The following is a theory of mine that I have been thinking about for a little while now. Adrenal dysfunction seems to be such a tough nut to crack, and there's no doubt everyone may have a different cause such as underlying infection, methylation, toxicity or deficiency, however there often seems to be a pattern that fits a circadian rhythm mismatch. The body appears to forget when to produce cortisol during the right time, and this leads to some lows during the day. Cortisol and melatonin have an inverse relationship: http://s1v2.kjhosting.com/~judithk/wp-content/uploads/2012/09/cortisol-melatonin-graph.jpg It makes sense then that cortisol would suppress melatonin and melatonin would suppress cortisol. It has been seen however, that large doses of melatonin could potentially suppress morning cortisol, the opposite of what we want. However, the most important step is resetting our circadian rhythm which must be achieved by going to bed the same time every night and waking up at the same time every morning for a sufficient period of time, >30 days. However, while doing this we may need to trick the body into resetting the hormonal balance as well, and perhaps mega dosing melatonin 5-20 mg's for a short period of time, maybe 1 week on, and 1 week off, could jump start this process. This is similar to therapies used to restore circadian ryhthms for other sleep disorders, but I'm not seeing much about adrenal dysfunction. Futhermore, I have a hetereozygous mutation on the CLOCK gene. According to SNPedia: rs1801260, a SNP in the CLOCK gene known as 3111 T/C, has been reported to influence sleep and activity patterns in patients affected by bipolar depression. [PMID 17221848] From this article's abstract: "Compared to T/T homozygotes, carriers of the C allele had a similar degree of severity of depression, but showed higher activity levels in the evening, a delayed sleep onset (mean 79 min later), and a reduced amount of sleep during the night (mean 75 min less)." Could it be that many AF'ers have CLOCK gene mutations? I've always had "sleep" issues even when I was "well." The CLOCK gene is considered part of your HPA axis and endocrine system. So if your genetically predisposed to less sleep, and a hindered circadian rhythm, could this cause your cortisol rhythm to become out of whack? Your levels go high at night, so by the morning you are depleted, and then experience adrenal fatigue during the day. But if they were lower at night, you may have enough reserves for the day, and if you could restore the rhythm, it would release the proper amount at the proper time.