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Before pregnancy Diagnosed hypothyodism • Counseling • Increase administration of FT4 or start treatment (goal for TSH: < 2.5 mU/L and FT4 within reference limits NO known hypothyroidism • Counseling and estimation of risk • Clinical and biochemical (TSH reflex) assessment and ultrasonography when goiter or nodules are present • Start l-T4 treatment if hypothyroidism is detected Pregnancy • Measure FT4 e TSH and increase l-T4 dose • Involve gynaecologist I - II trimester • Monitor TSH and FT4 bimonthly • Fetal ultrasonography (each trimester) • Thyroid ultrasonography when goiter or nodules are present III trimester • Measure TSH, FT4 and TRAb • Involve paediatrician/neonatologist Delivery • Avoid antisepsis with iodine in newborn and mother • Carry out neonatal screening indicating the mother's disease • Measure TRAb if positive in mother Post-partum Mother: • Decrease l-T4 within one month • Measure FT3, FT4, TSH after 3-9 months Newborn: • Use milk supplemented with iodine • If screening positive involve the pediatrician • Start treatment if TSH increased • In hypothyroidism carry out ultrasonography and measure thyroglobulin and TRAb. -------------------------------------------------------------------------------- Reaxys Database Information

Iodine intake varies with age and physiological status: in pregnant and lactating women, recommended iodine intake ranges from 200 to 250 mg/day. Recent epidemiological studies in France demonstrate the presence of moderate iodine deficiency in the majority of pregnant and lactating women. This iodine deficiency induces maternal thyroid hyperplasia and then development of goiter in women, as well as impaired thyroid parameters. Maternal hypothyroxinemia during the first trimester of pregnancy can be associated with abnormal cognitive development and intellectual outcomes in the newborn and the children. According to the recent World Health Organization recommendations for the prevention and control of iodine deficiency in pregnant and lactating women, systematic iodine supplementation is indicated in France: 100 microg/day for women of reproductive age and 200 microg/day in pregnant and lactating women in order to eradicate iodine deficiency during pregnancy and lactation, and prevent the maternal and fetal consequences.

The main changes in thyroid function associated with the pregnant state are increased thyroid hormone requirements. These increased requirements can only be met by a proportional increase in hormone production, that directly depends upon the availability of dietary iodine. When the iodine intake is adequate, normal "physiological" adaptation takes place. When the intake is restricted, physiological adaptation is progressively replaced by pathological alterations, in parallel with the degree of iodine deprivation, leading to excessive glandular stimulation, hypothyroxinemia, and goiter formation. Thus, pregnancy acts typically as a revelator of underlying iodine restriction and gestation results in an iodine deficient status, even in conditions with only a moderately restricted iodine intake, characteristic of many European regions. Iodine deficiency during pregnancy has important repercussions for both mother and fetus, namely thyroid underfunction and goitrogenesis. Furthermore, iodine deficiency may be associated with alterations of the psychoneuro-intellectual outcome in the progeny. The risk of an abnormal progeny's development is further enhanced because mother and offspring are exposed to iodine deficiency, both during gestation and the postnatal period. Because iodine deficiency is still prevalent in many European regions and remains a subject of great concern, investigators have proposed, since several years, that iodine prophylaxis be introduced systematically during pregnancy, in order to provide mothers with an adequate iodine supply. In areas with a severe iodine deficiency, correcting the iodine lack has proved highly beneficial to prevent mental deficiency disorders. The many actions undertaken to eradicate severe iodine deficiency have allowed to prevent the occurrence of mental retardation in millions young infants throughout the world. In most public health programmes dealing with the correction of iodine deficiency disorders, iodized salt has been used as the preferred strategy in order to convey the iodine supplements to the household. Iodized salt, however, is not the ideal vector in the specific instance of pregnancy (or breastfeeding) or in young infants, because of the necessity to limit salt intake. Hence, particular attention is required in our countries to ensure that pregnant women have an adequate iodine intake, by administering multi-vitamin tablets containing iodide supplements (+125 micro g/d). Finally, it is with some concern that the results of a recent nutritional survey in the USA have disclosed that iodine deficiency, long thought to have been eradicated since many years, may actually show a resurgence, particularly in women in the child-bearing period. This issue needs to be considered seriously by the medical community and public health authorities.

