ex. I have family history and symptoms of hypothyroidism. I've had 3 doctors test T4&TSH, then shrug and say everything is fine. My dad had a similar experience before landing on a doc who shrugged and said "let's just try the meds anyway and see what happens."
I got WGS out of curiosity, annotated the VCF with REVL scores, and sorted by score. The first entry was a low-frequency (121 hits in TopMed) NR1D1 missense variant. I couldn't find any literature on that variant, so I looked at the downstream THRA impact and found papers that talked about disruption to thyroid signaling, and said that T4 & TSH would look normal, so you need to check T3/rT3.
I bounce this off my endo and ask if she'll order a T3 & rT3 test. She won't because endo society guidelines says that rT3 tests aren't clinically useful. I order my own tests from a labcorp reseller. My T3 & rT3 results reflect what the papers saw, so I get grey market thyroxine. Screw up the dosing and get a day of racing heart. Fix dosing and hypothyroid symptoms went away.
After this I find out that there's a whole community of people with normal T4 & TSH results, hypothyroid symptoms, and wonky T3/rT3. Also that there's some kind of culture clash between normal docs and functional medicine docs about this.</shrug>
I shouldn't have to resort to days of messing with bioinformatics tooling, a week of reading papers, and questionable sourcing of meds to test something that any doc should have been able to deduce if they bothered to have some curiosity about how I could have those symptoms if their normal test came back normal :(