Malformations in the offspring of women with thyroid cancer treated with radioiodine for the ablation of thyroid remnants

Malformações na prole de mulheres com câncer de tireóide tratadas com radioiodo para ablação de remanescentes tireoideanos

ARTIGO ORIGINAL

Malformations in the offspring of women with thyroid cancer treated with radioiodine for the ablation of thyroid remnants

Malformações na prole de mulheres com câncer de tireóide tratadas com radioiodo para ablação de remanescentes tireoideanos

Pedro Weslley S. do Rosário^I; Álvaro Luís Barroso^II; Leonardo Lamego Rezende^II; Eduardo Lanza Padrão^II; Michelle A. Ribeiro Borges^I; Saulo Purisch^I

^IDepartment of Thyroid, Endocrinology and Metabolism Service, Santa Casa de Belo Horizonte, MG

^IINuclear Medicine Service, Santa Casa de Belo Horizonte, MG

^{Endereço para correspondência}

ABSTRACT

RATIONALE: Since ovarian function is only temporarily compromised by radioiodine therapy, many women with thyroid cancer treated with radioiodine can become pregnant. The present study evaluated the evolution of these pregnancies and the consequences for the offspring.

PATIENTS AND METHODS: We retrospectively analyzed 78 pregnancies of 66 women submitted to total thyroidectomy, followed by radioiodine therapy (3.7­5.5 GBq ¹³¹I, mean 4.64 GBq). In all patients, conception occurred one year after ablative therapy (mean of 30 months). Age ranged form 19 to 36 years (mean of 30.6 years) at the time of radioiodine treatment and from 23 to 39 years (mean of 32.8 years) at the time of conception.

RESULTS: Four (5.1%) of the 78 pregnancies resulted in spontaneous abortions. Three (4%) of the 74 deliveries were preterm and there was no case of stillbirth. The birthweight was > 2500 g in 94.6% of the children (mean ± SD: 3350 ± 450 g) and only one infant (1.3%) presented an apparent malformation at birth (intraventricular communication). No difference in the age at the time of radioiodine therapy or conception or in radioiodine dose was observed between pregnancies with an unfavorable outcome and those with a favorable outcome.

CONCLUSION: We conclude that pregnancies that occur 12 months after ablative therapy are safe.

Keywords: Malformations; Radioiodine; Thyroid cancer

RESUMO

ARRAZOADO: Uma vez que a função ovariana está apenas temporariamente comprometida pela terapia com radioiodo, muitas mulheres com câncer de tireóide tratadas com radioiodo podem engravidar. O presente estudo avaliou a evolução dessas gravidezes e suas conseqüências para a prole.

PACIENTES E MÉTODOS: Analisamos retrospectivamente 78 gravidezes de 66 mulheres submetidas a tiroidectomia total seguida de radioiodoterapia (3,7­5,5 GBq ¹³¹I, média 4,64 GBq). Em todas, a concepção ocorreu um ano após a terapia ablativa (média de 30 meses). A idade variou de 19 a 36 anos (media de 30,6) à época do tratamento com radioiodo e de 23 a 39 anos (média de 32,8) na época da concepção.

RESULTADOS: Quatro (5,1%) das 78 gravidezes resultaram em abortamento espontâneo. Três (4%) dos 74 partos foram pré-termo, mas não houve nenhum natimorto. O peso ao nascer foi >2.500 g em 94,6% das crianças (média ± DP: 3.350 ± 450 g) e somente uma delas (1,3%) apresentou uma malformação aparente ao nascimento (comunicação intraventricular). Nenhuma diferença quanto à idade na época da radioiodoterapia ou na concepção ou na dose de radioiodo foi observada entre as gravidezes com ou sem um desfecho favorável.

CONCLUSÃO: Gravidezes que ocorrem 12 meses após terapia ablativa com radioiodo são seguras.

Descritores: Malformações; Radioiodo; Câncer de tireóide.

