Clinical Characteristics and Outcomes of Thyroid Stimulating Hormone-Secreting Adenomas

Introduction: Pituitary adenomas that secrete thyroid stimulating hormone (TSH) are extremely rare and there exists a need in the literature to expound upon their clinical characteristics, management, and outcomes.

Methods: TSH-secreting adenomas were defined as those with immunohistochemical staining for TSH, even if they also stained for other hormones. The records of 4,145 pituitary adenoma patients from a single institution were retrospectively reviewed for TSH-secreting adenomas, yielding 37 diagnoses between 1989 and 2018. Statistical significance was determined via Fisher's exact tests.

Results: Our cohort consisted of 37 patients (17 females, 20 males). The mean age at diagnosis was 47.7 years and 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 (2 on methimazole). Fourteen patients (37.8%) did not exhibit preoperative hyperthyroidism, but presented with other endocrine dysfunction, with the most common being elevated IGF-1 (n = 9, 24.3%). Preoperatively, 29 patients (78.3%) were symptomatic, with the most common symptoms being weight gain (n = 13, 35.1%), headache (n = 8, 21.6%), and fatigue (n = 5, 13.5%). The mean time between diagnosis and surgery was 0.5 years. All patients underwent surgical resection via a transsphenoidal approach, with 73% undergoing gross total resection. 5 patients (13.5%) with residual tumor underwent postoperative radiation (4 gamma knife radiosurgery, 1 radiation therapy). Six patients (16.2%) had recurrence requiring repeat surgery (mean time to operative recurrence was 7.2 years). When lineage staining was performed, all tumors exhibited immunohistochemical positivity for TSH and PIT1, with 14% also exhibiting SF1 positivity. Twenty-eight patients (75.7%) stained for hormones in addition to TSH, specifically prolactin (n = 22, 59.4%) and human growth hormone (n = 19, 51.4%). The rate of preoperative hyperthyroidism was higher in unihormonal adenomas than those that secreted multiple hormones (57.1 vs. 14.3%; p = 0.034). Postoperatively, all patients experienced normalization of hyperthyroidism, except for 1 patient with a unihormonal TSH-secreting adenoma. Postoperatively, all patients experienced normalization of TSH, except for 1 patient (stained for PIT1, TSH, prolactin, human growth hormone). Rates of preoperative elevated TSH did not significantly differ between unihormonal versus plurihormonal tumors. The most common new endocrine dysfunction postoperatively was hypothyroidism, and this did not significantly differ by adenoma type. Postoperatively, weight gain resolved in 12 out of 13 patients, headache resolved in 7 out of 8 patients, and fatigue resolved in 5 out of 5 patients.

Conclusions: TSH-secreting pituitary adenomas are rare tumors that typically present as macroadenomas with diverse symptoms. While most patients do not present with hyperthyroidism, patients with unihormonal TSH-secreting adenomas are more likely to present with elevated free T4 levels. This may indicate that, despite being less prevalent, unihormonal TSH-secreting adenomas are biologically distinct and more endocrinologically aggressive than adenomas that secrete other hormones in addition to TSH, even if they originated from the same PIT1 lineage. Future studies aimed at analyzing factors predicting the aggressiveness of TSH-secreting adenomas are warranted, ideally in a multicenter fashion given the rarity of these tumors.

No conflict of interest has been declared by the author(s).

Publication History

Article published online:
01 February 2023