Symptom cluster

Autonomic dysfunction and POTS

Racing heart, dizziness, and feeling worse upright, when standing becomes the hardest part of the day. This page covers: Orthostatic tachycardia (HR rise on standing), Orthostatic intolerance (dizziness, lightheadedness), Fatigue, Exercise intolerance, Exercise intolerance / reduced VO2.

What causes it

The leading explanations, each with its evidence grade and audit status.

GPCR autoantibodies (a/b-adrenergic, M2 muscarinic, AT-II receptor) produces Orthostatic tachycardia (HR rise on standing).

gradelow-moderateauditcontested

sources: S06, S09

Autonomic/small-fiber neuropathy + vagus nerve injury produces Orthostatic tachycardia (HR rise on standing).

gradelow-moderateauditwell-founded

sources: S01

Hypovolemia / blood-volume dysregulation produces Orthostatic tachycardia (HR rise on standing).

gradelowauditthin

sources: S07

Platelet storage pool deficiency / low serotonin produces Orthostatic tachycardia (HR rise on standing).

gradelowauditthin

sources: S08

Mast cell activation produces Orthostatic tachycardia (HR rise on standing).

gradelow-moderateauditemergingendpointpatient-reported-outcome

sources: S140, S74

Cytokine inflammation driving sympathetic activation produces Fatigue.

gradelow-moderateauditthin

sources: S06

Physical deconditioning contested-cause Exercise intolerance.

graderefuted-leaningauditcitation-inertiasafetydrives harmful GET prescription

sources: S23, S26, S27

Mitochondrial / metabolic dysfunction produces Exercise intolerance / reduced VO2.

grademoderateauditwell-founded-for-associationnotenormal tests can miss this

sources: S101, S103, S104, S64, S69, S97

Deconditioning (as cause) contested-cause Exercise intolerance / reduced VO2.

graderefuted-leaningauditcitation-inertiasafetydrives harmful GET prescription

sources: S26, S64, S70

Dysautonomia / autonomic dysfunction produces Exercise intolerance / reduced VO2.

grademoderateauditwell-foundedendpointphysiologic-surrogatenotenormal tests can miss this

sources: S95, S96, S98, S99

What has been tried

No treatment is approved. Each row shows how strong the evidence is, what it was measured on, and any safety or conflict flag.

Ivabradine relieves Orthostatic intolerance (dizziness, lightheadedness).

gradenegativeauditwell-foundedendpointpatient-reported-outcome

sources: S14, S17, S18, S20

Coordinated nonpharmacologic care (bundle) relieves Orthostatic intolerance (dizziness, lightheadedness).

grademoderate-emergingauditwell-foundedendpointpatient-reported-outcome

sources: S17, S20

Midodrine relieves Orthostatic intolerance (dizziness, lightheadedness).

gradelow-moderateauditthinendpointpatient-reported-outcome

sources: S12, S14

Salt + fluid loading relieves Orthostatic intolerance (dizziness, lightheadedness).

gradehigh-lived / low-formalauditwell-foundedendpointpatient-reported-outcome

sources: S17, S32

Compression garments relieves Orthostatic intolerance (dizziness, lightheadedness).

gradelowauditthinendpointpatient-reported-outcome

sources: S17

Pyridostigmine relieves Orthostatic intolerance (dizziness, lightheadedness).

gradelowauditthinendpointpatient-reported-outcome

sources: S34

Pyridostigmine improves Exercise intolerance / reduced VO2.

gradelow-moderateauditemergingendpointphysiologic-surrogate

sources: S76, S77, S79

Recumbent / supine-biased rehabilitation (PEM-bounded) manages Exercise intolerance / reduced VO2.

gradelowauditthinendpointpatient-reported-outcomesafetymust respect PEM threshold

sources: S102, S99

How it is measured

NASA lean / active stand test diagnoses Orthostatic tachycardia (HR rise on standing).

gradestandardauditwell-founded

sources: S04

Invasive CPET (iCPET) diagnoses Exercise intolerance / reduced VO2.

gradereference-standardauditwell-founded

sources: S104, S95

Under review

Ivabradine lowered heart rate but did not improve symptoms in RECOVER-AUTONOMIC: a surrogate-positive, patient-negative split the page keeps visible.