WOMEN OF FERTILE AGE correspond to a significant portion of patients with differentiated thyroid carcinoma in whom radioiodine therapy is widely used (1). Ovarian function is only temporarily compromised by radioiodine (2-5), with permanent infertility being rare (2). Thus, many women with thyroid cancer treated with radioiodine may become pregnant, and it is therefore important to evaluate the evolution of these pregnancies and the consequences for the offspring. A higher risk of abortion has been reported for the first year after application of the ¹³¹I dose (6-8) and it is recommended that conception be avoided during this period (9); however, malformations or more serious consequences for the offspring do not seem to be frequent in these cases (6-8,10-12).

We report here the outcome of pregnancies of patients with thyroid cancer treated with radioiodine at our service.

MATERIAL AND METHODS

We retrospectively evaluated 78 pregnancies of 66 women with thyroid carcinoma (50 with papillary and 16 with follicular carcinoma) submitted to total thyroidectomy followed by radioiodine therapy (single ¹³¹I dose of 3.7­5.5 GBq, mean 4.64 GBq). In all patients, conception occurred one year after ablative therapy (15 to 74 months, mean 30 months) as advised at the time of treatment (9). Age ranged from 19 to 36 years (mean 30.6 years) at the time of radioiodine therapy and from 23 to 39 years (mean 32.8 years) at the time of conception. None of the patients presented important clinical co-morbidities that would affect the evolution of pregnancy and all women attended regular prenatal visits since the first trimester of pregnancy. The patients were maintained on suppressive levothyroxine therapy (TSH< 0.3 mIUIl) even during pregnancy.

At the time of ablative therapy, all patients had received vigorous oral hydration and in cases of intestinal constipation, laxatives were administered for the adequate elimination of I¹³¹ in order to reduce ovarian exposure to radiation (13).

Spontaneous abortions, preterm deliveries, stillbirths, infant birthweight, and the presence of congenital malformations apparent at birth or during the first year of life were considered for analysis.

The study was approved by the Research Ethics Committee of our Institution and all patients signed an informed consent form to participate.

Differences in continuous variables between the patients with unfavorable outcome and those with favorable outcome were estimated using a nonparametric Mann-Whitney U test. For dichotomous variables, Fisher's exact test was used.

RESULTS

None of the patients had iodine-accumulating distant metastases and uptake in the thyroid bed was < 10% on post-treatment scans in all women.

Four (5.1%) of the 78 pregnancies resulted in spontaneous abortions without apparent cause. Three (4%) of the 74 deliveries were preterm, two at 32 and one at 33 weeks of gestation, and there was no case of stillbirth. The birthweight was > 2500 g in 94.6% of the children (mean ± SD: 3350 ± 450 g). Only one infant (1.3%) presented an apparent malformation at birth (intraventricular communication), while no anomaly was diagnosed during the first year of life in the other children. These rates were not higher than those found in the general population of the municipality where the patients were living (Belo Horizonte, MG) (14). No difference was observed in age at the time of radioiodine therapy or conception, interval between treatment and conception, histological type or radioiodine dose between pregnancies with an unfavorable outcome (abortion, prematurity and malformation) and those with a favorable outcome (table 1).

The characteristics of patients with pregnancies presenting an unfavorable outcome are shown in table 2.

DISCUSSION

Radioiodine therapy may temporarily compromise ovarian function, but recovery of the menstrual cycles and normalization of FSH levels generally occur within 12 months (3-5), with permanent infertility being rare and occurring only in cases in which high doses (29 GBq or more) are applied (2). Thus, pregnancy is possible after radioiodine therapy, and knowledge about the effect of ablative therapy on the evolution of these gestations becomes important.

