Clinical Reasoning: A 66-Year-Old Man With Chronic Orthostatic Hypotension, 2025, Abhishek Lenka

[Mij]

Abstract​

A 66-year-old man presented with a 9-year history of chronic orthostatic intolerance and recurrent syncope. A review of systems also revealed several other symptoms including dry eyes and mouth, chronic nausea and bloating, constipation, urinary urgency and urge incontinence, and erectile dysfunction. He had no motor, sensory, or cognitive concerns. He took no medications that could cause autonomic dysfunction. His neurologic examination was unremarkable. The tilt table test revealed neurogenic orthostatic hypotension. His plasma norepinephrine level was low. Eventually, a treatable etiology of autonomic failure was identified, and the patient had excellent response to treatment.
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[Chandelier]

The patient was diagnosed with idiopathic autoimmune autonomic ganglionopathy (AAG).

…
Our patient reported excellent improvement in his overall symptoms in response to an initial course of IVIg infusions (40 g daily for 3 days). He reported improvement in orthostatic intolerance, gastroparesis, and bladder symptoms. Owing to problems with insurance coverage, IVIg could not be continued and symptoms relapsed. Subsequently, he was treated with rituximab infusions, followed by significant clinical improvement in all symptoms.

Conclusion​

Isolated autonomic failure, presenting with OH along with features of cholinergic dysfunction, should alert neurologists to an autoimmune etiology of autonomic dysfunction, especially AAG. When available, pupillometry can be used to look for premature pupillary dilation, a feature unique to AAG. Because it is potentially treatable, timely diagnosis through appropriate autoantibody testing and optimal treatment with immunomodulating agents can lead to excellent outcomes.

 

[Evergreen]

Very interesting.

His plasma norepinephrine level was low.

Walitt et al. 2024 found no difference between patients and controls in plasma norepinephrine, but cerebrospinal norepinephrine "correlated with both time to failure and effort preference in PI-ME/CFS participants" (i.e. with patients' ability to sustain hand grip and patients choosing to rapidly tap with pinky).

Figs 6d & e from Walitt et al. 2024: