Graves' disease and pregnancy.

This section deals with the specificities of managing Graves' disease during pregnancy. Graves' disease incurs risks of fetal, neonatal and maternal complications that are rare but may be severe: fetal hyper- or hypothyroidism, usually first showing as fetal goiter, neonatal dysthyroidism, premature birth and pre-eclampsia. Treatment during pregnancy is based on antithyroid drugs alone, without association to levothyroxine. An history of Graves' disease, whether treated radically or not, with persistent maternal anti-TSH-receptor antibodies must be well identified. Fetal monitoring should be initiated in a multidisciplinary framework that should be continued throughout pregnancy. Neonatal monitoring is also crucial if the mother still shows anti-TSH-receptor antibodies at end of pregnancy or underwent antithyroid treatment. The risk of recurrence of hyperthyroidism in the weeks following delivery requires maternal monitoring. The long-term neuropsychological progression of children of mothers with Graves' disease is poorly known.

Follow-up of newborns of mothers with Graves' disease.

BACKGROUND: Overt neonatal Graves' disease is rare, but may be severe, even life threatening, with deleterious effects on neural development. The main objective of this study was to describe the course of thyrotropin (TSH) and free thyroxin (fT4) levels, as well as postnatal weight gain in relation to fT4 levels, in neonates born to women with Graves' disease without overt neonatal thyrotoxicosis. Such information is important to deduce the optimal schedule for evaluation. METHODS: We conducted a retrospective chart review of neonates born to mothers with Graves' disease between January 2007 and December 2012. The records were reviewed for sex, gestational age, birth weight, maternal treatment during pregnancy, and maternal thyroid stimulating immunoglobulin (TSI) level. For each visit in the clinic, the data included growth parameters, presence of symptoms suspected for hyperthyroidism, blood test results (levels of TSH, fT4, and TSI), and treatment. RESULTS: Ninety-six neonates were included in the study (49 males), with a total of 320 measurements of thyroid function tests (TSH and fT4). Four neonates (4%) had overt neonatal Graves' disease; one of them along with nine others were born preterm. In 77 (92.9%) of the remaining 83 neonates (the subclinical group), fT4 levels were above the 95th percentile on day 5. All had normal fT4 on day 15. A negative association was found between fT4 and weight gain during the first two weeks. CONCLUSIONS: In this cohort, most neonates born to mothers with Graves' disease had a subclinical course with abnormal fT4 levels that peaked at day 5. After day 14, all measurements of fT4 returned to the normal range, although measurements of TSH remained suppressed for up to three months. Elevated fT4 was associated with poor weight gain.

The goiter of a newborn from a mother with Graves´ disease.

INTRODUCTION: Congenital goiter is a rare condition which can be associated with both fetal hyper- and hypothyroidism. It may result from different situations in maternal-fetal thyroid function because antithyroid medication, iodine as well as stimulatory and inhibitory antibodies readily cross the placenta. Aim of the study is the presentation of a newborn infant with congenital goiter and neonatal thyroid suppression that could be attributed to either an in utero exposure to antithyroid drug - propylthiouracil (PTU) or mother´s blocking antibodies. CASE REPORT: Full term neonate was born with enlarged thyroid and signs (laboratory findings) of congenital hypothyroidism. The mother was treated due to hyperthyroidism between 8 and 12 week of pregnancy and presented thyroid-stimulating immunoglobulins (TSI) after delivery. During the treatment with replacement doses of L-thyroxin in infancy period no thyroid antibodies in the child were detected. CONCLUSIONS: The most probable reason was the negative influence of PTU: very high thyroid stimulating hormone (TSH) level since delivery and goiter development indicate that fetal hypothyroidism had been developing for a long time.

Thyroid disorders during pregnancy.

Thyroid physiology is altered during pregnancy as a result of an increase in thyroid-binding globulin, the stimulatory effect of hCG on TSH receptors, and increased peripheral thyroid hormone requirements. In addition, hyper and hypothyroid disorders are prevalent among women of reproductive age, and most of them have a significant impact on the gravida, fetus and neonate. Aberrant thyroid function can be readily recognized and treated during pregnancy, avoiding such complications. Here, we will review the thyroid function changes occurring during pregnancy, the different disorders, their maternal and fetal implications, and the ways to screen, prevent and treat these conditions.

Hypocalcaemia following therapy of thyrotoxicosis in an infant.

UNLABELLED: A 2-mo-old infant born to a mother with Graves' disease and having symptoms of thyrotoxicosis was started on antithyroid drugs. Life-threatening hypocalcaemia requiring high-dose calcium infusions developed 1 mo after starting therapy. Serum alkaline phosphatase and paratharmone levels were elevated. This communication may serve to alert treating physicians about this rare complication in infants with thyrotoxicosis after initiation of antithyroid therapy. CONCLUSION: Severe hypocalcaemia may follow initiation of antithyroid therapy in infants with thyrotoxicosis.

Thyroid dysfunction in the offspring of mothers with autoimmune thyroid diseases.

