MON-226 - Cerebral Venous Sinus Thrombosis with Intracranial Hypertension during Recombinant Human IGF-1 Therapy for Severe Primary IGF-I Deficiency

Introduction: Laron syndrome is caused by pathogenic variants in the growth hormone receptor (GHR) and is characterized by severe postnatal growth failure and severe insulin-like growth factor (IGF-I) deficiency (SPIGFD). Treatment consists of recombinant human IGF-1 (rhIGF-1). Hypoglycemia is the most common adverse event (AE) associated with rhIGF-1, while increased intracranial pressure (ICP) is a rare serious AE that typically occurs early in treatment. We describe a patient who developed cerebral venous sinus thrombosis (CVST) with increased ICP after more than eight years of rhIGF-1 therapy.

Case Presentation: An 11-year-old male with SPIGFD due to a homozygous pathogenic variant in the extracellular domain of the GHR presented for routine follow-up while receiving rhIGF-1, 120 mcg/kg/dose subcutaneously twice daily. In retrospect, he had experienced headaches for 3–4 months, initially attributed to a sinus infection by his local provider and treated with oral antibiotics and glucocorticoids. His headaches persisted, and he subsequently presented with a seizure characterized by right arm and then generalized shaking. Dilated ophthalmologic examination showed no papilledema. However, head computed tomography (CT) demonstrated findings consistent with increased ICP (including partially empty sella, dilation of the bilateral optic nerve sheaths, and tortuosity of the intraorbital optic nerves), along with increased attenuation of a left bridging vein. Subsequent CT and magnetic resonance venography revealed multifocal CVST. Laboratory evaluation showed severe iron deficiency anemia (Hgb 6.9 g/dL, ferritin 2.5 ng/mL). Evaluation for thrombophilia and occult bleed was unrevealing. Although iron deficiency anemia is a known risk factor for CVST, given the uncommon, atypical presentation and the inability to exclude a contributory role of rhIGF-1 in the development of increased ICP, rhIGF-1 therapy was paused. He was treated with acetazolamide for ICP management, enoxaparin followed by rivaroxaban for anticoagulation, and red blood cell transfusion and iron repletion for anemia. Headaches resolved within one week, and follow-up imaging at three months demonstrated decreased clot burden.

Conclusion: This is the first reported case of CVST in a patient receiving rhIGF-1, occurring in the setting of severe iron deficiency anemia. This case underscores that persistent headache warrants consideration of increased ICP regardless of duration of rhIGF-1 therapy or absence of papilledema. Longitudinal follow-up is required to clarify the clinical course of his multifocal intracranial thrombosis and increased ICP, including consideration of the safety of rhIGF-1 reintroduction.

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