Propylthiouracil before 131I therapy of hyperthyroid diseases: effect on cure rate evaluated by a randomized clinical trial.

A randomized clinical trial was performed to clarify whether pretreatment with propylthiouracil (PTU) before radioiodine ((131)I) therapy influences the final outcome of this therapy, as has been indicated by retrospective studies. Untreated consecutive hyperthyroid patients with Graves' disease (n = 23) or a toxic nodular goiter (n = 57) were randomized to either PTU (+PTU; n = 39) or no pretreatment (-PTU; n = 41) before compensated (131)I therapy. The median PTU dose was 100 mg, which was discontinued 4 d before treatment. The median (131)I activity was 302 MBq (range, 87-600 MBq). After (131)I therapy, the serum free T(4) index increased in the +PTU group from 97.7 +/- 47.5(+/-sd) nmol/liter at the time of therapy to 152.3 +/- 77.6 nmol/liter at 3 wk (P < 0.001) and 140.4 +/- 75.9 nmol/liter at 6 wk (P < 0.001). In the -PTU group, the serum free T(4) index, which was initially 254.3 +/- 145.7 nmol/liter, decreased significantly to 212.0 +/- 113.0 nmol/liter at 3 wk (P < 0.05) and 165.8 +/- 110.0 nmol/liter at 6 wk (P < 0.005). After 1 yr of follow-up, the treatment failure rate in patients with a toxic nodular goiter was four times higher in the +PTU group than in the -PTU group (nine of 20 vs. three of 25 patients; P = 0.06), whereas the difference among patients with Graves' disease was less obvious (four of six vs. four of nine; P = 0.81). Patients in the +PTU group who were cured had higher serum TSH (s-TSH) levels at the time of (131)I therapy than those who were not cured. By adjusting for a possible interfactorial relationship through a regression analysis, including the s-TSH level and type of disease, only PTU pretreatment had a significant adverse effect on the cure rate (P = 0.03). In conclusion, this randomized trial demonstrates that PTU pretreatment reduces the cure rate of (131)I therapy in hyperthyroid diseases, although this adverse effect seems to be attenuated by the concomitant rise in s-TSH.

Myocardial perfusion imaging and coronary angiography in patients with known or suspected stable angina pectoris.

INTRODUCTION: The patho-physiological cause of angina pectoris is myocardial ischaemia, which can be objectified by myocardial perfusion imaging (MPI). METHODOLOGY: MPI was undertaken prior to coronary angiography (CAG) in 86 randomly selected patients with known or suspected stable angina pectoris. RESULTS: Among 78 adequately stressed patients, MPI was normal in 28 (36%) and showed reversible and irreversible perfusion abnormalities in 30 (38%) and 20 patients (26%), respectively. Coronary angiograms were normal in 28 (36%) and revealed at least one > or = 50% stenosis in 50 patients (64%) (16 with single and 34 with multi vessel disease). Using angiography as a reference, the sensitivity and specificity of MPI in detecting coronary artery disease was 88% and 93%, respectively. DISCUSSION: MPI demonstrates regional hypoperfusion whereas CAG depicts anatomical stenosis in epicardial arteries. Both modalities are potentially relevant in patients with stable angina pectoris. The functional significance of coronary artery lesions is, however, variable and MPI can demonstrate normal myocardial perfusion in the presence of moderate lesions. MPI exhibited a high sensitivity and specificity regarding significant lesions. More than one third of the subjects had a normal MPI and a normal CAG. Patients with stable angina pectoris and a normal MPI have a very low risk of cardiac events and do usually not require further invasive investigation or therapy. Reversible ischaemia and irreversible ischaemia with demonstration of viable tissue call for coronary revascularisation.

Interpretive intra- and interobserver reproducibility of rest/stress 99Tcm-sestamibi myocardial perfusion SPECT in a consecutive group of male patients with stable angina pectoris before and after percutaneous transluminal angioplasty.

