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Hans Perrild, Anette Grüters-Kieslich, Ulla Feldt-Rasmussen, David Grant, Enio Martino, Lars Kayser, and Francois Delange

Perrild H, Grüters-Kieslich A, Feldt-Rasmussen U, Grant D, Martino E, Kayser L, Delange F. Diagnosis and treatment of thyrotoxicosis in childhood. A European questionnaire study. Eur J Endocrinol 1994;131:467–73. ISSN 0804–4643

A covering letter and a questionnaire covering the diagnosis and treatment of thyrotoxicosis in childhood was circulated between October 1992 and February 1993 amongst 672 European members of the European Thyroid Association (ETA) and members of the European Society for Pediatric Endocrinology (ESPE). Almost 50% replied to the letter and 99 individuals or groups from 22 countries completed the questionnaire. A consensus was reached on the use of total thyroxine (T4) and/or free T4 and thyrotropin as routine diagnostic tools. Two-thirds included total triiodothyronine (T3) and/or free T3 and 32% used a thyrotropin-releasing hormone test. Surprisingly, thyroglobulin autoantibodies were used as a routine test by 78%; 63% included thyrotropin receptor antibodies and 60% microsomal antibodies, whereas only 50% measured thyroperoxidase antibodies. For thyroid imaging, 40% performed a thyroid scintigram and 56% measured the size of the thyroid gland by ultrasound. Antithyroid drugs (ATD) were the basic initial treatment of choice given by 99% of the respondents for children with uncomplicated Graves' disease. Carbimazole, methimazole and thiamazole were the most frequently used drugs, with a median initial dose of 0.8 mg · kg1 · day1. Two-thirds added betablockers and a few used sedatives. The ATD dose was adjusted for each patient by 39%, whereas 56% combined ATD with T4 for long-term treatment; 84% gave treatment for a fixed period (44% for 1–2 years). Surgery was considered the treatment of choice in children with an adenoma (83%), with a nodular (53%) or large goiter (16%) and recurrence after ATD (14%). Radioiodine was the treatment of choice by 18% of the respondents for patients with recurrence after surgery and recurrence after ATD (7%).

Hans Perrild, Department of Medicine B, Bispebjerg University Hospital, 2400 Copenhagen, Denmark

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Allan Carlé, Nils Knudsen, Inge Bülow Pedersen, Hans Perrild, Lars Ovesen, Lone Banke Rasmussen, and Peter Laurberg


To characterize thyroid hormone levels at the time of diagnosis in the nosological types of thyrotoxicosis diagnosed in the population and to analyze determinants for serum thyroxine (T4) and tri-iodothyronine (T3).


Population-based study of thyrotoxicosis at disease onset.


In the period 1997–2000, we prospectively identified all patients diagnosed with incident primary overt thyrotoxicosis in a Danish population cohort and classified patients into ten well-defined nosological types of disease (n=1082). Untreated levels of serum T3, T4, and T3:T4 ratio were compared and related to sex, age, level of iodine deficiency, smoking status, alcohol intake, iodine supplement use, co-morbidity, and TSH receptor antibodies (TRAbs) in multivariate models.


Graves' disease (GD) patients had much higher levels of T3 and higher T3:T4 ratio at diagnosis compared with other thyrotoxic patients, but with a profound negative association between hormone levels and age. In GD, patients diagnosed in the area with more severe iodine deficiency had lower levels of T3 and T4. TRAb-negative GD patients had biochemically mild thyrotoxicosis. Higher age was also associated with lower degree of biochemical thyrotoxicosis in nodular toxic goiter. We found no association between serum T3 and T4 and sex, smoking habits, iodine supplements, alcohol intake, or co-morbidity in any type of thyrotoxicosis.


The study gives new insight into the hormonal presentation of thyrotoxicosis and showed that young age, positive TRAb levels, but also residency in the area with higher iodine intake was positively associated with biochemical disruption in GD.

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J. Date, M. Blichert-Toft, U. Feldt-Rasmussen, and V. Haas

Abstract. The effect of subtotal thyroid resection for thyrotoxicosis on concentrations of serum thyroid hormones and thyroglobulin (Tg), was determined in 10 patients during operation and the subsequent 18 days. Mean serum Tg responded drastically, increasing from a pre-operative value of 0.30 nmol/l to a peak value of approximately 26 nmol/l during operation followed by a gradual decline to levels lower than before surgery on day 18. Mean serum total thyroxine was 114 nmol/l pre-operatively and free thyroxine index (FT4I) 105 units. Both fluctuated only slightly during operation. Postsurgically, the mean values decreased to below 50% of the pre-operative level. Mean serum total triiodothyronine (TT3) was 1.46 nmol/l pre-operatively. It decreased during operation, reaching a nadir of 0.55 nmol/l on day 2, whereafter the concentration increased slightly. Mean serum reverse T3 (rT3) was 0.45 nmol/l pre-operatively, increased 62% during surgery, and decreased postsurgically. The mean value of serum thyroid stimulating hormone (TSH) was 0.61 mU/l pre-operatively and remained below 1 mU/l during and after operation, but from day 10 concentration began to rise steadily. It is concluded that the vast release of Tg during thyroid resection did not contribute to the concentration of serum T4 to an extent of clinical relevance.

