Modalidades terapêuticas na doença de Basedow-Graves / Therapeutical approaches in Basedow-Graves disease

Neste artigo säo analisadas as três grandes modalidades terapêuticas do hipertireoidismo - o tratamento clínico, o radioiodo e a cirurgia -, discutindo-se detalhadamente cada uma delas, enfocando seus mecanismos de açäo, vantagens e desvantagens, principais indicaçöes e contra indicaçöes. A abordagem terapêutica também será analisada em grupos especiais como neonatos, crianças e adolescentes, gestantes e idosos

Sodium ipodate (oragrafin) in the preoperative preparation of Graves' hyperthyroidism.

Fourteen Graves' hyperthyroid patients who had been prepared for surgery with sodium ipodate (SI) 500 mg orally twice daily for 3 days were retrospectively studied. SI was administered in combination with propylthiouracil (10 cases) and beta blockers (all cases), which had been previously initiated. Free serum thyroxine (T4) and total triiodothyronine (T3) concentrations were measured before and after SI therapy on the morning of surgery. SI treatment significantly reduced total T3 concentration from 445.9 to 193.4 ng/dL (P < 0.0001) and free T4 concentration from 3.874 to 2.800 ng/dL (P = 0.0003). Preoperatively, only one patient had persistent tachycardia, and intraoperatively this same patient required beta blockers. Blood loss was unremarkable or reduced (average blood loss, 121 mL). On clinical examination glands were firm with normal or somewhat decreased vascularity. On histologic study all glands demonstrated changes consistent with treated Graves' disease. Preoperative treatment with SI appears to be a safe and efficacious method of preparing hyperthyroid patients for surgery.

Ipodate treatment of hyperthyroidism in cats.

OBJECTIVE: To evaluate the efficacy and safety of ipodate in the treatment of hyperthyroidism in cats. DESIGN: Prospective case series. ANIMALS: 12 cats with hyperthyroidism treated at The Animal Medical Center between November 1994 and March 1996. PROCEDURE: Each cat initially received 100 mg of ipodate/d, PO. The drug's effects on clinical signs, body weight, heart rate, and serum triiodothyronine (T3) and thyroxine concentrations were evaluated 2, 4, 6, 10, and 14 weeks after initiation of treatment. A CBC and serum biochemical analyses were performed at each evaluation to monitor potential adverse effects of the drug. Dosage of ipodate was increased to 150 mg/d and then to 200 mg/d at 2-week intervals if a good clinical response was not observed. RESULTS: 8 cats responded to treatment and 4 did not. Among cats that responded, mean body weight increased and mean heart rate and serum T3 concentration decreased during the study period. Among cats that did not respond, mean body weight decreased and mean heart rate and serum T3 concentration were not significantly changed. Serum thyroxine concentration remained high in all cats. Adverse clinical signs or hematologic abnormalities attributable to ipodate treatment were not reported in any of the cats. CLINICAL IMPLICATIONS: Ipodate may be a feasible alternative to methimazole for medical treatment of hyperthyroidism in cats, particularly those that cannot tolerate methimazole and are not candidates for surgery or radiotherapy. Cats with severe hyperthyroidism are less likely to respond to ipodate than are cats with mild or moderate disease, and cats in which serum T3 concentration does not return to the reference range are unlikely to have an adequate improvement in clinical signs.

[Treatment of neonatal hyperthyroidism with calcium iopodate]. / Traitement de l'hyperthyroïdie néonatale par l'iopodate de calcium.

BACKGROUND: Treatment of hyperthyroidism in those neonates born to mothers with Grave's disease is difficult. Calcium ipodate, an agent for oral cholecystography, inhibits extra-thyroid conversion of T3 to T4 and diminishes thyroid secretion. CASE REPORTS: Two neonates with clinical manifestations and biological findings of hyperthyroidism were given calcium ipodate orally, 400 mg every 3 days, from day 26 to 50 for the first patient and from day 9 to 18 for the second in association with a beta blocker. Clinical manifestations disappeared within 2 days and circulating levels of T3 and T4 were normalized within 2-5 days. CONCLUSIONS: This treatment was effective and well-tolerated in both patients and in three others previously reported; it should be confirmed in a larger number of patients and controlled by measuring levels of antibodies directed against thyrotropin-releasing hormone receptors in order to avoid relapse after cessation of treatment as seen in our second patient.

