What are the causes and symptoms of adrenal insufficiency (Addison's disease)?

From the Guidelines

Adrenal insufficiency (Addison's disease) is a potentially deadly, but treatable disease, caused by a lack of production of cortisol and aldosterone hormones, with the most common cause being autoimmunity.

Causes of Adrenal Insufficiency

• Autoimmunity is the most common cause of primary adrenal insufficiency (PAI) 1
• Other causes of PAI include infections, cancer, and genetic disorders
• Secondary adrenal insufficiency can be caused by a lack of production of adrenocorticotropic hormone (ACTH) from the pituitary gland, often due to prescribed glucocorticoid therapy 1

Symptoms of Adrenal Insufficiency

• Symptoms can include fatigue, weight loss, low blood pressure, and changes in skin pigmentation 1
• Adrenal crisis, a life-threatening complication, can occur due to stress, infection, or other triggers, and requires immediate treatment with hydrocortisone 1
• Patients with adrenal insufficiency are at risk of developing other autoimmune diseases and may experience reduced quality of life, fertility issues, and sexual dysfunction 1

Diagnosis and Treatment

• Diagnosis is often delayed, and biochemical proof of PAI is necessary for diagnosis 1
• Treatment involves replacement therapy with glucocorticoids, such as hydrocortisone, and mineralocorticoids, such as fludrocortisone 1
• Annual follow-up is necessary to evaluate replacement therapy, screen for associated autoimmune co-morbidities, and reiterate emergency measures 1

From the Research

Causes of Adrenal Insufficiency

• Primary adrenal insufficiency is caused by destruction or dysfunction of the adrenal glands, often due to autoimmune adrenalitis 2, 3, 4
• Secondary or tertiary adrenal insufficiency is caused by impairment of the hypothalamic-pituitary-adrenal axis, often due to pituitary disease 5, 2
• Exogenous corticosteroid therapy withdrawal or poor adherence to scheduled corticosteroid dosing can also cause acquired adrenal insufficiency 3, 6
• Suppression of adrenocorticotropic hormone by exogenous glucocorticoid or opioid medications can also lead to adrenal insufficiency 6

Symptoms of Adrenal Insufficiency

• Non-specific symptoms such as fatigue, anorexia, and weight loss are common 5, 2, 3, 6
• Other symptoms include:
  • Orthostatic hypotension 3
  • Hyperpigmentation 2, 3, 6
  • Hyponatremia and hyperkalemia 3
  • Hypoglycemia 3, 4
  • Muscle and abdominal pain 6
  • Salt cravings 6
  • Unintentional weight loss 6
  • Postural hypotension 6
  • Profound fatigue 6
• Symptoms can be vague and undefined, requiring a high index of suspicion for diagnosis 3