Graves' disease (GD) patients treated with antithyroid drugs (ATD) have overall relapse rates of 30-50% after ATD discontinuation. Conflicting data have been reported with regard to the usefulness of adding thyroxine (I-T4) during and after ATD treatment. Also, clinicians are still in search of useful factors to predict remission/recurrence after ATD withdrawal. Eighty two consecutive patients were treated with ATD for 15 months, combined with 12 months of I-T4. Then, patients were randomized (placebo-controlled double blind protocol) to continuing I-T4 versus a placebo for one year.I-T4 administration during and after ATD treatment did not affect favorably the outcome, the final recurrence rate being 31%, in both placebo and I-T4 groups. Two factors were identified as independent and synergistic markers of a significantly increased risk of recurrence after ATD withdrawal: smoking and TSH receptor antibodies (TSHR-Ab) remaining positive at the end of ATD. Non smoking patients with a negative TSHR-Ab (end ATD) had a low (18%) recurrence risk, while smoking patients also with a negative TSHR-Ab had a higher (57%) recurrence risk. Non smoking patients with a positive TSHR-Ab (end ATD) had a 86% recurrence risk. Finally, smoking patients with a positive TSHR-Ab (end ATD) all recurred within 6 months.1) T4 administration after ATD withdrawal does not improve recurrence rates; 2) two parameters, smoking and positive TSHR-Ab (at end ATD), were valid--albeit not absolute-predictors of the risk of recurrence in ATD-treated patients with Graves' disease.

Most thyroid nodules discovered during pregnancy are benign. In this article, we propose a pragmatic attitude for the diagnosis and treatment of such nodules, insisting particularly on the importance of thyroid echography and fine needle aspiration. For women who have successfully been treated for thyroid cancer before pregnancy, we discuss the adaptation of thyroxine substitution when they become pregnant, the obstetrical and fetal risks (spontaneous miscarriage, fetal abnormalities of the thyroid gland and others), and also potential later risks for the child, in relation with previous radioactive iodine administration to the mother. Finally, we evoke more difficult questions, such as the rare instances in which thyroid cancer is discovered during pregnancy, pregnancy occurring during the months immediately following radioiodine treatment, and exceptional cases where therapeutic radioiodine was inadvertently given during pregnancy.

In Belgium the iodine intake is restricted and even marginally insufficient. During pregnancy, the insufficient iodine supply is associated with chronic stimulation of the thyroid gland, leading to the development of gestational goiters and to an increased risk of foetal goitrogenicity. Also, approximately one third of pregnant women exhibit relative hypothyroxinemia. Moreover, women who present chronic autoimmune thyroiditis and in whom thyroid function is normal at the onset of pregnancy carry a significant risk of developing thyroid insufficiency during gestation. In conclusion, healthy pregnant women should be given the benefit of iodine supplementation, both during pregnancy and breastfeeding. This will allow them to maintain a well adapted thyroid function, prevent goitrogenicity, and ensure adequate foetal hormone production. For women with autoimmune thyroiditis, thyroid function should be closely monitored during pregnancy and the slightest indication of thyroid insufficiency should prompt the administration of thyroid hormone substitution.

The authors report on their experience with the treatment of hyperthyroidism using radioiodine (RI) over a period of 15 years in 516 patients. RI dosimetry was calculated from thyroid 24 hr uptake and weight, using linearly increasing RI doses (from 40 to 100 microCi/g) with increasing thyroid weight (between 10 and 100 g) for both diffuse (D) and multinodular (MN) toxic goiters. For solitary toxic (ST) nodules, a fixed dose of 250 microCi/g was used. In severe hyperthyroidism, antithyroid drugs (ATD) and KI (15 mg/d) were added 24 hours after RI and given during 1-4 months and 21 days, respectively. Combining RI + ATD/KI therapy allowed for a reduction of RI recirculation and release from the gland and also for more rapid return to a euthyroid status. The results showed that 88% of patients with ST, 68% with D, and 55% with MN were cured with a single dose of RI. Furthermore, the incidence of late hypothyroidism was relatively low, reaching 7% in ST, 36% in D, and 28% in MN after a follow-up period of fifteen years. Annual follow-up, however, showed that an additional 2.7% of patients (3.5% of D; 1.6% of MN; 2.4% of ST) exhibited--per year--an exaggerated TSH response to TRH even though these patients remained clinically and biochemically euthyroid (normal circulating basal hormones and TSH levels). In conclusion, 1) low doses RI combined with ATD/KI yielded a high success rate: less than 30% of patients required more than 1 dose and only 30% became hypothyroid after prolonged follow-up; 2) abnormalities of TRH test were not infrequent in patients with D and MN goiters, as well as ST nodules, thereby fully justifying the need for careful and prolonged follow-up of all hyperthyroid patients receiving RI therapy.

Though antithyroid medical therapy has been used for several decades in the medical treatment of hyperthyroidism, only recently has attention been drawn towards prospective controlled trials concerning the effect in relation to dosage as well as the dosage related to side effects. A review is given in relation to recent investigations on treatment strategies in various parts of the world as well as the most frequently used strategies in Europe. Special attention is given to treatment principles in relation to pregnancy, children and adolescents as well as patients with eye symptoms. Antithyroid drug therapy of hyperthyroidism is a frequent and successful treatment strategy in Europe. Globally, there are still large discrepancies in the treatment strategies, related rather to conventions than to a rational attitude.

