Doses Of Propylthiouracil Research Articles

Effects of Propylthiouracil and Methimazole on Fetal Thyroid Status in Mothers With Graves' Hyperthyroidism

Momotani, Naoko; Yoshimura Noh, Jaeduk; Ishikawa, Naofumi; Ito, Kunihiko Author Information

Effects of a soft diet and hypothyroidism on the oxidative capacity of the masseter muscle fibers of the young Japanese field vole Microtus montebelli.

Effects of a soft diet (reduction in mastication activity: an exogenous factor) and hypothyroidism (endogenous factors) on the oxidative capacity of the masseter muscles in the young Japanese field vole Microtus montebelli, consisting only of fast-twitch oxidative (FO) fibers in the adult vole, was investigated histochemically and electron microscopically. Oxidative enzyme activity and mitochondrial development in the muscle fibers were not affected by a soft diet, while they were suppressed by doses of propylthiouracil (PTU) (hypothyroidism). Thus, it was suggested that acquisition of the sustained contraction ability in the masseter muscles of the young vole is induced by the endogenous factors rather than the exogenous factor.

MANAGEMENT OF THYROTOXICOSIS IN PREGNANCY

SUMMARYBetween April 1985 and June 1995, 20 patients being treated for thyrotoxicosis became pregnant. These patients are reviewed. Control of thyrotoxicosis early in pregnancy using minimal doses of propylthiouracil or carbimazole, followed by subtotal thyroidectomy in the middle trimester, is safe for both mother and fetus.

Transient hypothyroidism reinitiates egg laying in turkey breeder hens: termination of photorefractoriness by propylthiouracil

A study was conducted to determine the effects of transient hypothyroidism induced by propylthiouracil (PTU) on termination of photorefractoriness and reinitiation of lay in turkey breeder hens. The PTU was given for 6- or 8-wk periods via the feed and at various doses to yearling hens that had been continuously exposed to long photoperiods [16 h light (L):8 h dark (D)] for at least 25 wk. There was a dose-dependent cessation of lay as well as deletion of thyroxine (T4) and triiodothyronine (T3) during the treatment period. Hens receiving 0.1% PTU or more had little or no circulating thyroid hormones after 2 wk of treatment. Furthermore, resumption of a normal rate and duration of egg laying occurred following withdrawal of the PTU, without any changes in photoperiod. However, this effect only occurred in those hens that had received PTU doses of 0.1% or more and only when the treatment had been given for greater than 6 wk. The resumption of normal levels of egg laying occurred in the absence of a typical preceding molt. Body weights, livability, and fertility and hatchability of eggs from these hens were similar to those of controls. Clearly, turkey hens can be effectively recycled by pharmacological manipulation of the thyroid gland and the results are supportive of thyroid hormone(s) involvement in maintaining photorefractoriness in turkey hens.

Methimazole and propylthiouracil equally cross the perfused human term placental lobule.

Propylthiouracil (PTU) is widely believed to cross the placenta less freely than methimazole (MMI) and is therefore regarded as the preferred drug for treatment of hyperthyroidism in pregnancy. Clinical studies comparing the two drugs show, however, no differences in maternal or fetal thyroid function. We investigated transfer from the maternal to the fetal circuit in the isolated perfused term human placental lobule of low and high doses of PTU (4 micrograms/mL and 40 micrograms/mL) and MMI (1.5 micrograms/mL and 15 micrograms/mL) in protein-free perfusate and low doses of both drugs with addition of 40 g/L of bovine albumin. Both drugs readily crossed the placenta, reaching equilibrium in all experiments in about 2 h. Drug concentrations in the two circuits fitted a two compartmental model. Transfer kinetics for the two drugs were similar, nonsaturable, and unaffected by addition of albumin. Clearances (mL.min-1.g-1, means +/- SD) of PTU from maternal to fetal circuits were: 0.229 +/- 0.110, 0.216 +/- 0.065, and 0.170 +/- 0.032; and for transfer of MMI: 0.165 +/- 0.025, 0.232 +/- 0.153, and 0.174 +/- 0.009 (for low doses without, low doses with, and high doses without albumin, respectively). Clearances of PTU from fetal to maternal circuits were: 0.147 +/- 0.072, 0.109 +/- 0.014, and 0.116 +/- 0.028; and for transfer of MMI: 0.095 +/- 0.029, 0.122 +/- 0.088, and 0.12 +/- 0.005 (in the same experiments). There was no significant difference between drugs or drug doses and no effect of addition of albumin. We conclude that PTU and MMI have similar placental transfer kinetics.

