xert their immunosuppressive effect by a direct inhibition of thyroid cell production of hormones has been reviewed by Volpe .
Long-Term Antithyroid Drug Therapy with Thiocarbamides
Propylthiouracil warning-Propylthiouracil and methimazole have for years been considered effectively interchangeable, and liver damage was considered a very rare problem. Recently a commission appointed by the FDA reevaluated this problem, and concluded that the rare but severe complications of liver failure needing transplantation, and death, were sufficient to contraindicate the use of PTU as the normal first-line drug (109.1). The Endocrine Society and other advisory groups have suggested that methimazole be used for treatment except in circumstances of inavailability of the drug, patient allergy, or pregnancy. Because of the association of scalp defects and probably a severe choanal syndrome with administration of methimazole during the first 12 weeks of pregnancy, current advice is to give PTU during the first trimester, and then switch to methimazole.
Selection of patients–
Many patients with Graves’ disease under age 40 – 45 are given a trial of therapy with one of the thiocarbamide drugs. Younger patients, and those with recent onset of disease, small goiters , and mild disease, are especially favorable candidates, since they tend to enter remission most frequently. It is generally found that one-fourth to one-third of these patients who satisfactorily complete a one year course have a long term or permanent remission. The remainder need repeated courses of drug therapy, must be maintained on the drug for years or indefinitely [111, 112], or must be given some other treatment. It appears that the percentage of patients responding has progressively fallen over the past years from about 50% to at present 25 – 30%[113, 114]. This change was thought to reflect an alteration in iodide in our diet , which increased from about 150 µg/day in 1955 to 300 – 600 µg/day. However other factors including greater precision in diagnosis and more complete data probably play major roles in establishing the response rate recognized at present. Many physicians do not consider antithyroid drug therapy to be the most efficacious means of treating thyrotoxic patients because of the high recurrence rate.
Patients are initially given 100 – 150 mg PTU (if used) every 8 hours or 10 – 15 mg methimazole (Tapazole) every 12 hours. The initial dosage is varied depending on the severity of the disease, size of the gland, and medical urgency. Antithyroid drugs must usually be given frequently and taken with regularity since the half-time in blood is brief — 1.65 hours or less for PTU . Frequent dosage is especially needed when instituting therapy in a severely ill patient. Methimazole has the advantage of a longer therapeutic half-life, and appears to produce fewer reactions when given in low dosage. Propylthiouracil is preferred in patients with very severe hyperthyroidism and in pregnancy[117, 118] In most thyrotoxic patients, the euthyroid state, as assessed by clinical parameters, and FTI, can be reached within 4 – 6 weeks. If the patient fails to respond, the dosage may be increased. Iodine-131 studies may be performed to determine whether a sufficiently large dose of medication is being employed , but these studies are rarely needed. In general, it is assumed that binding of the should be nearly completely blocked, but the 24-hour 131-Ithyroid uptake in the patient under therapy may range from O% to 40%. This iodide is partly unbound and is usually released rapidly from the gland by administration of 1 g potassium thiocyanate or 400 mg potassium 131-I perchlorate. If perchlorate or thiocyanate does not discharge the iodide, it is obvious that binding of iodide is occurring despite the thiocarbamide therapy. The quantity of drug administered may then be increased. In experimental animals, the thiocarbamides block synthesis of iodothyronines more readily than they block formation of MIT and DIT. This observation suggests that a complete block in organification of