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

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. To evaluate the safety and efficacy of long-term CSHI. Single-centre, open-label, phase 2 extension study. Five adults with classic CAH. Biomarkers of disease control, metabolic indices and health-related quality-of-life (HRQoL) estimates. 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. 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.

Mallappa A ，Nella AA ，Sinaii N ，Rao H ，Gounden V ，Perritt AF ，Kumar P ，Ling A ，Liu CY ，Soldin SJ ，Merke DP ... -  《-》

A Phase 2 Study of Continuous Subcutaneous Hydrocortisone Infusion in Adults With Congenital Adrenal Hyperplasia.

Nella AA ，Mallappa A ，Perritt AF ，Gounden V ，Kumar P ，Sinaii N ，Daley LA ，Ling A ，Liu CY ，Soldin SJ ，Merke DP ... -  《-》

24-Hour Profiles of 11-Oxygenated C(19) Steroids and Δ(5)-Steroid Sulfates during Oral and Continuous Subcutaneous Glucocorticoids in 21-Hydroxylase Deficiency.

Optimal management of androgen excess in 21-hydroxylase deficiency (21OHD) remains challenging. 11-oxygenated-C19 steroids (11-oxyandrogens) have emerged as promising biomarkers of disease control, but data regarding their response to treatment are lacking. To compare the dynamic response of a broad set of steroids to both conventional oral glucocorticoids (OG) and circadian cortisol replacement via continuous subcutaneous hydrocortisone infusion (CSHI) in patients with 21OHD based on 24-hour serial sampling. We studied 8 adults (5 women), ages 19-43 years, with poorly controlled classic 21OHD who participated in a single-center open-label phase I-II study comparing OG with CSHI. We used mass spectrometry to measure 15 steroids (including 11-oxyandrogens and Δ5 steroid sulfates) in serum samples obtained every 2 h for 24 h after 3 months of stable OG, and 6 months into ongoing CSHI. In response to OG therapy, androstenedione, testosterone (T), and their four 11-oxyandrogen metabolites:11β-hydroxyandrostenedione, 11-ketoandrostenedione, 11β-hydroxytestosterone and 11-ketotestosterone (11KT) demonstrated a delayed decline in serum concentrations, and they achieved a nadir between 0100-0300. Unlike DHEAS, which had little diurnal variation, pregnenolone sulfate (PregS) and 17-hydoxypregnenolone sulfate peaked in early morning and declined progressively throughout the day. CSHI dampened the early ACTH and androgen rise, allowing the ACTH-driven adrenal steroids to return closer to baseline before mid-day. 11KT concentrations displayed the most consistent difference between OG and CSHI across all time segments. While T was lowered by CSHI as compared with OG in women, T increased in men, suggesting an improvement of the testicular function in parallel with 21OHD control in men. 11-oxyandrogens and PregS could serve as biomarkers of disease control in 21OHD. The development of normative data for these promising novel biomarkers must consider their diurnal variability.

Turcu AF ，Mallappa A ，Nella AA ，Chen X ，Zhao L ，Nanba AT ，Byrd JB ，Auchus RJ ，Merke DP ... -  《Frontiers in Endocrinology》

Circadian hydrocortisone infusions in patients with adrenal insufficiency and congenital adrenal hyperplasia.

Merza Z ，Rostami-Hodjegan A ，Memmott A ，Doane A ，Ibbotson V ，Newell-Price J ，Tucker GT ，Ross RJ ... -  《-》

Continuous subcutaneous hydrocortisone infusion versus oral hydrocortisone replacement for treatment of addison's disease: a randomized clinical trial.

Oksnes M ，Björnsdottir S ，Isaksson M ，Methlie P ，Carlsen S ，Nilsen RM ，Broman JE ，Triebner K ，Kämpe O ，Hulting AL ，Bensing S ，Husebye ES ，Løvås K ... -  《-》