Midregional pro-adrenomedullin as a predictor for therapeutic response to midodrine hydrochloride in children with postural orthostatic tachycardia syndrome

J Am Coll Cardiol. 2012 Jul 24;60(4):315-20. doi: 10.1016/j.jacc.2012.04.025.


Objectives: This study was designed to explore the predictive value of the midregional fragment of pro-adrenomedullin (MR-proADM) in assessing the therapeutic efficacy of midodrine hydrochloride for children with postural orthostatic tachycardia syndrome (POTS).

Background: Midodrine hydrochloride is an important therapeutic option for children with POTS. However, there has not been any method to predict response to the drug. The MR-proADM is produced in equimolar amounts to adrenomedullin (ADM), and directly reflects levels of the rapidly degraded active peptide, ADM.

Methods: Fifty-seven children with POTS were designated as the POTS group. Twenty healthy children served as the control group. The children in the POTS group received midodrine hydrochloride treatment. The plasma concentration of MR-proADM was measured, using a sandwich immunoluminometric assay. A receiver-operating characteristic curve was used to explore the predictive value of MR-proADM.

Results: Plasma levels of MR-proADM were significantly higher in children with POTS (75.0 [62.5 to 96.0] pg/ml) than in the control group (58.5 [50.3 to 69.0] pg/ml). Plasma levels of MR-proADM in responders to midodrine hydrochloride was significantly higher than that of nonresponders (76.0 [66.0 to 91.0] pg/ml vs. 59.0 [54.0 to 65.5] pg/ml, p < 0.01]. A receiver-operating characteristic curve on the predictive value of MR-proADM showed that the area under the curve was 0.879 with a 95% confidence interval of 0.761 to 0.997. Using a cutoff value for MR-proADM of 61.5 pg/ml produced both high sensitivity (100%) and specificity (71.6%) in predicting the efficacy of midodrine hydrochloride therapy for treating POTS.

Conclusions: MR-proADM can help guide midodrine hydrochloride therapy in the management of POTS in children.

Publication types

  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adrenomedullin / blood*
  • Biomarkers / blood*
  • Blood Pressure / drug effects
  • Child
  • Female
  • Heart Rate / drug effects
  • Humans
  • Male
  • Midodrine / adverse effects
  • Midodrine / therapeutic use*
  • Peptide Fragments / blood*
  • Postural Orthostatic Tachycardia Syndrome / blood*
  • Postural Orthostatic Tachycardia Syndrome / drug therapy*
  • Predictive Value of Tests
  • Protein Precursors / blood*
  • ROC Curve
  • Sympathomimetics / adverse effects
  • Sympathomimetics / therapeutic use*
  • Tilt-Table Test
  • Treatment Outcome


  • Biomarkers
  • Peptide Fragments
  • Protein Precursors
  • Sympathomimetics
  • mid-regional pro-adrenomedullin, human
  • Adrenomedullin
  • Midodrine