An Update on Addison’s Disease

Abstract

Addison’s disease – the traditional term for primary adrenal insufficiency (PAI) – is defined as the clinical manifestation of chronic glucocorticoid- and/or mineralocorticoid deficiency due to failure of the adrenal cortex which may result in an adrenal crisis with potentially life-threatening consequences. Even though efficient and safe pharmaceutical preparations for the substitution of endogenous gluco- and mineralocorticoids are established in therapy, the mortality in patients with PAI is still increased and the health-related quality of life (HRQoL) is often reduced.PAI is a rare disease but recent data report an increasing prevalence. In addition to the common “classical” causes of PAI like autoimmune, infectious, neoplastic and genetic disorders, other iatrogenic conditions – mostly pharmacological side effects (e. g., adrenal haemorrhage associated with anticoagulants, drugs affecting glucocorticoid synthesis, action or metabolism and some of the novel anti-cancer checkpoint inhibitors) are contributing factors to this phenomenon.Due to the rarity of the disease and often non-specific symptoms at least in the early stages, PAI is frequently not considered resulting in a delayed diagnosis. Successful therapy is mainly based on adequate patient education as a cornerstone in the prevention and management of adrenal crisis. A focus of current research is in the development of pharmacokinetically optimized glucocorticoid preparations as well as regenerative therapies.

Pathophysiological Role and Therapeutic Implications of Vitamin D in Autoimmunity: Focus on Chronic Autoimmune Diseases

“…A steady increase of the prevalence of AD has been observed over the years, particularly in women [216]. AD clinically occurs with adrenal insufficiency, caused by an autoimmune-mediated destruction of adrenal cortex [217]. Although the pathogenesis of AD has not been completely elucidated, an interplay role between HLA haplotypes and environmental factors has been postulated [218,219].…”

The glucocorticoid receptor agonistic modulators CpdX and CpdX-D3 do not generate the debilitating effects of synthetic glucocorticoids

“…4B), thereby revealing the mechanism through which Dex but not CpdX compounds induces skin atrophy, osteoporosis, and inhibition of corticoids synthesis. Long-term treatments with a high dose of synthetic GCs (e.g., Dex and prednisolone) are known to induce an adrenal gland atrophy, similar to that occurring in Addison's disease (38). We have shown that a long-term treatment with Dex induces an adrenal insufficiency, whereas a similar treatment with CpdX, CpdX-D3, or any of their enantiomers did not induce an atrophy of the adrenal fasciculata and glomerulosa zones where the corticosterone and the aldosterone are produced, respectively.…”

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“…This special issue also highlights the importance of non-tumorous adrenal diseases with high morbidity, such as Addison's disease and congenital adrenal hyperplasia. In a timely review, Barthel et al [19] reflect upon current treatment standards in Addison's disease and improvements in long-term care. Reisch [20] summarizes the long-term sequelae observed in patients with congenital adrenal hyperplasia.…”