title: Significant attenuation of stimulated cortisol in early Graves disease without adrenal autoimmunity.
abstract: OBJECTIVE
  To investigate cortisol responses to adrenocorticotropic hormone during thyrotoxic (G1) and euthyroid (G2) phases in patients with Graves disease (GD) who were without adrenal autoimmunity.
  
  
  METHODS
  Fifteen patients with GD, who were thyrotropin receptor antibody positive and 21-hydroxylase antibody negative, were recruited to this prospective pilot study. A modified short Synacthen test (SST) was performed, in which cortisol was measured every 30 minutes for 2 hours during G1 and G2.
  
  
  RESULTS
  The median times to SST were 3 weeks (G1) and 27 weeks (G2) after diagnosis of GD. Integrated stimulated cortisol levels were significantly lower at G1 in comparison with G2: mean ± standard error of the mean for area under the curve was 78,091.6 ± 4,462.1 nmol/L (G1) versus 89,055 ± 4,434 nmol/L at 120 minutes (G2), P = .017; and for delta area under the curve was 36,309.9 ± 3,526 nmol/L (G1) versus 44,041.7 ± 2,147 nmol/L at 120 minutes (G2), P = .039. Mean cortisol levels were significantly lower for G1 versus G2 at 60, 90, and 120 minutes of the SST (P = .001 to .013). The cortisol level was abnormal in 2 patients (13%) at 30 minutes during G1 but in none during G2. There was no correlation of integrated cortisol with free thyroxine or thyrotropin receptor antibody. There was no significant difference in median adrenocorticotropic hormone level (17 versus 20.4 ng/mL at G1 and G2, respectively; P = .14).
  
  
  CONCLUSIONS
  Significant attenuation of stimulated cortisol occurs in the early thyrotoxic phase in comparison with the euthyroid phase in patients with GD without adrenal autoimmunity. Clinicians treating patients with GD should have a low threshold for investigating symptoms suggestive of hypoadrenalism at times of "stress."
authors.affiliation: Section of Diabetes and Endocrinology, Caerphilly Miners' Hospital, Caerphilly, UK.
authors.forename: Sally A
authors.initials: SA
authors.lastname: Price
authors.forename: Sravan
authors.initials: S
authors.lastname: Thondam
authors.forename: Laxmi N R
authors.initials: LN
authors.lastname: Bondugulapati
authors.forename: Chandan
authors.initials: C
authors.lastname: Kamath
authors.forename: Mohammed
authors.initials: M
authors.lastname: Adlan
authors.forename: Lakdasa D
authors.initials: LD
authors.lastname: Premawardhana
mesh_terms: D000311:Adrenal Glands / Q000276:immunology*; D000324:Adrenocorticotropic Hormone / Q000627:therapeutic use*; D000328:Adult; D000906:Antibodies / Q000097:blood; D015551:Autoimmunity / Q000502:physiology*; D005260:Female; D006111:Graves Disease / Q000097:blood* / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D011989:Receptors, Thyrotropin / Q000276:immunology; D013255:Steroid 21-Hydroxylase / Q000276:immunology; D013958:Thyroid Crisis / Q000097:blood; D013961:Thyroid Gland / Q000378:metabolism; D013963:Thyroid Hormones / Q000097:blood; D016896:Treatment Outcome
chemical_list: D000906:Antibodies; D011989:Receptors, Thyrotropin; D013963:Thyroid Hormones; D000324:Adrenocorticotropic Hormone; D013255:Steroid 21-Hydroxylase; D006854:Hydrocortisone