Four or five years ago I was prescribed 50 mcg of levothyroxine, which made me feel considerably better, and aided me in the realization that I've had fatigue issues pretty much my entire life. Then I was taken off these meds, diagnosed with low testosterone after going through a breakdown of intense insomnia, fatigue, and anxiety, and months later tried thyroid meds again. This time I started with Armour thyroid at 30 mg, then slow release T3 in conjunction with 50 mcg levothyroxine, and later 75 mcg of T4 only; all of these treatments caused significant increases in fatigue and brain fog. These responses weren't the ones you see with iatrogenic hyperthyroidism, or with having too little cortisol or iron. I eventually went on to try up to 30 mg of hydrocortisone in four divided doses throughout the day without any change in symptoms, and ferritin/iron levels are in range (I'm still currently supplementing with iron to bring ferritin to over 100, my usual level being around 70). This failure in treatment leads me to think something else is going on. Dr Ben Lynch has said that supplementing with thyroid hormone without taking care of mitochondrial issues basically hammers the mitochondria, causing the person to feel worse. I have below-the-range coq10 levels, and (according to Spectracell testing) slight-moderate low levels of glutathione, and my folate level is always very high, well above the cutoff (perhaps indicating lack of methylfolate). I have compound heterozygous MTHFR, CBS+/+, two COMT+/+, and SOD2 +/+, among other mutations. Anyone have any insight on this idea of mitochondrial insufficiency as a reason for thyroid meds causing me to feel more fatigued and brain fogged rather than (as with oversupplementation and low cortisol and iron) hyperthyroid?