L-thyroxine treatment in primary hypothyroidism does not increase the content of free triiodothyronine in cerebrospinal fluid: A pilot study

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.