Endocrinological Aggressiveness of Unihormonal versus Plurihormonal pit1-positive Tsh-secreting Pituitary Adenomas

Introduction: Understanding the distinctions between unihormonal and plurihormonal TSH-secreting adenomas will help guide clinical expectations.

Methods: We retrospectively reviewed 4145 pituitary adenoma patients diagnosed from 1970-2018 at a single institution to identify TSH-secreting adenomas.

Results: Our cohort comprised of 37 (17 female, 20 male) TSH-secreting adenomas. Mean (SD) age at diagnosis was 47.7 (13.0) years. 27 patients (73.0%) possessed macroadenomas. Preoperatively, 6 patients (16.2%) presented with elevated TSH, and 9 patients (24.3%) presented with elevated free T4. Preoperatively, 29 patients (78.3%) were symptomatic, with weight gain (n=13, 35.1%) and headache (n=8, 21.6%) being most common. Mean (SD) time between diagnosis and surgery was 0.49 (0.76) years. All patients underwent transsphenoidal resection (GTR in 73%). Five patients (13.5%) with residual underwent postoperative radiation (4 gamma knife radiosurgery, 1 radiation therapy). Six patients (16.2%) had recurrence requiring repeat surgery (mean (SD) time to operative recurrence was 7.2 (4.1) years). All tumors exhibited immunohistochemical positivity for TSH and PIT1, with 14% also exhibiting SF1 positivity. Twenty-eight patients (75.7%) stained for additional hormones, specifically prolactin (n=22, 59.4%) and human growth hormone (n=19, 51.4%). Preoperative hyperthyroidism was more common in unihormonal adenomas than plurihormonal adenomas (55.5% vs. 14.3%; p=0.02). Rates of preoperative elevated TSH did not significantly differ between unihormonal and plurihormonal tumors. Postoperatively, all patients experienced normalization of hyperthyroidism, except for 1 unihormonal patient. Postoperatively, all patients experienced normalization of TSH, except for 1 plurihormonal patient. Postoperatively, weight gain resolved in 12 out of 13 patients and headache resolved in 7 out of 8 patients.

Conclusion : TSH-secreting pituitary adenomas present as macroadenomas with diverse symptoms. Unihormonal TSH-secreting adenomas are more likely to present with elevated free T4 levels. This may indicate that, despite being less prevalent and originating from the same PIT1 lineage, unihormonal TSH-secreting adenomas are biologically distinct and more endocrinologically aggressive than plurihormonal TSH-secreting adenomas.