Long-Term Use of Continuous Subcutaneous Hydrocortisone Infusion Treatment in Six Adults with Congenital Adrenal Hyperplasia

Presentation Number: OR03-3
Date of Presentation: April 2nd, 2017

Ashwini Mallappa*1, Aikaterini A. Nella2, Hamsini Rao3, Verena Gounden2, Ashley F. Perritt2, Parag Kumar4, Ninet Sinaii2, Alexander Ling5, Chia-Ying Liu2, Steven J. Soldin2 and Deborah P. Merke5
1National Institutes of Health, Clinical Center, Bethesda,, MD, 2National Institutes of Health, Bethesda, MD, 3NIH Clinical Center, Bethesda, 4National Institutes of Health, Clinical Center, Bethesda, MD, 5NIH, Bethesda, MD


Background: Classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD) is characterized by cortisol and aldosterone deficiency and androgen excess. Current conventional glucocorticoid replacement therapies are suboptimal and fail to mimic physiologic cortisol levels. Six months of continuous subcutaneous hydrocortisone infusion (CSHI) in the treatment of CAH was shown to be safe and effective (1). Here we present preliminary results from our experience with long-term use of CSHI in patients with CAH.

Objective: Assess long-term safety and efficacy of CSHI therapy.

Methods: Six unrelated patients (four females, age 21 - 43 years) with difficult- to-control CAH enrolled in a six month phase 2 clinical trial using CSHI opted to continue therapy for an additional year. Following completion of the 6 months study phase, three of the four females were started on a combined oral contraceptive pill (OCP) with the goal to further reduce androgen production. CSHI rates were adjusted based on laboratory data and clinical symptomatology.

Results: At 18 months, ACTH, 17-hydroxyprogesterone and androstenedione levels were comparable to levels achieved following 6 month of CSHI therapy. Similarly, BMI and insulin resistance remained stable. Glucocorticoid dose (hydrocortisone equivalent) at 18 months on CSHI therapy was significantly lower compared to 6 months (15.1 ± 5.8 vs. 17.9 ± 3.8 mg/m2/day, P = 0.046). Concomitant use of OCP reduced glucocorticoid dose by 13 - 31%. As expected, minor local skin reactions were common and self-limited.

Conclusions: Long-term use of CSHI is safe and well-tolerated in adults with classic CAH. With long-term use of CSHI, androgen levels remained stable and glucocorticoid doses decreased. The addition of estrogen containing OCP contributed to reduced hydrocortisone dose. Analysis of metabolic indices and quality-of-life parameters are underway.


Disclosure: DPM: Principal Investigator, Diurnal, Principal Investigator, Millendo Therapeutics. Nothing to Disclose: AM, AAN, HR, VG, AFP, PK, NS, AL, CYL, SJS