Clinically silent pituitary macroadenomas: a clinicopathologic analysis
Sandra Pekic Djurdjevic1, Milica Skender Gazibara2, Angelina Obradovic3, E Manojlovic Gacic3, Mirjana Doknic1, Dragana Miljic1, Marina Djurovic1, Marko Stojanovic1 & Vera Popovic1
Background: The so-called silent pituitary adenomas are a subtype of pituitary tumors showing positive immunoreactivity for one or more pituitary hormones, but without any clinical manifestations for oversecretion of these hormones. They are clinically labeled as non-functional pituitary adenomas (NFPA), some of them with particularly aggressive behavior. Rare patients might present with big plurihormonal pituitary tumors which whisper hormones (GH or ACTH) and produce biochemical acromegaly or Cushings disease.
Objective: We undertook a systematic retrospective, single institution clinicopathologic study of the patients with NFPA seen over a period of 6 years. Clinical, biochemical and immunohistochemical data were analyzed.
Patients and methods: We examined the data of 50 patients with NFPA, 23 men (46%) and 27 women (54%). Mean age of patients at the time of the diagnosis and first operation was 52.9±1.9 years (range, 1979 years), females being significantly younger compared with males (49.5±3.0 vs 56.8±2.1 years; P<0.05).
Results: All tumors were macroadenomas. Most tumors were plurihormonal, featuring immunoreactivity for FSH (41 of 50 patients, 82%), LH (37 of 49 patients, 76%), PRL (36 of 48 patients, 75%), GH (9 of 27 patients, 33%), TSH (14 of 32 patients, 44%) or ACTH (19 of 36 patients, 53%); only two being immunonegative for hormones. There was a positive correlation between the intensity of ACTH immunostaining and proliferative index Ki67 (r=0.429, P<0.05). Male patients had significantly greater intensity of LH immunostaining compared with females (P<0.05). Although a radical resection was achieved in 42 cases (84%), reoperation for recurrence was required in 8 cases (16%), predominantly in females (n=7). In our study group, we identified four cases of whispering pituitary macroadenomas with GH (n=3) and ACTH (n=1) staining with biochemical evidence of hormone oversecretion but with no clinical signs or symptoms for acromegaly or Cushings disease.
Conclusion: Most pituitary macroadenomas labeled as NFPA are plurihormonal macroadenomas. Rare NFPA may be true GH- or ACTH-secreting tumors despite no obvious clinical stigmata for acromegaly or Cushings syndrome.