Management and follow-up of thyroid cancer in pregnant women.

Thyroid cancer, the most common endocrine malignancy, is often detected in young female patients. Therefore, pregnancy following thyroid cancer is not infrequent, and about 10% of thyroid cancers occurring during the reproductive years are diagnosed during pregnancy or in the early post-partum period. Differentiated thyroid cancer (DTC) in young people generally has an excellent prognosis, and disease-free survival among women with DTC diagnosed during pregnancy may not differ from that in age-matched non-pregnant women with similar disease. However, thyroid cancer detected during pregnancy may cause anxiety about the optimal timing of recommended treatments and about both maternal and neonatal morbidity, as weel as pregnancy following a diagnosis of thyroid cancer obviously needs both maternal and foetal management. The main objectives in clinical monitoring of pregnant thyroid cancer patients are: 1) to reach an adequate balance of maternal calcium and thyroid hormones that is absolutely required by the foetal central nervous system for normal maturation; 2) to maintain optimal levels of maternal thyroxin to avoid possible recurrence or spread of disease; and 3) to perform safe follow-up visits for the mother and to plan further therapy when needed. Data from a review of the literature and the authors' own experience show that in patients undergoing either suppressive or substitutive thyroxine therapy foetal thyroid growth is normal at ultrasound study, newborn thyroid status is normal, and the incidence of maternal morbidity is not influenced by the pregnancy. In this review, the authors underline that regular adjustment of levo-thyroxine and calcium therapy is of outmost importance for both maternal and foetal well-being and offer some insight, very interesting from a practical point of view, to provide a clear and simple pathway for the management of pregnancy-associated thyroid cancer.

Pregnancy and thyroid cancer: ultrasound study of foetal thyroid.

Thyroid cancer is the most common endocrine malignancy, more frequently diagnosed in young women during childbearing age and approximately 10% of all thyroid cancers are diagnosed during pregnancy or in the early post-partum period. Thyroid cancer in young people has generally an excellent prognosis, and survival among women with thyroid cancer diagnosed during pregnancy may not differ from that in age-matched non-pregnant women with similar cancer. Pregnancy after treatment of thyroid carcinoma requires both maternal and foetal controls. Of utmost importance is to ensure adequate maintenance of maternal levels of levothyroxine, needed by both the foetal central nervous system for its normal maturation and the mother to avoid possible recurrence or spread of the disease. In the present investigation, to confirm normal foetal growth and foetal thyroid development, an ultrasound study of the foetal thyroid was performed in 40 full term pregnancies in 32 women receiving levothyroxine treatment for previously treated thyroid cancer. In patients undergoing either suppressive or substitutive levothyroxine treatment, foetal thyroid growth was noted to be normal in all the cases, newborn thyroid status was always normal, and the incidence of maternal morbidity was not influenced. In the present study group, pregnancy does not appear to compromise mother's disease-free interval, nor to be compromised by thyroid cancer treatment. Results of the present study confirm that regular adjustment of levothyroxine treatment is of utmost importance for both maternal and foetal well-being and that foetal thyroid ultrasound study may add useful and reassuring data about child well-being.

Intrauterine growth of normal thyroid.

In this study we describe fetal thyroid growth during gestation and establish normal reference values using a simple linear ultrasound measurement of the thyroid. A total of 1180 normal singleton pregnancies, with no known risk factors for thyroid disorders, were enrolled from 12 to 39 weeks of gestation. The thyroid antero-posterior diameter was measured on a transverse axial plane through the fetal neck. The best fit regression was a power equation: thyroid diameter = 0.2412 weeks(1.0278) (r(2) = 0.55). The percentiles smoothed curves were calculated for each week. In conclusion, the results of the present study support previous findings that the fetal thyroid grows between 12 and 39 weeks of gestation with a steepest increase during the second trimester, that is when the fetal thyroid becomes functionally active. The normal ranges of this simple index of thyroid growth can be useful both as screening and for the clinical evaluation of pregnant patients with thyroid disorders.

Maternal compound W serial measurements for the management of fetal hypothyroidsm.

