History of stress-related health changes: a cue to pursue a diagnosis of latent primary adrenal insufficiency

Intern Med. 2014;53(3):183-8. doi: 10.2169/internalmedicine.53.1156.


Objective: Routine delays in the diagnosis of primary adrenal insufficiency (PAI) are well known and conceivably attributable to the absence of cues, other than anti-adrenal autoantibodies, to pursue subclinical PAI. Subclinical PAI is latent unless the afflicted patient encounters stress such as an acute illness, surgery, psychosocial burden, etc. It remains to be demonstrated whether a history of stress-related health changes is a useful cue to pursue a diagnosis of latent PAI.

Methods: The patients were selected for a history of recurrent symptoms, i.e., gastrointestinal symptoms, fatigue, or lassitude, aggravated by stress and alleviated by the removal of stress, and signs, i.e., weight loss, hypotension, and hyperpigmentation. As the early morning cortisol levels were low or low-normal and the adrenocorticotropic hormone (ACTH) levels were within the reference ranges, provocation tests, i.e., insulin-induced hypoglycemia tests and low-dose (1 μg) corticotropin tests (LDTs), were used to estimate the hypothalamus-pituitary-adrenal (HPA) axis status. Patients with the HPA axis dysfunction on two provocation tests were supplemented with physiologic doses of glucocorticoids (GCs). The effects of GC supplementation on stress-related health changes were observed.

Results: The ACTH levels after insulin-induced hypoglycemia were higher and the cortisol levels were lower in the patients than in the control subjects. The cortisol levels in the patients were increased less significantly by LDT than those observed in the control subjects. Stress-related health changes ceased to recur and signs, i.e., a low body weight, hypotension, and hyperpigmentation, were ameliorated following GC supplementation.

Conclusion: A history of stress-related health changes is useful as a cue to pursue latent PAI in patients with low or low-normal early morning cortisol levels.

MeSH terms

  • Addison Disease / blood
  • Addison Disease / diagnosis*
  • Addison Disease / psychology
  • Adrenocorticotropic Hormone / blood
  • Adult
  • Aged
  • Cues*
  • Female
  • Health Status*
  • Humans
  • Hydrocortisone / blood
  • Hypothalamo-Hypophyseal System / metabolism
  • Male
  • Middle Aged
  • Pituitary-Adrenal System / metabolism
  • Stress, Psychological / blood
  • Stress, Psychological / diagnosis*
  • Stress, Psychological / psychology


  • Adrenocorticotropic Hormone
  • Hydrocortisone