician’s experience. Neurosurg Focus. 2004;16:E1. PubMed

Sheehan JP, Xu Z, Lobo MJ. External beam radiation therapy and stereotactic radiosurgery for pituitary adenomas. Neurosurg Clin N Am. 2012;23:571–586. PubMed

Kovacs K, Horvath E, Bayley TA, Hassaram ST, Ezrin C. Silent corticotroph cell adenoma with lysosomal accumulation and crinophagy. A distinct clinicopathologic entity. Am J Med. 1978;64:492–499. PubMed

Horvath E, Kovacs K, Killinger DW, Smyth HS, Platts ME, Singer W. Silent corticotropic adenomas of the human pituitary gland: a histologic, immunocytologic, and ultrastructural study. Am J Pathol. 1980;98:617–638. PubMed PMC

Xu Z, Ellis S, Lee CC, Starke RM, Schlesinger D, Lee Vance M, et al. Silent corticotroph adenomas after stereotactic radiosurgery: a case-control study. Int J Radiat Oncol Biol Phys. 2014;90:903–910. PubMed

Young WF., Jr . Clinically nonfunctioning pituitary adenomas. Humana Press; Totowa: 2000.

Bradley KJ, Wass JA, Turner HE. Non-functioning pituitary adenomas with positive immunoreactivity for ACTH behave more aggressively than ACTH immunonegative tumours but do not recur more frequently. Clin Endocrinol. 2003;58:59–64. PubMed

Cho HY, Cho SW, Kim SW, Shin CS, Park KS, Kim SY. Silent corticotroph adenomas have unique recurrence characteristics compared with other nonfunctioning pituitary adenomas. Clin Endocrinol. 2010;72:648–653. PubMed

Cooper O, Ben-Shlomo A, Bonert V, Bannykh S, Mirocha J, Melmed S. Silent corticogonadotroph adenomas: clinical and cellular characteristics and long-term outcomes. Horm Cancer. 2010;1:80–92. PubMed PMC

Jahangiri A, Wagner JR, Pekmezci M, Hiniker A, Chang EF, Kunwar S, et al. A comprehensive long-term retrospective analysis of silent corticotrophic adenomas versus hormone-negative adenomas. Neurosurgery. 2013;73:8–17. (discussion 17–18) PubMed

Raverot G, Wierinckx A, Jouanneau E, Auger C, Borson-Chazot F, Lachuer J, et al. Clinical, hormonal and molecular characterization of pituitary ACTH adenomas without (silent corticotroph adenomas) and with Cushing’s disease. Eur J Endocrinol. 2010;163(1):35–43. PubMed

Roncaroli F, Scheithauer BW, Young WF, Horvath E, Kovacs K, Kros JM, et al. Silent corticotroph carcinoma of the adenohypophysis: a report of five cases. Am J Surg Pathol. 2003;27(4):477–486. PubMed

Scheithauer BW, Jaap AJ, Horvath E, Kovacs K, Lloyd RV, Meyer FB, et al. Clinically silent corticotroph tumors of the pituitary gland. Neurosurgery. 2000;47:723–729. (discussion 729–730) PubMed

Webb KM, Laurent JJ, Okonkwo DO, Lopes MB, Vance ML, Laws ER., Jr Clinical characteristics of silent corticotrophic adenomas and creation of an internet-accessible database to facilitate their multi-institutional study. Neurosurgery. 2003;53:1076–1084. (discussion 1084–1085) PubMed

Alahmadi H, Lee D, Wilson JR, Hayhurst C, Mete O, Gentili F, et al. Clinical features of silent corticotroph adenomas. Acta Neurochir. 2012;154:1493–1498. PubMed

Chen L, White WL, Spetzler RF, Xu B. A prospective study of nonfunctioning pituitary adenomas: presentation, management, and clinical outcome. J Neurooncol. 2011;102:129–138. PubMed

Ioachimescu AG, Eiland L, Chhabra VS, Mastrogianakis GM, Schniederjan MJ, Brat D, et al. Silent corticotroph adenomas: Emory University cohort and comparison with ACTH negative nonfunctioning pituitary adenomas. Neurosurgery. 2012;71:296– 303. (discussion 304) PubMed

Sheehan JP, Starke RM, Mathieu D, Young B, Sneed PK, Chiang VL, et al. Gamma Knife radiosurgery for the management of nonfunctioning pituitary adenomas: a multicenter study. J Neurosurg. 2013;119:446–456. PubMed

Snell JW, Sheehan J, Stroila M, Steiner L. Assessment of imaging studies used with radiosurgery: a volumetric algorithm and an estimation of its error. Technical note. J Neurosurg. 2006;104:157–162. PubMed

Murad MH, Fernandez-Balsells MM, Barwise A, Gallegos-Orozco JF, Paul A, Lane MA, et al. Outcomes of surgical treatment for nonfunctioning pituitary adenomas: a systematic review and meta-analysis. Clin Endocrinol. 2010;73(6):777–791. PubMed

Gopalan R, Schlesinger D, Vance ML, Laws E, Sheehan J. Long-term outcomes after Gamma Knife radiosurgery for patients with a nonfunctioning pituitary adenoma. Neurosurgery. 2011;69:284–293. PubMed

Pollock BE, Cochran J, Natt N, Brown PD, Erickson D, Link MJ, et al. Gamma knife radiosurgery for patients with nonfunctioning pituitary adenomas: results from a 15-year experience. Int J Radiat Oncol Biol Phys. 2008;70:1325–1329. PubMed

Cohen-Inbar O, Ramesh A, Xu Z, Vance ML, Schlesinger D, Sheehan JP. Gamma knife radiosurgery in patients with persistent acromegaly or Cushing’s disease: long-term risk of hypopituitarism. Clin Endocrinol. 2016;84:524–531. PubMed

Xu Z, Lee Vance M, Schlesinger D, Sheehan JP. Hypopituitarism after stereotactic radiosurgery for pituitary adenomas. Neurosurgery. 2013;72:630–637. PubMed

Ding D, Starke RM, Sheehan JP. Treatment paradigms for pituitary adenomas: defining the roles of radiosurgery and radiation therapy. J Neurooncol. 2014;117:445–457. PubMed

Hoybye C, Rahn T. Adjuvant Gamma Knife radiosurgery in non-functioning pituitary adenomas; low risk of long-term complications in selected patients. Pituitary. 2009;12:211–216. PubMed

Izawa M, Hayashi M, Nakaya K, Satoh H, Ochiai T, Hori T, et al. Gamma Knife radiosurgery for pituitary adenomas. J Neurosurg. 2000;93:19–22. PubMed

Jagannathan J, Sheehan JP, Pouratian N, Laws ER, Steiner L, Vance ML. Gamma Knife surgery for Cushing’s disease. J Neurosurg. 2007;106:980–987. PubMed

Starke RM, Williams BJ, Jane JA, Jr, Sheehan JP. Gamma Knife surgery for patients with nonfunctioning pituitary macroadenomas: predictors of tumor control, neurological deficits, and hypopituitarism. J Neurosurg. 2012;117:129–135. PubMed

Stereotactic radiosurgery for nonfunctioning pituitary tumor: A multicenter study of new pituitary hormone deficiency