We have measured eye muscle antibodies, in immunoblotting, in the serum from five patients with severe ophthalmopathy associated with Graves' hyperthyroidism who underwent plasmapheresis, correlating their levels with clinical features of the eye disorder and response to treatment. Blood taken before each plasma exchange was tested in SDS-polyacrylamide gel electrophoresis and Western blotting for antibodies reactive with pig eye muscle membrane (PEMM) antigens and in a 51Cr release assay for antibodies which are cytotoxic to human eye muscle cells in antibody-dependent cell-mediated cytotoxicity (ADCC). Antibodies reactive with a 64 kDa PEMM antigen were detected in three patients who had eye disease of less than six months duration, but not in the two with more chronic disease. Antibodies against a 95 kDa PEMM antigen were detected in one patient in whom anti-64 kDa antibodies were also demonstrated. All five patients showed significant improvement in their eye disease following plasmapheresis exchange and titres of the anti-64 kDa protein antibody decreased in the three patients with detectable levels before treatment. TSH receptor stimulating antibodies were detected in all five patients before treatment, falling during plasmapheresis in four and becoming undetectable in three by the end of treatment. There was no close correlation between levels of TSH receptor antibodies and titres of anti-64 kDa protein antibodies although both tended to fall during and following plasmapheresis. ADCC tests were negative in all five patients before plasmapheresis but, surprisingly, transiently positive in three following treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

The changes in thyroid function and in TSH receptor antibody titers were analyzed in a prospective sequential study before, during and after pregnancy in a group of 15 healthy women and 45 patients with Graves' disease. Twenty-five patients with Graves' disease were untreated before pregnancy (Group A) and twenty treated with carbimazole throughout pregnancy (Group B). In healthy pregnant women serum FT4 levels were slightly but significantly elevated early in pregnancy (p0.05) and lower during the third trimester (p0.01), compared to pregestational values (although within the reference range of nonpregnant subjects). During postpartum, serum FT4 reverted to values similar to those found before pregnancy. Serum TSH levels showed a slight increment during gestation with a significant decrease (p0.01) in the early postpartum period. There was a significant increase in serum thyroglobulin (Tg) during the first trimester (p0.01); Tg levels remaining markedly elevated throughout gestation. After delivery, Tg progressively decreased, but were still above normal, six months later in 27% of subjects. TSH-receptor antibody titers were normal but tended to decrease during late gestation; a significant rebound was observed in late postpartum, even though most individual values remained in the normal range. When we compared "active" and "remission" Graves' disease patients, the concentration of FT4 was significantly higher in group B ("active") than in group A ("remission" (p0.01) during early gestation. Serum Tg was also significantly higher in Group B than in Group A before pregnancy (p0.01), and during late gestation and postpartum (p0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

The main objectives of the workshop have been to re-evaluate the status of iodine nutrition in all European countries and to discuss practical measures for the normalization of their iodine intake. In this section we broadly summarize the information and discussions of the workshop and formulate conclusions and recommendations for the elimination of iodine deficiency disorders in Europe.

SummaryThe first part of a clinical thyroid chart relative to the diagnosis and the therapeutic plan is presented. The chart contains coded and uncoded data. The coded data will be transfered on two data sheets for optical reading in order to be fed into a computer. This mode of presentation allows the easy handling of 262 variables concerning the main data of thyroid clinic.

Five patients, who were treated with lithium at the time their hypothyroidism was discovered, are presented. Three of them had high levels of circulating antithyroid antibodies; one had been thyroidectomized several years ago and the last subject had congenital agenesis of one thyroid lobe. The relationship between hypothyroidism and preexisting thyroid abnormalities in patients receiving lithium is suggested.

In order to know how thyroid nodules and differentiated thyroid cancers are investigated and treated in 1988, an international inquiry was performed by mean of a questionnaire based on a well-defined case report of a 35-year-old female with a solitary small thyroid nodule. Clinicians were asked to indicate their diagnostic and therapeutic approaches to the reported case and to some variations. Analysis of the 157 responses from thyroid experts showed that three in vitro tests (sensitive-TSH, free T4 and total T4) and three in vivo tests (99mTc or radioiodide scintiscan, fine needle aspiration and ultrasonography) were performed most frequently. In the case of a solid and cold nodule and in the absence of fine needle aspiration results, 19% of respondents advocated suppressive therapy and 81% surgery. In the same clinical case, but whom fine needle aspiration had been performed and cytology was benign, surgery was advocated by 24%, suppressive therapy by 48% and a regular follow-up without treatment by 28% of respondents. When surgery was performed and the diagnosis was a differentiated thyroid cancer, (near) total thyroidectomy was more frequently chosen than partial thyroidectomy in both papillary (60 and 40%, respectively, of respondents) and follicular (74 and 26%, respectively, of respondents) cancers; 80% of clinicians did not change their surgical technique in relation to histological type of the tumour. Total thyroidectomy was more often recommended in most of the clinical or anatomical variations compared with the basic case report. Pre- or postoperative hormonal therapy was initiated with L-T4 and TSH suppression was controlled by sensitive-TSH and thyroglobulin determinations. After total thyroidectomy, 131I was used with similar modalities for papillary and follicular cancers to ablate a thyroid remnant.

