melphalan and Euthyroid-Sick-Syndromes

Cytokines have been implicated in the pathogenesis of the euthyroid sick syndrome. Isolated limb perfusion (ILP) with recombinant human tumor necrosis factor alpha (rTNF) and melphalan in patients with melanoma or sarcoma is accompanied by high systemic TNF levels. We examined the prolonged effects (7 days) of ILP on thyroid hormone metabolism with respect to induction and recovery of the euthyroid sick syndrome in six cancer patients. After ILP, when the limb is reconnected to the systemic circulation, leakage of residual rTNF resulted in systemic peak levels at 10 minutes postperfusion followed by a parallel increase in plasma interleukin-6 (IL-6) and cortisol, with maximum levels at 4 hours (P < .05). A rapid decrease was observed at 5 minutes for plasma triiodothyronine (T3), reverse T3 (rT3), thyroxine (T4), and thyroxine-binding globulin (TBG) (P < .05), whereas free T4 (FT4) and T3-uptake showed a sharp increase, with peak levels at 5 minutes (P < .05). T3, T4, and TBG levels remained low until 24 hours after ILP In contrast, rT3 increased above pretreatment values to maximum levels at 24 hours (P < .05). Plasma thyrotropin (TSH) showed an initial decrease at 4 hours postperfusion (P < .05) but exceeded pretreatment values from day 1 to day 7 (by +94%+/-43% to +155%+/-66%, P < .05), preceding the recovery of T4 and T3 levels. T3 and rT3 returned to initial values at day 4. T4 and TBG levels recovered at day 2. T4 exceeded basal values at days 5 to 7 (P < .05). It is concluded that ILP with rTNF induces a euthyroid sick syndrome either directly or indirectly through other mediators such as IL-6 or cortisol. The recovery from this euthyroid sick syndrome is, at least in part, TSH-dependent, since the prolonged elevation of TSH values preceded and persisted during the normalization of T3 and the elevation of T4 levels. This biphasic pattern of induction of and recovery from the euthyroid sick syndrome may be a general feature of nonthyroidal disease. The euthyroid sick syndrome should be interpreted not only in relation to the presence of nonthyroidal diseases but also in relation to the recovery from these diseases.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents, Alkylating; Cytokines; Euthyroid Sick Syndromes; Female; Humans; Hydrocortisone; Male; Melanoma; Melphalan; Middle Aged; Perfusion; Recombinant Proteins; Sarcoma; Soft Tissue Neoplasms; Thyroid Hormones; Thyrotropin; Thyroxine-Binding Proteins; Time Factors; Tumor Necrosis Factor-alpha

The relationship between endocrine regulation and immune system has recently become the subject of intense investigations. The aim of this study was the comparative assessment of serum levels of selected hormones and insulin-like growth factor-I (IGF-I) in patients with multiple myeloma (MM) during applied therapy.. The levels of prolactin, hGH, TSH, fT3, fT4 and IGF-I in serum of 13 untreated patients with MM and in 16 healthy controls were determined. The patients were treated in cyclic courses with melphalan plus prednisone, and investigations were carried out in the first four courses of this therapy. The results were compared in the following manner: (1) at entry between studied MM group and healthy subjects, and (2) during the therapy intragroup-intracyclic comparisons were made in paired serum samples collected from patients before and after every therapeutic course.. At entry, significantly lower levels of TSH and fT3 were obtained in MM patients. The means remained within low normal reference range. Slightly increasing levels of TSH and fT3 during treatment with lower concentrations of these hormones after every therapeutic course and a statistically significant difference of fT3 level in the fourth therapy course were revealed. The levels of fT4 were within the normal reference values and showed a tendency to decrease during therapy with significant differences in the first therapeutic course. After the third and the fourth therapy courses, concentrations of IGF-I were statistically significantly higher than initially.. Euthyroid sick syndrome can exist in MM patients, and the therapy with melphalan plus prednisone is accompanied by slightly expressed serum changes of thyroid hormone concentrations and IGF-I levels.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents, Alkylating; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Euthyroid Sick Syndromes; Female; Humans; Insulin-Like Growth Factor I; Male; Melphalan; Middle Aged; Multiple Myeloma; Prednisone; Thyroid Hormones