Orthostatic Hypotension as a Manifestation of Vitamin B₁₂ Deficiency

Abstract

A 90-year-old woman with orthostatic hypotension and near-syncope was found to have a low-normal level of vitamin B₁₂ and no other medical findings that could explain her orthostasis. Her symptoms responded to vitamin B₁₂ replacement therapy. This case shows that vitamin B₁₂ deficiency can induce orthostatic hypotension and syncope that are correctable by vitamin B₁₂ replacement.

Orthostatic hypotension (OH) is a common disorder, especially among elderly persons. Patients with OH usually undergo neurologic, cardiologic, and endocrine evaluation, because there are several causes for this presentation. One of these causes, vitamin B₁₂ deficiency, is well known among neurologists but is often overlooked by cardiologists. We describe a case of OH in an elderly woman whose condition improved with vitamin B₁₂ replacement therapy. This case brought the attention of our cardiology group to this vitamin deficiency and its importance as a potential diagnosis in cardiology patients.

Case Report

A 90-year-old woman with no history of hypertension was referred for evaluation because she reported feeling lightheaded after changing position from sitting to standing. The frequency of these attacks was approximately once per day. Evaluation by an otolaryngologist revealed no abnormality of the vestibular system, and magnetic resonance imaging of the brain produced normal findings. She was found to have orthostatic hypotension; when she stood up from sitting, her blood pressure declined from 170/74 mmHg to 110/70 mmHg. Extensive evaluation of her orthostasis, including an adrenocorticotropic hormone stimulation study (also known as the corticotropin or cosyntropin [Cortrosyn] stimulation test), produced normal findings. Her cardiac and endocrine evaluation revealed no abnormalities. Her blood test showed a normal hemoglobin level of 13 g/dL, a mean corpuscular volume of 102 fL (normal range, 80–100 fL), and a mean corpuscular hemoglobin level of 33.8 pg (normal range, 27–33 pg). These findings suggested macrocytosis and a possible vitamin B₁₂ deficiency. Her B₁₂ level was in fact at the low end of the normal range (208 pg/mL; normal range, 200–1,100 pg/mL). However, because of previous reports showing that between 5% and 10% of patients with B₁₂ levels between 200 and 400 pg/mL can experience various symptoms due to occult B₁₂ deficiency,^1–3 we decided to start her on B₁₂ replacement therapy (1 mg, sublingual, daily). Thereafter, the patient reported significant improvement in her symptoms—only one mild spell during the last 4 weeks of the 9-week follow-up period.

Discussion

Orthostatic hypotension, first described by Bradbury and Eggleston in 1925,⁴ is defined as a fall in systolic blood pressure of at least 20 mmHg or diastolic pressure of at least 10 mmHg during the first 3 minutes of standing. Approximately 0.4% of all hospitalizations in the United States are related to OH. In 17% of these cases, OH is the primary diagnosis.⁵ Its prevalence increases with age, because aging is associated with a decrease in baroreceptor sensitivity and responsiveness, reduced cardiac compliance, and attenuation of the vestibulosympathetic reflex.

Immediately after a person stands, 500 to 1,000 mL of blood pools in the lower extremities and splanchnic circulation. Venous return to the heart is reduced, which lowers cardiac output and blood pressure. The baroreceptors in the carotid sinus and aortic arch sense these changes. As part of the compensatory reflex, sympathetic outflow is increased and vagal activity is reduced. These responses cause an increase in peripheral resistance, venous return to the heart, and cardiac output, thus preventing the fall in blood pressure. If this reflex fails, OH occurs.⁶

Orthostatic hypotension can be asymptomatic, or it can manifest with one or more of its characteristic symptoms of lightheadedness, dizziness, and loss of consciousness, which can be very frequent. These symptoms can be disabling and extremely difficult to treat, especially when the patient has hypertension in a supine position. The many causes of OH include drugs, neurogenic and nonneurogenic causes, cardiac pump failure, and venous pooling (Table I). Peripheral neuropathy that results from vitamin B₁₂ deficiency is one of the rarer causes of OH.^7–9

TABLE I. Some Causes of Orthostatic Hypotension

Vitamin B₁₂ deficiency is a common disorder in elderly outpatients,¹⁰ and OH associated with this deficiency has been reported since the early 1960s. In 1962, Kalbfleisch and Woods¹¹ reported a case of OH associated with pernicious anemia; the patient completely recovered after 12 weeks of parenteral vitamin B₁₂ therapy. In 1981, White and colleagues¹² reported the first case of neurogenic OH as the initial symptom of vitamin B₁₂ deficiency.

Many investigators, including Beitzke and colleagues,¹³ have suggested that any patient with OH should be screened for vitamin B₁₂ deficiency, even in the absence of clinical neurologic signs or typical hematologic manifestations. We agree that in the process of evaluating patients with OH, it is important for cardiologists to test for this deficiency. This diagnosis is infrequently considered even though B₁₂ deficiency is readily treatable with oral vitamin B₁₂, which has replaced parenteral B₁₂ therapy.^14,15

Acknowledgment

Stephen N. Palmer, PhD, ELS, contributed to the editing of the manuscript.