Long-term use of continuous subcutaneous hydrocortisone infusion therapy in patients with congenital adrenal hyperplasia

Clin Endocrinol (Oxf). 2018 Oct;89(4):399-407. doi: 10.1111/cen.13813. Epub 2018 Aug 8.


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.

Trial registration: ClinicalTrials.gov NCT01859312.

Keywords: circadian; congenital adrenal hyperplasia; continuous subcutaneous hydrocortisone infusion.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Adrenal Hyperplasia, Congenital / blood
  • Adrenal Hyperplasia, Congenital / drug therapy*
  • Adult
  • Biomarkers / blood
  • Body Mass Index
  • Bone Density / drug effects
  • Female
  • Humans
  • Hydrocortisone / administration & dosage*
  • Hydrocortisone / adverse effects
  • Hydrocortisone / blood
  • Hydrocortisone / therapeutic use*
  • Male
  • Proton Magnetic Resonance Spectroscopy
  • Quality of Life


  • Biomarkers
  • Hydrocortisone

Associated data

  • ClinicalTrials.gov/NCT01859312