Combination therapy of pasireotide and pegvisomant for aggressive acromegaly with an immature PIT1-lineage PitNET.

Summary: A 29-year-old male presented with central scotoma and was suspected of having acromegaly based on enlargement of facial features and extremities. Serum growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels were elevated to 10.14 ng/mL and 571 ng/mL (74.8 nmol/L, +5.73 SDS), respectively. Magnetic resonance imaging revealed a giant pituitary neuroendocrine tumor (PitNET) measuring 48 × 48 × 58 mm with bilateral cavernous sinus invasion and high T2-weighted signal intensity. Because of poor GH suppression during an acute octreotide test (100 μg subcutaneously; nadir GH 6.25 ng/mL, 19% reduction from baseline) and the invasive tumor phenotype, preoperative pasireotide (PAS) 40 mg every 4 weeks was initiated. After 2 months, partial tumor removal was performed via transsphenoidal surgery. Histological analysis revealed an immature PIT1-lineage PitNET with strong membranous expression of somatostatin receptor subtypes 2 and 5. Persistently elevated IGF-1 after surgery led to re-initiation of PAS (40 mg every 4 weeks, escalated to 60 mg), followed by the addition of pegvisomant (PEG) 10 mg/day because biochemical control could not be achieved. Combination therapy with PAS and PEG normalized IGF-1 and maintained radiological tumor stability during long-term follow-up. This case highlights that biochemical response to somatostatin receptor ligands does not necessarily correlate with receptor expression in invasive PitNETs. Pathological classification using transcription factors may help guide individualized treatment strategies. Combination therapy with PAS and PEG may represent an effective option for aggressive acromegaly caused by immature PIT1-lineage PitNETs. Learning points: Immature PIT1-lineage PitNETs may demonstrate discordance between somatostatin receptor expression and clinical responsiveness to somatostatin receptor ligands. In patients with predictors of poor response to first-generation somatostatin analogs, such as T2-weighted MRI hyperintensity and poor GH suppression during acute octreotide testing, early consideration of pasireotide (PAS) or combination therapy with PAS and pegvisomant (PEG) may be appropriate. In this case, PAS up to 60 mg every 4 weeks failed to adequately control IGF-1 levels, whereas subsequent combination therapy with PAS and PEG achieved biochemical remission and tumor stabilization, highlighting the potential role of combination strategies in aggressive acromegaly.