BACKGROUND: Observer variability of 99Tcm-sestamibi myocardial perfusion imaging (MPI) has rarely been investigated. The aim of our study was to evaluate the interpretive reproducibility with this technique. PATIENTS: We report on 108 consecutive male patients with stable angina pectoris, investigated before and after percutaneous transluminal angioplasty (PTCA). METHODS: A 2-day rest/stress 99Tcm-sestamibi gated single photon emission computed tomography (SPECT) protocol was used. MPI was interpreted by two independent observers without knowledge of clinical data, using a 20-segment scoring model. RESULTS: Intra- and interobserver agreement was found to be good to excellent (kappa = 0.71-0.85) with regard to the overall diagnosis as well as the individual vessel diagnosis (kappa = 0.60-0.87). However, agreement was higher for left anterior descending coronary artery (LAD) and left circumflex coronary artery (LCX) vascular territories than for the right coronary artery (RCA) territory. Moderate to good intraobserver agreement (kappa = 00.54-0.68) and slightly lower interobserver agreement (kappa = 0.52-0.56) was found for segmental score interpretation. When comparing the interpretive reproducibility before and after PTCA intra- and interobserver agreement was better after PTCA, probably reflecting the increase in normal scans after revascularization. CONCLUSIONS: In a group of consecutive male patients with stable angina pectoris interpretive reproducibility (overall and individual vessel diagnosis) was good to excellent. However, segmental scoring reproducibility was moderate to good.

[Myocardial scintigraphy and coronary arteriography in patients with known or suspected stable angina pectoris]. / Myokardiescintigrafi og koronararteriografi hos patienter med kendt eller formodet stabil angina pectoris.

INTRODUCTION: Myocardial perfusion imaging (MPI) demonstrates regional hypoperfusion, whereas coronary angiography shows anatomical stenoses in epicardial arteries. Both modalities are potentially relevant in patients with stable angina pectoris. MATERIALS AND METHODS: MPI was undertaken before angiography in 86 randomly selected patients with stable angina pectoris. RESULTS: Of 78 adequately stressed patients, MPI was normal in 28 (36%) and showed reversible and irreversible perfusion abnormalities in 30 (38%) and 20 patients (26%), respectively. Coronary angiograms were normal in 28 (36%) and revealed at least one > or = 50% stenosis in 50 patients (64%) (16 with single vessel and 34 with multivessel disease). With angiography as reference, the sensitivity and specificity of MPI in the detection of coronary artery disease were 88% and 93%, respectively. DISCUSSION: Patients with stable angina pectoris and a normal MPI have a very low risk of cardiac events and do not usually require invasive investigation and therapy. Reversible ischaemia and irreversible ischaemia with viable tissue call for coronary revascularisation.

Transition of nodular toxic goiter to autoimmune hyperthyroidism triggered by 131I therapy.

The use of 131I treatment in nodular toxic goiter is widely accepted. In this article, we describe transition of nodular toxic goiter into an autoimmune toxic goiter with development of thyrotropin receptor antibodies (TRAb) as a side effect of 131I treatment. In this retrospective study, 149 patients with nodular toxic goiter (100 with multinodular goiter, 49 with a solitary autonomously functioning toxic nodule) were studied. Of these 149 patients 100 became permanently euthryoid after 1 dose of 131I, and due to persistent hyperthyroidism, 32 patients needed 2-5 doses to became euthyroid. After becoming euthyroid, none of these 132 patients had relapse of hyperthyroidism in the follow-up period. Based on evaluation of the thyroid hormone variables, 17 of 149 patients had a distinctly different pattern in the changes in thyroid hormones. They developed an increase in FT4I 3-6 months posttreatment after an initial fall in FT4I. Twelve of these 17 patients were treated with antithyroid drugs before the initial 131I dose. On samples of frozen sera (-20 degrees C) anti-thyroid peroxidase (TPO) and TRAb were followed for 6 months after 131I treatment in these 17 patients. A similar follow-up was done in 20 patients (10 with and 10 without antithyroid drug pretreatment), randomly selected from the patients who did not relapse. In the remaining 112 patients, anti-TPO and TRAb levels were measured only before the 131I treatment. Of the 17 patients with relapse, 6 developed TRAb concomitant with recurrence of hyperthyroidism (4% of the study group). In 5 of the 17 patients TRAb values remained absent throughout the follow-up period. The remaining 6 patients had elevated TRAb values before 131I treatment. Among the 132 patients who did not relapse, an additional 7 cases with presence of TRAb were found. A total of 9% of the study group was found to have TRAb before 131I pretreatment. Anti-TPO was found in 20 of 149 patients (13%) before 131I treatment. Complications, either hypothyroidism or TRAb-associated hyperthyroidism, were seen in 8 of 20 patients (40%) with anti-TPO before 131I treatment, compared to 9 of 129 (7%) without (p<0.005). In conclusion, TRAb and a Graves' like hyperthyroidism can be triggered by 131I treatment in patients with nodular toxic goiter. The presence of anti-TPO seem to be a marker of an increased risk of development of TRAb-associated hyperthyroidism as well as hypothyroidism, but both side effects can be seen despite the absence of anti-TPO autoantibodies.

