Adrenocorticotropic Hormone Therapy Improved Spasms and Sleep Disturbance in Smith–Magenis Syndrome: A Case Report

Smith–Magenis syndrome (SMS) is a complex disorder characterized by variable mental retardation, sleep disturbances, craniofacial and skeletal anomalies, self-injurious and attention-seeking behaviors, and speech and motor delays. The case of a 14-month-old girl with SMS who was experiencing spasm clusters and sleep disturbances with sleep–wake intervals of 1.5 to 2 h persisting from the neonatal period was examined. The patient’s spasms stopped and interictal electroencephalography did not show epileptic discharges after undergoing a high-dose adrenocorticotropic hormone (ACTH) therapy. Moreover, the patient’s sleep cycle stabilized 1 month after receiving the ACTH therapy. Dramatic reductions in the patient’s self-injurious behaviors were also noted. At 1 year following ACTH treatment, the patient’s improved sleep was maintained. High-dose ACTH treatment was considered to contribute to the normal adaptation of the hypothalamic–pituitary–adrenal axis by regulating the release of corticotropin-releasing hormone, resulting in improvement of the patient’s infantile spasms and sleep disturbances.

ACTH Treatment for Management of Nephrotic Syndrome: A Systematic Review and Reappraisal

Background. In recent years, the use of adrenocorticotropic hormone (ACTH) therapy for treatment of proteinuria due to nephrotic syndrome (NS) has been heavily explored. ACTH therapy, which comes in the natural (H. P. Acthar Gel) or synthetic (tetracosactide) form, has resulted in remission in patients with immunosuppressive and steroid-resistant NS. However, the exact efficacy of ACTH therapy in the NS etiologies, such as membranous nephropathy (MN), focal segmental glomerulosclerosis (FSGS), minimal change disease (MCD), lupus nephritis (LN), IgA nephropathy (IgAN), and membranoproliferative glomerulonephritis (MPGN), has not been determined. Objective. This systematic review analyzed the published literature on ACTH therapy in various NS etiologies to determine its efficacy. Methods. A comprehensive search of MEDLINE, EMBASE, and Cochrane databases was conducted for articles through June 2019. An additional search was performed on clinicaltrials.gov to search for additional trials and cross reference the results of our database search. The literature which studied synthetic or natural ACTH treatment in patients with known etiologies of NS was included. Studies were excluded when they consisted of a single case report or did not analyze the lone effect of ACTH in NS. Results. The initial search yielded a total of 411 papers, and 22 papers were included. In 214 MN patients, there was an overall remission of 40% (85/214) and an overall remission of 43% (42/98) in FSGS patients. In other etiologies, there were overall remissions of 78% (11/14), 31% (5/16), 40% (16/40), and 62% (8/13) in MCD, LN, IgAN, and MPGN patients, respectively. Conclusion. ACTH showed benefits in proteinuria reduction across all etiologies of NS. However, more randomized controlled studies with larger population sets and longer follow-ups are imperative to establish causal benefits. New studies into its efficacy in children are also necessary.

Adrenocorticotropic Hormone for Childhood Nephrotic Syndrome

Background and objectivesThere is renewed interest in adrenocorticotropic hormone (ACTH) for the treatment of nephrotic syndrome. We evaluated the efficacy and safety of ACTH in children with frequently relapsing or steroid-dependent nephrotic syndrome in a randomized trial.Design, setting, participants, & measurementsParticipants aged 2–20 years old with frequently relapsing or steroid-dependent nephrotic syndrome were enrolled from 16 sites in the United States and randomized 1:1 to ACTH (repository corticotropin injection) or no relapse-preventing treatment. ACTH treatment regimen was 80 U/1.73 m2 administered twice weekly for 6 months, followed by 40 U/1.73 m2 administered twice weekly for 6 months. The primary outcome was disease relapse during the first 6 months. Participants in the control group were offered crossover to ACTH treatment if they relapsed within 6 months. Secondary outcomes were relapse after ACTH dose reduction and treatment side effects.ResultsThe trial was stopped at a preplanned interim analysis after enrollment of 31 participants because of a lack of discernible treatment efficacy. Fourteen out of 15 (93%) participants in the ACTH arm experienced disease relapse in the first 6 months, with a median time to first relapse of 23 days (interquartile range, 9–32), compared with 15 out of 16 (94%) participants and at a median of 21 days (interquartile range, 14–51) in the control group. There was no difference in the proportion of relapsed patients (odds ratio, 0.93; 95% confidence interval, 0.05 to 16.40; P>0.99) or time to first relapse (hazard ratio, 1.03; 95% confidence interval, 0.50 to 2.15; P=0.93). Thirteen out of 16 participants in the control group crossed over to ACTH treatment. Three out of 28 participants completed 12 months of ACTH treatment; the others exited the trial because of frequent relapses or side effects. There were no disease relapses after ACTH dose reduction among the three participants. Most side effects were mild and similar to side effects of corticosteroids.ConclusionsACTH at 80 U/1.73 m2 administered twice weekly was ineffective at preventing disease relapses in pediatric nephrotic syndrome.