Abstract #1411806: A Case of Thyrotropin Secreting Adenoma and Review of Literature

Abstract

Elevations of TSH, FT4, and FT3 are a feature of secondary hyperthyroidism which could occur in the setting of resistance of thyroid hormone at the pituitary gland, alteration of certain deiodinase enzymes causing lower T3 at the pituitary or a TSH secreting tumor in the pituitary. Other conditions include pregnancy and the use of drugs (amiodarone, heparin). We present a case of secondary hyperthyroidism that was diagnosed with a TSH-secreting adenoma (TSHoma). A 72-year-old male presented with complaints of chest pain. He had a past medical history of primary hyperaldosteronism, occipital lobe ischemic infarct, osteoporosis with low-intensity rib, wrist, and vertebral fractures, coronary artery disease, and had undergone CABG. He was diagnosed with paroxysmal atrial fibrillation and had thyroid function testing which showed a TSH of 7.72μIU/mL (0.42-4.50), FT3 6.2pg/mL (2.0-4.4) and FT4 1.74ng/dL (0.70-1.48). A subsequent CT Head revealed a sellar mass measuring 1.4 cm craniocaudally with abutment of the optic chiasm. Repeat thyroid testing continued to show an elevated TSH, FT3, and FT4. αsubunit glycoprotein was 4.1ng/mL (< 0.5), IGF-1 by LC/MS was 31ng/mL (32-200), prolactin was 46.5ng/mL (4.0-15.2) and SHBG 131.6nmol/L (13.3-89.5). He was managed with methimazole and underwent trans-sphenoidal resection of the tumor. Pathology showed a 3.5 x 1.8 x 0.3 cm mass that on immunoperoxidase stains demonstrated expression of synaptophysin by many of the neoplastic cells. Some expressed GH, few expressed prolactin while rare neoplastic cells expressed TSH. TSHomas are rare pituitary adenomas with a prevalence of 1-2 cases/million. Up to 30% can be associated with hypersecretion of GH, prolactin, LH and FSH. The cells express TRH, somatostatin, and dopamine receptors. Clinical features include headaches, visual field defects, goiter, signs/symptoms of hyperthyroidism, pressure effects of the adenoma, cardiac manifestations (atrial fibrillation, heart failure, pericardial effusion) and vertebral fractures. αsubunit glycoprotein is elevated and an αsubunit to TSH molar ratio >1 can be used with 90% sensitivity to differentiate it from other causes of elevated TSH, FT3 and FT4. Elevations in SHBG are also found in patients. Resistance to the thyroid hormone at the pituitary level can give rise to a similar presentation. Elevated levels of SHBG and αsubunit glycoprotein seen in TSHoma can aid in differentiation. Dynamic testing such as a T3 suppression test with LT3 fails to suppress TSH production in cases of TSHoma. In addition, a TRH stimulation test fails to increase levels of TSH or αsubunit in TSHomas. Due to the presence of somatostatin receptors, TSH reduction starts to occur within hours after the use of somatostatin analogs. Surgical removal is the cornerstone of management and helps achieve normal TSH levels in more than 75% of patients. Pre-operative treatment with octreotide is shown to reduce TSH levels by up to 50% and cause a reduction in size by 20-50%. Undetectable TSH 1-week post-op has good prognostic value and a reduction in TSH on a T3 suppression test has optimal sensitivity and specificity to demonstrate cure.