Molecular aetiology of nodular goitre -- consequences for therapy?

Up to 15 % of the adult German population display an enlarged thyroid gland and up to 30 % present thyroid nodules. Iodine deficiency is the most important factor in the etiology of nodular goiter. Insulin-like growth factor-I is overexpressed in thyroids in severely iodine deficient areas. There is evidence that iodolactones are mediators of thyroid hormone autoregulation. However familial and twin studies demonstrated a genetic component in the etiology of nodular goiter. Linkage analysis identified two chromosomal regions (MNG-1, Xp 22) in multinodular goiter. Other possible candidate genes or markers such as TG, TPO, NIS, PDS and TSH-R were not identified. Nodular goiter certainly comprises a number of genotypes. TSH receptor mutations result in activation of the cAMP cascade. Cells with a constitutively activated cAMP cascade have an increased growth advantage due to their TSH independent cAMP stimulation. Alimentary iodine supply should be the first choice in primary prevention of nodular thyroid disease in iodine deficient areas, because prevalence of nodular goiter is negative correlated with individual iodine status in epidemiological surveys. Surgical removal of nodular goiters should include nearly the hold thyroid tissue to avoid recurrent goiter.     

Binding of bovine thyrotropin to specific sites in thyroid tissue from control and hemithyroidectomized rats

The binding of 125I-bovine thyrotropin to thyroid particulate fractions from sham-operated (control) and hemithyroidectomized rats was compared to determine if a change in either the number of bovine thyroid-stimulating hormone (bTSH) binding sites or their affinity for bTSH occurs in physiological situations that evoke changes in the intensity of thyroid stimulation. Following hemithyroidectomy serum TSH levels increase and the remnant thyroid lobe enlarges. Because of compensatory thyroid hypertrophy the concentration of TSH binding sites in the thyroid glands from hemithyroidectomized and control rats was related to particulate protein concentration, to the degree of thyroid cellularity as indicated by DNA concentration, and to the concentration of the plasma membrane markers, 5'-nucleotidase and magnesium-dependent ATPase. In each of four experiments, saturation studies revealed that the maximum specific binding of TSH per unit particulate protein and per thyroid lobe was greater in particulates from remnant than from control thyroid lobes. When related to DNA concentration, the concentration of TSH binding sites in remnant lobes was approximately twice that in control lobes. Because of an increase in plasma membrane markers per lobe after hemithyroidectomy, however, there was no difference in the number of TSH binding sites when related to the concentrations of the membrane marker enzymes in the particulate fractions. As judged from Scatchard analysis, the affinity of TSH binding was lower in remnant than in control lobes. This was partially but not completely due to the increased concentration of particulate protein in the remnant thyroid. These experiments demonstrate that the increase in serum TSH levels after hemithyroidectomy in the rat is associated with alterations in TSH receptor capacity and affinity.     

The effect of methimazole, iodine and splenocytes on thyroid transplants in BB/Wor rats.

BACKGROUND: BB/Wor rats develop spontaneous autoimmune insulin-requiring diabetes mellitus and lymphocytic thyroiditis (LT). Our investigations examined the effect of the thyroid-specific agents, iodine and methimazole (MMI) on thyroid graft survival in BB/Wor rats, compared the intrathyroidal cytokine mRNA expression of endogenous and engrafted thyroids, and ascertained whether unfractionated splenocytes could protect thyroid grafts from lymphocytic infiltration. METHODS: In study 1, 0.025% iodine water-treated LT-prone NB line BB/Wor rats were randomized to receive one of the following treatments: (1) 1.0 x 10(8) splenocytes, IV from LT-resistant WA line BB/Wor rats, (2) WA rat thyroid transplants, (3) both, or (4) neither (controls). In study 2, after thyroid transplantation, LT-prone BB/Wor rats were randomized to receive (1) WA splenocytes, (2) 0.025% iodine water, (3) 0.05% MMI water or, (4) tap water (controls). The incidence of LT was determined by microscopic inspection after hematoxylin and eosin staining. Lymphocytic infiltrates were characterized by immunohistochemistry. Cytokine mRNA was detected by RT-PCR. RESULTS: Grafts from MMI-treated rats had a significantly lower incidence of lymphocytic infiltration (MMI: 2/5; Tap: 5/5; I 5/5, P<0.05, chi2). IL-10 mRNA was expressed in 77% (7/9) endogenous thyroids and 20% (1/5) of the transplanted WA thyroids (P<0.05, chi2) from iodine-treated rats with LT. There was no difference in IL-12 mRNA expression. Lymphocytic infiltration occurred in 100% of the splenocyte-treated graft recipients. Both endogenous and engrafted thyroids contained CD4 and C8 T cells with scattered IgG staining. CONCLUSION: Target organ-specific interventions that suppress antigen presentation may have an adjunctive role in transplantation tolerance. The differential expression of IL-10 may indicate preferential Th2 lymphocyte activation in the endogenous tissues.     

