Clues for early detection of autoimmune Addison's disease - myths and realities

J Intern Med. 2018 Feb;283(2):190-199. doi: 10.1111/joim.12699. Epub 2017 Nov 3.


Background: Early detection of autoimmune Addison's disease (AAD) is important as delay in diagnosis may result in a life-threatening adrenal crisis and death. The classical clinical picture of untreated AAD is well-described, but methodical investigations are scarce.

Objective: Perform a retrospective audit of patient records with the aim of identifying biochemical markers for early diagnosis of AAD.

Material and methods: A multicentre retrospective study including 272 patients diagnosed with AAD at hospitals in Norway and Sweden during 1978-2016. Scrutiny of medical records provided patient data and laboratory values.

Results: Low sodium occurred in 207 of 247 (84%), but only one-third had elevated potassium. Other common nonendocrine tests were largely normal. TSH was elevated in 79 of 153 patients, and hypoglycaemia was found in 10%. Thirty-three per cent were diagnosed subsequent to adrenal crisis, in whom electrolyte disturbances were significantly more pronounced (P < 0.001). Serum cortisol was consistently decreased (median 62 nmol L-1 [1-668]) and significantly lower in individuals with adrenal crisis (38 nmol L-1 [2-442]) than in those without (81 nmol L-1 [1-668], P < 0.001).

Conclusion: The most consistent biochemical finding of untreated AAD was low sodium independent of the degree of glucocorticoid deficiency. Half of the patients had elevated TSH levels. Only a minority presented with marked hyperkalaemia or other nonhormonal abnormalities. Thus, unexplained low sodium and/or elevated TSH should prompt consideration of an undiagnosed AAD, and on clinical suspicion bring about assay of cortisol and ACTH. Presence of 21-hydroxylase autoantibodies confirms autoimmune aetiology. Anticipating additional abnormalities in routine blood tests may delay diagnosis.

Keywords: Addison; adrenal insufficiency; autoimmune disease; cortisol; electrolytes; endocrinology.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Addison Disease / blood
  • Addison Disease / complications
  • Addison Disease / diagnosis*
  • Adolescent
  • Adult
  • Aged
  • Biomarkers / blood
  • Blood Glucose / metabolism
  • Child
  • Child, Preschool
  • Early Diagnosis*
  • Female
  • Humans
  • Hydrocortisone / blood
  • Hyperkalemia / etiology
  • Hypoglycemia / etiology
  • Hyponatremia / etiology
  • Male
  • Middle Aged
  • Potassium / blood
  • Retrospective Studies
  • Sodium / blood
  • Thyrotropin / blood
  • Young Adult


  • Biomarkers
  • Blood Glucose
  • Thyrotropin
  • Sodium
  • Potassium
  • Hydrocortisone