Abstract #1406235: Silent Corticotroph Adenomas are More Aggressive than Other Nonfunctional Pituitary Adenomas

Abstract

Silent corticotroph adenomas (SCAs) are immunopositive for adrenocorticotropic hormone (ACTH) but do not cause Cushing disease. They account for approximately 20% of all corticotroph adenomas and 5% of nonfunctioning pituitary adenomas (NFAs). We present a case of an SCA with extensive invasion outside the sella turcica and causing pathology through mass effect on adjacent structures. A 48-year-old male was found to have a 3.8 cm pituitary mass with invasion of the left cavernous sinus and compression of the optic chiasm during an evaluation of headaches and diplopia. No signs of Cushing syndrome or acromegaly were apparent on examination. Metabolic evaluation was notable for secondary hypothyroidism (TSH 0.7 mIU/L, 0.45-5.33; free T4 0.3 ng/dL, 0.5-1.3) and hypogonadism (LH 2.2 mIU/L, 1.2-8.8; total testosterone 105 ng/dL, 270-1070), though serum prolactin (17.3 ng/mL, 2.6-13.2) and IGF-1 levels (133 ng/mL, 71-224) were unremarkable. ACTH level was increased on multiple measurements (69.9-146.8 μg/dL, 7.2-63.3), but 8 AM cortisol level during an overnight dexamethasone suppression test was only modestly elevated (1.9 μg/dL, expected < 1.8). The patient underwent transsphenoidal surgery (TSS) to remove accessible tumor and relieve symptoms of mass effect. Histopathology was notable for a pituitary adenoma with low Ki-67 proliferation index (< 5%) and 70-80% staining for ACTH. Symptoms recurred approximately 1 y later, and imaging revealed a substantial increase in volume of residual tumor. Unfortunately, the patient died from arterial bleeding during a second attempt at TSS. SCAs are more aggressive than NFAs that fail to stain for an intact pituitary hormone. Patients with SCAs are younger, more likely female, and have a greater likelihood of symptoms at diagnosis than patients with NFAs, though the proportion of SCAs present with extrasellar extension is equivalent to NFAs. SCAs and NFAs progress or recur at the same rate, but time to recurrence for SCAs is more than two-fold faster than for NFAs. Recurrence rate and time to recurrence for SCAs are unaffected by adjuvant radiation. SCAs with extensive staining for ACTH as in this case are more likely to be aggressive than tumors with limited staining for ACTH. Reduced expression of the mismatch repair gene MSH 6/2 may be a driver for the behavior of SCAs. This case illustrates SCAs are a small but challenging subset of NFAs with greater propensity to cause symptoms of mass effect and recur quickly than the typical NFA. Extensive ACTH staining is a poor prognostic sign for tumor recurrence.