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Q What is meant by replacement therapy? |
A Treatment of adrenal insufficiency involves replacing, or substituting, the hormones that the adrenal glands are not making. Cortisol is replaced with hydrocortisone, the synthetic form of our natural cortisol and sometimes with other corticosteroids.
Patients with primary adrenal insufficiency, Addison’s disease, also need replacement with a salt-conserving hormone due to lack of aldosterone. Replacing adrenal andogens is less well documented.
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| Q What is the current standard therapy for adrenal insufficiency? |
| A Cortisol is replaced with hydrocortisone or cortisone acetate, the synthetic form of our natural cortisol and sometimes with other corticosteroids, such as, prednisone or dexamethasone. Normal, or physiologiscal, cortisol production in the body follows a distinct 24-hour pattern with high levels just before waking in the morning, tapering off over the day and ending with a cortisol-free interval at night. Currently available products are unable to deliver replacement therapy in a way that adequately mimics this normal pattern of cortisol release. Furthermore, current therapy is 30-40 years old and the only treatment innovation for decades has been to better define patients’ individual doses and to give two or three daily administrations in order to crudely mimic the normal pattern of cortisol. Current research indicates that patients may be suffering higher rates of mortality and disease than previously thought, likely contributed to by the non-physiological medications to which they now have access. |
| Q What are the main problems with present treatments? |
A
1. Existing administration forms cannot adequately mimic the normal 24 hour pattern of cortisol in the body and this result in too-high and too-low levels at different times of the day, which can adversely affect patients’ well-being.
2. Multiple daily dosing can result in failure to fully comply with treatment, exposing the patient to risk.
3. By virtue of the dosage forms, patterns of administration, type of glucocorticoid used and patient needs and preferences, the total daily dose of glucocorticoid replacement is too high in some patients.
The primary aim in all endocrinology is to achieve hormone replacement with an endogenous hormone and to perform it as physiologically as possible. A hydrocortisone formulation that could more adequately mimic the normal profile of cortisol with a simpler dosing regimen would therefore be a step forward in improving cortisol replacement therapy. |
| Q Why is a new therapy needed when the current established therapy seems to work well? |
A Patients with adrenal insufficiency can suffer from obesity, cardiovascular disease, other long-term side effects and higher rates of mortality. We believe that the solution to the problem is a truly once-a-day therapy that better mimics the body’s own release pattern of cortisol.
Replacement of cortisol is very difficult. We know that both too much and too little is bad for health. Missed doses and too little during an intercurret illness may lead to high fever, diarrhoea, a drop in blood pressure and a critical illness called adrenal crisis. Too high doses over a long period of time can induce obesity and its related disorders such as hypertension and diabetes. As there is no blood test or urinary test that can be used to see whether the dose and regime of cortisol replacement is adequate, careful clinical evaluation must be done by the treating physician in collaboration with the patient. A once daily administration that better mimics the body’s own serum cortisol profile should make the treatment easier and thereby safer.
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