Endocrine Abstracts

Introduction

Heterozygous familial hypercholesterolemia is one of the most common genetic disorders and it is associated with an at least ten times higher risk of coronary heart disease. Frequently, it is necessary to medicate the patients with PCSK9 inhibitors (PCSK9i) so they can reach LDL-c target values. In Portugal, the only evolocumab is available and the most commonly reported adverse effects are local pruritus and upper airway symptoms.

Case report

A 42-year-old woman was referred to our department because of a poorly controlled hypercholesterolemia despite being on maximal doses of statin and ezetimibe. She had a family history of premature coronary disease and had a serum total cholesterol level of 415 mg/dl and an LDL-c level of 327 mg/dl. Her Dutch Lipid Clinical Network score was above 8 points. As so, she underwent genetic testing which revealed a pathogenic mutation in heterozygosity. She started evolocumab and responded well to the first dose (LDL-c reduction of 53%) but reported transient headaches, nausea and myalgia. After the second dose, she developed self-limited headaches, dizziness, myalgia and an acute confusional state with spatial disorientation and horizontal binocular diplopia. Both a brain CT scan and an MRI were performed and showed no relevant findings. The patient also underwent neurological, psychiatric and otorhinolaryngological assessments which excluded other etiologies. Thus, evolocumab was suspended. 6 months later, her cholesterol levels had risen to alarmingly high levels and the PCSK9i was reintroduced – the patient once again developed a worrisome confusional syndrome and evolocumab was permanently suspended. As an alternative, she started lipoprotein apheresis and responded well to this treatment (LDL-c reduced by 57%). Since then, she has an apheresis session every two weeks and no adverse effects have been reported.

Discussion

This case report demonstrates an association between evolocumab and the development of neurocognitive symptoms. Other potential explanations would be the induced hypocholesterolemia or the abrupt cholesterol reduction. However, it has already been proved that LDL-c reductions to values below 25 mg/dl due to the action of PCSK9i occur safely. Furthermore, a similar LDL-c reduction was achieved with the lipoprotein apheresis without any adverse effects. In fact, although extremely rare, the association between PCSK9i and neurocognitive symptoms has been described in some clinical trials. As so, the authors intend to raise awareness on the need to monitor neurocognitive symptoms in patients taking evolocumab.