ABSTRACT
Cervical radiation therapy is often applied to patients with head and neck cancers because radiation has a high sensitivity to these cancers and permits the preservation of functions and physical form. However, it has been shown that various complications can result from radiation therapy. We have encountered some patients who showed hypercholesterolemia resulting from cervical radiation. Therefore, we have paid close attention to the relationship between hypercholesterolemia after cervical radiation and hypothyroidism. Thyroid hormone tests in these patients with hypercholesterolemia after cervical radiation showed high thyroid stimulating hormone (TSH) and low free thyroxine (fT4), indicating the presence of hypothyroidism. After administration of levothyroxine Na, their fT4 levels increased and both TSH levels and serum total cholesterol levels decreased. In conclusion, in patients who have received cervical radiation, we recommend monitoring serum total cholesterol periodically to detect hypothyroidism easily before the appearance of its symptoms.
Subject(s)
Cholesterol/blood , Hypothyroidism/diagnosis , Hypothyroidism/etiology , Radiotherapy/adverse effects , Aged , Biomarkers/blood , Female , Head and Neck Neoplasms/radiotherapy , Humans , Hypercholesterolemia/drug therapy , Hypercholesterolemia/etiology , Hypothyroidism/drug therapy , Male , Middle Aged , Monitoring, Physiologic , Thyroxine/therapeutic use , Treatment OutcomeABSTRACT
PURPOSE: The interaction between amiodarone and digoxin has been known to increase serum concentrations of digoxin in humans and rats. In this study, we assessed the molecular mechanism(s) of that drug interaction, focusing on digoxin transport mediated by P-glycoprotein (Pgp) and by rat liver organic anion transporter (oatp2). METHODS: Digoxin transport by Pgp and oatp2 was assessed using Pgp-overexpressing transfectant LLC-GA5-COL150 monolayers and oatp2-expressing Xenopus oocytes, respectively. The digoxin uptake into the isolated rat hepatocytes was also examined. RESULTS: Amiodarone (10 microM) inhibited slightly the transcellular transport of digoxin in LLC-GA5-COL150 monolayers, whereas itraconazole (10 microM), a potent Pgp inhibitor, markedly blocked the transport. The digoxin uptake by the isolated rat hepatocytes and by the oatp2-expressing Xenopus oocytes was decreased markedly in the presence of amiodarone but not in the presence of itraconazole. In addition, amiodarone inhibited the oatp2-mediated digoxin uptake in a competitive manner with an apparent inhibition constant value of 1.8 microM. CONCLUSION: These findings suggest that rat oatp2 rather than Pgp may be one of the interaction sites for digoxin and amiodarone in the liver.