Circadian variation in neuroendocrine response to L-dopa in patients with restless legs syndrome

Sleep. 2004 Jun 15;27(4):669-73.


Study objective: To investigate circadian changes in dopaminergic function by means of a neuroendocrine challenge (growth hormone and prolactin responses to an acute oral administration of L-dopa) in patients with idiopathic restless legs syndrome (RLS) and controls.

Design: Randomized administration of the L-dopa neuroendocrine challenge.

Setting: Sleep disorders laboratory at a 500-bed academic hospital.

Patients or participants: Twelve patients diagnosed with idiopathic RLS and 12 age- and sex-matched healthy controls.

Interventions: Following a comprehensive evaluation that included nocturnal polysomnographic study, all participants underwent the L-dopa neuroendocrine challenge on 2 occasions (11 am and 11 pm). Subjects were previously randomly assigned to the time of first challenge (11 am or 11 pm). On each occasion, subjects took 200 mg of L-dopa (plus 50 mg carbidopa) by mouth. Blood was drawn 20 minutes and 5 minutes before administration of the drug, as well as 15, 30, 45, 60, 75, 90, 102, and 120 minutes after administration.

Results: Prechallenge levels of plasma values of growth hormone or prolactin did not differ in the 2 subject groups. Following only the nighttime administration of L-dopa, RLS patients manifested a more pronounced inhibition of prolactin release and an increase in growth hormone secretion. Prolactin plasma levels were significantly correlated to the periodic limb movement index on the polysomnogram.

Conclusions: These findings may reflect enhanced circadian variations in dopaminergic function and support an increased sensitivity at night of dopamine receptors in patients with RLS.

Publication types

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

MeSH terms

  • Antiparkinson Agents / administration & dosage
  • Antiparkinson Agents / pharmacology
  • Antiparkinson Agents / therapeutic use*
  • Circadian Rhythm / physiology*
  • Drug Administration Schedule
  • Female
  • Humans
  • Hydrocortisone / metabolism
  • Levodopa / administration & dosage
  • Levodopa / pharmacology
  • Levodopa / therapeutic use*
  • Male
  • Middle Aged
  • Polysomnography
  • Prolactin / metabolism
  • Restless Legs Syndrome / diagnosis
  • Restless Legs Syndrome / drug therapy*
  • Tomography, Emission-Computed, Single-Photon


  • Antiparkinson Agents
  • Levodopa
  • Prolactin
  • Hydrocortisone