For example, Ish-Shalom et al. [20] performed in vitro studies and found that the PTH receptor-coupled adenylyl cyclase system was normal in bone cells from patients with PHP1A, despite clinical evidence of impaired hormone-responsive adenylyl cyclase in other tissues, including the kidney; (2) PTH-resistance usually develops in the first few years of life in PHP1A patients, with hyperphosphatemia and elevated PTH generally preceding hypocalcemia. Here, PTH is linked to hyperphosphatemia.