A case of non‐functioning pituitary adenoma with Cushing's syndrome upon recurrence

Abstract

A 49-year-old woman presented with left visual disturbance. No signs of Cushing's disease were evident. Basal levels of serum cortisol and plasma adrenocorticotropic hormone (ACTH) were 16.8 microg/dL and 66.0 pg/mL, respectively. MRI demonstrated an irregularly shaped large pituitary tumor, and the patient then underwent transsphenoidal surgery. By light microscopy the tumor represented a chromophobic adenoma with a few of the adenoma cells showing immunoreactivity for ACTH. On the basis of clinical and light microscopic examinations, the diagnosis of silent corticotroph adenoma was made. Electron microscopy, however, demonstrated the honeycomb Golgi complex that has been reported as a typical finding of gonadotroph adenomas. MRI taken 7 months after the first operation revealed adenoma regrowth. Transcranial surgery was performed, and histology demonstrated a chromophobic pituitary adenoma with most cells immunopositive for ACTH. She was treated with gamma knife postoperatively. Three months later, MRI revealed remarkable shrinkage of the adenoma, but she developed typical signs and symptoms of Cushing's disease. Thus, the hormone immunostaining and biological activity of pituitary adenomas may change with time.

Silent corticotroph adenomas

“…Subtype II adenomas are chromophobic, lack cytokeratin filaments, have scattered PAS staining, sparse ACTH staining, and lower Tpit expression [1] [12,16,20]. In addition to corticotroph features, SCAs incorporate gonadotroph elements as evidenced by the presence of honeycomb Golgi [48,64] and increased mitochondrial density [64]. In our series, two SCAs tested were categorized as SCA subtype II while the remainder incorporated elements of both corticotroph and gonadotroph adenomas.…”

“…A number of individual cases of SCAs were reported to transform to symptomatic functioning Cushing Disease, notably after receiving radiotherapy [3,4,6,14,32,60,64]. However, in large series of SCAs, 2 groups each reported only 1 case transforming to biochemical Cushing disease but without clinical stigmata [19,61].…”

ACTH adenomas transforming their clinical expression: report of 5 cases

“…Indeed, just a few similar cases have been reported, mostly in isolated case reports or series not focused on this topic, and no overall view of this phenomenon and its clinical implications has been provided. 1,3,6,13,[15][16][17]20 Vaughan et al 17 and Cooper et al 6 were among the first to report the development of Cushing disease from a previously silent ACTH adenoma. Subsequently, a few other authors have reported this same phenomenon and have shown the potential of silent ACTH adenomas to shift to a functioning form during the follow-up period, even many years after the initial diagnosis.…”

“…Subsequently, a few other authors have reported this same phenomenon and have shown the potential of silent ACTH adenomas to shift to a functioning form during the follow-up period, even many years after the initial diagnosis. 1,13,15,16,20 It is interesting to note that Brown et al 3 demonstrated the possibility of silent ACTH adenomas evolving into corticotropin-secreting carcinomas long after the initial diagnosis (16 years).…”

“…This peculiar and unique clinical behavior of originally silent corticotropic adenomas has been reported sporadically. 1,3,6,13,[15][16][17]20 In this study, we reviewed a series of patients with pituitary adenomas and studied 5 cases of corticotropic tumors that presented this "shift" from silent adrenocorticotropic hormone (ACTH) adenomas to functioning tumors or vice versa; our aim was to analyze this phenomenon, which can have relevant clinical implications in the management of these patients.…”