Ipodate therapy in patients with severe destruction-induced thyrotoxicosis.

We describe 4 patients with severe destruction-induced thyrotoxicosis who had a rapid clinical response to oral sodium ipodate (500 mg daily). The underlying thyroid disorders in the patients were postpartum thyroiditis, subacute thyroiditis, silent thyroiditis, and radiation-induced thyroiditis. Ipodate therapy was given for 6 to 10 weeks until restoration of thyroid function to normal. In all patients, an almost complete resolution of symptoms occurred by the third day of ipodate treatment. In the patient with radiation thyroiditis, a daily clinical score of thyrotoxicosis declined within 2 to 3 days. The score remained low as long as the patient was receiving ipodate, but 2 attempts to discontinue ipodate therapy while thyroxine levels were elevated resulted in a rise of the thyrotoxicosis clinical score. This suggests that ipodate therapy, by rapidly reducing triiodothyronine levels through inhibition of the 5' monodeiodination and blockage of the peripheral effects of thyroid hormone, controls severe thyrotoxicosis mediated by destruction and should be considered in this setting in conjunction with beta-adrenergic blockade.

Use of sodium ipodate in management of hyperthyroidism in subacute thyroiditis.

Five hyperthyroid patients (two men and three women) with typical features of subacute thyroiditis were treated with sodium ipodate (Oragrafin; 0.5 g, orally daily or every other day) for 15-60 days; the treatment was stopped when both serum T4 and T3 levels were normal. All patients studied demonstrated a prompt normalization of serum T3, improvement in clinical symptoms of hyperthyroidism, and/or weight gain. We observed no side-effects of treatment with sodium ipodate. Our data suggest that sodium ipodate is a safe and effective agent for management of hyperthyroidism in subacute thyroiditis.

Sodium ipodate and methimazole in the long-term treatment of hyperthyroid Graves' disease.

A prospective study was conducted to evaluate the effect of prolonged treatment of hyperthryoid Graves' disease with methimazole (MMI) for 12 months or Na ipodate for only 6.6 +/- 1.1 months, since the drug had to be discontinued because of persistent or recurrent hyperthyroidism during treatment. The eight patients who were treated with MMI alone for 12 months became euthyroid, and seven remained in remission for at least 6 months after MMI was discontinued. In contrast, only two of 10 patients treated with Na ipodate alone became euthyroid and remained so during therapy. No ipodate was discontinued in the eight patients who did not respond, and they were then treated with MMI. One patient had recurrent hyperthyrodism after NA ipodate was discontinued, and she was then treated with MMI. MMI was efficacious in treating these nine patients, and all patients were euthyroid by the third month of MMI administration. Five of these nine patients remained euthyroid for at least 6 months after MMI was discontinued, a remission rate that was not significantly different from that observed in the eight patients treated only and initially with MMI (Fisher's Exact Test). There was no significant change in serum thyroid peroxidase antibodies during treatment with MMI alone, Na ipodate alone, or Na ipodate followed by MMI.(ABSTRACT TRUNCATED AT 250 WORDS)

Therapy of Graves' disease with sodium ipodate is associated with a high recurrence rate of hyperthyroidism.

