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 NICE NG243.

• 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 NICE NG243. In children, additional features to consider are early puberty, hypoglycaemia, faltering growth, hypotensive crisis, and prolonged neonatal jaundice NICE NG243.
• Hyperpigmentation Considerations: Be aware that hyperpigmentation may not be visible on black or brown skin NICE NG243. 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 NICE NG243.
• 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) NICE NG243. It should also be considered in those taking glucocorticoids at physiological equivalent doses or above who have experienced physiological stress NICE NG243. Other risk factors include taking certain medications such as opioids, checkpoint inhibitors, adrenal enzyme inhibitors, antifungals, or antiretrovirals NICE NG243. 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 NICE NG243. A history of cranial, pituitary, hypothalamic, or nasopharyngeal radiotherapy is also a relevant factor NICE NG243. 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 NICE NG243.