UNLABELLED: An integrated three-compartment thyroid model exists during gestation: pregnancy influences thyroid function in several ways, the placenta plays an active role in TRH-thyroid and iodide transport and metabolism, and the fetus develops its own hypothalamic-pituitary-thyroid axis. This commentary reviews some basic and new data, especially in the maternal-offspring relationship in the case of maternal autoimmune thyroid diseases. CONCLUSION: The careful control of maternal autoimmune thyroid disease is essential in order to avoid pathological changes in the offspring.

Risk factors of primary thyroid dysfunction in early infants born to mothers with autoimmune thyroid disease.

AIM: To assess whether the state of maternal thyroid function and the pattern of thyroid alterations during gestation would affect the infants' thyroid function and to evaluate the risk factors affecting early infants' thyroid function by means of multiple logistic regression. METHODS: In a cross-sectional study, 78 neonates born to mothers with Graves disease or Hashimoto thyroiditis were examined and followed clinically and biochemically. Neonates born to healthy mothers during the same period were set as controls. Tests of thyroid function, antithyroid peroxidase antibody (TPOAb), antithyroglobulin antibody (TGAb), anti-TSH receptor antibody (TRAb) and antithyroid-stimulating antibody (TSAb) were performed both in early infants and their mothers. All possible maternal and/or infantile risk factors for thyroid dysfunction during early infancy were analysed by means of multiple-factor logistical regression. RESULTS: The overall prevalence of underlying subtle thyroid abnormalities in these 78 infants was 52.6%, which was significantly higher than that witnessed among infants from healthy mothers (5.4 per thousand, p<0.01). By using multiple logistic regression analysis, the state of maternal thyroid function in gestation, the type of autoimmune thyroid disease during pregnancy and the level of TRAb in the newborn were significantly correlated with the early infants' thyroid dysfunction. CONCLUSION: Maternal autoimmune thyroid disease during pregnancy will affect infant thyroid function. Therefore, appropriate management of maternal autoimmune thyroid disease throughout pregnancy is essential in the prevention of undesirable neonatal outcomes.

Congenital hyperthyroidism: autopsy report

Relata-se a necropsia de natimorto com hipertireoidismo congenito, filho de mae portadora de doenca de Graves nao tratada, que teve como causa de obito insuficiencia cardiaca congestiva. Os achados fundamentais foram vistos no cranio, tireoide, coracao e placenta. As suturas cranianas encontravam-se fechadas, com acavalgamento dos ossos cranianos. A tireoide apresentava aumento de volume e congestao sanguinea intensa e, histologicamente, os foliculos mostravam hiperatividade. O coracao estava aumentado de volume, amolecido, com cavidades dilatadas e sufusoes hemorragicas no epicardio...

[Neonatal hyperthyroidism with early onset and protracted course]. / Ipertiroidismo neonatale ad insorgenza precoce ed a decorso protratto.

Neonatal hyperthyroidism has often been described as a rare, transient disorder in which the mother has hyperthyroidism during her pregnancy. We have found 99 cases mentioned in recent literature, but not in all reports the clinical characteristics were described. This survey has shown that the prolonged clinical course, though less common than the transient one, is to be taken into account. A case of a female child who had signs of hyperthyroidism soon after the birth is presented. Now, at the age of 7.8 years, she continues to have hyperthyroidism with several problems in treatment.

Neonatal Graves' disease.

A newborn boy was noted by his mother to have a prominent left eye at birth, but an eye examination was delayed until age 7 months, at which time his ophthalmologist diagnosed exophthalmos. Computed tomography was interpreted as showing mild, diffuse, optic nerve thickening bilaterally suggestive of optic nerve gliomas. Subsequent examination in our clinic revealed pseudoproptosis secondary to retraction of the left upper eyelid. Magnetic resonance imaging demonstrated normal orbital structures. The mother was noted to be clinically hyperthyroid, and abnormal thyroid function tests confirmed the diagnosis. Although the infant was euthyroid, neonatal Graves' ophthalmopathy was diagnosed. He was managed by close observation while his mother was treated for her hyperthyroidism.

Clinical applications of assays for thyrotropin-receptor antibodies in Graves' disease.

Graves' disease is characterized by hyperthyroidism, diffuse goitre, infiltrative ophthalmopathy and, rarely, pretibial myxedema. In 1956 a substance capable of prolonged thyroid stimulation was discovered in the serum of some patients with Graves' disease and termed long-acting thyroid stimulator (LATS). It was shown to be an antibody that could interact with the receptor for thyroid-stimulating hormone (TSH). The term LATS is usually reserved for the activity measured in a laborious in-vivo bioassay in mice. Today the activity of TSH-receptor antibodies (TSH-R Ab) can be measured by in-vitro bioassays or by radioreceptor assays. These assays are now becoming commercially available. TSH-R Ab assays may be useful in predicting the response to therapy for Graves' disease, investigating euthyroid ophthalmopathy and predicting the likelihood of neonatal hyperthyroidism.