To evaluate the long-term efficacy of sodium ipodate (IPO) in the treatment of hyperthyroid Graves' disease, we studied 12 consecutive patients with Graves' hyperthyroidism treated only with 500 mg IPO po daily for several weeks to 22 months. Serum thyroid hormone concentrations markedly decreased and serum free T3 values normalized in all patients within 7 days of therapy. Five patients (42%, Group 1) were euthyroid after 6 weeks of IPO treatment and remained so until IPO was discontinued after 22 months. Recurrence of hyperthyroidism after drug withdrawal occurred in only one of these Group 1 patients, who was promptly responsive to a second course of IPO. In contrast, seven of 12 patients (58%, Group 2) relapsed with recurrent hyperthyroidism between 14 and 42 days of IPO therapy. After IPO was withdrawn, these Group 2 patients were treated with methimazole (20-30 mg/day, initial dose), but the therapeutic response was poor and delayed. Two patients were still hyperthyroid after 6 months of methimazole treatment. Elevated serum FT3 concentrations were observed in the Group 2 patients at 21 days following the early normalization of serum FT3 concentrations. No changes in serum thyroglobulin and thyroid microsomal and TSH-receptor autoantibody titers were observed in either groups during IPO therapy. In conclusion, the results of the present study demonstrate that IPO rapidly restores euthyroidism, but its prolonged administration is associated with a high rate of relapse of hyperthyroidism and a poor response to subsequent methimazole treatment and that long-term IPO administration does not affect humoral markers of thyroid autoimmunity.

[Shortened preoperative preparation in diffuse hyperthyroid goiter: experience in 34 patients]. / Preparación preoperatoria abreviada en los bocios difusos hipertiroídeos. Experiencia en 34 pacientes.

Conventional preparation of goitrous hyperthyroid patients using lugol and propranolol may take 2 weeks. This period may be shortened using sodium iopodate and dexamethasone. We used 500 mg of sodium iopodate and 1 mg dexamethasone for 4 days in 34 hyperthyroid patients. Surgical indication derived from failure to medical treatment (68%), large goiter (27%) or adverse reaction to PTU (6%). Clinical euthyroidism was achieved after 4 days in all patients. T3 levels decreased from 482 +/- 26.2 to 137.6 +/- 3.7 ng/dl and T4 from 20.6 +/- 1.04 to 15.2 +/- 0.5 micrograms/dl (p < 0.005). Surgery was uneventful in 33 patients, one subject developed supraventricular tachycardia responsive to verapamil. Electron microscopy of the removed thyroid tissue revealed marked decrease of superficial villi and large phagosomes. Thus, sodium iopodate and dexamethasone are effective and safe for preoperative preparation of hyperthyroid patients.

Acute L-thyroxine overdose; therapy with sodium ipodate: evaluation of clinical and physiologic parameters.

Two children with acute L-thyroxine overdose were treated with sodium ipodate, an oral cholecystographic agent. Initial thyroxine (T4) levels were elevated to 98.5 mcg/dL and 134.1 mcg/dL, with associated triiodothyroxine (T3) levels of 354 ng/dL and 402 ng/dL. T3 levels increased to a maximum of 662 ng/dL and 468 ng/dL. With administration of sodium ipodate, the T3 decreased with a simultaneous increase of rT3 level. Sodium ipodate effect lasted 72 hours. No toxic effect was noted. Interestingly, thyroid hormone levels correlated with systolic blood pressure but with no other physiologic parameter. Sodium ipodate appears to be a viable treatment modality for acute thyroid overdose in children.

Further studies on the long-term treatment of Graves' hyperthyroidism with ipodate: assessment of a minimal effective dose.

We have previously described that sodium ipodate (500 mg/day, p.o.) is effective in normalizing serum T3 and T4 levels in most patients with Graves' hyperthyroidism. In this study, we examined serum T3, T4, and rT3 levels in 14 hyperthyroid patients with Graves' disease during treatment with a lower dose (500 mg, every other day, p.o.) of sodium ipodate for a period of 3-30 weeks (mean 15.5 weeks). Three types of responses were observed. In group I (4 patients), both serum T3 and T4 were in the normal range at the end of treatment [baseline: mean +/- SEM T3, 6.8 +/- 0.96 nmol/L (normal 0.92-3.0)] and T4 [256 +/- 44 nmol/L (normal 62-167); post-ipodate: T3, 2.0 +/- 0.46 nmol/L and T4 107 +/- 28 nmol/L]. In group II (n = 5), either serum T3 (3 patients) or serum T4 (2 patients) did not become normal (baseline: T3 7.7 +/- 1.1 and T4 228 +/- 3.9; post-ipodate: T3 2.9 +/- 0.57 and T4 188 +/- 27 nmol/L). In group III (5 patients), neither serum T3 nor serum T4 returned to normal following ipodate treatment (baseline: T3 11.9 +/- 1.8 and T4 260 +/- 23; post-ipodate: T3 7.5 +/- 0.49 and T4 322 +/- 17 nmol/L). The mean serum rT3 concentration increased during ipodate treatment to a peak value of 100% above baseline and remained elevated (20-75% above baseline) throughout the study. Some improvement in hyperthyroidism was suggested by increase in body weight during ipodate treatment in most cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Sodium ipodate in the treatment of toxic diffuse goiter. Short-term and long-term effects on thyrotoxicosis.

