Clinical and biochemical implications of low thyroid hormone levels (total and free forms) in euthyroid patients with chronic kidney disease.
OBJECTIVE
In this study, we explore the associations of decreased thyroid hormone levels with inflammation, wasting and survival in biochemically euthyroid patients with end-stage renal disease (ESRD).


METHODS
After exclusion of 23 patients with thyroid-stimulating hormone (TSH) values outside the normal range (0.1-4.5 mIU L(-1)), 187 clinically and biochemically euthyroid incident ESRD stage 5 patients starting dialysis were followed for a median of 20 (range 1-60) months. Measurements of total and free forms of thyroid hormones, s-albumin, hs-CRP, interleukin (IL)-6, vascular adhesion molecule (VCAM)-1 and insulin-like growth factor 1 (IGF-1) were performed at baseline.


RESULTS
In this population, 17 out of 210 patients (8%) were defined as subclinically hypothyroid. Multivariate analysis, according to receiver operating characteristic (ROC) curves, showed that mortality was best predicted by total triiodothyronine (T3). When using the cut-off levels derived from ROC, low T3 levels were associated with increased inflammation (higher hs-CRP, IL-6 and VCAM-1) and lower concentration of both s-albumin and IGF-1. Finally, low T3 but not low free triiodothyronine was associated with worse all-cause (Likelihood ratio = 45.4; P < 0.0001) and cardiovascular mortality (Likelihood ratio = 47.8; P < 0.0001) after adjustment for confounding factors.


CONCLUSIONS
This study showed that low T3 levels are independent predictors of all-cause and also cardiovascular disease mortality in biochemically euthyroid patients, perhaps due to an intimate association with inflammation. Based on these results, the use of T3 levels in studies assessing the relationship between thyroid dysfunction and mortality risk is recommended.
Carrero
J J
JJ
Division of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
Qureshi
A R
AR
Axelsson
J
J
Yilmaz
M I
MI
Rehnmark
S
S
Witt
M R
MR
Bárány
P
P
Heimbürger
O
O
Suliman
M E
ME
Alvestrand
A
A
Lindholm
B
B
Stenvinkel
P
P
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D002318:Cardiovascular Diseases / Q000097:blood / Q000276:immunology / Q000401:mortality; D004812:Epidemiologic Methods; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000276:immunology / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D006435:Renal Dialysis; D013963:Thyroid Hormones / Q000097:blood; D014284:Triiodothyronine / Q000097:blood*; D019282:Wasting Syndrome / Q000097:blood / Q000276:immunology / Q000401:mortality
D015415:Biomarkers; D015850:Interleukin-6; D013963:Thyroid Hormones; D014284:Triiodothyronine; D002097:C-Reactive Protein