What are the key clinical features to consider when diagnosing Addison's disease in a primary care setting?

When considering Addison's disease (primary adrenal insufficiency) in a primary care setting, key clinical features to look for include unexplained hyperpigmentation, or the presence of one or more persistent symptoms, signs, or features without another clinical explanation ¹.

• Specific Symptoms and Signs: These include weight loss, salt craving, nausea or vomiting, lack of appetite or inability to eat a full meal, diarrhoea, dizziness or light-headedness on standing, hyponatraemia, hyperkalaemia, lethargy, and a feeling of muscle weakness ¹. In children, additional features to consider are early puberty, hypoglycaemia, faltering growth, hypotensive crisis, and prolonged neonatal jaundice ¹.
• Hyperpigmentation Considerations: Be aware that hyperpigmentation may not be visible on black or brown skin ¹. In such cases, it is important to ask the person if they have noticed a change in their skin colour and to assess the buccal mucosa or any surgical scars ¹.
• Increased Risk Factors and Coexisting Conditions: Adrenal insufficiency is more common in individuals who have recently stopped using glucocorticoids after more than 4 weeks (if aged 16 and over) or more than 3 weeks (if under 16) ¹. It should also be considered in those taking glucocorticoids at physiological equivalent doses or above who have experienced physiological stress ¹. Other risk factors include taking certain medications such as opioids, checkpoint inhibitors, adrenal enzyme inhibitors, antifungals, or antiretrovirals ¹. Coexisting conditions like primary hypothyroidism, type 1 diabetes, premature ovarian insufficiency, autoimmune polyendocrinopathy syndrome, hypothalamic or pituitary tumours, or hypothalamo-pituitary disease (including infections and infiltrative disorders) also increase the likelihood ¹. A history of cranial, pituitary, hypothalamic, or nasopharyngeal radiotherapy is also a relevant factor ¹. In babies and children, the possibility of adrenal insufficiency should be considered if they present with differences in sex development, such as ambiguous genitalia or bilateral undescended testes ¹.