OBJECTIVE: In Graves' hyperthyroidism treated with antithyroid drugs (ATD), the overall relapse rate reaches 30-50% following ATD discontinuation. Conflicting results have previously been reported with regard to the usefulness of combining ATD with thyroxine (l-T4), and thereafter maintaining l-T4 treatment after ATD withdrawal. Also, clinicians are in search of useful parameters to predict the risk of a recurrence of hyperthyroidism after ATD treatment. DESIGN: Eighty-two consecutive patients (70 women and 12 men; mean age 36 years) with a first episode of Graves' hyperthyroidism were investigated prospectively; they were treated with ATD for a total of 15 months, combined with l-T4 (for at least 12 months) after they had reached euthyroidism, with the aim of maintaining serum TSH below 2.5 mU/l during the combined therapy. Following ATD discontinuation, the patients were randomly assigned (double-blind placebo-controlled trial) to taking 100 microg/day l-T4 (vs placebo) for an additional year. METHODS: The following determinations were carried out at initial diagnosis: serum total T4 and tri-iodothyronine (T3), free T4 and T3, TSH, TSH-receptor antibodies (TSHR-Ab), thyroid scintigraphy and echography. During ATD treatment, serum free T4 and T3 and TSH concentrations were recorded after 1 (optional), 2, 4, 6, 9, 12 and 15 months, and echography at the end of ATD treatment. During the randomized trial, serum free T4 and T3 and TSH concentrations were checked every 3 months (or until a recurrence). TSHR-Ab titers were measured at initial diagnosis, after 6 months with ATD, and at the end of ATD treatment. RESULTS: l-T4 administration, both during and after ATD treatment, did not improve the final outcome and recurrence rates were similar in placebo and l-T4-treated patients (30%). Two parameters were identified that might be useful to help predict recurrence risks after ATD: (i) positive TSHR-Ab (at the end of ATD treatment) was significantly associated with a greatly increased recurrence risk; and (ii) despite the relatively small number of patients who were smokers, regular cigarette smoking was shown, for the first time, to be significantly associated with an increased recurrence risk. Also, the deleterious effect of smoking was shown to manifest its impact independently of TSHR-Ab titers at the end of ATD treatment. Thus, compared with the overall 30% recurrence risk, non-smoking patients with a negative TSHR-Ab (at the end of ATD) had a lower (18%) recurrence risk; smoking patients with negative TSHR-Ab (at the end of ATD) had a 57% recurrence risk; non-smoking patients with positive TSHR-Ab (at the end of ATD) had a high (86%) recurrence risk; the recurrence risk was 100% in those few patients who both smoked and maintained a positive TSHR-Ab at the end of ATD treatment. CONCLUSIONS: The present study confirmed that l-T4 administration during and after ATD withdrawal did not improve remission rate. Two factors, namely positive TSHR-Ab at the end of ATD treatment and regular smoking habits may represent clinically useful (albeit not absolute) predictors of the risk of recurrence in patients with Graves' hyperthyroidism treated with ATD. However, due to the relatively small number of smoking patients in the present cohort, this conclusion needs to be confirmed by a larger study.
Y. Ingenbleek, P. De Nayer and M. De Visscher
RT3U3) is significantly elevated (P < 0.001) in the acute stage of kwashiorkor and returns to normal after 2 weeks of appropriate refeeding. RT3U is characterized by a high negative correlation with TBGcap. This negative correlation is maximal on admission (r = −0.88) and gradually declines to normal value (r = −0.63) with clinical recovery. This finding is consistent with the main role attributed to TBG in determining RT3U level.
The collected data emphize the importance of the protein plasma levels in the evaluation of the thyroid function with RT3U in protein-calorie malnutrition.
M. Lambert, A. G. Burger, P. De Nayer and C. Beckers
Abstract. In order to test the reactivity of TSH to TRH during amiodarone treatment we investigated 7 hypothyroid subjects treated with 50 μg T3/day. A TRH test (200 μg iv) was performed before and after 6 weeks of treatment with 400 mg amiodarone/day. Amiodarone treatment induced a significant increase in serum total and free T3 (from 2.17 ± 0.13 to 3.55 ± 0.58 nmol/l and from 5.6 ± 0.61 to 9.46 ± 1.41 pmol/l). Basal TSH levels were significantly decreased and the maximal stimulation of TSH 20 min after TRH injection was only 20.0 ± 3.3 mU/l during amiodarone treatment compared with 61.4 ± 10.4 mU/l before treatment. These results indicate that in hypothyroid patients treated with amiodarone, the TSH response to TRH is blunted and that this is likely to be related to the higher total and free T3 levels or to a direct effect of amiodarone at the pituitary level.
O Alexopoulou, C Beguin, P De Nayer and D Maiter
OBJECTIVE: We studied the clinical and hormonal profiles of patients with central hypothyroidism (CH), the adequacy of levothyroxine (L-T4) treatment and the influence of other pituitary hormone replacement therapies. METHODS: We reviewed medical records of 108 adult patients with child-onset (CO; n=26) or adult-onset (AO; n=82) CH. RESULTS: At diagnosis, the most frequently reported symptoms were fatigue and headaches in AO patients, and growth retardation in CO patients. Serum TSH was normal in a majority of CH patients, low in 8% and elevated in 8%. Serum free thyroxine (fT(4)) was usually reduced, but remained within the low normal range in 28% of the study population (mostly CO patients). Similarly, serum total T(4) (tT(4)), total triiodothyronine (tT(3)) and free T(3) (fT(3)) were found to be within the normal range in significant subsets of patients. Interestingly, the clinical and biochemical characteristics of CH patients with normal f/t T(4) levels were not different from those of the patients with low fT(4) values. The thyroid hormonal profile was not influenced by gender, etiology or by the number of hormone deficiencies. At last evaluation, the mean dose of L-T(4) was 1.6+/-0.5 microg/kg/day and was negatively correlated to current age (P<0.001) but positively correlated to the number of hormone deficiencies (P<0.05). Treatment suppressed TSH in 75% of the patients, induced normal fT(4) in 94%, but normal fT(3) in only 49% of them. Male GH-treated patients and estrogen-treated females needed a higher L-T(4) dose compared with non-treated patients. CONCLUSIONS: fT(4) is clearly the best indicator of CH, but remains in the low normal range in a significant subset of patients, especially in those with CO disease. Adequacy of therapy is mostly reflected by the combination of upper normal fT(4) and low normal fT(3) levels. Pituitary hormone replacement therapy may require an adjustment of T(4) treatment, as female patients under estrogen treatment and male patients under GH treatment will need a higher T(4) dose in order to remain in the euthyroid range.