Revival of autochthonous adrenocortical stem cells in autoimmune Addison's disease

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The cortex of the adrenal gland manufactures two steroid hormones, cortisol and aldosterone, that are essential for life. The activity of the adrenal cortex, including cortisol and aldosterone production, is controlled by a master regulatory hormone known as ACTH (adrenocorticotrophic hormone). Too much ACTH causes the adrenal glands to expand and to make too much cortisol. In contrast, too little ACTH causes the adrenals to shrink, and results in serious illness owing to steroid deficiency. All the cells of the adrenal cortex start life by dividing from their parent stem cells which are located around the outer edge of the adrenal gland. The proliferation and growth of these parent stem cells is also strongly regulated by the same hormone, ACTH. Untreated, autoimmune Addison?s disease is an invariably fatal condition. The adrenal cortex becomes destroyed by an immune system attack, leading to deficiency of the vital steroid hormones, cortisol and aldosterone. During the development of Addison?s disease, the body senses the steroid hormone deficiency, so blood ACTH levels become very high (typically 20-times higher than normal). This is an attempt by the body to stimulate the adrenal cells to divide and make more of the essential steroid hormones. However, once diagnosed and treated with replacement steroid tablets, the ACTH levels fall. Critically, this leads to a worsening of the function of any remaining adrenal stem cells and further reduction in functioning adrenal tissue. The idea of the current project is to give back ACTH to people with treated autoimmune Addison?s disease in order to stimulate the stem cells in their adrenal glands back into activity. The treatment with ACTH would initially be by daily injection for 10 weeks. This could ultimately lead to recovery of adrenal gland function and people with Addison?s disease may then be able to stop their steroid medications. Their condition could be cured.