Iodinated radiocontrast medication has been successful in the treatment of thyrotoxicosis when used for short periods up to 21 days, but experience with long-term use is lacking. In the first part of this study, a group of seven patients each taking 1.5 g. sodium ipodate daily was observed for 21 days and compared to a similar group of seven thyrotoxic patients taking 400 mg. propylthiouracil (PTU) daily. Sodium ipodate brought about a more significant decrease in serum total T3 and T4 levels, and more prominent increase in reverse T3 levels in the first ten days of the treatment. In the second part, a group of seven patients with thyrotoxicosis were given sodium ipodate, 1.5 g, daily for 20 days and 0.75 g. thereafter and were compared to a similar group of seven patients who took PTU, 300 mg. daily for the first 20 days and 150 mg. daily afterwards. Serum thyroid hormone levels decreased in both groups at the end of the first month of treatment, but rose again, along with worsening of symptoms, in five patients on ipodate treatment. Therefore, sodium ipodate, an iodinated radiocontrast agent is unable to control thyrotoxicosis for longer than a month.

Comparison of methimazole, methimazole and sodium ipodate, and methimazole and saturated solution of potassium iodide in the early treatment of hyperthyroid Graves' disease.

We have evaluated three regimens for the rapid control (10 days' therapy) of thyrotoxicosis in hyperthyroid Graves' disease: methimazole (MMI, 40 mg/day), MMI and sodium ipodate (MMI + Na Ipodate, 1 g/day and MMI and saturated solution of potassium iodide (MMI + SSKI, 6 drops twice daily). When serum T4 and T3 concentrations were analysed as the percent change from pre-treatment values, the following results were observed. Serum T4 concentration decreased in the three treatment groups and the decrease was similar in the MMI and MMI + SSKI groups but significantly lower than in the MMI + Na ipodate group. The serum T3 concentration decreased to the normal range in all seven MMI + Na Ipodate treated patients by the fourth day of treatment and the per cent decrease in serum T3 from pre-treatment values was significantly greater than in the MMI and MMI + SSKI treated patients. The decrease in serum T3 was similar in the latter two groups. Heart rate decreased in all three groups, but the decrease was significantly more in the MMI + Na Ipodate-treated patients. The present findings suggest that the rapid control of hyperthyroid Graves' disease is similar in patients treated with MMI and MMI + SSKI and that the combination of MMI + Na Ipodate is more efficacious since the decrease in serum T3 concentrations and heart rate was significantly greater in the MMI + Na ipodate-treated patients.

Treatment of neonatal hyperthyroidism due to Graves' disease with sodium ipodate.

We describe the effect of administration of repeated doses of sodium ipodate in a newborn infant with hyperthyroidism due to transient Graves' disease. Pretreatment (day 3) serum T4 and T3 concentrations were 49 micrograms/dl and 590 ng/dl, respectively. With 24 h after the first dose of ipodate, serum T3 fell by 40%, and it subsequently ranged from 209-278 ng/dl throughout the 39-day ipodate treatment period. Serum T4 also decreased after ipodate administration to 69% and 41% of the pretreatment value after 72 h and 7 days of treatment, respectively; values thereafter during treatment ranged from 19-22 micrograms/dl. These plateau values are in the upper range of normal for the neonatal period. Rapid clinical improvement occurred as the hyperiodothyroninemia abated. Serum rT3 concentrations increased from 468-672 ng/dl to greater than 1400 ng/dl 24 h after each ipodate dose. Thyroid-stimulating immunoglobulin was present in maternal and cord sera, and the half-life of serum thyroid-stimulating immunoglobulin in the infant was approximately 12 days. Antithyroglobulin and antimicrosomal antibodies were present in the infant at 10 days of age, and the titers decreased progressively thereafter; the half-life for the antimicrosomal antibody titer was 3 weeks. The data suggest that sodium ipodate can be useful for treatment of neonatal hyperthyroidism due to Graves' disease.

