Hi All,
My good friend works for the Animus Pump company and I have asked her to try get a meeting for me with their researchers about this. These posters(below) were displayed at the 2005 Endocrine Society meeting in San Diego last month. It is very exciting work! Hopefully, we can get Animus to fund a clinical trial on using the pump for HC. We will write something in our newsletter as we get developments. Kathy G., could you please email me at kelly@caresfoundation.org ?
Best to all!
Kelly

P1-628] Use of Continuous Subcutaneous Hydrocortisone Infusion To Maximise Control in a Patient with Congenital Adrenal Hyperplasia.

Peter C Hindmarsh, Sinead Bryan. London Ctr for Paediat Endocrinol, Univ Coll London Hosps, London, UK

Poor control in patients with congenital adrenal hyperplasia CYP21 deficiency is often observed in adolescence. We describe a 16-year-old boy who required high and frequent doses of oral hydrocortisone in order to maintain plasma cortisol concentrations of 300 nmol/l, but which were inadequate to fully suppress the hypothalamo pituitary adrenal axis with ambient serum 17 hydroxyprogesterone (17OHP) concentrations of 400 nmol/l and androstenedione concentrations of 24.9 nmol/l. Pharmacokinetic and dynamic studies revealed a reduction in cortisol half life after intravenous hydrocortisone administration of 40 min (normal range 60-80 min), reduced bioavailability of 75% (normal range 90%-100% ) following oral administration but normal suppression of ACTH secretion with overnight dexamethasone.
Using an intravenous infusion of hydrocortisone the normal circadian rhythm of cortisol was mimicked precisely with an infusion regimen of 4 mg/hr between 24.00 and 1200 hrs, 3 mg/hr from 1200-1800 and 2 mg/hr from 1800-2400. Complete suppression of serum 17OHP concentrations were obtained over the first 24 hr period. The bioavailability of subcutaneous versus intravenous hydrocortisone was determined to be 100% and a programme of subcutaneous delivery of hydrocortisone (Effcortesol, GlaxoSmithKline) using the above infusion rates commenced using the Medtronic Minimed 712 infusion pump delivery system. Over a period of 3 months serum 17OHP concentrations remained suppressed at < 2 nmol/l, and androstenedione concentrations reduced to 4.5 nmol/l. During the same time serum testosterone concentration rose from 4.5 nmol/l to 15.5 nmol/l. and symptoms suggestive of hydrocortisone insufficiency, headaches and nausea disappeared. At the end of the 3 month period suppression of serum 17OHP concentrations were maintained with an infusion rate that was 50% of that at start.
The continuous subcutaneous delivery of hydrocortisone may prove a useful adjunct to the management of patients with congenital adrenal hyperplasia CYP21 deficiency. Intervention should be considered particularly in those who display a rapid clearance of hydrocortisone from the circulation a situation that is not uncommon during puberty and in those where high and frequent doses of hydrocortisone fail to achieve adequate control.

Saturday, June 4, 2005 11:00 AM

POSTER SESSION: CLINICAL - Case Reports I (11:00 AM-12:00 PM and 2:30 PM-3:30 PM)

[P3-432] Replacement Therapy in Cortisol Deficiency According to the Natural Circadian Rhythm: Impact on ACTH and 17-OHP.

Zayd Merza, Amin Rostami-Hodjegan, Geoffrey T Tucker, Richard J Ross. Div of Clin Scis (North), Univ of Sheffield, Sheffield, UK; Acad Unit of Clin Pharmacol, Univ of Sheffield, Sheffield, UK

Conventional hydrocortisone replacement results in low morning cortisol and high ACTH levels which may cause fatigue in Addisons disease and high adrenal androgens in congenital adrenal hyperplasia (CAH). We have investigated the potential of using circadian hydrocortisone therapy. A series of programmed intravenous infusions were used to simulate normal cortisol profile in 6 subjects (2 healthy volunteers, 2 patients with Addisons disease and 2 with CAH). The study was approved by the South Sheffield Ethics Committee and all patients gave written informed consent. Subjects were investigated on 2 occasions, one involving conventional treatment (patients) or no administration of hydrocortisone (healthy volunteers). Serum cortisol, ACTH and 17-OHP were measured at regular intervals up to 24 hours, starting at 9.00 am in all study arms. The natural secretion of cortisol was suppressed throughout the 24 hours by oral dexamethasone during programmed hydrocortisone infusion in the 2 healthy volunteers.
There was no significant difference in the mean cortisol concentration over 24 hours (p= 0.3) and between midnight and 9.00 am (p=0.95) when comparing normal production to the hydrocortisone infusions in two healthy volunteers. There was no significant difference in the mean cortisol over 24 hours in 4 adrenally insufficient cases when comparing hydrocortisone infusion to conventional treatment (p=0.16). During conventional treatment the patients had a greater mean cortisol during daytime (9.00 am-9.00 pm) and lower mean cortisol during night time (9.00 pm-9.00 am) (p < 0.05). The mean ACTH after midnight was significantly lower on the hydrocortisone infusion compared to conventional treatment when comparing the mean values for five case studies relevant to CAH and Addisonian patients (p = 0.02). Similarly, serum 17-OHP concentrations after midnight were lower on hydrocortisone infusion compared to conventional treatment in 2 CAH patients but, owing to small numbers, statistical analysis was not possible. In conclusion: Suppression of early morning levels of ACTH and 17-OHP with maintenance of serum cortisol levels that mimic the circadian rhythm is achievable with a programmed delivery of intravenous hydrocortisone. A similar system using a delayed onset-slow release oral formulation may have therapeutic advantages in such patients.

Monday, June 6, 2005 11:00 AM

POSTER SESSION: CLINICAL - Glucocorticoids (11:00 AM-12:00 PM and 2:30 PM-3:30 PM)

Kelly R. Leight, Executive Director
CARES Foundation, Inc.
(Congenital Adrenal hyperplasia Research, Education and Support)
973-912-3895
866-227-3737 (toll free)
email: kelly@caresfoundation.org
URL: www.caresfoundation.org
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