Most of you will probably go, "POTS? What’s POTS?" Let me explain.

I have Hyperadrenergic POTS, so feel free to ask any questions.

POTS (Postural Orthostatic Tachycardia Syndrome) is when a person’s heart rate speeds up 30 beats per minute or more without much change in blood pressure on standing, people may have orthostatic intolerance (OI). Because upright heart rate is usually greatly increased, the more common term used now is Postural Tachycardia Syndrome, or POTS. The increase in heart rate may be a sign that the cardiovascular system is working hard to maintain blood pressure and blood flow to the brain. This results in a lack of blood flow to the brain.

Hypovolemia is an abnormal decrease in blood volume, or more specifically an abnormal decrease in the volume of blood plasma. This sometimes occurs in POTS patients. It may occur due to blood pooling in the abdomen and legs.

POTS is most frequently seen in young women, often less than 35 years of age.

Hyperadrenergic POTS is defined as POTS associated with a systolic BP increment ≥10 mmHg during 10 minutes of HUT, and an orthostatic plasma norepinephrine ≥600 pg/mL.

As a part of the definition, POTS is associated with a hyperadrenergic state. In many such cases, the hyperadrenergic state is secondary to a partial dysautonomia or hypovolemia. There are some cases, however, in which the primary underlying problem seems to be excessive sympathetic discharge. These patients often have extremely high levels of upright norepinephrine. While we require the upright norepinephrine level to be >600 pg/ml for the diagnosis of POTS, the hyperadrenergic subgroup often has upright norepinephrine level >1000 pg/ml and it is occasionally >2000 pg/ml. These patients sometimes have large increases in blood pressure on standing, indicating that baroreflex buffering is somehow impaired.

Central hyperadrenergic POTS in its most florid form is much less common than neuropathic POTS, comprising only ~10% of patients. Thus therapy in these cases usually targets a decrease in sympathetic tone both centrally and peripherally.

Central sympatholytics such as methyldopa or clonidine can be used. Peripheral beta-adrenergic blockade may be better tolerated by these patients than by those with neuropathic POTS.

A specific genetic abnormality has been identified in a kindred with hyperadrenergic POTS. These individuals have a single point mutation in the norepinephrine transporter (NET). The resultant inability to adequately clear norepinephrine produces a state of excessive sympathetic activation in response to a variety of sympathetic stimuli. While rare, this mutation has taught us much about the importance of a functional NET.

Although functional NET mutations might be infrequent, pharmacological NET inhibition is very common. Many antidepressant and attention deficit medications work at least in part through inhibition of NET. This includes traditional drugs such as tricyclic antidepressants, and newer medications which are pure NET inhibitors (e.g. atomoxetine or reboxetine). It’s been found that pharmacological NET inhibition can recreate an orthostatic tachycardia phenotype in susceptible healthy volunteer subjects. Yohimbine, a central alpha-2 antagonist that will also increase synaptic norepinephrine, can also cause orthostatic tachycardia.

How do you test for a genetic hNET mutation? What is the test for it?

Thanks,
Rachel E.