MON-105 - When Refractory Hypothyroidism Is Central Hyperthyroidism: TSH-Secreting Pituitary Adenoma Unmasked by Levothyroxine Withdrawal

Background

TSH‑secreting pituitary adenomas (TSHomas) are rare causes of hyperthyroidism and account for a small minority of pituitary tumors, yet they are frequently misdiagnosed as primary hypothyroidism when an elevated TSH is interpreted in isolation. This misclassification can lead to years of inappropriate levothyroxine escalation despite biochemically inappropriate TSH and free thyroid hormone levels.

Case Presentation

A 57‑year‑old woman with “acquired hypothyroidism” on levothyroxine for many years was referred for persistently elevated TSH despite dose escalation to 125 mcg daily. Her diagnosis had been based solely on elevated TSH without T3 or T4 measurement. At presentation, TSH was 8.86 uIU/mL, free T4 2.2 ng/dL, and free T3 4.6 ng/dL, yet she was clinically euthyroid. Workup for thyroid hormone resistance revealed a negative THRB mutation, normal alpha‑subunit (1.1 ng/mL), and an elevated alpha‑subunit/TSH molar ratio >1, though interpretation was limited by her postmenopausal status. Pituitary evaluation showed normal ACTH, LH, FSH, prolactin, cortisol, estradiol, and DHEA‑S, indicating preserved pituitary‑adrenal and gonadal axes. Over three years, levothyroxine was tapered and discontinued. Off therapy, TSH remained elevated (6.1 uIU/mL) with high free T4 (1.9 ng/dL) and free T3 (6.1 ng/dL), and she remained clinically euthyroid. Thyroid antibodies (anti‑TPO, TSI) were negative, and a normal‑appearing thyroid on ultrasound. Repeat pituitary testing was normal, including ACTH, FSH, LH, Prolactin, IGF‑1, cortisol, and sex hormone‑binding globulin. MRI brain revealed a 0.4 × 0.4 × 0.6 cm right‑sided pituitary lesion consistent with a microadenoma, and a TSH‑secreting microadenoma was diagnosed. She was managed conservatively, given the absence of compressive symptoms and near‑normal thyroid hormone levels.

Conclusion

This case highlights a diagnostic pitfall in which discordant thyroid function tests are overlooked and elevated TSH is reflexively equated with primary hypothyroidism, resulting in prolonged, unnecessary levothyroxine treatment in a patient with central hyperthyroidism. The key pattern that should prompt evaluation for TSHoma is elevated or inappropriately normal TSH with high free T4 and/or free T3, particularly when this pattern persists after levothyroxine taper or withdrawal and other pituitary axes are intact. A structured approach to the “syndrome of inappropriate TSH secretion”—including repeat TFTs, exclusion of assay interference and thyroid hormone resistance, alpha‑subunit measurement, and pituitary imaging was essential to establish the diagnosis in this patient and should be systematically applied in similar cases. This case shows that TSHomas may present subtly and are often detected only when clinicians re-examine refractory “hypothyroidism” using a pattern-recognition lens.

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