SUN-061 - From Seizures to Sella: Macro-TSH in A Giant Pit-1 Lineage TSH-Predominant Pituitary Tumor

Thyrotropin (TSH)–secreting pituitary neuroendocrine tumors (PitNETs) are rare and typically present with central hyperthyroidism. Macro-TSH, a complex of TSH bound to immunoglobulins, can cause spuriously elevated TSH concentrations with minimal clinical thyrotoxicosis. We report a case of a TSH-predominant PitNET in which concomitant macro-TSH significantly complicated biochemical interpretation and diagnosis.

A 25-year-old man with no prior medical history presented with new-onset seizures following several months of headaches, peripheral vision loss, weight gain, and erectile dysfunction. Physical examination was otherwise unremarkable. Brain MRI demonstrated a 6.5-cm giant sellar/suprasellar mass with brain invasion, mass effect, midline shift, transtentorial herniation, and optic chiasm compression.

Laboratory evaluation revealed mildly elevated free T4 and T3 with markedly elevated TSH (179.7 mIU/L). Given the disproportionate TSH elevation, assay interference was suspected. Polyethylene glycol (PEG) precipitation repeatedly demonstrated ≥50% reduction in measured TSH (179.7→37.9, 31.46→12.97, 39.40→7.84 mIU/L), consistent with macro-TSH. The α-subunit was elevated (46 ng/mL). Additional findings included mild IGF-1 elevation, mild hyperprolactinemia, central hypogonadism, and preserved hypothalamic–pituitary–adrenal axis function.

The patient underwent staged endoscopic transsphenoidal debulking, followed by revision transsphenoidal resection and craniotomy. Histopathology revealed a Pit-1 lineage PitNET with TSH immunoreactivity in a subset of tumor cells, scattered GH-positive cells, and rare lactotrophs. The tumor demonstrated diffuse PIT-1 positivity, was negative for T-PIT, and showed strong somatostatin receptor type 2 (SSTR2) expression. These findings supported a diagnosis of a TSH-predominant Pit-1 lineage PitNET with concomitant macro-TSH. Postoperatively, the course was complicated by central diabetes insipidus, and the patient was started on levothyroxine for central hypothyroidism.

Markedly elevated TSH with only modest free T4 elevation and minimal clinical thyrotoxicosis should prompt evaluation for macro-TSH, particularly in the presence of a pituitary mass. PEG precipitation is a practical and accessible method to identify macro-TSH and avoid misdiagnosis. Integration of clinical features, α-subunit measurement, imaging, and Pit-1 lineage immunohistochemistry was critical in confirming a TSH-predominant PitNET and distinguishing it from thyroid hormone resistance or isolated assay interference. In the presence of macro-TSH, thyroid hormone replacement should be guided by free T4 levels and clinical status rather than TSH. Strong SSTR2 expression supports consideration of somatostatin analog therapy if residual tumor persists.

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