RESUMO
BACKGROUND: Hyperparathyroidism is uncommon in adolescence and is more likely to persist after parathyroidectomy than in adults. Cinacalcet HCl is a new calcimimetic that has been used successfully for the treatment of primary and secondary hyperparathyroidism in adults, but its use in adolescents has not been reported. CASE: A 16 year-old male presented with hypercalcemia that had persisted for 1.5 years after parathyroidectomy for primary hyperparathyroidism. Parathyroid hormone (PTH) concentrations were nonsupressed despite a mean (SD) serum calcium concentration of 2.82 (0.06) mmol/L. Treatment with cinacalcet HCl was initiated and a pharmacodynamic profile was obtained for serum calcium, phosphorus, and PTH. Cinacalcet HCl normalized serum calcium. The changes in PTH were assay dependent. ISSUES: We use this case conference to review the evaluation of hypercalcemia in adolescents, examine the changes in relevant laboratory results during treatment with cinacalcet HCl, and discuss differences among assays for PTH. CONCLUSIONS: Interpretation of PTH results in patients treated with cinacalcet HCl requires consideration of the pharmacodynamic effects of the drug and the nature of the PTH assay.
Assuntos
Hipercalcemia/tratamento farmacológico , Hiperparatireoidismo Primário/cirurgia , Naftalenos/uso terapêutico , Adolescente , Cálcio/sangue , Cinacalcete , Diagnóstico Diferencial , Humanos , Hipercalcemia/etiologia , Masculino , Hormônio Paratireóideo/sangue , Paratireoidectomia/efeitos adversos , Fósforo/sangueRESUMO
Estrogen receptor alpha (ER alpha) degradation is regulated by ubiquitination, but the signaling pathways that modulate ER alpha turnover are unknown. We found that extracellular signal-regulated kinase 7 (ERK7) preferentially enhances the destruction of ER alpha but not the related androgen receptor. Loss of ERK7 was correlated with breast cancer progression, and all ER alpha-positive breast tumors had decreased ERK7 expression compared to that found in normal breast tissue. In human breast cells, a dominant-negative ERK7 mutant decreased the rate of endogenous ER alpha degradation >4-fold in the presence of hormone and potentiated estrogen responsiveness. ERK7 targets the ER alpha ligand-binding domain for destruction by enhancing its ubiquitination. Thus, ERK7 is a novel regulator of estrogen responsiveness through its control of ER alpha turnover.
