Question:  I recently attended a meeting with other adrenal insufficiency patients and was surprised to find out that some of them had personalized dosing of hydrocortisone and were taking smaller but more frequent doses, some 4x a day.  I’ve been taking two daily doses for years but the idea of having a small third dose to potentially avoid my semi-frequent crashes in the evenings sounds very appealing.  Is this a generally accepted practice amongst Endocrinologists?  My doctor has never mentioned doing it that way, but then again, I haven’t asked.  I want to discuss personalizing my dosing without him thinking I’m trying to get more steroids.  Is there anything I should be especially concerned about if I try adjusting my dose on my own?

Answer:  There are many variations in the ways that doctors prescribe glucocorticoids (cortisol-like medicines)—sometimes based on what they have learned and what other colleagues do, and sometimes based on the patient’s response.  I like to use hydrocortisone because it is cortisol, and doesn’t last as long in the blood as do other glucocorticoids, like dexamethasone.  If we give two or three doses a day we can very roughly mimic the normal circadian rhythm of cortisol in the blood.  Theoretically, it seems a good idea to give a replacement that is as close to normal as possible.  However, some patients don’t want to take more than one (or two) doses each day, and seem to do fine on just one or two.  Others complain of nighttime “crashes” (as in the question) and seem to do better with a third dose.  In the US, most endocrinologists seem to give two doses a day, divided roughly 2/3 in the morning and 1/3 in the afternoon.  In Europe, and especially in the UK, three doses are given about as often (“thrice daily dosing”) as are two, and one or four doses is very uncommon.¹

In deciding how to split the dose, there are a few principles to use:  First, the total daily dose should remain the same. I generally use 10 – 12 mg/M2 body surface area, and not just weight.  The amount decreases over the day:  2/3 – 1/3 for two doses; 50-35-15 for three, and so on.  Since it is hard to prescribe less than 2.5 mg dose, the amounts will vary depending on the number of doses and body size.  Second, it is important to give the first dose as early as possible in the morning, but the timing of the afternoon dose can be varied by the patient.  The evening dose timing can also be varied but generally should be given early enough so that there is a perceived effect, and not so late that it disrupts sleep.

So for a more specific answer to the question, it is important to figure out the best total daily dose, and modify that number as needed.  Then it can be split up in different ways, always with the highest dose on wakening, and the timing of subsequent doses can be varied by the patient.

¹ Murray RD, Ekman B, Uddin S, Marelli C, Quinkler M, Zelissen PM; the EU-AIR Investigators. Management of glucocorticoid replacement in adrenal insufficiency shows notable heterogeneity – data from the EU-AIR. Clin Endocrinol (Oxf). 2017 Mar;86(3):340-346.

By Dr. Lynnette Nieman, NIH, Bethesda, MD (Summer 2018)