Hashimoto's thyroiditis and carcinoma of the thyroid gland

Seven cases of Hashimoto's disease (HT) occurring in association with carcinoma of the thyroid gland are presented. The diagnosis of HT was not reached before surgery in any of the cases; it was an incidental histopathological finding. There was no case of pure papillary cancer: two specimens showed mixed papillary and follicular cancers, four revealed follicular carcinomas (one of them with anaplastic areas) and one medullary neoplasm. Other authors, however, have reported that pure papillary carcinoma occurred with significantly greater frequency in thyroids also displaying Hashimoto's disease. Total thyroidectomy was performed in all seven patients and one patient with anaplastic follicular cancer also received external irradiation. TSH suppressive therapy was given postoperatively. All these patients are alive with no evidence of further disease after seven to 17 years of follow-up study, whereas the mortality in our total series of thyroid cancers, even in patients with low-grade malignancy, was about 9%. Thus the prognosis of patients with carcinoma of the thyroid gland with coexisting Hashimoto's disease is better than that of patients with carcinoma of the thyroid gland alone. Hashimoto's thyroiditis does not seem to be a premalignant lesion. There was no evidence suggesting that thyroid carcinoma originated in the proliferating epithelium of Hashimoto's thyroiditis. It would appear that thyroid carcinoma stimulates the development of HT in some patients and that the presence of the autoimmune inflammatory reaction and the circulating antibodies retard growth and dissemination of carcinoma of the thyroid gland.     

术前TSH水平与甲状腺结节良恶性关系

目的：探讨血清促甲状腺激素（TSH）浓度与甲状腺结节良恶性的关系。 方法：回顾性分析近3年间收治的421例甲状腺结节患者的临床资料,其中结节性甲状腺肿347例,甲状腺癌74例。比较良恶性甲状腺结节患者血清TSH浓度差异,并分析TSH浓度与甲状腺结节的恶性风险以及甲状腺癌不同病理类型与血清TSH浓度的关系。 结果：甲状腺癌患者血清TSH浓度明显高于结节性甲状腺肿患者[（2.57±3.32）mIU/L vs. （1.67±2.90）mIU/L]（P<0.05）;甲状腺结节的恶性风险随血清TSH浓度的升高而逐渐升高,当TSH>5 mIU/L时,恶性率为50.0%;甲状腺癌不同病理类型间血清TSH浓度无统计学差异（P>0.05）。 结论：甲状腺结节恶性风险随血清TSH浓度的升高而增加,术前血清TSH测定可以作为甲状腺结节良恶性判断的一个辅助性指标。     

Iodine deficiency produces hypercalcemia and hypercalcitonemia in rats

To determine the effect of thyroid-stimulating hormone (TSH) on secretion of calcitonin by the thyroid, 50 male Sprague-Dawley rats were randomly separated into seven groups. The groups received different diets, medications, or operations [propylthiouracil (PTU), iodine-deficient diet, (LID), acute or chronic thyroxine treatment, sham operation (SO), hemithyroidectomy (Htx), and total thyroidectomy (Ttx)]. two weeks to six months later, serum TSH concentrations were increased in the Htx, Ttx, and LID groups when compared with SO animals. Serum calcitonin concentrations were increased in the LID- and PTU-treated groups and were decreased in animals that chronically received thyroxine. Serum calcium concentrations were increased in the LID animals, decreased in the Ttx animals, and were similar in the other groups. These findings suggest that TSH stimulates both follicular and parafollicular cells in the rat thyroid and that iodine deficiency causes hypercalcemia and hypercalcitonemia.     

