Restoration of detectable melatonin after entrainment to a 24-hour schedule in a 'free-running' man

Psychoneuroendocrinology. 1997 Jan;22(1):39-52. doi: 10.1016/s0306-4530(96)00038-8.


We evaluated a 37-year-old male with a non-24-h sleep-wake disorder. His environment gave him little exposure to bright light. Circadian profiles of temperature, melatonin, thyrotropin, cortisol and testosterone were obtained along with endocrine challenges of the thyroid, adrenal, growth hormone and gonadal axes. Multiple endocrine abnormalities were detected. Testosterone was low and nocturnal thyrotropin levels were erratic. Serum melatonin was undetectable throughout the day and night on multiple occasions, and responses to infusions of TRH, GnRH and GRF-44 were abnormal. Responses to CRH infusion were normal. The patient was successfully entrained to a 24-h schedule by daily exposure to 2500 lux light from 0700h to 0900h, avoidance of light (by wearing dark goggles) from 1800h to 2300h, and strict enforcement of a dark environment from 2300h to 0700h. After entrainment, a normal pattern of nocturnal melatonin secretion was found. GH response to GRF-44 also normalized, although abnormal responses to TRH and GnRH persisted. This case raises the possibility that a complex interaction of light exposure with the circadian system can reversibly suspend pineal gland secretion of melatonin indefinitely. It also suggests that circadian rhythm disorders be considered in the differential diagnosis of abnormal endocrine function.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Body Temperature Regulation / physiology
  • Circadian Rhythm / physiology*
  • Dark Adaptation / physiology
  • Humans
  • Hydrocortisone / blood
  • Hypothalamo-Hypophyseal System / physiopathology
  • Male
  • Melatonin / blood*
  • Phototherapy
  • Pituitary-Adrenal System / physiopathology
  • Sleep Deprivation / physiology
  • Sleep Wake Disorders / physiopathology*
  • Sleep Wake Disorders / therapy
  • Testosterone / blood
  • Thyrotropin / blood
  • Wakefulness / physiology*


  • Testosterone
  • Thyrotropin
  • Melatonin
  • Hydrocortisone