When Thyrotropin Meets Growth Hormone: The Clinical Challenges of a Mixed GH/TSH-Secreting PIT1-Lineage Pituitary Neuroendocrine Tumour

Background: Acromegaly is most commonly caused by a growth hormone (GH)-secreting pituitary neuroendocrine tumour (PitNET). Plurihormonal PIT1-lineage PitNETs are uncommon, and combined GH and thyroid-stimulating hormone (TSH) secretion poses distinctive diagnostic and therapeutic challenges. We report a mixed GH/TSH-secreting PIT1-lineage PitNET in which the biochemical response to preoperative lanreotide supported the clinical suspicion of a functionally relevant thyrotroph component before targeted pathological reassessment. Case Presentation: A 39-year-old woman presented with a two-year history of progressive acral enlargement, headaches, hyperhidrosis, snoring, and voice deepening. Biochemical evaluation showed IGF-1 1128 ng/mL (reference range 93.1–281), GH 61 µg/L, TSH 1.5 µIU/mL (0.35–4.94), FT4 1.66 ng/dL (0.7–1.5), and FT3 7.0 pg/mL (1.8–4.2). Pituitary MRI demonstrated a 15 × 14 × 10.5 mm macroadenoma. Lanreotide 120 mg every four weeks reduced IGF-1 to 846 ng/mL and GH to 14 µg/L while normalizing FT4 (1.04 ng/dL) and FT3 (3.9 pg/mL), reinforcing the suspicion of mixed GH/TSH secretion. Transsphenoidal surgery was performed in October 2024. The tumour was initially classified as a densely granulated somatotroph PitNET; prompted by the preoperative biochemical phenotype, additional β-TSH immunostaining demonstrated positivity in numerous tumour cells, leading to reclassification as a mature plurihormonal PIT1-lineage PitNET (Ki-67 approximately 1%). Postoperative biochemical remission was not achieved, and MRI demonstrated a 7 mm residual lesion. Lanreotide was resumed, with the sustained control of the thyrotroph component but persistent GH/IGF-1 excess. Because residual disease persisted with slight cavernous sinus extension, Gamma Knife radiosurgery was performed in July 2026. Conclusions: Mixed GH/TSH-secreting PIT1-lineage PitNETs may be overlooked when TSH is inappropriately normal rather than frankly elevated. This case illustrates the value of integrating biochemical findings, treatment response, and targeted histopathological reassessment. Persistent disease despite surgery and somatostatin receptor ligand therapy further highlights the frequent need for multimodal, long-term management.