C32-01 Hereditary Angioedema With Normal C1 Inhibitor Complicated by Compressive Multinodular Goiter Requiring Thyroidectomy and Tracheostomy

Angioedema can be categorized as histaminergic or bradykinin-mediated. Histaminergic forms respond to epinephrine, antihistamines, and corticosteroids and resolve within 48 hours. In contrast, bradykinin-mediated forms are often refractory and require C1 inhibitor concentrate or fresh frozen plasma. Symptoms can persist 2 to 5 days, while severe cases may last longer. Airway protection is paramount, and in the setting of mass effect, surgical intervention is necessary to secure the airway. We present a rare case of hereditary angioedema with normal C1 inhibitor (HAE-nC1INH) complicated by compressive multinodular goiter necessitating partial thyroidectomy and tracheostomy. A 71-year-old Black female presented with acute aphasia and right-sided weakness. CT angiography of the head and neck was performed. Following iodinated contrast administration, she acutely developed severe facial and oropharyngeal swelling with airway compromise. No obvious urticaria or hemodynamic collapse was observed. She was intubated and received dexamethasone, famotidine, montelukast, corticosteroids, and fresh frozen plasma, yet airway edema persisted for over two weeks. Laboratory testing revealed elevated C4 levels, normal C1 Esterase Inhibitor function, and antigen levels. She had no prior exposure to angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB). The findings were highly suggestive of hereditary angioedema with normal C1 esterase inhibitors. Her clinical course was further complicated by a toxic multinodular goiter that enlarged after iodinated contrast exposure. Graves’ Disease was diagnosed, and methimazole was started. She eventually required a partial thyroidectomy after 17 days of intubation. Contrast-induced angioedema has been reported in the gastrointestinal tract. However, isolated, sustained airway edema without urticaria or hemodynamic collapse, especially in the context of an evolving large multinodular goiter with a mass effect, has not been described. A protracted course of airway swelling despite treatment with steroids, epinephrine, and antihistamine, and in the absence of ACEi and ARB use, suggests bradykinin-mediated mechanism. Furthermore, elevated C4 with normal C1 esterase inhibitor function and protein levels are inconsistent with classic Type I and II hereditary angioedema, as well as acquired C1-inhibitor deficiency. This is highly suspicious of HAE-nC1INH, a rare genetically heterogeneous disorder linked to variants in several genes. This autosomal dominant condition with variable penetrance should be considered when airway edema persists beyond 2 to 4 days of standard management. In such cases, bradykinin-mediated process should be in the differential, and empiric therapy should be pursued. However, for patients with airway compromise from angioedema that is complicated by underlying etiologies, early surgical evaluation should also be considered.