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

ABSTRACT

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

Abstract.

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

Objective

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).

Design

Population-based study of thyrotoxicosis at disease onset.

Methods

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.

Results

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.

Conclusions

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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Enio Martino, Alessandro Pacchiarotti, Fabrizio Aghini-Lombardi, Lucia Grasso, Giovanni Bambini, Lidio Baschieri, and Aldo Pinchera

Abstract. The serum free thyroxine concentration was measured by direct radioimmunoassay in 38 untreated T3-thyrotoxic patients with elevated serum total and free triiodothyronine, normal serum thyroxine and free thyroxine index, no TSH response to TRH, and with clinical evidence of hyperthyroidism. An elevation of circulating free thyroxine values was observed in 58% of the patients, whereas total serum thyroxine concentration was within the normal range. It is suggested, therefore, that T3-thyrotoxicosis should be reserved for patients with elevated serum total T3 and free T3 concentrations and normal serum total T4 and free T4 concentrations. Serum thyroxine-binding globulin concentrations were significantly lower (P < 0.025) in patients with an elevated serum free thyroxine (18.7 ± 3.6 μg/ml: mean ± sd) as compared with those in patients with a normal free thyroxine concentration (23.4 ± 2.6 μg/ml). In addition, no daily fluctuations in total and free thyroxine concentration were observed in 6 patients over a 4–8 day period.

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Angel A. Zaninovich

ABSTRACT

The peripheral metabolism of thyroxine (T4) was studied before and after the administration of oestrogens in 21 patients with Graves' disease and in 5 subjects with thyrotoxicosis factitia. In addition, 6 patients with Graves' disease while receiving oestrogen treatment were given 600 mg of diphenylhydantoin (DPH) orally daily; the study on the peripheral metabolism of T4 was similarly performed. Oestrogens induced the following changes in T4 metabolism: a decrease in the concentration of free T4 in the serum, an increase in serum total T4, slowing of the fractional turnover, and contraction of the distribution space. The extrathyroidal T4 pool remained unchanged. These changes led to a decrease in daily T4 degradation rate from 469 μg in the control period to 348 μg during oestrogen therapy (P < 0.001). Fifteen of these patients showed apparent clinical improvement. The 2 subjects with T4-thyrotoxicosis factitia had decreased T4 degradation and remission of symptomatology following oestrogen administration; on the other hand, 3 subjects with T3-thyrotoxicosis factitia had no appreciable amelioration of their symptoms. The administration of DPH to oestrogen-treated patients with Graves' disease induced a slight acceleration of the absolute T4 turnover. It is concluded that the decreased T4 degradation induced by oestrogens in spontaneous and iatrogenic hyperthyroidism was mediated by an increase in T4-binding globulin capacity in the serum.

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J. Penhaligon and M. L. Wellby

Abstract.

A kindred with a high prevalence of hereditary serum thyroxine-binding globulin (TBG) is described. Seventeen of the 29 members of the kindred have the increased TBG trait as demonstrated by a combination of increased serum total thyroxine (T4) and total triiodothyronine (T3) and decreased T3 resin uptake. In 12 of the 17, the anomaly was confirmed by measuring serum TBG activity as maximum binding capacity of T4. The pattern of increased TBG is consistent with X-linked inheritance. One of the affected members had proven thyrotoxicosis and two others were subjected to sub-total thyroidectomy.

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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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L Druetta, H Bornet, G Sassolas, and B Rousset

Thyroglobulin (Tg) present in the serum of normal individuals and patients with thyroid disorders could be partly newly synthesized non-iodinated Tg and partly Tg containing iodine and hormone residues originating from the lumen of thyroid follicles. With the aim of examining the contribution of the latter source of Tg to the elevation of serum Tg concentration in thyroid pathophysiological situations, we devised a procedure to identify thyroxine (T4) and tri-iodothyronine (T3) residues on Tg from unfractionated serum. A two-step method, basedon (i)adsorption of Tg on an immobilized anti-human Tg (hTg) monoclonal antibody (mAb) and (ii)recognition of hormone residues on adsorbed Tg by binding of radioiodinated anti-T4 mAb and anti-T3 mAb, was used to analyze serum Tg from patients with either Graves' disease (GD), subacute thyroiditis (ST) or metastatic differentiated thyroid cancer (DTC). Purified hTg preparations with different iodine and hormone contents were used as reference. Adsorption of purified Tg and serum Tg on immobilized anti-hTg mAb ranged between 85 and 90% over a wide concentration range. Labeled anti-T4 and anti-T3 mAbs bound to adsorbed purified Tg in amounts related to its iodine content. Tg adsorbed from six out of six sera from ST exhibited anti-T4 and anti-T3 mAb binding activities. In contrast, significant mAb binding was only observed in one out of eight sera from untreated GD patients and in 1 out of 13 sera from patients with DTC. The patient with DTC, whose serum Tg contained T4 and T3, represented a case of hyperthyroidism caused by a metastatic follicular carcinoma. In conclusion, we have identified, for the first time, T4 and T3 residues on circulating Tg. The presence of Tg with hormone residues in serum is occasional in GD and DTC but is a common and probably distinctive feature of ST.

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Per Anders Dahlberg and Rolf Jansson

Abstract. During a 4 year period 19 women with post-partum onset of thyroid dysfunction have been seen in our clinic. Five women had high radioiodine uptake thyrotoxicosis (Graves' disease). Twelve women had hypothyroid symptoms starting within 3–6 months of delivery. All of these women had thyroid microsomal and/or cytoplasmic autoantibodies and thyroid lymphocytic infiltration suggesting aggravation of pre-existing subclinical autoimmune thyroiditis (Hashimoto's disease). At follow-up thyroid function gradually improved in all but signs of persistent thyroid hypofunction remained in seven. Thus women developing symptomatic postpartum hypothyroidism should be followed regularly and when thyroxine treatment is commenced in the post-partum period, it has to be continued indefinitely in many cases.

Two women presented with transient low radioiodine uptake thyrotoxicosis and a small painless goitre. Thyroid cytology revealed thyroiditis but they had no thyroid autoantibodies. When followed after a succeeding delivery none of these women developed post-partum thyroid dysfunction in contrast to women in the autoimmune group. Probably the aetiology of thyroid dysfunction in these 2 women was different.