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The most prevalent cause of primary adrenal insufficiency, or Addison's disease, is autoimmune adrenalitis. This happens when the immune system mistakenly targets the adrenal cortex, gradually destroying the cells that make hormones. This causes a decreased production of important hormones, such as cortisol and aldosterone, which are important for stress response, metabolism, blood pressure management, and electrolyte balance.

The illness usually progresses slowly, with early signs that may be nonspecific, such as fatigue, weight loss, muscle weakness, and poor appetite. As the disease worsens, additional specific indications emerge, such as skin discolouration, low blood pressure, a need for salt, and gastrointestinal upsets. In severe circumstances, patients may go into an adrenal crisis—a life-threatening condition that involves shock, dehydration, and electrolyte imbalance.
Autoimmune adrenalitis may develop alone or as part of Polyglandular Autoimmune Syndrome, where numerous endocrine glands are damaged. Diagnosis is by hormonal tests that measure cortisol and adrenocorticotropic hormone (ACTH) levels, as well as the identification of adrenal autoantibodies, which are antibodies that attack the adrenal glands.

Treatment involves lifelong hormone replacement therapy with glucocorticoids and, if needed, mineralocorticoids. Early diagnosis and adequate management increase quality of life and reduce problems greatly.