27th May 2025

Diagnosis

The history is key to diagnosis of SAI, particularly regarding exogenous steroid exposure. Risk factors include systemic glucocorticoids, high doses and prolonged treatment (>3 weeks). Systemic glucocorticoid exposure can result in suppression of the HPA after 4-5 days, whereas intra-articular glucocorticoids can result in suppression in 1-4 weeks depending on dose and frequency. Adrenal crisis can occur when glucocorticoids are rapidly weaned, abruptly ceased or not increased in intercurrent illness. 

Symptoms may be similar to PAI, but signs on examination can suggest SAI. For example, in SAI, there may be Cushingoid features from long-term exogenous glucocorticoids such as moon facies, abdominal striae, dorsocervical fat pads and proximal muscle wasting. Another differentiating factor is the absence of hyperpigmentation, which is seen in PAI due to α-melanocyte-stimulating-hormone produced as a byproduct of ACTH. 

First-line investigations are as above for PAI, including FBC, U&Es, bone profile, LFTs, glucose, morning cortisol, ACTH and ACTH stimulation (synacthen) testing. The insulin tolerance test (ITT) can be impractical but can assess for partial adrenal suppression, where a normal ACTH stimulation test may be obtained (as the adrenal glands respond to ACTH stimulation) but ITT will reveal an inability of the adrenals to respond to the stress of hypoglycaemia induced in the ITT. Here 0.1 to 0.15 units/kg short-acting insulin IV is given, and plasma glucose and cortisol levels are measured at 0, 30 and 60 minutes. In partial adrenal suppression, despite symptomatic hypoglycaemia (<2.2 mmol/L) an insufficient cortisol response (<497 nmol/L) is mounted. An alternative to this test is the overnight metyrapone test.