OBJECTIVE: The diagnosis of fetal hypothyroidism is based at present on measurements of TSH and free thyroxine (FT4) in fetal blood samples obtained by cordocentesis. The measurement of maternal serum and urinary concentrations of compound W, immunologically similar to but chromatographically distinct from diiodothyronine sulfate (T2S), has been advocated as a new possible marker for fetal hypothyroidism. DESIGN: In this paper, we measured serum compound W levels in 84 pregnant women, 20 with and 64 without thyroid disorders before and during specific treatment. Compound W was also assessed in fetal blood obtained by cordocentesis from 49 normal fetuses and 4 fetuses with suspected hypothyroidism due to transplacental passage of propylthiouracil (PTU). Compound W levels were measured by T2S RIA in maternal and fetal serum. To assess the possible usefulness of 3, 5,3'-triiodothyroacetic acid (TRIAC) for therapy of fetal hypothyroidism we evaluated the transplacental passage of TRIAC by administering the drug to four pregnant women before therapeutic abortion. RESULTS: In normal pregnancies, both maternal and fetal compound W levels increased progressively during gestation with a significant direct correlation (P<0.001, in both mothers and fetuses). Moreover, a significant positive correlation was observed between fetal compound W and fetal FT4 values (P<0.005), whereas no correlation was observed between maternal serum compound W and maternal FT4 in either euthyroid or hyperthyroid women, suggesting the fetal origin of compound W. The hypothyroid fetuses of PTU-treated mothers showed low compound W levels, and maternal compound W values were in the low normal range and did not show the typical increase during progression of gestation. A significant increase of maternal compound W was observed when the PTU dose was reduced. TRIAC was documented to cross the placental barrier and the treatment of a hyperthyroid pregnant woman on PTU caused the high fetal TSH levels and goiter to normalize. CONCLUSIONS: Serial measurements of 3,3'-T2S crossreactive materials (compound W and 3, 3'-diiodothyroacetic acid sulfate) in maternal blood and the administration of TRIAC to the mother may represent a useful and safe alternative to invasive techniques for the diagnosis and therapy of fetal hypothyroidism.

Malformations in offspring of women with epilepsy: a prospective study.

PURPOSE: The incidence of malformations among infants of mothers with epilepsy treated with antiepileptic drugs (AEDs) during pregnancy is higher than that found in the general population. The aim of this study was to contribute to providing a definition of the rate of congenital anomalies in the offspring of mothers with epilepsy and to detect possible risk factors. METHODS: Since 1977, 517 pregnancies were followed up at the San Paolo Hospital in Milan by a team of epileptologists and obstetricians. The patients received monthly obstetric and neurologic examinations, and the blood levels of AEDs were tested monthly. During pregnancy the patients underwent ultrasound investigations to evaluate fetal morphology and development. At the time of delivery, the infants were submitted to a standardized examination by a pediatrician, and a more detailed clinical examination was performed on day 5. Malformations were classified as (a) genetic and chromosomic, (b) severe and mild malformations, and (c) deformities. RESULTS: The overall rate of malformations was 9.7%: of these, 5.3% were structurally severe, 2.2% were mild, 0.4% were chromosomic-genetic, and 1.8% were deformities. No malformation was detected in the 25 untreated patients. CONCLUSIONS: The risks of teratogenicity have been regarded as multifactorial, involving such factors as genetic predisposition, although most prospective studies show that AED-related factors are the primary risk factors for an increased incidence of congenital malformations.

Prenatal diagnosis of thyroid hormone resistance.

