February 29, 2024

First-of-its-kind Hormone Replacement Therapy Improves Symptoms in Patients with Adrenal Conditions

A groundbreaking hormone replacement therapy has demonstrated significant improvement in symptoms for patients with adrenal conditions. The therapy, developed by researchers at the University of Bristol, closely mimics the natural circadian and ultradian rhythms of hormones. The results of the clinical trial, led by the University of Bristol, have been published in the Journal of Internal Medicine.

Adrenal conditions, such as Addison’s disease and Congenital Adrenal Hyperplasia, often result in low levels of cortisol, a key hormone that plays a crucial role in regulating various processes in the body. When cortisol levels are low, patients can experience debilitating symptoms including fatigue, nausea, muscle weakness, low blood pressure, and depression. While these conditions are rare, they require lifelong daily hydrocortisone replacement therapy.

Although existing oral hormone replacement treatments can restore cortisol levels, they are associated with a reduced quality of life for patients. Researchers believe this is due to the current treatment’s failure to replicate the body’s natural physiological timing, leading to a lack of cortisol’s expected increase and the absence of its underlying ultradian and circadian rhythms.

The new therapy, called “Pulsatility,” is the result of a decade of research by the Bristol team. It delivers standard hydrocortisone replacement therapy to patients through a pump that more closely follows cortisol’s natural rhythmic secretion pattern. The pulsatile subcutaneous pump has shown promising results in its initial clinical trial.

During the six-week double-blinded PULSES trial, twenty participants between the ages of 18 and 64 with adrenal insufficiency conditions were evaluated. They were randomly assigned to receive either the pump therapy or the standard three times daily oral treatment with hydrocortisone replacement therapy. While the trial only measured psychological and metabolic symptoms, the results showed that the pump therapy led to a 10% decrease in fatigue, improved mood, and a 30% increase in energy levels in the morning, which is a critical time when many patients struggle. MRI scans of the patients also revealed changes in the way the brain processes emotional information.

Stafford Lightman, a neuroendocrinology expert and Professor of Medicine at Bristol Medical School, and one of the study’s lead authors, explained, “Besides the reduction in dosage, cortisol replacement has remained unchanged for many decades. It is widely recognized that current replacement therapy is unphysiological due to its lack of pre-awakening surge, ultradian rhythmicity, and post-dose supraphysiological peaks. The new therapy clearly shows that the timing of cortisol delivery – in line with the body’s own rhythmic pattern of cortisol secretion – is important for normal cognition and behavior.”

The findings support the use of hormone therapy that mimics natural physiological patterns and represent one of the most significant advancements in adrenal insufficiency treatment to date.

Joe Miles, a participant in the PULSES trial, described the therapy as life-changing. He noticed a rapid improvement compared to tablets during the trial and could not cope with returning to his previous condition after the study ended. As a result, he reached out to multiple doctors to have the therapy prescribed. Miles has been using the therapy for six years and has introduced it to others with Addison’s disease, all of whom have reported life-changing benefits.

Dr. Russell, another researcher involved in the trial, stated, “Approximately 1% of the UK population is taking steroids at any moment in time, and these individuals can experience debilitating psychological side effects. This trial has shown that even at physiological levels, brain functioning is disrupted, and that we need to explore not only the dose but the pattern of steroid delivery when considering any type of steroid treatment.”

The study was funded by the Medical Research Council and Bristol & Weston Hospitals Charity, formerly known as Above & Beyond. The research team now plans to conduct a larger trial that examines the personalization of steroid replacement therapy using hormone secretion patterns from over 200 healthy volunteers.