Delay in Diagnosis of Thyroid-Stimulating Hormone-Secreting Pituitary Adenomas: Clinical and Endocrinological Profiles from a Retrospective Cohort Study

Abstract

Thyrotropin (thyroid-stimulating hormone)-secreting pituitary adenomas are a rare cause of hyperthyroidism that frequently presents diagnostic and therapeutic challenges. This study characterizes the clinical, biochemical, radiological, and histopathological features of thyrotropin-secreting pituitary adenomas, evaluates long-term outcomes, and identifies factors influencing remission and recurrence. We retrospectively analysed 12 patients with thyrotropin-secreting pituitary adenomas treated between January 2003 and February 2025 at a tertiary endocrine referral centre. Clinical presentation, hormonal profiles, imaging characteristics, histopathology, management, and follow-up were reviewed. Diagnostic criteria included inappropriately normal or elevated thyroid-stimulating hormone levels with increased free thyroid hormones and pituitary imaging confirming an adenoma. Remission was defined as clinical and biochemical normalization without ongoing therapy. Subgroup analysis examined the impact of diagnostic delay on tumour size, invasiveness, and outcome. The cohort comprised nine men (75%) and three women (25%) with a mean age at diagnosis of 47.8±17.2 years. Excluding one multiple endocrine neoplasia type 1 case with early detection, the mean diagnostic delay was 42.5 months (range: 4–156). Magnetic resonance imaging revealed macroadenomas in 75% of patients and Knosp grade 3–4 invasion in 41.7%. Longer diagnostic delay was correlated with significantly larger tumours (17.9±3.6 mm vs 9.8±1.0 mm; p=0.004). All patients underwent surgery; 50% achieved remission, while 33.3% required additional therapy (somatostatin analogues and/or radiotherapy). At a median 7.8-year follow-up, 66.7% remained in sustained remission. No patient experienced thyroid storm; transient postoperative hypothyroidism occurred in 25%. Thyrotropin-secreting pituitary adenomas often present with heterogeneous and misleading biochemical profiles leading to diagnostic delay, larger and more invasive tumours, and a greater need for multimodal therapy. Early recognition of discordant thyroid function tests—elevated free T3/T4 with non-suppressed thyroid-stimulating hormone—is critical to avoid unnecessary thyroid ablation and improve surgical outcomes.

Keywords

TSH-secreting pituitary adenoma - hyperthyroidism - transsphenoidal surgery - somatostatin analogues - pituitary tumours

