TY - JOUR
T1 - Long-term use of continuous subcutaneous hydrocortisone infusion therapy in patients with congenital adrenal hyperplasia
AU - Mallappa, Ashwini
AU - Nella, Aikaterini A.
AU - Sinaii, Ninet
AU - Rao, Hamsini
AU - Gounden, Verena
AU - Perritt, Ashley F.
AU - Kumar, Parag
AU - Ling, Alexander
AU - Liu, Chia Ying
AU - Soldin, Steven J.
AU - Merke, Deborah P.
N1 - Publisher Copyright:
Published 2018. This article is a U.S. Government work and is in the public domain in the USA
PY - 2018/10
Y1 - 2018/10
N2 - Background: In a phase 2 short-term (6 months) study of patients with congenital adrenal hyperplasia (CAH), continuous subcutaneous hydrocortisone infusion (CSHI) was found to be a safe, effective and well-tolerated method of replacing cortisol with improved disease and patient-related outcomes. Objective: To evaluate the safety and efficacy of long-term CSHI. Design: Single-centre, open-label, phase 2 extension study. Patients: Five adults with classic CAH. Measurements: Biomarkers of disease control, metabolic indices and health-related quality-of-life (HRQoL) estimates. Results: Six of eight patients chose to continue on long-term CSHI therapy. Compared to baseline, eighteen months of CSHI resulted in decreased (P = 0.043) 0700-hour ACTH, 17-hydroxyprogesterone, androstenedione and progesterone; increased whole-body lean mass (P = 0.024); and improved HRQoL, especially symptoms of adrenal insufficiency (P = 0.003). Findings at six and eighteen months did not differ, and improvements achieved in androgen control, lean body mass and HRQoL after 6 months of CSHI were maintained at eighteen months. The hydrocortisone dose appeared to decrease with time [6 vs 18 months: 38.3 ± 8.8 vs 33.6 ± 12.2 mg/day (P = 0.062)], especially in women receiving oral contraceptives. Reduction of testicular adrenal rest and adrenal size observed at 6 months remained stable. In one patient, an adrenal adenoma continually decreased over time. Subjective improvement in hirsutism was reported. Conclusions: Long-term use of CSHI is a safe and well-tolerated treatment option in a select set of adults with classic CAH. Improvements observed short term in disease control and subjective health status continued long term.
AB - Background: In a phase 2 short-term (6 months) study of patients with congenital adrenal hyperplasia (CAH), continuous subcutaneous hydrocortisone infusion (CSHI) was found to be a safe, effective and well-tolerated method of replacing cortisol with improved disease and patient-related outcomes. Objective: To evaluate the safety and efficacy of long-term CSHI. Design: Single-centre, open-label, phase 2 extension study. Patients: Five adults with classic CAH. Measurements: Biomarkers of disease control, metabolic indices and health-related quality-of-life (HRQoL) estimates. Results: Six of eight patients chose to continue on long-term CSHI therapy. Compared to baseline, eighteen months of CSHI resulted in decreased (P = 0.043) 0700-hour ACTH, 17-hydroxyprogesterone, androstenedione and progesterone; increased whole-body lean mass (P = 0.024); and improved HRQoL, especially symptoms of adrenal insufficiency (P = 0.003). Findings at six and eighteen months did not differ, and improvements achieved in androgen control, lean body mass and HRQoL after 6 months of CSHI were maintained at eighteen months. The hydrocortisone dose appeared to decrease with time [6 vs 18 months: 38.3 ± 8.8 vs 33.6 ± 12.2 mg/day (P = 0.062)], especially in women receiving oral contraceptives. Reduction of testicular adrenal rest and adrenal size observed at 6 months remained stable. In one patient, an adrenal adenoma continually decreased over time. Subjective improvement in hirsutism was reported. Conclusions: Long-term use of CSHI is a safe and well-tolerated treatment option in a select set of adults with classic CAH. Improvements observed short term in disease control and subjective health status continued long term.
KW - circadian
KW - congenital adrenal hyperplasia
KW - continuous subcutaneous hydrocortisone infusion
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U2 - 10.1111/cen.13813
DO - 10.1111/cen.13813
M3 - Article
AN - SCOPUS:85052479303
SN - 0300-0664
VL - 89
SP - 399
EP - 407
JO - Clinical Endocrinology
JF - Clinical Endocrinology
IS - 4
ER -