Adrenocortical function and plasma growth hormone pattern were investigated in 15 patients with chronic obstructive lung disease, in a period of acute respiratory failure and again after recovery. During the acute period, secretion rate and plasma concentrations of cortisol were markedly enhanced; urinary excretion of cortisol metabolites was only slightly increased, suggesting an alteration of the catabolism of cortisol under these conditions; adrenocortical sensitivity to corticotropin and capacity of maximal adrenal secretion were normal. The increase of cortisol secretion was probably due to hypoxemia and/or hypercapnia acting through the hypothalamo-pituitary axis. During the chronic phase of respiratory insufficiency, adrenocortical secretion and responsiveness were within the normal range. Finally, respiratory failure did not stimulate the secretion of growth hormone.

A short trial with high doses of prednisolone to treat a 62 year-old woman with malignant ophthalmopathy due to Graves disease yielded an unsatisfactory improvement after 5-6 days. The authors decided therefore to use plasmapheresis, 4 plasma exchanges of 2.5 liters each associated with prednisolone (80 ng/day) and azathioprine (100 mg/day). This therapeutic approach resulted in a spectacular improvement obtained after less than 2 weeks: normalization of thyroid function, improvement of all ophthalmological indices confirmed by radiology (C.A.T.) of the retroocular region. The rapid and important improvement obtained after such a short period of time is in favor or the major role of plasmapheresis in this combined therapy of malignant Graves' ophthalmopathy.

Transmission electron microscope and scanning electron microscope studies in a case of congenital goitre associated with cretinism revealed the existence of two cell types: the first with rounded endoplasmic cisternae and normal lysosomes; the second characterized by an abundance of lysosomes and/or lipofuscin granules. Intermediary aspects suggested that the second cell type was the progeny of the first type. As colloid droplets and apical pseudopods engulfing colloid were nearly absent, and as NBE127I was elevated in the plasma, it is suggested that iodoprotein secretion occurred by a process different from colloid phagocytosis as observed after acute TSH stimulation.

The authors reviewed the literature concerning the side effects of lithium on thyroid function. Two kinds of side effects are reported: the first ones are minor, temporary, without important modification of thyroid function and must not be treated; the second ones are major and followed by hypothyroidism. This situation is mostly in relation with the preexistence of an autoimmune thyroiditis or another thyroid abnormality. The authors describe the mechanisms responsible for lithium side effects, suggest different thyroid examinations that should be done in patients before and during lithium therapy and discuss the indications of thyroxine administration.

In a retrospective study of 100 patients operated on between 1974 and 1979 in our institution for thyroid cold nodules, an 8% incidence of thyroid cancer was found at surgery. Since 1979, F.N.A. was performed in 160 patients with thyroid cold nodules. Adequate cytological material was aspirated in 90% (144) of the cases; of those, a benign cytological lesion was diagnosed in 128 (89%) and suspicion of cancer in 16 (11%). To date fifty-one patients were operated: 41 with benign cytology and 10 with cancer suspicion; benignity was confirmed in 39/41 cases with benign cytology and malignity in 5/10 with suspect cytology. In conclusion, clinical diagnosis of thyroid cold nodules is greatly improved by the use of F.N.A. Despite the limitations of the technique, preoperative suspicion of cancer was increased 7-fold. Caution is recommended in the follow-up cases with benign cytology since, in these preliminary results, 2 false-negatives were found.

In the present work, we demonstrate in the serum of patients with progressive exophthalmos, the presence of circulating immunoglobulin which is able to induce an experimental exophthalmos in goldfish. This immunoglobulin disappears when exophthalmos becomes residual. In parallel, we describe an easy technique for the measurement of delayed hypersensitivity which is positive for thyroid or retroorbital antigens in progressive exophthalmos but negative in residual exophthalmos. We also demonstrate in patients with exophthalmos an increase in urinary glycosaminoglycans. We propose a new therapeutic approach in treatment of acute exophthalmos which consists of intensive plasma exchange followed during a few months, by the administration of small amounts of corticosteroids. The plasma exchange mechanism consists of the extraction of the antibody directed against retroorbital eye muscle antigen. In addition, plasma exchange produces the extraction of glycosaminoglycans from retroorbital tissue. These hygroscopic molecules are responsible for the marked oedema in retroorbital tissue.