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HB Shahbazian, F Sarvghadi, and F Azizi

OBJECTIVE: To determine the prevalence of postpartum thyroiditis (PPT), one of the autoimmune disorders of the thyroid which usually occurs in women in the first year after parturition. PPT presents with periods of transient thyrotoxicosis and hypothyroidism, in many cases resulting in permanent hypothyroidism. DESIGN: The study involved 1040 mothers who had contacted five health centers in Tehran for vaccination of their children. METHODS: Signs and symptoms of hypothyroidism and thyrotoxicosis, and the presence of goiter (using the World Health Organization classification), were sought. Serum T3, T4, TSH, anti-TPO and anti-Tg antibodies were measured at 3, 4.5, 6 and 9 months after parturition. In those with hypothyroidism or thyrotoxicosis and a matched group of normal women, thyroid sonography was performed. RESULTS: The prevalence of thyroiditis was 11.4%. Hypothyroidism and thyrotoxicosis occurred in 68 and 42 mothers respectively. Nine had thyrotoxicosis followed by hypothyroidism. There was one case of Graves' disease. Out of 68 hypothyroid patients, 33 women underwent treatment with levothyroxine (because of the severity of symptoms) for 12 months. Six women showed increased TSH at 6 weeks after discontinuation of thyroxine. Stage II goiter (World Health Organization classification) were observed in 21.8% of patients and in 6.7% of pospartum euthyroid women (P<0.001). Positive anti-TPO was found in 61.5% of patients and in 19% of the control group; positive anti-Tg was found in 58% of patients and in 6% of the control group (P<0.001). Sonographic changes were observed in 96% of the patients and in 7% of the control group (P<0.001). There was no significant correlation between the occurrence of thyroiditis and parity, the age of the mother, a previous history of thyroid disease in the patient or family, breast-feeding, or the gender of the child. CONCLUSION: The results of this study show a high prevalence of PPT in Tehranian women. This may be due to the length and frequency of follow-up and/or the transition from low to adequate iodine intake. The major difference with respect to other studies is the low frequency of the biphasic form of PPT.

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Issac Sachmechi and George C Schussler

Sachmechi I, Schussler GC. Familial dysalbuminemic hyperthyroxinemia in pregnancy. Eur J Endocrinol 1995;133:729–31. ISSN 0804–4643

A 16-year-old pregnant Puerto Rican woman who had been treated for thyrotoxicosis previously was evaluated for goiter, increased total thyroxine (T4) and triiodothyronine (T3) and free T4 estimate, despite a normal thyroid-stimulating hormone (TSH) concentration. These findings are consistent with a TSH-producing pituitary adenoma or the syndrome of generalized thyroid hormone resistance. However, sera from the patient, her mother and subsequently her newborn daughter demonstrated the increased albumin binding of T4 but not T3 that is characteristic of familial dysalbuminemic hyperthyroxinemia (FDH). The free T4 estimate had been elevated artefactually by the increased affinity of FDH albumin for the analog in a one-step assay. The T3 and T4 concentrations were increased by pregnancy and T4 was increased further by FDH. This first report of FDH recognized during pregnancy emphasizes that the effects of pregnancy on thyroid hormone and TSH concentrations complicate the diagnosis of FDH. It is particularly important to distinguish this benign condition from thyrotoxicosis during pregnancy, because inappropriate treatment may affect fetal development.

Issac Sachmechi, Dept. of Medicine, Queens Hospital Center, 82-68 164th Street, Queens, New York, USA

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N. J. B. Christiansen, K. Siersbæk-Nielsen, J. E.M. Hansen, and L. Korsgaard Christensen


Serum thyroxine (T4) and other thyroid function tests were studied in 14 patients with subacute thyroiditis and compared with the same parameters in 32 patients with untreated thyrotoxicosis. The mean values of serum T4 and protein-bound iodine (PBI) were found to be elevated to the same extent in the two groups and the calculated T4 iodine did not differ significantly from the PBI in any of the groups. The resin-T3-test and the basal metabolic rate (BMR) mean values were significantly lower in patients with subacute thyroiditis than in patients with thyrotoxicosis. The serum T4 determination based on competitive protein-binding was not influenced by other organic iodinated products, and our results indicate that the elevated serum PBI in subacute thyroiditis is largely due to T4. The lower BMR in patients with subacute thyroiditis is possibly explained by a difference in the thyroxine binding protein (TBP) binding capacity and free T4 in the serum between patients with subacute thyroiditis and those with thyrotoxicosis.

