An assessment of optimal hydrocortisone replacement therapy.
OBJECTIVE
To assess the management of hydrocortisone replacement therapy in one institution, and derive recommendations for optimum starting and maintenance replacement therapy with hydrocortisone.


METHODS
Retrospective survey of clinical management using a clinical information system and the patient case notes.


METHODS
Using the department's clinical information system, 210 patients were identified who had been treated with hydrocortisone. Case notes were reviewed and 130 patients were identified whose records contained the results of at least one valid hydrocortisone day curve. Data on 174 day curves performed on these patients (65 on twice daily and 109 on thrice daily hydrocortisone regimes) formed the basis of this analysis.


METHODS
Hydrocortisone day curves had been performed as part of routine clinical management: patients collected a 24 h urine for free cortisol on the day prior to the test and took their morning hydrocortisone at the normal time, at home, on wakening. During a day-case attendance serum cortisol was then measured at 0900 h, 1230 h (prior to any lunchtime dose) and 1730 h (prior to the evening dose). 'Optimal replacement' was arbitrarily defined as that dose which achieved a UFC and 09:00 h cortisol within the reference range for the normal population (to avoid over-replacement) combined with 1230 h and 1730 h cortisol above 50 nmol/l, and ideally above 100 nmol/l (to avoid under-replacement). Raw data from all hydrocortisone day curves was analysed in an Excel spreadsheet to determine the effect of different dose regimens on the percentage of patients achieving each and all of these 4 criteria, and on an overall 'quality score' (comprising 1 point for each of the 4 criteria attained).


RESULTS
Patients on twice daily hydrocortisone regimes achieved optimal replacement in 15% of cases compared to 60% on thrice daily regimes (P < 0.001 by chi 2); mean overall 'quality scores' for these regimens were 2.72 and 3.49 respectively (P < 0.001 by t-test). Of individual dose regimens with sufficient cases for valid comparison, a dose of 10 mg/5 mg/5 mg (rising/lunch/evening) achieved optimal replacement in 66% and mean 'quality score' of 3.62 (n = 53), compared to 50% and 3.32 for 10 mg/ 10 mg/5 mg (n = 28) and 10% and 2.48 for 20 mg/-/10 mg (n = 29).


CONCLUSIONS
The use of arbitrary, but logical, criteria to assess the quality of hydrocortisone replacement regimens indicates that optimal replacement is achieved with thrice daily hydrocortisone regimens, and that the traditional twice daily regime results in a 0900 h cortisol above normal in one-third, and late afternoon cortisol below 50 nmol/l in one-half of patients thus treated. An appropriate starting dose of hydrocortisone of 10 mg/5 mg/5 mg (rising/lunch/evening) is suggested, with subsequent individual adjustment based on simple hydrocortisone day curves.
Howlett
T A
TA
Leicester Royal Infirmary, UK.
D000307:Adrenal Gland Diseases / Q000188:drug therapy* / Q000652:urine; D000315:Adrenalectomy; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000627:therapeutic use / Q000652:urine; D002985:Clinical Protocols; D004334:Drug Administration Schedule; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage* / Q000627:therapeutic use / Q000652:urine; D012189:Retrospective Studies
D000893:Anti-Inflammatory Agents; D006854:Hydrocortisone