title: Defining adrenal status with salivary cortisol by gold-standard insulin hypoglycemia.
abstract: BACKGROUND
  Insulin-induced hypoglycemia (IHT) is considered the gold standard test for evaluating the HPA axis. Serum free cortisol or its surrogate, salivary cortisol as opposed to total cortisol concentrations, offers a better reflection of the activation of HPA axis. Our study aimed to derive reference ranges for the normal salivary cortisol levels in healthy patients and patients with adrenal insufficiency.
  
  
  METHODS
  Serum cortisol concentrations, using the gold standard of IHT, and salivary cortisol were obtained. 36 patients referred to our outpatient endocrine testing unit for evaluation of adrenal function were included in the study. Most subjects had a history of suspected hypothalamic/pituitary disease causing adrenal insufficiency.
  
  
  RESULTS
  We found a strong linear correlation between the serum and salivary cortisol concentrations in simultaneously collected samples (r=0.81, 95% CI 0.74-0.86, p<0.0001). The corresponding salivary cortisol equivalent to a serum cortisol of 500 nmol/L, using a linear-regression equation, was 16.7 nmol/L (95% CI 13.3-20.1 nmol/L, p=0.0001). A salivary cortisol of 13.3 nmol/L has a specificity of 89.3% to detect abnormal HPA function. Using the upper 95% CI result of salivary cortisol 20.1 yields a sensitivity of 87.5%.
  
  
  CONCLUSIONS
  With the present assay, adrenal insufficiency may be diagnosed with reasonable confidence if a random salivary cortisol is lower than 13.3 nmol/L and excluded if a random salivary cortisol is higher than 20.1 nmol/L. Future studies should correlate these thresholds with clinical outcomes.
authors.affiliation: Faculty of Medicine, Division of Endocrinology, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Karpman
authors.forename: Madalina
authors.initials: M
authors.lastname: Neculau
authors.forename: Valerian C
authors.initials: VC
authors.lastname: Dias
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Kline
mesh_terms: D000311:Adrenal Glands / Q000378:metabolism* / Q000503:physiopathology; D000309:Adrenal Insufficiency / Q000175:diagnosis* / Q000378:metabolism* / Q000503:physiopathology; D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D007003:Hypoglycemia / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism / Q000503:physiopathology; D007328:Insulin; D008297:Male; D008875:Middle Aged; D010913:Pituitary-Adrenal System / Q000378:metabolism / Q000503:physiopathology; D012044:Regression Analysis; D012469:Salivary Glands / Q000737:chemistry*; D012680:Sensitivity and Specificity
chemical_list: D007328:Insulin; D006854:Hydrocortisone
keywords: Adrenal function; Adrenal insufficiency; Free cortisol; HPA; IHT; Insulin hypoglycemia test; Salivary cortisol; hypothalamus–pituitary–adrenal; insulin-induced hypoglycemia test