Enhanced expression of LHPP, also known as Phospholysine phosphohistidine inorganic pyrophosphate phosphatase, is closely associated with hyperthyroidism, while its decreased expression is related to neoplastic states. But, in current study, the mechanistic basis of the regulation of LHPP expression in the thyroid remains unclear.

    LHPP is expressed only in thyrocytes, but not in stromal endothelial cells, fibroblasts, and adipocytes within various lesions of the thyroid. In addition, LHPP is more prominently displayed in hyperfunctional state of the thyroid, e.g., Graves’ disease and autonomously functional thyroid nodule (AFTN) than others. Tumor cell types of follicular adenoma and papillary carcinoma show decreased expression of LHPP. Especially, papillary carcinoma undergoes both local invasion and lymphatic metastases. Thus, LHPP may not be linked to invasive and metastatic ability of the neoplastic cell type. This also suggests that the functions of the tumor cells may be different from those of normal thyrocytes in terms of thyroid hormone synthesis.

    This suggests that LHPP could be a new functional predictor in the thyroid. In addition, nuclear expression of LHPP in thyrocytes of Graves’ disease and AFTN is lost in culture. Thus, it seems likely that the determination of mechanisms of nuclear translocalization of LHPP opens way to address the regulatory mechanisms of hyperthyroidism.

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