(6.02) Old Friend Revisited: Phenobarbital to the Rescue

Before the advent of thionamides, iodine and phenobarbital were used preoperatively to control thyrotoxic symptoms. Phenobarbital was shown to decrease serum thyroxine concentration by enhancing hepatic metabolism, which led to an increased biliary excretion. Major site for deiodination of thyroid hormone was the liver, where it was conjugated with glucuronic acid and then excreted in bile. Phenobarbital accelerated the hepatic thyroxine metabolism by enzyme induction of glucuronyl transferase and hepatic bilirubin binding Y-protein which led to an increased clearance of FT4.

Case(s) Description :

46 year-old women initially presented to our clinic for weight loss, palpitations and heat intolerance. Her thyroid function tests (TFTs) showed TSH < 0.05 uIU/mL, free T4 (FT4) 6.45 ng/dL, free T3 (FT3) 22.8 pg/mL and TRAb of 10.44 IU/L. She was started on methimazole 30 mg daily and atenolol 25 mg daily. On follow-up visit 1 month later, the patient was clinically improved and her TFTs revealed TSH < 0.05 uIU/mL, FT4 3.85 ng/dL, FT3 12.30 pg/mL. However, she developed a diffuse pruritic rash attributed to methimazole use. Patient's regimen was switched to propylthiouracil (PTU) 50 mg TID and later raised to 100 mg TID for persistent biochemical hyperthyroidism on follow up visit. PTU was held prior to thyroid uptake scan, which showed an elevated 24-hour thyroid uptake of 48%. Patient was given 24.8 mCi of I-131 and PTU 100 mg BID was restarted 5 days later for persistent thyrotoxic symptoms. One month post-radioactive iodine (RAI) treatment, the patient demonstrated an urticarial rash over her entire body, this time related to PTU use. She was still clinically and biochemically hyperthyroid (TSH < 0.05 uIU/mL, FT4 4.92 ng/dL, FT3 18.30 pg/mL) accompanied by severe anxiety symptoms. We initiated the patient on phenobarbital 30 mg BID which alleviated her symptoms without excessive fatigue. Four weeks later, the patient became biochemically hypothyroid with TSH 15.30, FT4 0.81. Atenolol and phenobarbital were subsequently discontinued, and the patient was started on levothyroxine for post-ablative hypothyroidism.

Discussion :

Our patient unfortunately developed an allergic reaction to both methimazole and PTU. Only limited literature is available on alternative therapy. Phenobarbital use was curtailed in the 1970’s with the advent of beta blockade. However, phenobarbital’s use was restricted in any case by side effects and prolonged action. For patients with allergic reaction to thionamides, phenobarbital could be used an adjunct to beta blockade for pending RAI therapy, immediate post-treatment radiation-induced thyroiditis, or temporary control of hyperthyroidism until full action of radioactive iodine takes place.