In the present study, all patients were advised to avoid conception during the first year after ablative therapy (9), a period during which the risk of abortions is known to be higher (6-8). With conception occurring 12 months after therapy, no increase in the abortion and prematurity rates, birthweight or malformations of the offspring was observed when compared to the general population. These data agree with various studies clearly demonstrating that pregnancy is safe in patients when the interval between radioiodine treatment and conception is longer than one year (6-8,10-12). However, we did not evaluate patients who received high radioiodine doses or those with iodine-accumulating pelvic metastases, situations in which the ovaries are exposed to higher radiation (13).

We conclude that pregnancies starting 12 months after ablative therapy are safe in patients who received a mean dose of 4.6 GBq and who do not present iodine-accumulating pelvic metastases.

Recebido em 27/12/05

Revisado em 02/06/06

Aceito em 20/06/06

• 1. Schlumberger MJ. Medical progress papillary and follicular thyroid carcinoma. N Engl J Med 1998;338:297-306.
• 2. Maxon III HR. The role of I-131 in the treatment of thyroid cancer. Thyroid Today 1993;16:1-9.
• 3. Raymond JP, Izembart M, Marliac V, Dagousset F, Merceron RE, Vulpillat M, et al. Temporary ovarian failure in thyroid cancer patients after thyroid remnant ablation with radioactive iodine. J Clin Endocrinol Metab 1989;69:186-90.
• 4. Vini L, Hyer S, Al-Saadi A, Pratt B, Harmer C. Prognostic for fertility and ovarian function after treatment with radioiodine for thyroid cancer. Postgrad Med J 2002;78:92-3.
• 5. Souza Rosario PW, Fagundes TA, Fagundes AS, Barroso AL, Lamego Rezende L, Lanza Padrão E, et al. Ovarian function after radioiodine therapy in patients with thyroid cancer. Exp Clin Endocrinol Diabetes 2005;113:331-3.
• 6. Schlumberger M, Vathaire F, Ceccarelli C, Delisle MJ, Francese C, Couette JE, et al. Exposure to radioactive iodine-131 for scintigraphy or therapy does not preclude pregnancy in thyroid cancer patients. J Nucl Med 1996;37:606-12.
• 7. Krassas GE. Thyroid disease and female reproduction. Fertil Steril 2000;74:1063-70.
• 8. Schlumberger M, De Vathaire F, Ceccarelli C, Francese C, Pinchera A, Parmentier C. Outcome of pregnancy in women with thyroid carcinoma. J Endocrinol Invest 1995;18:150-1.
• 9. Brandão CD, Antonucci J, Correa ND, Corbo R, Vaisman M. Radioiodine therapy effects on offspring of patients with differentiated thyroid carcinoma. Radiol Bras 2004;37:51-5.
• 10. Lin JD, Wang HS, Weng HF, Kao PF. Outcome of pregnancy after radioactive iodine treatment for well-differentiated thyroid carcinomas. J Endocrinol Invest 1998;21:662-7.
• 11. Dottorini ME, Lomuscio G, Mazzucchelli L, Vignati A, Colombo L. Assessment of female fertility and carcinogenesis after iodine-131 therapy for differentiated thyroid carcinoma. J Nucl Med 1995;36:21-7.
• 12. Casara D, Rubello D, Saladini G, Piotto A, Pelizzo MR, Girelli ME, et al. Pregnancy after high therapeutic doses of iodine-131 in differentiated thyroid cancer: potential risks and recommendations. Eur J Nucl Med 1993;20:192-4.
• 13. Maxon HR 3^rd, Smith HS. Radioiodine-131 in the diagnosis and treatment of metastatic well differentiated thyroid cancer. Endocrinol Metab Clin North Am 1990;19:685-718.
• 14. Lansky S, Franca E, Leal Mdo C. Avoidable perinatal deaths in Belo Horizonte, Minas Gerais, Brazil, 1999. Cad Saúde Pública 2002;18:1389-400.

Publication Dates

• Publication in this collection
  04 Dec 2006
• Date of issue
  Oct 2006

History

• Accepted
  20 June 2006
• Reviewed
  02 June 2006
• Received
  27 Dec 2005