trochemiluminescence immunoassay (ECLIA). These latter immunoassays provide greater precision, accuracy and a wider range of measurement [5].A high level of TSH generally indicates hypothyroidism. However, we should consider the cases of TSH-producing tumor, resistance to thyroid hormone (RTH: Refetoff syndrome), and false elevation of TSH due to heterophile antibodies specific to the reagents [6]. Autoimmunity against TSH is rare and has not been evaluated in sufficient detail, although several reviews have been published on heterophile antibodies.We examined a case with extremely high TSH levels. We decided to perform the polyethylene glycol (PEG) precipitation test. Furthermore, the TSH value was shown to be markedly low by PEG precipitation test. We eventually found macro-TSH, a unique anti-TSH autoimmune complex which may have caused the unexpectedly high elevation of TSH. Abstract. We encountered a 60-year-old woman with remarkably elevated thyroid-stimulating hormone (TSH) level as measured by electrochemiluminescent immunoassay (ECLIA), but with no specific symptoms, and with normal levels of free T3 and free T4. We performed the following investigations: polyethylene glycol (PEG) precipitation test, human antimouse IgG antibody (HAMA) interference test, and 3 additional TSH measurements by chemiluminescent immunoassay (CLIA). We then performed 2 gel filtration chromatography (GFC) procedures; one was at pH 7.2, and the other was at pH 3.0. Although the recovery of TSH shown by the PEG precipitation test was 4% which was extremely low, no HAMA interference was observed. Moreover, 3 CLIA instruments also showed various high values. The first GFC showed that the main peak of TSH immunoreactivity by ECLIA was located at a slightly larger molecular weight position than that of IgG. By the second GFC, the sample from the peak fraction of the first GFC showed that the TSH peak disappeared completely at the previous retention time but newly appeared at the same retention time as the TSH monomer. Protein G-Agarose gel removed the majority of the TSH complex. In conclusion, the majority of TSH in her serum was macro-TSH; TSH and anti-TSH IgG autoantibody complex. We should keep the possibility of macro-TSH in mind in cases with unexpectedly high TSH values, especially in autoimmune thyroidal disorders.

Heart failure often presents with prognosis-relevant impaired renal function. To investigate whether the chronic activation of guanylate cyclase-A (GC-A) protects both heart and kidney, we examined the effects of TDT, a neprilysin (NEP)-resistant natriuretic peptide (NP) derivative, on cardiac and renal dysfunction in Dahl salt-sensitive hypertensive (DS) rats. Pretreatment with NEP or NEP inhibitor did not influence GC-A activation by TDT both in vitro and in vivo, resulting in a long-acting profile of TDT compared with native human atrial NP (hANP). The repeated administration of TDT to DS rats suppressed the progress of cardiac hypertrophy, systolic/diastolic dysfunction, and proteinuria in a dose-dependent manner. Compared with vehicle and hANP, salt diet-induced podocyte injury was reduced by TDT, as analyzed by urinary podocalyxin concentration, renal expression of nephrin mRNA, and glomerular expression of desmin protein. Since glomerular TRPC6 plays detrimental roles in podocyte homeostasis, we examined the renal expression of TRPC6 in DS rats and found that salt diet upregulated the expression of TRPC6. Importantly, TRPC6 induction was significantly decreased in TDT-treated rats, compared with vehicle and hANP. Consistently, in primary-culture podocytes from DS rats, TDT inhibited ATP-induced calcium influx, similar to TRPC inhibitor SKF96365. Finally, TDT-mediated protection of podocytes was abolished by protein kinase G inhibitor KT5823. In conclusion, TDT treatment attenuated heart and kidney dysfunction, accompanied by podocyte protection through inhibition of TRPC6. Thus, long-acting NPs could be a new avenue for treatment of heart failure.

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