ENDOCRINOLOGY IN THE TIME OF COVID-19: Management of adrenal insufficiency

Abstract

We provide guidance on prevention of adrenal crisis during the global COVID-19 crisis, a time with frequently restricted access to the usual level of healthcare. Patients with adrenal insufficiency are at an increased risk of infection, which may be complicated by developing an adrenal crisis; however, there is currently no evidence that adrenal insufficiency patients are more likely to develop a severe course of disease. We highlight the need for education (sick day rules, stringent social distancing rules), equipment (sufficient glucocorticoid supplies, steroid emergency self-injection kit) and empowerment (steroid emergency card, COVID-19 guidelines) to prevent adrenal crises. In patients with adrenal insufficiency developing an acute COVID-19 infection, which frequently presents with continuous high fever, we suggest oral stress dose cover with 20 mg hydrocortisone every 6 h. We also comment on suggested dosing for patients who usually take modified release hydrocortisone or prednisolone. In patients with adrenal insufficiency showing clinical deterioration during an acute COVID-19 infection, we advise immediate (self-)injection of 100 mg hydrocortisone intramuscularly, followed by continuous i.v. infusion of 200 mg hydrocortisone per 24 h, or until this can be established, and administration of 50 mg hydrocortisone every 6 h. We also advise on doses for infants and children.

Figure 1

Steroid emergency card for patients with adrenal insufficiency issued by the UK National Health Service in March 2020 (downloadable at https://www.endocrinology.org/media/3563/new-nhs-emergency-steroid-card.pdf).

Figure 2

Prediction of 24-h oral hydrocortisone delivery dependent on timing and dosing. Prediction based on parameter estimates of circulating cortisol concentrations in a three-compartment model after (A) doubling of immediate release hydrocortisone doses administered at the usual times of two typical routine hydrocortisone regimens (two and three daily doses, respectively) and (B) oral administration of four equal doses in evenly spaced, 6-h intervals. This illustrates that the 6-h once administration ensures steady delivery of cortisol, while increasing hydrocortisone at the usual administration times results in a long stretch of time without appropriate hydrocortisone cover. For details on the employed modelling approach see (19); figure reproduced with permission.

Figure 3

(Panels A, B, C and D) Serum total cortisol (nmol/L) in ten otherwise healthy, unstressed adult patients with adrenal insufficiency who paused their regular replacement and underwent frequent serum sampling after administration of 200 mg hydrocortisone/24 h in four different administration modes: 50 mg orally every 6 h (ORAL), 50 mg per i.m. bolus injection every 6 h (IM), 50 mg per i.v. bolus injection (IVI) and via continuous i.v. hydrocortisone infusion of 200 mg/24 h (CIV). Data are presented as median (black line) and range (shaded grey area). (Panels E and F) Linear pharmacokinetic modelling, based on serum cortisol measurements by tandem mass spectrometry after i.v. IVI and CIV hydrocortisone administration, to predict expected serum cortisol concentrations after 50 mg (E) and 100 mg (F) i.v. bolus injection, each followed by CIV infusion of 200 mg hydrocortisone/24 h. Figure modified after (20); reproduced with permission.