A phase 2 study of continuous subcutaneous hydrocortisone infusion in adults with congenital adrenal hyperplasia

Aikaterini A. Nella, Ashwini Mallappa, Ashley F. Perritt, Verena Gounden, Parag Kumar, Ninet Sinaii, Lori Ann Daley, Alexander Ling, Chia Ying Liu, Steven J. Soldin, Deborah P. Merke

Research output: Contribution to journalArticlepeer-review

39 Scopus citations


Context: Classic congenital adrenal hyperplasia (CAH) management remains challenging, given that supraphysiologic glucocorticoid doses are often needed to optimally suppress the ACTHdriven adrenal androgen overproduction. Objective: This study sought to approximate physiologic cortisol secretion via continuous subcutaneous hydrocortisone infusion (CSHI)andevaluate the safetyandefficacy of CSHI in patients with difficult-to-treat CAH. Design: Eight adult patients with classic CAH participated in a single-center open-label phase I-II study comparing CSHI to conventional oral glucocorticoid treatment. All patients had elevated adrenal steroids and one or more comorbidities at study entry. Assessment while receiving conventional therapy at baseline and 6 months following CSHI included: 24-hour hormonal sampling, metabolic and radiologic evaluation, health-related quality-of-life (HRQoL), and fatigue questionnaires. Main Outcome Measures: The ability of CSHI to approximate physiologic cortisol secretion and the percent of patients with 0700-hour 17-hydroxyprogesterone (17-OHP)≤1200 ng/dL was measured. Results: CSHI approximated physiologic cortisol secretion. Compared with baseline, 6 months of CSHI resulted in decreased 0700-hour and 24-hour area under the curve 17-OHP, androstenedione, ACTH, and progesterone, increased osteocalcin, c-telopeptide and lean mass, and improvedHRQoL (and SF-36 Vitality Score), and fatigue. One of three amenorrheic women resumed menses. One man had reduction of testicular adrenal rest tissue. Conclusions: CSHI is a safe and well-tolerated modality of cortisol replacement that effectively approximates physiologic cortisol secretion in patients with classic CAH poorly controlled on conventional therapy. Improved adrenal steroid control and positive effects on HRQoL suggest that CSHI should be considered a treatment option for classic CAH. The long-term effect on established comorbidities requires further study.

Original languageEnglish (US)
Pages (from-to)4690-4698
Number of pages9
JournalJournal of Clinical Endocrinology and Metabolism
Issue number12
StatePublished - Dec 2016
Externally publishedYes

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical


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