(5.01) The Challenges Associated with Diagnosing Thyrotropin (TSH)-Secreting Pituitary Adenomas- A Case Series

Thyrotropin (TSH)-secreting pituitary adenomas (TSHomas) represent less than 1% of the pituitary tumors. Clinical presentation is variable. Diagnosis can be challenging, especially since the thyrotropin-releasing hormone (TRH) test that was used in the past to differentiate different thyroid problems is no longer available. We present a series of two patients with abnormal thyroid function tests who were later found to have TSHomas.

Case(s) Description :

Patient(A)- 36-year-old male presented to the clinic for evaluation of abnormal thyroid function tests. Initial lab work showed unsuppressed TSH (4.15 mIU/L [0.270-4.200]) with elevated thyroid hormone levels (free T4 2.0 ng/dL [ 0.9-1.7]). He denied any signs/symptoms. Repeat thyroid function tests were similar. Heterophilic antibodies test did not suggest interference. The patient had a Triiodothyronine (T3) suppression test with 25 ug/day of T3 for ten days, but TSH remained unsuppressed. Alpha-subunit was elevated (0.8 ng/mL [< 0.5]). MRI of the pituitary showed a 1.1 cm pituitary adenoma. He underwent surgical resection, and pathology showed positive staining for TSH. Post-surgery, his thyroid function tests normalized (TSH 1.42 mIU/L, fT 1.2 ng/dL).

Patient (B)- 42-year-old female presented with tachycardia, fatigue, and weight loss. Thyroid labs showed elevated TSH (4.27 mIU/L) and thyroid hormone levels (fT4 2.4 ng/dL). She had elevated alpha-subunit (1.8 ng/mL). CT sella with contrast showed a 1.5 cm mass. She underwent surgical resection, and pathology confirmed TSHoma. Post-surgery, she developed hypothyroidism and was given thyroid hormone.

Discussion :

Patients with TSHomas present with a wide range of symptoms, from mild to severe thyrotoxicosis. Laboratory work-up reveals elevated thyroid hormones with unsuppressed/elevated TSH. It is important to rule out other causes that present with similar thyroid function profiles, such as resistance to thyroid hormone (RTH) or assay interference.
In the past, TRH stimulation test was used to differentiate between central causes of hyperthyroidism, including pituitary RTH (TSH responds to TRH stimulation) and TSHomas (no response to TRH stimulation). However, this test is no longer available.
T3 suppression test is useful for ruling out RTH in patients lacking obvious symptoms of hyperthyroidism, such as patient (A). However, this test needs close monitoring and should be avoided in patients with cardiac issues. Patients typically take T3 for 7-10 days, and TSH is measured afterward. Unsuppressed TSH strongly suggests TSHoma. Once a diagnosis is made, transsphenoidal surgery is the first-line treatment.