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Bernhard E. Schreiber, Hugo M. Ortner, Georg Leb, and Otto Eber


An assay of stable 3,5,3′-triiodo-L-thyronine (T3) in serum of 54 patients was performed, using a new simple chromatographic procedure. With samples of 5 ml serum, the lower detection limit was 0.04 μg/100 ml. The total time required for a complete analysis was less than 3 hours, which was accomplished by partial automatization of the procedure. The range of the T3-concentration was 0.22 ± 0.05 (sd) μg/100 ml in 18 normal subjects, 0.67 ± 0.3 in 15 thyrotoxic patients and 0.08 ± 0.04 in 8 patients with hypothyroidism. Among 13 patients with normal serum thyroxine (T4) levels after thyroid surgery owing to thyrotoxicosis, there were 3 with marked increases in serum T3. In spite of normal T4-levels, symptoms of hyperthyroidism were still present in these patients. It is concluded, that serum T3-determinations may be useful for diagnosing cases of hyperthyroidism where clinical findings do not correspond with serum T4 or PBI-findings.

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Harry R. Maxon, Kenneth D. Burman, Bhartur N. Premachandra, I-Wen Chen, Albert Burger, Phillip Levy, and Leon P. Georges


Elevations of serum thyroxine without thyrotoxicosis or binding protein abnormalities have been documented in 8 of 13 family members, representing 4 generations. This syndrome appears to represent an elevated threshold for the amount of free thyroxine substrate required to maintain adequate T3 production form the peripheral monodeiodination of T4. It reiterates the need for a prudent re-evaluation of all clinically euthyroid patients with elevated serum thyroxine concentrations before concluding that they are indeed thyrotoxic.

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J. Chakravarty, A. R. Guansing, S. Chakravarty, and C. V. Hughes


Systolic time intervals consisting of indices of electromechanical systole (QS2-I), left ventricular ejection time (LVET-I) and pre-ejection period (PEP-I) were calculated serially during therapy in 12 euthyroid, 9 hypothyroid and 9 hyperthyroid individuals. These parameters were analyzed sequentially together with the changes in serum thyroxine (T4), triiodothyronine (T3) and thyrotrophin (TSH) in order to determine the sensitivity of these non-invasive procedures in monitoring peripheral thyroid hormone effect. The results are expreseed in mean ± sem. QS2-I (506.3 ± 8.2 ms) and PEP-I (102.9 ± 4.2) were shortened (P < 0.02 and P < 0.001, respectively) in hyperthyroidism and prolonged (579.3 ± 7.3 and 169.6 ± 3.6 ms) in hypothyroidism (P < 0.01 and P < 0.001, respectively) compared to euthyroid controls (538.1 ± 8.8 and 130.3 ± 5.3 ms), while LVET-I did not change significantly in either condition. Simultaneous determinations of circulating T4, T3 and TSH showed changes appropriate to both hypo- and hyperthyroid states. In 2 patients with T3-thyrotoxicosis, PEP-I was decreased to an average of 103.1 ms, while in 2 patients with compensated hypothyroidism (normal T4 but elevated TSH) this was prolonged to 163.7 ms (average) compared to euthyroid controls. During treatment the hypothyroid group showed significant sequential correlation of TSH and PEP-I. In the hyperthyroid individuals, PEP-I correlated significantly with T4 and T3. PEP-I may be a useful, sensitive, quantitative biologic indicator of thyroid hormone effect on myocardial function.

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Kyuzi Kamoi, Terunori Mitsuma, Hiroshi Sato, Motoharu Yokoyama, Kazuo Washiyama, Rhuichi Tanaka, Okuhiro Arai, Nobuyuki Takasu, and Takashi Yamada

Abstract. A 46-year-old woman had signs of thyrotoxicosis and galactorrhoea. Serum immunoreactive TSH and its α-subunit increased in the presence of high serum triiodothyronine (T3), thyroxine (T4), and free T4 concentrations, whereas β-subunit TSH was undetectable. Exogenous TRH failed to increase serum TSH. Serum TSH was markedly suppressed by glucocorticoid, but was increased by antithyroid drug. l-Dopa or bromocriptine partially suppressed, but nomifensine had no influence on serum TSH.

Serum prolactin (Prl) was above normal and markedly increased by TRH, but depressed by bromocriptine and not suppressed by nomifensine. Plasma TRH was normal in the hyperthyroid state, but was increased by glucocorticoid and antithyroid drug. Excess thyroid hormone depressed plasma TRH concentrations. Basal serum GH levels were constantly low. Transsphenoidal removal of the tumour normalized serum hormones (T3, T4 free T4, TSH, α-subunit and Prl), and eradicated the clinical signs of hyperthyroidism and galactorrhoea. Histological study of the tumour tissue demonstrated both thyrotrophes and somatotrophes. A reciprocal relationship between serum TSH and T4 concentrations shifted to a higher level before but was normalized after removal of the tumour. Ten months later, the clinical signs of thyrotoxicosis and the increase in serum thyroid hormone recurred without a concomitant increase in serum TSH and its α-subunit. Thyroidal auto-antibodies were slightly positive, but thyrotrophin-binding inhibitor immunoglobulin (TBII) was negative. Administration of antithyroid drug produced a euthyroid state, but 3 years later, discontinuation of the treatment resulted in recurrent hyperthyroidism without suppressed plasma TRH and with no evidence of regrowth of the pituitary tumour.

It is suggested that the patient initially had hyperthyroidism owing to excessive TSH secretion from the tumour caused by abnormal TRH secretion, and subsequently had hyperthyroidism owing to Graves' disease.