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Non-thyroidal illness, also called the low T3 syndrome or the sick euthyroid
syndrome, is primarily characterized by a low serum T3. Serum TSH may be
suppressed and in serious cases T4 may be low as well. This syndrome occurs
in any acute or chronic disease and during caloric deprivation. Samuels
et al., Portland, OR, investigated the question whether the mild elevation
in serum cortisol, seen during fasting, may be responsible for the TSH
suppression that is present in this state. They investigated 8 healthy
subjects: A. during ad lib diet, B. during 56 hours of total caloric deprivation,
C. during a hydrocortisone infusion at a dose and pattern that reproduced
cortisol levels during each subject's fasting study. The results were that,
during fasting serum cortisol levels increased by a mean of 50%, while
serum TSH levels and TSH pulse amplitude decreased by 64-82%. Hydrocortisone
infusion decreased TSH levels and TSH pulse amplitude by 45-50% below non-fasting
levels, suggesting that fasting-induced serum cortisol elevations may account
for about half of the observed suppression of TSH secretion.
Boelen et al., Amsterdam, The Netherlands, previously found that administration of bacterial endotoxins (LPS) to mice, released a variety of cytokines including interferon-gamma (IFN-gamma) and also demonstrated that administration of IFN-gamma to mice induced a low serum T3 and T4 in a dose dependent manner. To further investigate this aspect they administered LPS to wild type (= normal) mice and to IFN-gamma receptor (IFN-gamma-R) knock-out mice (these mice cannot react to IFN-gamma because they do not express IFN-gamma-R due to genetic manipulation). They found that after LPS administration the decrease in serum T3 and T4 was smaller in the knock-out mice than in the wild type. However, if mice were starved, the decrease in serum T3 and T4 was similar in both groups. The authors conclude that the LPS-induced decrease in thyroid hormones is smaller in the knock-out mice and therefore suggest that IFN-gamma may be involved in the development of the non-thyroidal illness, induced by LPS. (Comment: Their findings, that the decrease in thyroid hormone after LPS in fasted mice of both groups is similar, show that other factors than IFN-gamma should play a role as well in the induction of non- thyroidal illness.) Feelders et al., Rotterdam, Amsterdam, and Veldhoven, The Netherlands, analyzed thyroid function parameters in 6 carcinoma patients who were treated with recombinant tumor necrosis factor (rTNF) as TNF has been shown to induce non-thyroidal illness when administered to humans. All patients were treated with isolated limb perfusion during 90 min with rTNF (2 mg/arm or 4 mg/leg). Melphalan was given concomitantly. Plasma was obtained at 24h and 0 min before treatment, and 5, 10, and 30 min, 4h and 24h after treatment, and then daily for 7 days. The results were that a rapid fall occurred in total values of serum T3, T4, and rT3, that were explained on the basis of a decreased serum TBG (= thyroid hormone binding globulin). In contrast, serum FT4 and cortisol increased. This increase could explain the initial fall in serum TSH. Recovery of serum abnormalities occurred in 4 days, followed by a supranormal increase of serum total T3 and T4, TBG, and TSH, but not FT4. |