Publication History

Received: 28 October 2025

Accepted after revision: 02 December 2025

Accepted Manuscript online:
03 December 2025

Article published online:
21 January 2026

• References

• 1 Beck-Peccoz P, Giavoli C, Lania A. A 2019 update on TSH-secreting pituitary adenomas. J Endocrinol Invest 2019; 42: 1401-1406
• 2 Dutta A, Jain N, Rai A. et al. The outcome of TSHoma from a tertiary care institute in India. Surg Neurol Int 2021; 12: 161
• 3 Deng F. Yang Z yu, Zhang Y ping, et al. TSH adenoma and syndrome of resistance to thyroid hormones-Two cases report of syndrome of inappropriate secretion of thyrotropin. Brain Behav 2021; 11: 5
• 4 Yang Y, Liu J, Deng K. et al. Clinical and Therapeutic Characteristics of Pituitary TSH-Secreting Adenoma in Adolescent-Onset Patients: Six Case Studies and Literature Review. Front Endocrinol 2021; 12: 771-773
• 5 Mouslech Z, Somali M, Sakali AK. et al. TSH-secreting pituitary adenomas treated by gamma knife radiosurgery: our case experience and a review of the literature. Horm Athens Greece 2016; 15: 122-128
• 6 Luo P, Zhang L, Yang L. et al. Progress in the Pathogenesis, Diagnosis, and Treatment of TSH-Secreting Pituitary Neuroendocrine Tumor. Front Endocrinol 2020; 11: 58-64
• 7 Rotermund R, Riedel N, Burkhardt T. et al. Surgical treatment and outcome of TSH-producing pituitary adenomas. Acta Neurochir (Wien) 2017; 159: 1219-1226
• 8 Amlashi FG, Tritos NA. Thyrotropin-secreting pituitary adenomas: epidemiology, diagnosis, and management. Endocrine 2016; 52: 427-440
• 9 Fang HJ, Fu Y, Wu HW. et al. Short-term Preoperative Octreotide for Thyrotropin-secreting Pituitary Adenoma. Chin Med J (Engl) 2017; 130: 936-942
• 10 Fukuhara N, Horiguchi K, Nishioka H. et al. Short-term preoperative octreotide treatment for TSH-secreting pituitary adenoma. Endocr J 2015; 62: 21-27
• 11 Shimatsu A, Nakamura A, Takahashi Y. et al. Preoperative and long-term efficacy and safety of lanreotide autogel in patients with thyrotropin-secreting pituitary adenoma: a multicenter, single-arm, phase 3 study in Japan. Endocr J 2021; 68: 791-805
• 12 De Herdt C, Philipse E, De Block C. ENDOCRINE TUMOURS: Thyrotropin-secreting pituitary adenoma: a structured review of 535 adult cases. Eur J Endocrinol 2021; 185: R65-R74
• 13 Sözen M, Bayrak BY, Selek A. et al. A reference center study in thyrotropin-secreting pituitary adenomas: clinicopathological, therapeutic and long-term follow-up outcomes. Endocrine 2023; 82: 622-630
• 14 Rindi G, Mete O, Uccella S. et al. Overview of the 2022 WHO Classification of Neuroendocrine Neoplasms. Endocr Pathol 2022; 33: 115-154
• 15 Tjörnstrand A, Nyström HF. DIAGNOSIS OF ENDOCRINE DISEASE: Diagnostic approach to TSH-producing pituitary adenoma. Eur J Endocrinol 2017; 177: R183-R197
• 16 Zhou J, Guo X, Duan L. et al. Moving toward a standardized diagnostic statement of pituitary adenoma using an information extraction model: a real-world study based on electronic medical records. BMC Med Inform Decis Mak 2022; 22: 319
• 17 Yamada S, Fukuhara N, Horiguchi K. et al. Clinicopathological characteristics and therapeutic outcomes in thyrotropin-secreting pituitary adenomas: A single-center study of 90 cases. J Neurosurg 2014; 121: 1462-1473
• 18 Liu J, Yang Y, Duan L. et al. Combination of transsphenoidal endoscopic surgery and presurgical somatostatin analogs in thyrotropin (TSH)-secreting pituitary adenomas: Treatment outcome and long-term remission at a single pituitary center. Front Endocrinol 2022; 13: 1029-1106
• 19 Khan AA, Ibrahim SI, Ata F. et al. Clinical characteristics and outcomes of patients with TSH-secreting pituitary adenoma and Graves’ disease – a case report and systematic review. Thyroid Res 2024; 17: 1-12
• 20 Yoon JH, Choi W, Park JY. et al. A challenging TSH/GH co-secreting pituitary adenoma with concomitant thyroid cancer; a case report and literature review. BMC Endocr Disord 2021; 21: 177
• 21 Araujo-Castro M, Cancela AA, Vior C. et al. Radiological Knosp, Revised-Knosp, and Hardy–Wilson Classifications for the Prediction of Surgical Outcomes in the Endoscopic Endonasal Surgery of Pituitary Adenomas: Study of 228 Cases. Front Oncol 2022; 11: 807-840
• 22 Gatto F, Grasso LF, Nazzari E. et al. Clinical outcome and evidence of high rate post-surgical anterior hypopituitarism in a cohort of TSH-secreting adenoma patients: Might somatostatin analogs have a role as first-line therapy?. Pituitary 2015; 18: 583-591
• 23 Losa M, Albano L, Barzaghi LR. et al. Gamma knife radiosurgery is effective in patients with thyrotropin-secreting pituitary adenomas. J Endocrinol Invest 2024; 47: 1923-1930
• 24 Korbonits M, Blair JC, Boguslawska A. et al. Consensus guideline for the diagnosis and management of pituitary adenomas in childhood and adolescence: Part 2, specific diseases. Nat Rev Endocrinol 2024; 20: 290-309
• 25 Karlekar M, Diwaker C, Sarathi V. et al. Gonadotropin-secreting and thyrotropin-secreting pituitary adenomas: A single-center experience. Arch Endocrinol Metab 2023; 68: 270-272
• 26 Amir J, Guiot MC, Garfield N. Plurihormonal pituitary adenoma cosecreting ACTH and GH: a rare cause of Cushing’s disease. BMJ Case Rep 2022; 15: 251-254
• 27 Giustina A, Aimaretti G, Bondanelli M. et al. Primary empty sella: Why and when to investigate hypothalamic-pituitary function. J Endocrinol Invest 2010; 33: 343-346
• 28 Zhao W, Ye H, Li Y. et al. Thyrotropin-secreting pituitary adenomas: diagnosis and management of patients from one Chinese center. Wien Klin Wochenschr 2012; 124: 678-684
• 29 Persani L, Lania A, Beck-Peccoz P. Thyrotropin-Secreting Pituitary Adenomas. The Pituitary 2025; 615-636
• 30 Zhu J, Wang Z, Zhang Y. et al. Suprasellar pituitary adenomas: a 10-year experience in a single tertiary medical center and a literature review. Pituitary 2020; 23: 367-380
• 31 Unger N, Theodoropoulou M, Schilbach K. Clinically active pituitary tumors. Inn Med Heidelb Ger 2024; 65: 672-680
• 32 Gezer E, Selek A, Cetinarslan B. et al. The coexistence of infundibular pituicytoma and Cushing’s disease due to pituitary adenoma: A case report. Endocr Regul 2019; 53: 263-267
• 33 Hwang J, Seol HJ, Nam DH. et al. Therapeutic Strategy for Cavernous Sinus-Invading Non-Functioning Pituitary Adenomas Based on the Modified Knosp Grading System. Brain Tumor Res Treat 2016; 4: 63-69