Effect of sodium ipodate and iodide on free T4 and free T3 concentrations in patients with Graves' disease.

Graves' hyperthyroid patients were treated daily for 10 days with 1 g sodium ipodate, a cholecystographic agent which exerts a blocking effect on the peripheral conversion of T4 to T3, or with 12 drops of saturated solution of potassium iodide (SSKI). Serum concentrations of free T4 (FT4) and free T3 (FT3) were measured before, during and 5 and 10 days after the administration of each drug. Sodium ipodate treatment induced a rapid decrement of serum FT4 concentrations which declined from 48.9 +/- 6.6 pg/ml to 26.0 +/- 2.7 pg/ml. In these patients serum FT3 concentrations declined from 12.4 +/- 2.0 pg/ml to 2.5 +/- 0.4 pg/ml. Ten days after sodium ipodate withdrawal, serum FT4 and FT3 concentrations returned to baseline values. In patients treated with SSKI serum FT4 concentrations declined from 51.1 +/- 8.8 pg/ml to 11.3 +/- 1.4 pg/ml and FT3 from 15.7 +/- 2 pg/ml to 2.6 +/- 0.3 pg/ml. Moreover, after therapy interruption serum free thyroid hormone concentrations returned to baseline values in these patients. Serum FT4 pattern during the study was not different between the two groups of subjects whereas serum FT3 concentrations were significantly lower in patients treated with sodium ipodate. These findings indicate that SSKI and sodium ipodate are effective in inducing a rapid decrement of serum free thyroid hormone concentrations. Therefore the employment of these drugs may be useful in the treatment of patients with thyroid storm and those undergoing thyroidectomy.

Hipodato sódico como tratamiento preparatorio en pacientes hipertiroideos candidatos a la cirugía / Sodium hypodate as preparatory treatment for surgery in patients with hyperthyroidism

Se utilizó hipodato sódico como tratamiento preparatorio en 10 pacientes hipertiroideos candidatos a cirugía, del Servicio de Endocrinología del Hospital México, San José, Costa Rica. Siete pacientes fueron femeninos y 3 masculinos, con edad media de 40.9 años (ámbito: 15-65). Las indicaciones para el tratamiento quirúrgico fueron: enfermedad de Graves: 7 casos (4 con exoftalmopatía infiltrativa, 1 puberal, 1 con alergia a propitiouracilo y metimazole, y 1 caso con antecedente de eritrodermia y agranulocitosis secundaria a propiltiouracilo); enfermedad de Plummer: 3 casos. El hipodato sódico se administró por vía oral, 3 gramos inicialmente, y luego 1 gramo diario hasta 2-3 días post-cirugía. Las pruebas de función tiroidea se normalizaron a las 72 horas en 4 pacientes. Dos pacientes tenían pruebas basales normales, por tratamiento previo con propitiouracilo e dos y medio años y 9 meses de duración, respectivamente, y persistieron normales. Los 4 pacientes restantes tuvieron una respuesta tardía. El tiempo promedio entre el inicio del hipodato y la cirugía fue de 24 días, excluyendo un pacietne poco confiable. No se tuvieron complicaciones quirúrgicas ni anestésicas. La vascularidad tiroidea se encontró aumentada en 1 caso, moderada en otro y sin particularidades en los otros casos. Observamos somnolencia transitoria en 1 paciente y un leve brote cutáneo en 2 pacientes. Reportamos un caso reciente de "shock" anafiláctico reversible por hipodato, en una paciente de 15 años con enfermedad de Graves y un síndrome similar a lupus por propiltiouracilo y metimazole. El hipodato sódico representa el tratamiento actual de elección en la tormenta tiroidea y es muy útil en el hipertiroidismo usuario de cirugía, pero su uso debe reservarse a casos especiales, en una unidad especializada y con vigilancia estrecha

Long term treatment of Graves' hyperthyroidism with sodium ipodate.

