Why do so many people fail to feel much better with levothyroxine despite an apparently adequate serum FT4 level?
Could it be that the cerebro-spinal fluid levels of free T3 fail to rise in line with either FT3 in blood serum, or with FT4 in serum and CSF?
This paper certainly provides grounds for asking what is going on, why, and what needs to be done. Not sure I'd be very comfortable about CSF being sampled on a regular basis!
Scand J Clin Lab Invest. 2011 Feb;71(1):63-7. doi: 10.3109/00365513.2010.541931.
L-thyroxine treatment in primary hypothyroidism does not increase the content of free triiodothyronine in cerebrospinal fluid: a pilot study.
Sjöberg S, Eriksson M, Werner S, Bjellerup P, Nordin C.
Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden. email@example.com
The association between cerebrospinal fluid (CSF) and serum concentration of thyroid hormones and pituitary thyrotropin stimulating hormone (TSH) was studied in nine hypothyroid patients (HT) before and in seven after L-thyroxine treatment. With L-thyroxine, median free T4 increased 4-fold in serum (3.5 pmol/L vs 17.5 pmol/L) and 3-fold in CSF, (3.9 pmol/L vs 11.5 pmol/L). Correspondingly, total T3 in serum increased two-fold (0.9 nmol/L vs 2.2 nmol/L). Unexpectedly, free T3 concentration in CSF was similar (1.5 pmol/L vs.1.5 pmol/L) before and during treatment. In HT, TSH in serum correlated with TSH in CSF as did free T4 in serum and in CSF. During L-thyroxine, the correlation with TSH in serum and CSF remained. Likewise, the free T4 concentration in serum correlated with that in CSF. However, no correlation was found between T3 in serum and free T3 in CSF. It seems evident that free T4 in serum equilibrates with that in the CSF both in the HT and during L-thyroxine. Despite a two-fold increase in total serum T3, free T3 in CSF remained unchanged, which agrees with previous results in rats showing that T3 is less exchangeable between serum and CSF. Alternatively, an accelerated conversion of T4 to T3 might have maintained the concentration of T3, due to strongly increased levels of TSH found in the hypothyroid state. The notion that free T4 in serum reflects the CSF concentration of free T4 is consistent with previous reports from studies in animals.
PMID: 21214501 [PubMed - indexed for MEDLINE]
With the full text behind a paywall here:
Image is of a lumbar puncture (colloquially called a spinal tap) being performed. Note the swirls of tincture of iodine!