Effects of Developmental Hypothyroidism on Auditory and Motor Function in the Rat

Deafness is a common result of severe hypothyroidism during development in humans and laboratory animals; however, little is known regarding the sensitivity of the auditory system to more moderate changes in thyroid hormone homeostasis. The current investigation compared the relative sensitivity of auditory function, motor function, and growth to the effects of moderate to severe perinatal hypothyroidism in the rat. Rats received propylthiouracil (PTU) in drinking water at concentrations of 0, 1, 5, and 25 ppm from Gestation Day 18 until postnatal day (PND) 21, and the effects on their offspring were evaluated. At 1 ppm, PTU did not affect any of the measured endpoints. Serum thyroxin concentrations were sharply reduced in the 5 and 25 ppm PTU groups at all ages sampled (PND 1, 7, 14, and 21). Marked reductions in serum triiodothyronine (T3) concentrations were also detected for all ages ≥7 at 25 ppm PTU, whereas no effects of 5 ppm PTU on serum T3 were apparent until PND 21. Compared to the controls, pups exposed to the highest dose of PTU demonstrated a delay in eye opening, reduced body weights, decreased and/or delayed preweaning motor activity, and persistent, postweaning hyperactivity. Only slight and transient effects on eye opening and ontogeny of motor activity were seen at the intermediate dose of PTU (5 ppm). Reflex modification audiometry revealed that, compared to controls, adult offspring from the 5 and 25 ppm treatment groups showed dose-dependent auditory threshold deficits (35 to >50 dB) at all frequencies tested (1, 4, 16, 32, and 40 kHz). Such dose-dependent effects indicate that the developing auditory system may be sensitive to mild hypothyroidism, suggesting the possible need for routine audiometric screening for infants and children at risk for iodine deficiency, myxedema, and/or exposure to thyrotoxic environmental agents.

Effect of propylthiouracil on the ethanol-induced increase in liver oxygen consumption in awake rats

It has been postulated that the beneficial effects of the antithyroid drug propylthiouracil in the treatment of alcoholic liver disease depend primarily on the action of propylthiouracil in suppressing the increase in hepatic oxygen consumption induced by ethanol. The evidence for this effect of propylthiouracil is derived from studies in which liver oxygen consumption has been determined in in vitro preparations. In our study the effects of ethanol and propylthiouracil on liver oxygen consumption were assessed in vivo in an unrestrained and unanesthetized rat model, where liver blood flow and hepatic vein and portal vein oxygen content can be measured. Data show that the liver oxygen consumption increased in rats treated with ethanol-containing liquid diets for 4 to 6 wk, both on withdrawal of alcohol (30%, p < 0.01), and after readministration of ethanol (50%, p < 0.01). Single-dose ethanol administration increased portal tributary blood flow without affecting hepatic arterial blood flow in both controls and rats withdrawn from long-term ethanol treatment. Long-term ethanol administration per se had no effect on portal tributary blood flow; however, hepatic arterial blood flow was increased by 38% (p < 0.01). Treatment with propylthiouracil for 5 days resulted in complete suppression of the increase in liver oxygen consumption induced by long-term ethanol administration. Propyithiouracil treatment also attenuated the increase in portal tributary blood flow after the administration of a single dose of ethanol. These determinations were made 24 hr after the last dose of propylthiouracil. In conclusion, use of a new in vivo model with unrestrained and unanesthetized rats has confirmed that long-term administration of ethanol increases liver oxygen consumption. For the first time, it has been shown in vivo that propylthiouracil abolishes the ethanol-induced increase in liver oxygen consumption that follows long-term ethanol administration. (HEPATOLOGY 1993;18:415–421).

Effect of propylthiouracil on the ethanol-induced increase in liver oxygen consumption in awake rats

It has been postulated that the beneficial effects of the antithyroid drug propylthiouracil in the treatment of alcoholic liver disease depend primarily on the action of propylthiouracil in suppressing the increase in hepatic oxygen consumption induced by ethanol. The evidence for this effect of propylthiouracil is derived from studies in which liver oxygen consumption has been determined in in vitro preparations. In our study the effects of ethanol and propylthiouracil on liver oxygen consumption were assessed in vivo in an unrestrained and unanesthetized rat model, where liver blood flow and hepatic vein and portal vein oxygen content can be measured. Data show that the liver oxygen consumption increased in rats treated with ethanol-containing liquid diets for 4 to 6 wk, both on withdrawal of alcohol (30%, p < 0.01), and after readministration of ethanol (50%, p < 0.01). Single-dose ethanol administration increased portal tributary blood flow without affecting hepatic arterial blood flow in both controls and rats withdrawn from long-term ethanol treatment. Long-term ethanol administration per se had no effect on portal tributary blood flow; however, hepatic arterial blood flow was increased by 38% (p < 0.01). Treatment with propylthiouracil for 5 days resulted in complete suppression of the increase in liver oxygen consumption induced by long-term ethanol administration. Propylthiouracil treatment also attenuated the increase in portal tributary blood flow after the administration of a single dose of ethanol. These determinations were made 24 hr after the last dose of propylthiouracil.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of hypothyroidism with treatment of an anti-thyroid drug, propylthiouracil on immune responses in chickens

The effect of a wide range of doses of propylthiouracil (PTU, 0.01–5%) on the immune responses of young male chickens was examined. One-day-old chickens were rendered hypothyroid by PTU supplemented in the feed for 4 weeks. At all doses PTU treatment caused a significant dose-related reduction in body weight (except at 0.01%) and in relative lymphoid organ weights. Skin response to phytohemagglutinin (PHA) was significantly greater in the chickens treated with low doses of PTU (0.01–0.1%) and significantly less in the chickens treated with high doses of PTU (1.5–5%) than that in control chickens. Number of splenic plaque forming cells (PFC) to sheep red blood cells (SRBC) was significantly increased in the chickens treated with low doses of PTU. Concentrations of serum 3,3′,5-triiodothyronine (T 3) and thyroxin (T 4) were significantly lower in the chickens treated with all doses of PTU. Addition of T 3 to the feed supplemented with 0.01% PTU replaced the serum T 3 concentration and reduced the skin response to PHA and the number of the splenic PFC. These data confirm our previous observations that a low dose of PTU enhances and a high dose suppresses the immune responses of young male chickens.

Increased testis growth and sperm production in adult rats following transient neonatal goitrogen treatment: optimization of the propylthiouracil dose and effects of methimazole

Treatment of male rat pups with the reversible goitrogen 6-propyl-2-thiouracil (PTU), administered by adding 0.1% PTU to the mother's drinking water from birth to day 25, increases their testis size and daily sperm production (DSP) at 160 days of age by up to 80% and 140%, respectively. The purpose of this study was to examine the effectiveness of various concentrations of PTU and determine the PTU dose that would maximize testis growth while minimizing side effects such as decreased maternal water consumption and decreased pup growth. Whether this effect was specific to PTU was determined by evaluating the effects of another commonly used goitrogen, methimazole (MMI), in increasing adult testis size and sperm production. Dams were given PTU (0.1-0.0004% w/v) or 0.025% MMI (w/v) in their water from birth to day 25 post partum, then given no further treatment. Thyroxine concentrations were measured in all groups of pups at 25, 35 and 45 days, and testis weight and DSP were determined at 90 days of age. At 25 days of age, thyroxine concentrations were maximally decreased by PTU treatments of 0.0015% or greater; less severe decreases were produced by 0.0004% PTU or 0.025% MMI. Thyroxine concentrations increased in all treated groups at day 35 compared with day 25, and returned to normal by day 45. At 90 days of age, testis weight was increased by about 40% in rats whose mothers had been treated with doses of 0.006% PTU or greater, whereas testis weights in groups given 0.0015 and 0.0004% PTU or 0.025% MMI were increased 31, 15 and 18%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Relationships between the thyroid and somatotropic axes in steers I: Effects of propylthiouracil-induced hypothyroidism on growth hormone, thyroid stimulating hormone and insulin-like growth factor I

The effects of propylthiouracil (PTU)-induced thyroid hormone imbalance on GH, TSH and IGF-I status in cattle were examined. In the first study, four crossbred steers (avg wt 350 kg) were fed a diet dressed with PTU (0, 1, 2 or 4 mg/kg/d BW) in a Latin square design with four 35-d periods. On day 29 in each period, steers were challenged with an intrajugular bolus of thyrotropin releasing hormone (TRH, 1.0 μg/kg). Blood samples were obtained to assess the change in plasma GH and TSH as affected by PTU. Plasma IGF-I was measured from blood samples obtained before and after (every 6 hr for 24 hr) intramuscular injection of bovine GH (0.1 mg/kg, day 31). Doses of 1 and 2 mg/kg PTU increased plasma T 4 (P<.01). At 4 mg/kg, PTU depressed T 4 concentrations to 30% of control (P<.01). Plasma T 3 linearly decreased with increasing doses of PTU (P<.01). Plasma TSH increased when PTU was fed at 4 mg/kg (P<.05) while the TSH response to TRH declined with increasing PTU (P<.02). Neither basal nor TRH-stimulated plasma concentration of GH was affected by PTU; the IGF-I response to GH tended to increase at the 1 and 2 mg/kg PTU (P<.01). In a second study 24 crossbred steers were fed PTU (1.5 mg/kg) for 119 d in a 2 × 2 factorial design with implantation of the steroid growth effector, Synovex-S (200 mg progesterone + 20 mg estradiol), as the other main effect. Basal plasma GH and IGF-I were not affected by PTU treatment. Synovex increased plasma concentration (P<.01) of IGF-I without an effect on plasma GH. The data suggest that mild changes in thyroid status associated with PTU affects regulation of T 3, T 4 and TSH more than GH or IGF-I in steers.

Modified Model of Hypothyroidism During the Preweanling Period

Propylthiouracil (PTU) has received widespread use as a means of inducing hypothyroidism in experimental animals. Doses of PTU used in these studies are high (doses of 200 mg/kg are frequently cited) and no reference is made as to the degree of hypothyroidism attained. Experiments were conducted to determine the minimum dose of PTU required to maximally suppress plasma thyroid hormone levels in the developing rat. It was found that PTU doses of 8.8 mg/kg body weight provide maximal suppression of plasma thyroid hormone levels. This dose of PTU was also shown to inhibit Purkinje cell dendritic maturation in the cerebellum, a hallmark of congenital hypothyroidism. The brain and body weight deficits seen with a PTU dose of 8.8 mg/kg were eliminated using physiological replacement doses of L-thyroxine. These results indicate that doses of PTU used in typical hypothyroid models are far in excess of what is required to induce hypothyroidism in the developing rat. Consequently, the lower doses of PTU identified in this study can be utilized to achieve maximal suppression of thyroid hormone levels, reducing the possibility of potential nonspecific effects of higher doses.

Diagnosis and management of Graves' disease in pregnancy.

Most of the hyperthyroidism seen in association with pregnancy is Graves' disease. The best treatment is prevention. For most patients there is an opportunity to treat the hyperthyroidism decisively with radioiodine or surgery before the patient becomes pregnant. Pregnancy complicated by hyperthyroidism is often a consequence of the conscious decision to treat hyperthyroidism in women in the childbearing years with antithyroid drugs. Propylthiouracil (PTU) is the preferred treatment for hyperthyroidism in pregnancy, but it does cross the placenta and can induce fetal goiter, with mental and physical retardation. Hence, the lowest possible PTU dose should be used. One should aim for high normal or slightly elevated thyroid function in the mother. Patients should be followed at 3-week intervals if progress is satisfactory, more often otherwise. Thyroid function should be monitored by the free T4 assay. PTU dosage should be reduced progressively in anticipation of the customary steady amelioration in the hyperthyroidism that occurs in later stages of pregnancy. Since pregnant hyperthyroid patients are sometimes irresponsible and continue PTU without supervision, PTU prescriptions should be limited to the amount required for the time until the next scheduled visit. For about one third of patients, PTU can be discontinued in the second half of the pregnancy. After the pregnancy is terminated, persistent or recurrent hyperthyroidism should be treated definitively to prevent another episode of pregnancy complicated by hyperthyroidism.

Recovery from Foetal Hypothyroidism

SUMMARY We assessed the post-natal thyroid function in eight infants of mothers with Graves' disease whose thyroid function at birth was suppressed by maternal ingestion of propylthiouracil during pregnancy. These mothers continued taking propylthiouracil after delivery and breast-fed exclusively (two mothers supplemented their breast milk with a small amount of baby food). The cord free T4 level was slightly but uniformly below the normal range in all eight infants, and the cord TSH level was above the normal in seven infants. The dose of propylthiouracil after delivery ranged from 50 to 300 mg daily, which was equal to, or higher than, that before delivery. All these abnormal values normalized in the infant after birth. Serum samples, from seven of the eight mothers, taken at delivery were examined for TSH receptor antibodies; all were positive. The antibody titre, however, was too low, and/or free T4 and TSH levels were examined too long after delivery, for the antibodies to be the cause of the restoration of the infants’thyroid function. These results assure the safety of breast-feeding for the infants of mothers with Graves' disease taking propylthiouracil.

Recovery from foetal hypothyroidism: evidence for the safety of breast-feeding while taking propylthiouracil.

We assessed the post-natal thyroid function in eight infants of mothers with Graves' disease whose thyroid function at birth was suppressed by maternal ingestion of propylthiouracil during pregnancy. These mothers continued taking propylthiouracil after delivery and breast-fed exclusively (two mothers supplemented their breast milk with a small amount of baby food). The cord free T4 level was slightly but uniformly below the normal range in all eight infants, and the cord TSH level was above the normal in seven infants. The dose of propylthiouracil after delivery ranged from 50 to 300 mg daily, which was equal to, or higher than, that before delivery. All these abnormal values normalized in the infant after birth. Serum samples, from seven of the eight mothers, taken at delivery were examined for TSH receptor antibodies; all were positive. The antibody titre, however, was too low, and/or free T4 and TSH levels were examined too long after delivery, for the antibodies to be the cause of the restoration of the infants' thyroid function. These results assure the safety of breast-feeding for the infants of mothers with Graves' disease taking propylthiouracil.

Adverse effects related to thionamide drugs and their dose regimen

The authors studied 389 Graves' hyperthyroid patients receiving either high propylthiouracil (PTU) or methimazole (MMI) daily doses or low doses to evaluate whether adverse effects were related to the thionamide drugs or its daily dose regimen. Group 1 patients (n = 286) received high PTU (728 +/- 216 mg/day, n = 92) or MMI (60 +/- 19 mg/day, n = 94) doses, and group 2 patients (n = 103) were treated with low PTU (255 +/- 85 mg/day, n = 39) or MMI (23 +/- 10 mg/day, n = 64) doses. Major adverse effects were observed in 11 (2.8%) patients. Of these, four (1.0%) had agranulocytosis, two (0.5%) were granulocytopenic and five (1.3%) had hepatotoxicity. Agranulocytosis occurred in two patients from each group, 0.7% and 1.9%, respectively from group 1 and group 2. There was no significant difference between the groups or the types of thionamide. There also was no correlation with the patients' age. All of the patients were hyperthyroid, and its onset occurred in the first to third month of treatment. Full recovery was achieved in all cases after drug withdrawal. Four of 5 patients with hepatotoxicity were treated with high PTU doses, and one patient received low MMI doses (p less than .05). All patients were euthyroid. Arthralgias, skin rash and gastric intolerance, the minor adverse effects of thionamides studied, were observed in 52 (13.4%) of the patients. Although no significant differences were found, most of the patients experiencing side effects were from group 1 an received MMI therapy. These adverse effects did not demand drug withdrawal.(ABSTRACT TRUNCATED AT 250 WORDS)

Regulation of liver angiotensinogen mRNA by glucocorticoids and thyroxine

This study examines the immediate and longer-term changes in angiotensinogen mRNA and in plasma angiotensinogen which follow the withdrawal and replacement of glucocorticoids or thyroxine. RNA from rat liver was analysed by Northern blot and dot-blot hybridization with a 40-mer oligodeoxynucleotide probe specific for angiotensinogen mRNA. Adrenalectomy decreased plasma angiotensinogen and angiotensinogen mRNA to 55 and 50% of control values respectively over a period of 16 days. Similar decreases were obtained after propylthiouracil (1 mg/kg for 16 days) treatment, except when injected simultaneously with T 3 (3 μg/kg/day). Over the same period plasma renin activity increased in adrenalectomized rats from 4.1 ± 0.8 to 7.0 ± 1.5 pmol angiotensin I (AI)/ml/h, and decreased in propylthiouracil-treated rats from 3.8 ± 0.4 to 1.6 ± 0.4 pmol AI/ml/h. Approximate half-times of 2–3 days were calculated for both plasma angiotensinogen and angiotensinogen mRNA post-adrenalectomy or after propylthiouracil treatment. Dexamethasone (400 μg/kg i.m.) given to intact rats rapidly increased angiotensinogen mRNA to a maximum of 250% of control by 8 h and with a half-maximal response of 2.8 h. Plasma angiotensinogen responded similarly, apart from an initial delay of 2 h. Treatment with different doses of propylthiouracil and dexamethasone showed that responses were dose-related. We conclude that changes in plasma angiotensinogen and angiotensinogen mRNA are closely correlated, and that under various physiological circumstances angiotensinogen mRNA has a rapid rate of accumulation but a slow rate of decay.

Effects of propylthiouracil (PTU) on the immunological status of the chicken

Effects of propylthiouracil (PTU) using different treatment schedules on immune functions in young male chicken were studied. Antibody productions to sheep red blood cells (SRBC) and Brucella abortus (BA) were found to rise in the chicks treated with 0.1% and 1% PTU. Furthermore, the chicks treated with 1% PTU exhibited a significantly greater reaction to phytohemagglutinin (PHA) in skin test using the wing web than the control did. Treatment of 5% PTU, however, inhibited the antibody productions to SRBC and BA and the reaction for the skin test to PHA. Antibody titers to both antigens and serum IgG level were lower in the chicks after cessation of PTU treatment. The most conspicuous histology was the lymphatic depletion of the lymphoid organs in chicks treated with 5% PTU. The bursa of Fabricius, thymus and spleen were severely atrophied. The total WBC and the number of lymphocytes and monocytes were significantly reduced in the presence of 0.1% and 1% PTU at 8 weeks of age. Although, concentrations of serum thyroxin (T 4) and 3,5,3′-triiodothyronine (T 3) were significantly lower in the chicks treated with all doses of PTU, the cessation of the treatment was followed by an increase in the concentrations of serum T 4 and T 3 to levels not different from in the untreated control chicks. These data showed that PTU at 0.1% and 1% concentrations did not suppress immune responses in chickens unlike the case reported in mammals.

Cyclic Sinus Node Dysfunction in a Patient With Hyperthyroidism

In a 54-year-old woman with hyperthyroidism, episodic sinus node dysfunction (SND) recurred in a cyclic fashion. The SND occurred suddenly during normal sinus rhythm and progressed to marked sinus bradycardia; occasionally, sinus arrest developed with or without ventricular escape beats. A 1-mg dose of intravenous atropine sulfate suppressed the occurrence transiently. After a 200-mg dose of propylthiouracil and a 20-mg dose of prednisolone every six hours, the SND was completely abolished within 21 hours. It is probable that, together with a pathologic process induced by hyperthyroidism, the autonomic nervous system participated in our patient's episodic SND.

61 PROPYLTHIOURACIL AND METHIMAZOLE PHARMACOLOGY IN CHILDREN AND ADOLESCENTS WITH GRAVES DISEASE

Concentrations of propylthiouracil (PTU) and methimazole (MMI) in plasma and thyroid glands were measured. A single oral dose of the drugs (100 to 280 mg/m2 of PTU or 20 mg/m2 of MMI) induced a rapid increase of plasma levels reaching a peak within 1 hr for both PTU and MMI. Peak PTU values ranged from 7.2 to 18 μg/m1 with the administered dose. Its mean plasma half-life was 1.36 hrs, and its mean distribution volume was 326 ml/kg. Plasma levels of MMI showed a mean peak value of 1.03 μg/ml, a mean half-life of 4.56 hrs, and a mean distribution volume of 630 ml/kg. Intrathyroidal concentrations of PTU were measured in needle biopsy specimens and were 2.06 - 4.31 μg/g, 4.56 - 17.8 μg/g and 1.09 - 4.48 μg/g at 2, 12 and 24 hrs after 200 mg/m2 of MMI respectively. Intrathyroidal MMI was measured in surgically obtained specimens and was 1.1- 1.3 μg/g and 0.78 - 1.40 μg/g at 5 and 18 hrs after 10 - 20 mg/m2 of MMI respectively. These values far exceeded the plasma values at the respective times except for 2 hrs after PTU. Our results indicate: 1) elimination of PTU and MMI from the thyroid gland is much slower than from plasma, and 2) a single daily dose of PTU or MMI is adequate for the treatment of Graves disease.