To investigate the long term usefulness of sodium ipodate (Oragrafin) in the management of Graves' hyperthyroidism, we studied the effects of ipodate (500 mg, orally, daily for 23-31 weeks) on serum T3, T4, rT3, and some clinical parameters in five newly diagnosed Graves' hyperthyroid patients. Mean pretreatment serum T3, T4, and rT3 concentrations were 780 ng/dl, 25.4 micrograms/dl, and 118 ng/dl, respectively. One day after the first dose of ipodate, serum T3 decreased by 62% (P less than 0.01), and it was within the normal range thereafter throughout treatment. The serum T4 concentration decreased by 20% (P = 0.09) at 24 h and by 43% (P less than 0.05) at 14 days. Subsequently, serum T4 was 41-65% lower than before treatment throughout the study; rT3 increased 24 h after the first dose of ipodate (118% above baseline; P = 0.1), remained elevated (97-109%) for 10 weeks, and then gradually decreased to the pretreatment level. A marked gain in body weight [5.1 +/- 1.1 (+/- SEM) kg] occurred in all patients. After discontinuation of ipodate, mean thyroid radioiodine (RAI) uptake values increased serially in four patients and were similar to pretreatment values: pretreatment, 74 +/- 6% (+/- SEM); after 7 days, 66 +/- 8%; after 14 days, 71 +/- 7%; after 28 days, 69 +/- 7%. The fifth patients's RAI uptake was 12-16% (vs. a pretreatment value of 48%) from 7-28 days after the end of a 31-week course of ipodate. He remained euthyroid without further treatment for the subsequent 4 months. We conclude that 1) ipodate (500 mg daily) reduces serum T4 and T3 levels as fast and as much as does the 1-g daily dose studied previously; 2) long term use (for 23-31 weeks) of ipodate for the treatment of Graves' hyperthyroidism is clinically feasible; no adverse effects occurred during or after ipodate treatment; and 3) RAI uptake returns to pretreatment levels as early as 7 days after the discontinuation of ipodate. Hence, use of ipodate does not prevent use of 131I therapy for those patients for whom it is otherwise desirable.

Comparative effects of sodium ipodate and iodide on serum thyroid hormone concentrations in patients with Graves' disease.

Patients with thyrotoxic Graves' disease were treated daily for 10 d with 1 g sodium ipodate, an iodine rich X-ray contrast agent which impairs outer ring (5'-) deiodination of T4 to T3, or with 12 drops of a saturated solution of potassium iodide (SSKI). T4, T3 and reverse T3 (rT3) concentrations were measured before, during, and 5 and 10 d after the administration of each drug. SSKI therapy induced a decrease in the serum T4 concentration from 14.7 +/- 1.3 microgram/dl (mean +/- SE) to a nadir of 7.9 +/- 0.9 on days 9 and 10 of therapy, all values reaching the normal range by day 9; a decrease in the serum T3 concentration from 402 +/- 43 ng/dl to a nadir of 143 +/- 20 on day 10, remaining elevated in all patients until day 5 and decreasing into the normal range in all except one patient on days 9 and 10; and no change in the serum rT3 concentration. Serum T4 and T3 concentrations returned to baseline values 10 d after withdrawal of SSKI. In contrast sodium ipodate therapy induced only a modest decrease in the serum T4 concentration from 15.1 +/- 0.7 micrograms/dl to a nadir on day 9 of 11.3 +/- 1.0 and serum T4 remained above the normal range in most patients until day 8; a striking and rapid decrease (within 12 h) in ther serum T3 concentration from 340 +/- 36 ng/dl to mean values ranging from 79 to 85 during the last 5 d of therapy, with most values below the normal range during the last 3 d; and a marked increase in the serum rT3 concentration from 111 +/- 15 ng/dl to a peak value of 376 +/- 59 on day 5.(ABSTRACT TRUNCATED AT 250 WORDS)