Investigation

Investigations include: (1,2)

• biochemistry
  • damage to adrenal cortex results in mineralocorticoid deficiency causing low serum sodium, and raised serum potassium
  • serum urea and albumin are raised because of dehydration
  • serum renin is raised due to sodium depletion.
  • in secondary hypoadrenalism, electrolytes are usually normal as aldosterone-secreting cells are normal
• serum cortisol level (ideally between 8-9 am)
  • random measurements have a low sensitivity for Addison's disease due to the pulsatile nature and diurnal variation of cortisol secretion
  • if level of serum cortisol is
    • <100 nmol/L - adrenal insufficiency is highly likely ( if the patient is not on oral or inhaled steroids)
    • >400 nmol/L - adrenal insufficiency is unlikely (diagnosis is not excluded if the patient is acutely unwell at the time since cortisol values may increase during illness)
    • between 100 and 400 nmol/L - refer to a specialist for further investigations e.g. - synacthen test
• blood glucose may be low - insulin-induced hypoglycaemia
  
  
• possible ECG findings are detailed - click here

Secondary care investigations carried out to confirm the diagnosis and to find the cause include:

• plasma rennin
• markedly elevated plasma ACTH - greater than 80 ng per litre - with low or normal serum cortisol on presentation or in the morning after omitting replacement therapy is an early indication of primary hypoadrenalism
• synacthen test:
  • short test may confirm suspected hypoadrenalism
  • depot test may discriminate primary and secondary causes
• adreno-cortical antibodies - often present in autoimmune adrenalitis - more common in women - 80% - than men - 10%
• abdominal film - calcified adrenals of tuberculosis
• chest radiology - tuberculous lesions, areas of malignancy and calcification
• clinical or serological evidence of other organ specific autoimmune disease

Reference:

1. Husebye ES, Pearce SH, Krone NP, et al. Adrenal insufficiency. Lancet. 2021 Feb 13;397(10274):613-29.
2. Bancos I, Hahner S, Tomlinson J, Arlt W. Diagnosis and management of adrenal insufficiency. Lancet Diabetes Endocrinol. 2015 Mar;3(3):216-26
3. Betterle C, Presotto F, Furmaniak J. Epidemiology, pathogenesis, and diagnosis of Addison's disease in adults. J Endocrinol Invest. 2019 Dec;42(12):1407-33.