title: Plasma adrenocorticotropin (ACTH) values and cortisol response to 250 and 1 microg ACTH stimulation in patients with hyperthyroidism before and after carbimazole therapy: case-control comparative study.
abstract: BACKGROUND
  Although the production and metabolic clearance rate of cortisol is increased during thyrotoxic state, the net effect on adrenocortical reserves is not clear.
  
  
  OBJECTIVE
  We assessed circulating ACTH levels, cortisol binding globulin (CBG), and adrenocortical reserves in hyperthyroid patients (before and after carbimazole therapy) and healthy controls.
  
  
  METHODS
  This was a case-control investigative study in a tertiary care setting.
  
  
  METHODS
  Plasma ACTH and free cortisol index (FCI; serum cortisol/CBG) were measured in 49 consecutive patients with hyperthyroidism and 50 controls. ACTH(1-24) stimulation tests (250 and 1 microg) were carried out in the first 29 patients and 15 controls. Peak FCI less than the mean -3 sd of healthy controls was considered subnormal. ACTH(1-24) stimulation tests were repeated in 24 patients in the euthyroid state.
  
  
  RESULTS
  The mean basal plasma ACTH and FCI were higher and CBG was lower in thyrotoxic patients in comparison with controls. The peak cortisol was less than 18 microg/dl in 10 of 29 and 14 of 29 on 250 and 1 microg ACTH(1-24) stimulation. Peak FCI was subnormal only in three of 27 (11.1%) and two of 21 (7.4%) on 250 and 1 microg ACTH(1-24) stimulation, respectively. The mean plasma ACTH, basal FCI, and subnormal peak FCI (two of the three) normalized after euthyroidism. Plasma ACTH and FCI did not correlate with severity of thyrotoxicosis.
  
  
  CONCLUSIONS
  Up to 11% of thyrotoxics have subnormal peak FCI on ACTH(1-24) stimulation. Such changes occur despite high basal plasma ACTH and FCI. Use of FCI, rather than total cortisol, is required for the interpretation of cortisol values in thyrotoxicosis due to the variation in CBG.
authors.affiliation: Department of Endocrinology and Metabolism, All India Institute of Medical Sciences, New Delhi, India 110029.
authors.forename: Sunil Kumar
authors.initials: SK
authors.lastname: Mishra
authors.forename: Nandita
authors.initials: N
authors.lastname: Gupta
authors.forename: Ravinder
authors.initials: R
authors.lastname: Goswami
mesh_terms: D000304:Adrenal Cortex Function Tests; D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000328:Adult; D013956:Antithyroid Agents / Q000627:therapeutic use*; D002231:Carbimazole / Q000627:therapeutic use*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D006980:Hyperthyroidism / Q000097:blood* / Q000188:drug therapy*; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D013268:Stimulation, Chemical; D013971:Thyrotoxicosis / Q000097:blood / Q000188:drug therapy; D014156:Transcortin / Q000378:metabolism
chemical_list: D013956:Antithyroid Agents; D002231:Carbimazole; D000324:Adrenocorticotropic Hormone; D014156:Transcortin; D006854:Hydrocortisone