A 29-yr-old woman with pituitary resistance to thyroid hormones (PRTH) was found to harbor a novel point mutation (T337A) on exon 9 of the thyroid hormone receptor beta (TRbeta) gene. She presented with symptoms and signs of hyperthyroidism and was successfully treated with 3,5,3'-triiodothyroacetic acid (TRIAC) until the onset of pregnancy. This therapy was then discontinued in order to prevent TRIAC, a compound that crosses the placental barrier, from exerting adverse effects on normal fetal development. However, as the patient showed a recurrence of thyrotoxic features after TRIAC withdrawal, we sought to verify, by means of genetic analysis and hormone measurements, whether the fetus was also affected by RTH, in order to rapidly reinstitute TRIAC therapy, which could potentially be beneficial to both the mother and fetus. At 17 weeks gestation, fetal DNA was extracted from chorionic villi and was used as a template for PCR and restriction analysis together with direct sequencing of the TRbeta gene. The results indicated that the fetus was also heterozygous for the T337A mutation. Accordingly, TRIAC treatment at a dose of 2.1 mg/day was restarted at 20 weeks gestation. The mother rapidly became euthyroid, and the fetus grew normally up to 24 weeks gestation. At 29 weeks gestation mild growth retardation and fetal goiter were observed, prompting cordocentesis. Circulating fetal TSH was very high (287 mU/L) with a markedly reduced TSH bioactivity (B/I: 1.1 +/- 0.4 vs 12.7 +/- 1.2), while fetal FT4 concentrations were normal (8.7 pmol/L; normal values in age-matched fetuses: 5-22 pmol/L). Fetal FT3 levels were raised (7.1 pmol/L; normal values in age-matched fetuses: <4 pmol/L), as a consequence of 100% cross-reactivity of TRIAC in the FT3 assay method. To reduce the extremely high circulating TSH levels and fetal goiter, the dose of TRIAC was increased to 3.5 mg/day. To monitor the possible intrauterine hypothyroidism, another cordocentesis was performed at 33 weeks gestation, showing that TSH levels were reduced by 50% (from 287 to 144 mU/L). Furthermore, a simultaneous ultrasound examination revealed a clear reduction in fetal goiter. After this latter cordocentesis, acute complications occured, prompting delivery by cesarean section. The female neonate was critically ill, with multiple-organ failure and respiratory distress syndrome. In addition, a small goiter and biochemical features ofhypothyroidism were noted transiently and probably related to the prematurity of the infant. At present, the baby is clinically euthyroid, without goiter, and only exhibits biochemical features of RTH. In summary, although further fetal studies in cases of RTH are necessary to determine whether elevated TSH levels with a markedly reduced bioactivity are a common finding, our data suggest transient biochemical hypothyroidism in RTH during fetal development. Furthermore, we advocate prenatal diagnosis of RTH and adequate treatment of the disease in case of maternal hyperthyroidism, to avoid fetal thyrotrope hyperplasia, reduce fetal goiter, and maintain maternal euthyroidism during pregnancy.

Percutaneous umbilical blood sampling: indication changes and procedure loss rate in a nine years' experience.

A 9 years' experience with percutaneous umbilical blood sampling (PUBS) has been appraised. A total number of 1,272 procedures have been performed in our institution between 1986 and 1994; 861 before the 24th week of gestation and 411 after 24 weeks. The indications for PUBS changed throughout these years because of the rapid evolution of molecular biology and because of the fact that certain conditions can now be diagnosed at earlier stages of gestation by chorionic villi sampling and amniocentesis. Sampling at a later gestational age reflected changes in indications. PUBS loss rate has been calculated for 482 fetuses less than 24 weeks, retrospectively found to be negative for the suspected condition and has been related to gestational age, duration of the procedure and number of needle insertions. Total procedure-related loss rate was 2.3%: 1.6% intrauterine fetal deaths within 48 h of the procedure and 0.7% spontaneous abortions in the 2 weeks following the procedure. Gestational age at the time of the procedure and duration of the procedure were significantly related to fetal losses within 48 h.

Genetic amniocentesis in biamniotic twin pregnancies by a single transabdominal insertion of the needle.

We present a technique to aspirate amniotic fluid from both sacs in biamniotic twin pregnancies using a single abdominal insertion with a spinal needle. It was successful in 48 out of 55 cases of biamniotic twin pregnancies referred to our perinatal unit between 1985 and 1994. The single insertion technique was used when the inter-amniotic membrane was clearly evident and two separate free amniotic fluid pools could be reached by the operator with a single puncture. An adequate amount of amniotic fluid was sampled from both sacs to make a cytogenetic diagnosis in all cases. There were four fetuses with trisomy 21 in three twin pregnancies. In two cases, only one twin was affected whilst the co-twin was normal, so that a selective feticide was performed. No miscarriages due to genetic amniocentesis were reported. After 1990, all genetic amniocenteses in biamniotic twin pregnancies (except for one case due to late booking) were performed between 14 and 15 weeks of gestation and with all cases except one, it was possible to sample both twins by a single puncture. We suggest that early amniocentesis (14-15 weeks) by a single abdominal puncture could be a reliable and safe alternative to first-trimester chorionic villus sampling in twin pregnancies.