TSH suppression in the management of thyroid nodules and thyroid cancer

Clinical and experimental data concerning TSH suppression, by giving exogenous thyroid hormone, in patients with goiter and in patients with thyroid cancer show a beneficial effect. In the goiter patients, TSH suppressive therapy seems most effective in young patients with diffuse or newly discovered goiters, in hypothyroid patients, and in patients with chronic lymphocytic thyroiditis or compensatory thyroid hypertrophy after partial thyroidectomy. With TSH suppressive therapy about 2/3 of thyroid nodules become smaller, but only about 5% to 10% disappear. In patients with differentiated thyroid cancer (papillary, mixed papillary-follicular, and follicular), tumor recurrence, tumor progression, and long-term survival all seem to be influenced favorably by TSH suppressive therapy. Experimental investigations demonstrate that both benign thyroid adenomas and differentiated thyroid carcinomas have TSH receptors situated on the plasma membranes. These TSH receptors appear to be coupled to the activation of adenylate cyclase in a one-to-one relationship. Experimental and clinical studies strongly support the use of thyroid hormone both for the treatment of patients after thyroidectomy for thyroid cancer and as prophylaxis to prevent the development of thyroid cancer in high-risk irradiated patients. The dose of thyroxine recommended for adequate TSH suppression is the lowest dose of thyroxine that will completely block the TSH response to TRH (usually 0.2 to 0.25 mg).Supported in part by a grant from the Veterans Administration.     

Primary tissue cultures of benign and malignant human thyroid tumors: effect of TSH

Many thyroid carcinomas seem to be dependent upon the thyroid growth-promoting properties of the thyroid stimulating hormone (TSH). The purpose of the present investigation was to compare the in vitro effect of TSH on tissue cultures derived from malignant and benign thyroid tumors. The results indicate that TSH can affect the morphology and protein synthesis of primary tissue cultures derived from benign and malignant thyroid tumors differently. The addition of TSH to cultures derived from benign tumors resulted in a reorganization of follicle-like structures of the monolayer and in a reduction of protein synthesis. In contrast to this, monolayers derived from carcinomas of the thyroid were not able to reorganize and their protein synthesis was not inhibited in the presence of TSH. For a better understanding of TSH suppressive therapy, we suggest testing the influence of TSH on a large number of tissue cultures derived from benign and malignant tumors of the thyroid.     

TSH水平与甲状腺乳头状微小癌之间的关系探讨

目的探讨促甲状腺激素(TSH)与甲状腺乳头状微小癌之间的关系。方法回顾性分析2006年1月至2016年2月手术治疗的341例甲状腺结节患者,根据病理结果分为两组:甲状腺乳头状微小癌组104例,良性甲状腺结节组237例,收集并比较各组临床实验资料。数据分析采用SPSS 19.0统计软件,计量资料采用(x珋±s)表示,患者在年龄、结节直径、TSH浓度、淋巴结转移与TSH关系比较使用t检验;甲状腺乳头状微小癌发生率与TSH的关系采用χ2趋势检验,以P0.05表示差异具有统计学意义。结果甲状腺乳头状微小癌组患者结节直径平均为(1.92±1.13)cm,低于良性甲状腺结节组患者的(2.82±1.44)cm(t=-5.654,P0.05);甲状腺乳头状微小癌组患者TSH平均为(3.01±1.51)μIU/ml,高于良性甲状腺结节组患者的(1.90±1.32)μIU/ml(t=6.836,P0.05),差异均有统计学意义;按照TSH水平分为0.34μIU/ml、0.34~1.00μIU/ml、1.01~2.00μIU/ml、2.01~5.60μIU/ml和5.60μIU/ml,甲状腺乳头状微小癌组发生比例分别为11.76%、14.29%、23.94%、39.06%和53.33%,检验结果显示TSH水平越高其甲状腺乳头状微小癌的发生率越高(χ2=28.783,P0.05);甲状腺乳头状微小癌伴淋巴结转移患者TSH为(5.07±1.31)μIU/ml、明显高于无淋巴结转移患者的(2.83±1.55)μIU/ml,差异比较有统计学意义(t=5.844,P0.05)。结论 TSH可作为预测甲状腺乳头状微小癌风险的指标之一,可为临床诊断提供参考依据。     

甲状腺腺瘤术后内分泌治疗的研究

目的 探讨甲状腺腺瘤术后内分泌治疗的必要性。方法 对１００例次手术后甲状腺腺瘤标本用ＳＰ法测定ＴＳＨ受体,瘤体周围的甲状腺组织连续病理切片检查有无存在微小瘤灶,并按随机抽签法将病人分成Ａ、Ｂ两组,Ａ组口服甲状腺片治疗,Ｂ组不用任何治疗。术后定期测定血Ｔ３,Ｔ４,ＴＳＨ浓度,＾１３１Ｉ扫描及Ｂ超检查残存甲状腺。结果 甲状腺瘤１００％存在ＴＳＨ受体,８％有微小瘤灶。Ａ组病人血Ｔ３,Ｔ４,ＴＳＨ及残存甲     

Factors influencing the growth of normal and neoplastic thyroid tissue

TSH activates the adenylate cyclase and the phosphoinositide turnover-protein kinase C-calcium systems in thyroid cells and appears to have an important but variable role in controlling the growth of both normal and neoplastic thyroid tissues. Species differences, experimental conditions, and tissue or tumor cell heterogeneity may account for this variability. Although TSH seems to be an important physiologic growth factor, it is neither the exclusive growth factor for the thyroid gland nor absolutely necessary for the effect of other thyroid growth factors. TSH may work in concert with other growth factors such as EGF. Some growth factors influence thyroid growth through TSH, whereas others do not.     

Sensitivity of the thyroid and parathyroid glands to radiation

Iodine-125 seeds selectively inhibited thyroid compared with parathyroid function. Stimulation of thyroid tissue by TSH and suppression of thyroid tissue by thyroxine did not alter the sensitivity of thyroid tissue to radiation, since serum TSH concentrations were not different in the thyroxine-suppressed, control, or TSH-stimulated animals 9 weeks after discontinuing the radiation. TSH stimulation by the low iodine diet and TSH suppression by exogenous thyroxine did alter the function of the parafollicular C cells of the thyroid, since serum calcitonin concentrations were increased in the former and decreased in the latter. Serum calcium concentrations were also increased in the rats receiving the low iodine diet, but the reason for this increase is not known.     

Initiation of rejection of established islet allografts by third-party thyroid allografts and splenic dendritic cells

Due to concerns of cross-reactivity between renal and islet allografts in initiation of rejection, we determined the ability of donor-specific and third-party splenic dendritic cells (DCs) and thyroids (whole-organ transplant) to initiate rejection of established islet allografts. Purified islets from neonatal F-344 (RT1Lv1) rats were transplanted bilaterally under the kidney capsule of Wistar-Furth (W/F, RT1u) rats without immunosuppression. The islet allografts were not rejected by 21 days posttransplantation. On day 22, freshly isolated or cultured DCs were injected intraperitoneally into the host. Both freshly isolated and cultured donor-specific (F-344) and some third-party (Buffalo, RT1b; ACI, RT1a) DCs initiated rejection of the islets as indicated by lymphocyte infiltration and destruction of the allograft. DCs, whether freshly isolated or cultured for 8 days from the recipient strain (W/F) and one third-party rat (Brown Norway, RT1n), did not initiate rejection. Splenic DCs from the Lewis (RT1l) rat, which has the same class I and II antigen haplotype as F-344 islet donor rats, also initiated rejection. Only 10(3)-10(4) DCs isolated from the spleen of donor rats were required to initiate rejection of the allograft. In a parallel series of W/F rats with islet allografts, a thyroid (half lobe) from the islet donor strain (F-344), recipient strain (W/F), or third-party rat (Buffalo, Brown Norway, or ACI) was inserted under the kidney capsule at 22 days post-islet transplantation. At 35 days, all thyroids and most islet allografts exhibited active or complete rejection after thyroid transplant from Buffalo, F-344, or ACI rats.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of tumor necrosis factor on growth and function in FRTL5 cells.

Tumor necrosis factor (TNF) is a cytokine produced by inflammatory macrophages and monocytes. FRTL5 cells are a continuous line of functional, nontransformed rat thyroid cells that depend on thyroid-stimulating hormone (TSH) for sustained growth. The following experiments characterize the effects of TNF on growth and differentiated functions in FRTL5 cells. Cells were incubated with different concentrations of TNF (1 to 100 ng/ml), alone or with TSH. FRTL5 cell proliferation was assessed by 3H-thymidine incorporation assays. Differentiated functions were studied by measuring radioactive iodine uptake (RAI) and triiodothyronine (T3) production. TNF inhibited FRTL5 cell growth both in basal conditions and after cells had been exposed to TSH. TNF caused small inhibition of both basal RAI uptake and T3 release but greatly decreased TSH-stimulated RAI uptake and T3 secretion. In summary, TNF appears to affect both growth and differentiated functions in the FRTL5 cell line. Although it is difficult to extrapolate these in vitro results to the human disease state, we postulate that TNF production in septic states may contribute to the pathogenesis of the low T3 syndrome; moreover, locally produced TNF may modulate thyroid function in autoimmune thyroid diseases.     

Estrogen and thyroid-stimulating hormone (TSH) receptors in neoplastic and nonneoplastic human thyroid tissue

Estrogen-binding receptors (ER) and thyroid-stimulating hormone (TSH) receptors were observed in the cytosol and in a membrane particulate fraction, respectively, in most neoplastic and nonneoplastic human thyroid tissues. Fourteen of 15 thyroid neoplasms and 6 of 15 nonneoplastic thyroid specimens had estrogen receptors (assuming the sensitivity of our estrogen receptor assay is 0.2 fmole/mg protein), and 14 of 15 thyroid neoplasms and 11 of 15 nonneoplastic thyroid specimens had a high affinity, low capacity TSH receptor. Neoplastic thyroid tissue had more ER (2.35 +/- 0.70/fmole/mg protein) than nonneoplastic thyroid tissue (0.57 +/- 0.181/fmole/mg protein) removed from the same patients (P less than 0.05). The Kd for ER did not differ in nonneoplastic (0.41 +/- 0.090 nM) and neoplastic (0.311 +/- 0.048 nM) thyroid tissue. The number of TSH receptors was comparable in neoplastic (0.609 +/- 0.191 pmole/mg protein) and in nonneoplastic (0.765 +/- 0.181 pmole/mg protein) thyroid tissue removed from the same patients who had the ER studies. The maximal adenylate cyclase response to TSH was greater in the neoplastic (147 +/- 26.9 pmole/mg protein/30 min) than in nonneoplastic thyroid tissue (32.8 +/- 6.69 pmole/mg protein/30 min) (P less than 0.001) suggesting a greater metabolic responsiveness of the neoplastic thyroid tissue to TSH. No correlation was evident, however, between the number of estrogen and TSH receptors in nonneoplastic and neoplastic thyroid tissue (r = 0.226). This study demonstrates that neoplastic human thyroid tissues have both estrogen receptors and TSH receptors. The neoplastic tissue also has a greater AC response to TSH than nonneoplastic thyroid tissue.     

Stimulatory effect of vasoactive intestinal polypeptide on human normal and neoplastic thyroid tissue

Recent investigations suggest that although thyroid-stimulating hormone (TSH) is the major regulator of thyroid gland function, it is not the only hormone that regulates the thyroid gland. Another factor regulating thyroid gland function is vasoactive intestinal polypeptide (VIP), which is present in nerves that innervate thyroid blood vessels and follicles. Previous studies have documented that VIP stimulates adenylate cyclase (AC) activity in cultured normal and hyperplastic (Graves) thyroid tissue, thus increasing intracellular cyclic AMP concentration. To our knowledge, however, there is no information concerning the effect of VIP on neoplastic thyroid tissue. Therefore we studied the effect of VIP on normal and neoplastic human thyroid tissue from 10 patients (follicular adenomas, 4; follicular carcinomas, 3; and papillary carcinomas, 3). Adenylate cyclase activity was measured in a 8000 g membrane preparation in the basal state and when incubated with VIP, TSH, and both. VIP increased AC activity in normal tissue and tumor in a dose-dependent manner, with maximal stimulation at 10(-6) mol/L (p less than 0.05). In normal tissue, 10(-6) mol/L VIP and a maximally stimulating concentration of TSH (300 mU/ml) stimulated AC to the same degree. In tumors, although both TSH and VIP increased AC activity, the response to TSH was greater (p less than 0.01). VIP and TSH had an additive effect in normal tissue (p less than 0.05), whereas in tumors the AC response to VIP and TSH was the same as with TSH alone (p = 0.66). This study documents that VIP is a potent stimulator of adenylate cyclase in both normal and neoplastic human thyroid tissues. The magnitude of this effect is similar to that produced by TSH, which implies that VIP plays a physiologically important role in the regulation of the secretion and growth of normal and neoplastic thyroid tissues.     

促甲状腺素（TSH）与绝经后甲状腺功能正常的 2 型糖尿病女性患者骨密度的相关性研究

目的探讨促甲状腺素(TSH)与停经1年以上的绝经后甲状腺功能正常的2型糖尿病女性患者骨密度的相关性。方法选取307例绝经后甲功正常2型糖尿病女性患者,根据TSH值的水平分层,分为A、B组,收集并比较两组间一般资料、骨密度的差异。结果 TSH与腰椎骨密度呈正相关,与股骨颈、Ward三角、股骨大转子、股骨干、股骨全部无明显相关关系。结论在甲功正常绝经后2型糖尿病女性患者中,维持TSH在正常高值水平,有利于预防骨质疏松的发生。     

Enhancement of thyroid allograft survival following organ culture. Alteration of tissue immunogenicity

Hyperbaric oxygen (95%, O2, 25 psi, 48-hr culture) resulted in prolonged thyroid allograft (B10.A) survival in both primary and sensitized recipients (B10.AQR). Recipients receiving noncultured thyroid allografts uniformly rejected the graft by 35 days, while 100% of cultured grafts survived. Noncultured thyroid grafts transplanted to skin-graft-primed recipients were rejected by 21 days. In contrast, 86% of cultured grafts transplanted to primed recipients were still functioning at 35 days. Donor spleen cells or peritoneal exudate cells transferred at the time of thyroid transplant were unable to stimulate cultured allograft rejection. Allografts histologically examined 35 days after transplant revealed, in some grafts, focal cellular infiltrates adjacent to normal, uninfiltrated tissue. To determine if tissue modification was the mechanism of prolonged allograft survival, hyperbaric-oxygen-cultured thyroids were examined for MHC class I expression. Immunoperoxidase staining with monoclonal antibody to MHC class I molecules showed that cultured thyroids were unstained in contrast to fresh thyroids that were uniformly stained. Cytotoxic T lymphocytes specific for H-2Kk administered 10 days following thyroid transplant were unable to eliminate cultured grafts (80% survival) but completely destroyed noncultured grafts. These results indicate that hyperbaric oxygen culture altered MHC class I expression such that it was no longer detectable by monoclonal antibody or cytotoxic T lymphocytes. Thus, the mechanism, explaining graft prolongation after hyperbaric culture in addition to passenger cell depletion, may be alteration of graft antigenicity such that the graft is no longer perceived as foreign.     

Heterotopic mediastinal goitre

The unusual coexistence in a woman of 34 years of a cervical thyroid and a heterotopic mediastinal thyroid is recorded. Both thyroids had undergone non-toxic nodular enlargement. Recurrent enlargement was noted in the cervical gland 12 months after transpleural thoracic removal of the mediastinal goitre, whilst no corresponding change has so far been noted in the mediastinum. The literature on heterotopic thyroid is briefly reviewed and the diagnosis discussed.     

Is there any relation between thyroid gland function and kidney transplant function?

INTRODUCTION: Patients with chronic renal failure exhibit abnormalities of thyroid function. Reports regarding thyroid function in kidney transplant recipients (TX) are rare, particularly those individuals on long-term immunosuppression. The aim of this study was to investigate correlations between FT3, FT4, TSH concentrations, thyroid volume, and graft function. MATERIAL AND METHODS: The study enrolled 46 kidney allograft recipients (aged 27-67 years,) engrafted between years 1994 and 2000 and clinically stable. The mean time after TX was 45.3 +/- 37.4 months. Transplanted patients received prednisone, cyclosporine, and azathioprine. The control group included 22 patients with normal renal function. In addition to serum creatinine, TSH, FT3, and FT4 concentrations, thyroid examinations were performed with a 7.5-MHz linear probe to calculated the thyroid volume. RESULTS: Thyroid volume in TX patients was 25.3 +/- 13.3 mL. A positive correlation existed between thyroid volume and serum creatinine (P <.05), and a negative one between thyroid volume and TSH (P <.05). No correlation was observed between TSH, FT4, and serum creatinine. The time after TX was negatively related to TSH (P <.05). A negative correlation existed also between FT3 and creatinine in TX patients (P <.05). In the control group the concentrations of TSH and FT3 were within normal ranges. CONCLUSION: The FT3 concentration correlates with function of the renal graft. In TX patients the supplementary thyroid hormone therapy should be considered.