From the Guidelines
A patient with steroid-induced adrenal insufficiency taking hydrocortisone 15 mg and 5 mg twice daily may develop lower extremity pitting edema due to mineralocorticoid effects of the medication, and management options should prioritize reducing the hydrocortisone dose if possible or switching to a glucocorticoid with less mineralocorticoid activity. The patient's current dosing regimen totals 40 mg daily, which exceeds the typical physiologic replacement dose of 15-25 mg daily, as recommended by the consensus statement on the diagnosis, treatment, and follow-up of patients with primary adrenal insufficiency 1. According to the management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: ASCO guideline update, the mineralocorticoid effects of hydrocortisone become more pronounced at higher doses, typically above 20 mg daily, leading to sodium and water retention in the kidneys and fluid accumulation in the tissues, particularly in dependent areas like the lower extremities 1. Other contributing factors may include the patient's underlying condition, concurrent medications, dietary sodium intake, and kidney function. Management options include:
- Reducing the hydrocortisone dose if possible
- Switching to a glucocorticoid with less mineralocorticoid activity like prednisone or dexamethasone
- Adding a diuretic
- Recommending sodium restriction The edema typically resolves when the steroid dose is optimized or the medication is changed to one with less mineralocorticoid activity. It is essential to note that the patient's treatment should be individualized, and the decision to adjust the hydrocortisone dose or switch to a different glucocorticoid should be made in consultation with an endocrinologist, as recommended by the ASCO guideline update 1. Additionally, the patient should be educated on stress dosing, emergency injections, and the importance of wearing a medical alert bracelet or necklace, as emphasized in the consensus statement on primary adrenal insufficiency 1.
From the Research
Possible Causes of Lower Extremity Pitting Edema
- The patient's hydrocortisone dosage of 15 mg and 5 mg twice daily may be contributing to the development of lower extremity pitting edema, as excess glucocorticoid replacement can lead to oedema formation 2.
- Mineralocorticoid deficiency may also play a role in the development of oedema, as patients with primary adrenal failure on replacement therapy who had oedema were found to have evidence of mineralocorticoid deficiency, with increased supine and erect plasma renin activity and greater postural fall in blood pressure 2.
- The mechanism of oedema formation in patients with adrenal insufficiency on replacement therapy is unclear, but it may be related to the direct action of glucocorticoids on vascular tone, alteration of capillary permeability, or influence on other factors such as atrial natriuretic peptide 2.
Management of Adrenal Insufficiency
- The current standard treatment regimen for adrenal insufficiency involves twice- or thrice-daily dosing with a glucocorticoid, most commonly oral hydrocortisone 3.
- Monitoring of glucocorticoid replacement quality is largely based on clinical grounds, as there is a lack of objective assessment tools 4.
- Patients with adrenal insufficiency are at risk of adrenal crisis, and early dose adjustments are required to cover the increased glucocorticoid demand in stress 5.
Diagnosis and Treatment of Glucocorticoid-Induced Adrenal Insufficiency
- The diagnosis of glucocorticoid-induced adrenal insufficiency is made with a stimulation test such as the ACTH test 6.
- Treatment of severe glucocorticoid-induced adrenal insufficiency should follow the principles for treatment of central adrenal insufficiency 6.
- The clinical implications and indication to treat mild-moderate adrenal deficiency after glucocorticoid withdrawal have not been established, and the indication of adding stress dosages of glucocorticoid during ongoing glucocorticoid treatment remains unclear 6.