Biochemical Markers Reflecting Thyroid Function in Athyreotic Patients on Levothyroxine Monotherapy.

BACKGROUND: Some investigators reported that among athyreotic patients on levothyroxine (LT4) monotherapy following total thyroidectomy, the patients with normal serum thyrotropin (TSH) levels had mildly low serum free triiodothyronine (fT3) levels, whereas the patients with mildly suppressed serum TSH levels had normal serum fT3 levels, and the patients with strongly suppressed serum TSH had elevated serum fT3 levels. The objective of the present study was to clarify which of these three patient groups is closer to their preoperative euthyroid condition. METHODS: A total of 133 consecutive euthyroid patients with papillary thyroid carcinoma who underwent a total thyroidectomy were prospectively studied. The patients' serum levels of lipoproteins, sex hormone-binding globulin, and bone metabolic markers measured preoperatively were compared with the levels measured at postoperative LT4 therapy 12 months after the thyroidectomy. RESULTS: The postoperative serum sex hormone-binding globulin (p < 0.001) and bone alkaline phosphatase (p < 0.01) levels were significantly increased in the patients with strongly suppressed TSH levels (≤0.03 µIU/mL). The postoperative serum low-density lipoprotein cholesterol levels were significantly increased (p < 0.05), and the serum tartrate-resistant acid phosphatase-5b levels were significantly decreased (p < 0.05) in the patients with normal TSH (0.3 < TSH ≤5 µIU/mL). In the patients with mildly suppressed TSH (0.03 < TSH ≤0.3 µIU/mL) and fT3 levels equivalent to their preoperative levels, all metabolic markers remained equivalent to their preoperative levels. CONCLUSIONS: The serum biochemical markers of thyroid function in patients on LT4 following total thyroidectomy suggest that the patients with mildly suppressed TSH levels were closest to euthyroid, whereas those with normal TSH levels were mildly hypothyroid and those with strongly suppressed TSH levels were mildly hyperthyroid. These data may provide novel information on the management of patients following total thyroidectomy for thyroid cancer or benign thyroid disease.

Effect of the presence of remnant thyroid tissue on the serum thyroid hormone balance in thyroidectomized patients.

OBJECTIVE: We and others recently reported that in total thyroidectomy (TT), serum triiodothyronine (T3) levels during levothyroxine (L-T4) therapy were low compared to the preoperative levels, suggesting that the presence of the thyroid tissue affects the balances of serum thyroid hormone levels. However, the effects of remnant thyroid tissue on these balances in thyroidectomized patients have not been established. METHODS: We retrospectively studied 253 euthyroid patients with papillary thyroid carcinoma who underwent a TT or hemithyroidectomy (HT). We divided the cases into the TT+supplemental L-T4 (+L-T4) group (n=103); the HT+L-T4 group (n=56); and the HT-alone group (n=94). We compared the postoperative serum levels of free T4 (FT4) and free T3 (FT3) and the FT3/FT4 ratio in individual patients with those of controls matched by serum TSH levels. RESULTS: The TT+L-T4 group had significantly higher FT4 (P<0.001), lower FT3 (P<0.01) and lower FT3/FT4 (P<0.001) levels compared to the controls. The HT+L-T4 group had FT4, FT3 and FT3/FT4 levels equivalent to those of the controls. The HT-alone group had significantly lower FT4 (P<0.01), equivalent FT3 (P=0.083), and significantly higher FT3/FT4 (P<0.001) ratios than the controls. CONCLUSIONS: The presence of the remnant thyroid tissue was associated with different thyroid hormone balances in thyroidectomized patients, suggesting that T3 production by remnant thyroid tissue has a substantial effect on the maintenance of postoperative serum T3 levels.

Rapid bioassay for detection of thyroid-stimulating antibodies using cyclic adenosine monophosphate-gated calcium channel and aequorin.

BACKGROUND: Thyroid-stimulating antibodies (TSAb) are known to be responsible for hyperthyroidism in Graves' disease (GD). The conventional methods to measure TSAb depend on cell-based assays that require cumbersome procedures and a sterilized tissue culture technique. The aim of the present study was to develop a ready-to-use cell-based assay for measuring TSAb activity without requiring sterilized conditions. METHODS: We developed a new assay kit using a frozen Chinese hamster ovary cell line expressing the thyroid-stimulating hormone receptor, cyclic adenosine monophosphate (cAMP)-gated calcium channel and aequorin, tentatively named the aequorin TSAb assay. Activated stimulatory G-protein-coupled adenylate cyclase increases intracellular cAMP, which then binds to the cyclic nucleotide-gated calcium channel. Activation of this channel allows Ca(2+) to enter the cell, and the influx of Ca(2+) can be measured with aequorin, which is quantified by a luminometer. Results can be obtained in only 4 h without sterilized conditions. TSAb activities were expressed by international units using the NIBSC 08/204 standard. RESULTS: Positive results of aequorin TSAb were obtained in 197 of 199 (98.9%) of untreated patients with GD. Only 1 of 42 (2.3%) patients with painless thyroiditis had a weakly positive aequorin TSAb. All 45 patients with subacute thyroiditis and 185 normal subjects showed negative aequorin TSAb. As for chronic thyroiditis, all 52 euthyroid patients showed negative aequorin TSAb, but 8 of 50 (16.0%) hypothyroid patients had a positive reaction. However, these positive reactions were not induced by serum thyroid-stimulating hormone (TSH) and were thought to be induced by the stimulating activity of anti-TSH receptor immunoglobulins. Conventional porcine TSAb and Elecsys thyroid-stimulating hormone receptor antibodies were positive in 69.3 and 95.5% of GD, respectively. CONCLUSION: The aequorin TSAb assay was positive in 98.9% of GD and was more sensitive than the conventional assay. This assay can be conducted in only 4 h without sterilized conditions and is practically useful in general clinical laboratories.

Association between IL-18 gene promoter polymorphisms and CTLA-4 gene 49A/G polymorphism in Japanese patients with type 1 diabetes.

Interleukin-18 (IL-18) is a potent proinflammatory cytokine which is strongly associated with the development of diabetes in NOD mice. To test the putative involvement of IL-18 gene polymorphism in predisposition to human type 1 diabetes, the SNPs at position -607 (C/A) and -137 (G/C) in the promoter region of IL-18 gene were analyzed by sequence-specific PCR in 116 patients with type 1 diabetes and 114 normal controls. A linkage disequilibrium found only three of the four possible haplotypes defined by these SNPs. The distribution of the IL-18 gene genotypes at position -607 was significantly different between patients with type 1 diabetes and normal controls (P=0.023). Furthermore, there was a significant increase in haplotype 1 (-607C/-137G) in the patients compared with controls (P=0.006). The association study of the susceptible CTLA-4 genotype (GG at nucleotide position 49 in exon 1) or HLA-DR4-DQB1*0401 and type 1 diabetes showed that the predisposing IL-18 gene haplotype modulates the risk on CTLA-4 GG genotype, but not on HLA-DR4-DQB1*0401 haplotype. Among subjects carrying the CTLA-4 GG genotype, the frequency of IL-18 haplotype 1 in patients with type 1 diabetes was significantly higher than that in controls (91% vs. 71%, P=0.012). However, IL-18 haplotype 1 was not frequent in patients who do not exhibit the CTLA-4 high-risk genotype. These results suggest that the IL-18 gene polymorphism is associated with a type 1 diabetes susceptibility, and there might be a gene-gene interaction between IL-18 gene with susceptible CTLA-4 gene.