title: Usefulness of Time-Point Serum Cortisol and ACTH Measurements for the Adjustment of Glucocorticoid Replacement in Adrenal Insufficiency.
abstract: BACKGROUND
  Adjustment of daily hydrocortisone dose on clinical criteria lacks sensitivity for fine tuning. Long term hydrocortisone (HC) over-replacement may lead to increased morbidity and mortality in patients with adrenal insufficiency (AI). Biochemical criteria may help detecting over- or under-replacement but have been poorly evaluated.
  
  
  METHODS
  Multicenter, institutional, pharmacokinetic study on ACTH and cortisol plasma profiles during HC replacement in 27 AI patients compared to 29 matched controls. All AI patients were administered HC thrice daily at doses of 6, 10 and 14 mg/m2/d. Blood samples were drawn hourly from 0800h to 1900h. The main outcome measures were: i) plasma peak cortisol and cortisol area under the curve (AUC) in AI patients compared to controls, ii) correlations between cortisol AUC vs single-point cortisol or ACTH decrease from baseline (ΔACTH) and iii) the predictive value of the two latters for obtaining AI patients' cortisol AUC in the control range.
  
  
  RESULTS
  Cortisol peaks were observed 1h after each HC intake and a dose response was demonstrated for cortisol peak and cortisol AUC. The comparison of AI patients' cortisol AUC to controls showed that 81.5% AI patients receiving 6mg/m2/d were adequately replaced, whereas most patients receiving higher doses were over-replaced. The correlation coefficient between 1000h/1400h cortisol concentrations and 0800-1900h cortisol AUC were 0.93/0.88 respectively, whereas the 0800-1200h ΔACTH fairly correlated with 0800-1900h cortisol AUC (R = 0.57). ROC curve analysis indicated that the 1000h and 1400h cortisol concentrations best predicted over-replacement.
  
  
  CONCLUSIONS
  Patients receiving a 6mg/m2 hydrocortisone daily dose exhibited the most physiological daytime cortisol profile. Single point plasma cortisol correlated with daytime cortisol AUC in AI patients. Although hydrocortisone dose should be currently determined on clinical grounds, our data suggest that single point plasma cortisol may be an adjunct for further hydrocortisone dose adjustment in AI patients.
authors: Department of Endocrinology, Caen University Hospital, 14033, Caen, France.
authors: Elise
authors: E
authors: Rousseau
authors: Department of Endocrinology, Caen University Hospital, 14033, Caen, France.
authors: Michael
authors: M
authors: Joubert
authors: Department of Endocrinology, Caen University Hospital, 14033, Caen, France.
authors: Géraldine
authors: G
authors: Trzepla
authors: Department of Clinical Research, Caen University Hospital, 14033, Caen, France; University of Caen Basse-Normandie, Medical School, Caen, F-14032, France.
authors: Jean Jacques
authors: JJ
authors: Parienti
authors: UFR Pharmaceutical Sciences, EA4259, University of Caen Basse-Normandie, 14032, Caen, France; University of Caen Basse-Normandie, Medical School, Caen, F-14032, France.
authors: Thomas
authors: T
authors: Freret
authors: Department of Endocrinology, Lille University Hospital, 59037, Lille, France.
authors: Marie Christine
authors: MC
authors: Vanthygem
authors: Department of Endocrinology, Amiens University Hospital, Hopital SUD, 80054, Amiens, France.
authors: Rachel
authors: R
authors: Desailloud
authors: Department of Endocrinology and INSERM U413, IFRMP23, Rouen University Hospital, 76031, Rouen, France.
authors: Hervé
authors: H
authors: Lefebvre
authors: Department of Pharmacology, Caen University Hospital, 14033, Caen, France; University of Caen Basse-Normandie, Medical School, Caen, F-14032, France.
authors: Antoine
authors: A
authors: Coquerel
authors: Department of Endocrinology, Caen University Hospital, 14033, Caen, France; University of Caen Basse-Normandie, Medical School, Caen, F-14032, France.
authors: Yves
authors: Y
authors: Reznik
mesh_terms: D000309:Adrenal Insufficiency / Q000097:blood / Q000188:drug therapy*; D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000328:Adult; D000368:Aged; D005260:Female; D020249:Hormone Replacement Therapy / Q000379:methods*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged
chemical_list: D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone