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The first choice for treatment of Graves'disease should be anti-thyroid
drugs or radioiodine? This question was answered by Arancibra
and co-workers (Santiago, Chile). It was noted that, due to lack
of compliance and frequent recurrences during ATD, there was an increasing
tendency for therapeutic use of radioiodine. A group of 118 patients were
treated initially with ATD (64 patients, 17-63y) or RAI (54 patients, 26-76y).
After six months of each type of treatment a T3 suppression
test (T3st) was performed and TRAb auto-antibodies
were assayed. In the event that the T3 was negative
(no suppression of thyroid RAI uptake) and TRAb was more than 16% the patient
was referred for surgery or, alternatively, to RAI. The ATD therapy was
maintained if T3 was positive and TRAb <16%. The
ATD group was followed up to 3 years. The RAI treated group received a
mean ± SEM of 5.4 ± 1.9 mCi and was followed up to 24 months.
About two-thirds (67.2%) of patients on ATD were euthyroid at the end of
the observation period. In contrast only 21.2% of RAI treated patients
were euthyroid, most individuals in this group had a diagnosis of hypothyroidism.
In conclusion the authors comment that ATD therapy of Graves'disease is
definitively better than RAI to conduct the patients to euthyroidism. The
major problem with RAI is the elevated relative proportion of hypothyroidism
at the end of less than 2 years of treatment.
Graves' hyperthyroid patients treated with antithyroid drugs were evaluated for spontaneous hypothyroidism and level of serum auto- antibodies by Moraes et al. (Sào Paulo, Brazil). This group studied retrospectively 139 hyperthyroid patients treated from 1976 to 1995 with propylthiouracil (PTU) or methimazole (MMI) without any periods of recurrence. Thirteen patients with a median age of 41 years (range 24-48 years) developed spontaneous hypothyroidism. The diagnosis was made by clinical and biochemical characteristics; high concentration of TSH (above 10 µU/mL in the RIA or above 6 µU/mL in the 3rd generation assay) and T4 concentration below the lower limit (normal 4 µg/mL). The prevalence of hypothyroidism was 9.4% (13/139 patients) and the incidence was 2.1% per year (12/563.6 patients/year of observation). The development of hypothyroidism occurred after 4 to 144 months (median of 48 months) after withdrawing ATD. The period of ATD treatment was from 11 to 45 months (median of 15.5 months). Two cases were treated with MMI (10 to 20 mg/day), five patients received MMI (20 to 60 mg/day) combined with LT3 (75 µg/day). Two other patients were treated with PTU (100 to 150 mg/day) and four patients received PTU (600 to 800 mg/day) combined with LT3 (75 µg/day). Also a significant (chi-square = 4.793, p <0.029) increase of anti-TPO titers was observed in 69.2% (9/13) of patients compared with 34% (43/126) of patients who remained euthyroid. In conclusion, the prevalence of spontaneous hypothyroidism in patients with GD treated with ATD does not depend on the drug used, the dose or the combination with thyroid hormone administration. The correlation of spontaneous hypothyroidism with anti-TPO titers might suggest an immunological effect of the thyroid autoantibodies on thyroid destruction. The combined treatment of Graves' disease with methimazole and LT4 was analyzed by Mano and co-authors (Sào Paulo, Brazil). They studied 38 thyrotoxic GD patients treated with decreasing dose of MMI (40 to 10 mg daily) combined with L-T4 (100 µg daily). The L- T4 was maintained during six months after MMI withdrawal. After cessation of therapy, 25 patients (65.8%) remained euthyroid for 26 ± 14.3 (10-72 months) of follow-up and 13 patients (34.2%) relapsed. No significant differences in the mean age (mean ± SD: 37.5 ± 12 vs. 41.2 ± 13.1 yr.), goiter size (41 ± 12.7 vs. 43 ± 18 g), period of treatment (25.6 ± 8.9 vs. 26.6 ± 6.2 months), serum T3 (390 ± 130 vs. 456 ± 193 ng/dL) and serum T4 levels (19.8 ± 5.7 vs. 19.6 ± 4.9 µg/dL) between the two groups were noted. The TSH receptor antibody (TRAb) values decreased in the remission group from 30 ± 21 to 9 ± 6 U/L (p <0.001). On the contrary, no significant change was observed (23 ± 22 vs. 13 ± 9 U/L) in the relapsed group. The serum TSH concentration in the relapsed group did not show differences before (1.11 ± 0.15 µU/mL), during (1.14 ± 1.61 µU/mL) combined therapy or on L-T4 therapy alone (0.27 ± 0.44 µU/mL. However, in the remission patients an increase in TSH levels was noted during combined therapy (1.15 ± 1.27 µU/mL) compared with values, before therapy (0.04 ± 0.11 µU/mL; p <0.001) and on L-T4 therapy (0.51 ± 0.63 µU/mL; p <0.03). During combined therapy the serum TSH values were higher in remission than in relapsed patients. In 42% of patients (8 in each group) L- T4 addition provoked signs and symptoms of thyrotoxicosis. In conclusion these results contrast with Hashizume et al. (NEJM, 1993) data and indicate a lack of influence of TSH suppression in the outcome of GD therapy and are in accordance with Werner et al. (Thyroid, 1991) and Tamai et al. (JCEM, 1995). The outcome of 120 patients with thyrotoxicosis with Graves' disease treated with radioiodine was evaluated by Di Ninno and co-workers (from Sào Paulo, Brazil). They have followed 120 patients (97 women and 23 men) during 10 years after treatment. The primary goal of the therapy is to render the patient euthyroid, but due to difficulties to obtain the optimal radioiodine dose the hypothyroid state after treatment was accepted as a reasonable outcome. The dosage of radioiodine was calculated as a function of the RAI uptake and the size of the gland. The choice of microcuries per gram of thyroid tissue was empirical and larger doses were applied in patients with a relatively low uptake, large goiters, and severe thyrotoxicosis. The mean dose of radioiodine in this series was 9.2 mCi. Six months after the treatment 27 patients (22.5%) were euthyroid, 50 patients (41.6%) were hypothyroid using thyroxine (T4) and 43 patients (35.9%) were still hyperthyroid using ATD. One year after the first dose, 84.1% of patients were euthyroid or hypothyroid using T4 and 15.9% of patients were still hyperthyroid and on ATD; 2 years after the first dose 90.7% of patients were euthyroid or hypothyroid on T4; 3 years after the first dose 92.4% of patients were euthyroid or hypothyroid using T4; 4 years after the first dose 94.5% of patients were euthyroid or hypothyroid on T4. In 34 patients a second or third dose was necessary to achieve euthyroidism or hypothyroidism. Besides the expected hypothyroidism, no other complications of therapy were seen. The results indicate that therapy with radioactive iodine is effective in terms of the control of thyrotoxicosis in patients with Graves' disease. Thyrotoxic periodic paralysis was reported by Silva and collaborators (Sào Paulo, Brazil). Eight patients with the diagnosis of thyrotoxic periodic paralysis were seen between 1981 and 1996. All were men with a mean age of 22.5 years (range 19 to 26 years), without a familial history of periodic paralysis; 4 were white and 4 mulatto. They had one or more episodes of flaccid paralysis of the legs at night, especially in the period immediately before awakening, with a mean duration of 2 to 4 hours and with complete recovery afterwards; 3 patients also had involvement of the arms and one had respiratory symptoms. Two patients had the onset of paralytic crisis after the ingestion of a meal rich in carbohydrates and 2 after prolonged physical exertion. The neurological examination was very uniform in all patients, with leg paralysis and areflexia during the crisis. Seven patients showed low serum potassium during the crisis, but one had normal values at all times. Five of the patients were diagnosed only after the third crisis. All presented clinical features of Graves'disease, with variable degrees of thyrotoxicosis, goiter and ophthalmopathy, always associated with elevated serum concentrations of thyroid hormones. Five patients diagnosed more recently showed elevated titers of anti-thyroid antibodies. In some patients a muscle biopsy specimen showed vacuolar myopathy; electromyography was unremarkable in the few cases analyzed. One patient developed paralysis of muscles that control respiration, causing respiratory insufficiency, metabolic acidoses, dehydration, cardiac insufficiency and sepsis which reverted after some days in the intensive care unit. Another patient developed polyuria, polydypsia, weight loss (30 kg in 2 months) and diabetic ketoacidoses. Antithyroid treatment with methimazol or propylthiouracyl improved the symptoms of thyrotoxicosis and in all patients paralysis disappeared; the patient with diabetes was treated with radioactive iodine. This study shows that thyrotoxicosis is an important cause of secondary periodic paralysis in Brazil, even in patients without Asiatic background, and that a late diagnosis can produce severe complications. Craniosynostosis as a complication of fetal hyperthyroidism was communicated by Arancibia and collaborators (Santiago, Chile). They present the case of a pregnant young female (30y old), prima gravida, with Graves' disease treated previously (3 months) with radioiodine. At 35th week of gestation fetal tachycardia, growth retardation and oligoamnion was noted. The maternal TRAb was elevated (58.8%). The mother was delivered by cesarean section: a boy weighing 2,410 g, 45 cm, small for gestational age, with a cranial circumference of 32.5 cm. The Apgar score was 8.9 at 5 min. Cord blood yielded the following thyroid function tests: T4 20 µg/dL, TRAb 5.8% and TSH <0.03 µU/mL. At the 5th day exophthalmos, hyperactivity, tachycardia and goiter was noted. PTU treatment was instituted until euthyroidism (at 8 weeks of age). Craniosynostosis was present on the skull X-rays and was attributed to the hyperthyroid state. |