[Transient neonatal hyperthyroidism in the child of a treated hyperthyroid mother. Subsequent appearance of sexual precocity]. / Hipertiroidismo neonatal transitorio e hijo de madre hipertiroidea tratada. Posterior aparición de precocidad sexual.

We report a newborn female with neonatal hyperthyroidism, born to a mother with Graves disease treated with potassium iodide and carbimazole. At four months she had some breast development, a bone age advance of one year, and elevated levels of FSH and estradiol. Later on the prolactin level was also raised, while LH and TSH values continued low. Posteriorly, irregular cutaneous pigmentation, brown in colour, was evident on the neck and trunk, and a McCune-Albright syndrome was suspected. The relationship between these conditions and treatment of them is discussed.

Graves' disease in pregnancy years after hypothyroidism with recurrent passive-transfer neonatal Graves' disease in offspring. Therapeutic considerations.

Symptoms and signs of severe hypothyroidism developed in a young woman at age 15. These symptoms progressed for a year; at age 16, she was found to have a firm goiter, thyroid autoantibodies, very low serum thyroxine and high thyrotropin values, indicating autoimmune thyroiditis with hypothyroidism. She received L-thyroxine, 0.20 mg per day, and was well until age 24 when she became pregnant. In the first trimester, manifestations indicative of hyperthyroidism developed; these were only ultimately recognized immediately after delivery of a 32-week still-born goitrous baby. Despite the discontinuation of thyroxine therapy, the hyperthyroidism persisted and was confirmed as Graves' disease by elevated thyroxine, triiodothyronine, and radioactive iodine uptake values, a diffuse scanning result, and the presence of thyroid-stimulating antibody. The patient was treated with propylthiouracil and became pregnant while receiving that regimen. Later, several months after delivery, the patient was treated with radioactive iodine, ultimately became hypothyroid, and has been treated ever since with thyroxine. She became pregnant again and, because of the continuing high titers of thyroid-stimulating antibody, received propylthiouracil, 100 mg daily, commencing in the third trimester of pregnancy, to avoid probable fetal hyperthyroidism due to the transplacental transfer of thyroid-stimulating antibody. In each of the last two pregnancies, when the infants were born, they seemed normal (because of the transplacental effect of propylthiouracil), but passive-transfer neonatal hyperthyroidism developed in each within 10 days after delivery, ultimately requiring treatment by conventional means. This case illustrates the following points: (1) Hyperthyroidism occasionally develops years after hypothyroidism. (2) In young women, high titers of thyroid-stimulating antibody may produce fetal and neonatal passive-transfer hyperthyroidism even at a time when the mother herself is no longer hyperthyroid; transplacental treatment of the fetus by maternal propylthiouracil ingestion may thus be necessary during the last trimester, but only when there is a high degree of probability that the fetus is at risk. (3) Because the infants had been protected in utero by the placental transfer of propylthiouracil, neonatal hyperthyroidism did not develop until several days after delivery.(ABSTRACT TRUNCATED AT 400 WORDS)

[Neonatal Basedow's disease with premature craniosynostosis and stenosis of the aqueduct of Sylvius]. / Maladie de Basedow néonatale avec craniosynostose prématurée et sténose de l'aqueduc de Sylvius.

Newborn from mother with untreated Graves' disease, born with thyrotoxicosis and exophthalmia, treated with carbimazole from age 6 weeks. At age 8 months, persisting hyperthyroidism requiring the continuation of treatment, and premature craniosynostosis with dilatation of cerebral ventricles suggesting a stenosis of the aqueduct of Sylvius.

Immunoglobulin G inhibitor of thyroid-stimulating antibody is a cause of delay in the onset of neonatal Graves' disease.

Studies were carried out with the serum IgG from a mother and her two children who developed neonatal Graves' disease several weeks after birth. The maternal IgG: (a) stimulated the human thyroid in vitro, but maximal stimulation was found only with dilution of the IgG; (b) was very potent in the long-acting thyroid stimulator (LATS)-protector assay, but only when an inhibitor of the system was diluted out; (c) inhibited a standard preparation of LATS in the mouse bioassay; (d) was biphasic in the thyrotropin-binding inhibition (TBI) assay, i.e., enhanced binding at low concentrations of IgG and inhibited binding at high levels. Enhancement in the TBI assay was found only with particulate preparations of human thyroid membranes as receptor and not when that material was solubilized, nor with guinea pig fat cell membranes as receptor. Serial blood samples from the second child were obtained at birth and until 3 mo of age. In the thyroid slice (cyclic AMP) assay system there was a negative dose-response relationship in testing IgG until age 45 d when it became positive, coinciding with the clinical recognition that hyperthyroidism had developed. The data are compatible with a concept that this mother's IgG contained thyroid-stimulating antibody (TSAb) and another moiety that inhibited TSAb through an action on the thyroid cell membrane, thus delaying the onset of hyperthyroidism in the neonate until the inhibiting IgG was metabolically cleared to an ineffective concentration.