[Can radioactive iodine be used in the treatment of diffuse non-toxic goiter?]. / Kan radioaktivt jod anvendes i behandlingen af diffus atoksisk struma?

Traditional treatment modalities of diffuse nontoxic goitre are thyroid hormone suppression or surgery. When treating nodular nontoxic goitre with 131I treatment, a reduction in thyroid volume to about 50% is seen. In the present study we evaluated the effect of 131I treatment in 21 patients treated for a diffuse nontoxic goitre and followed by evaluation of thyroid volume measured by ultrasound. Thyroid volume declined in all patients from median of 66 ml (range 27-160 ml) to 21 ml (9-108 ml) over a year, a reduction of 62%. Three patients developed hypothyroidism in the follow-up period (14%), one of these had a temporary hyperthyroid fase. In conclusion, 131I treatment of diffuse nontoxic goitre reduces thyroid volume by approximately 60% within 12 months. Hypothyroidism developed in 14% during a limited follow-up period.

Thyroid volume and function after 131I treatment of diffuse non-toxic goitre.

OBJECTIVE: Traditional treatment of diffuse non-toxic goitre are thyroid hormone suppression or surgery. When treating nodular non-toxic goitre with 131I treatment a reduction in thyroid volume to about 50% has been observed. In the present study we evaluated the effect of 131I treatment of diffuse non-toxic goitre. DESIGN: Retrospective study of patients treated for a diffuse non-toxic goitre and followed by evaluation of thyroid volume measured by ultrasound. PATIENTS: Ten selected patients from our out-patient clinic with diffuse non-toxic goitre. MEASUREMENTS: Thyroid volume was measured by ultrasound and thyroid function by serum values of T4, T3, T3 uptake ratio, TSH, TSH receptor antibodies and thyroid peroxidase antibodies (anti-TPO). Measurements were performed before and 1, 3, 6 and 12 months (and 18 months (n = 7), thyroid volume measured in six patients)) after 131I treatment. RESULTS: Thyroid volume declined in all patients from median 41 (range 27-160) ml to 20 (range 9-108) ml over 1 year, a reduction of 47%. One patient developed transient and one persistent hypothyroidism in the follow-up period. Both had elevated anti-TPO levels before treatment (331 and 9185 U/ml) and demonstrated titre increases of 2.5 and 30 times after 3 and 6 months, respectively. Pretreatment values were reached after 1 year. The other eight patients had normal anti-TPO levels and free T4 and T3 indices did not change during follow-up, whereas serum TSH levels demonstrated upward trends within the normal range (P < 0.05). TSH receptor antibodies were normal and remained so in all patients. CONCLUSIONS: 131I treatment of diffuse non-toxic goitre reduces thyroid volume by approximately 50% within 12-18 months. Hypothyroidism, during a limited follow-up period, developed only in patients with positive anti-TPO levels before treatment.

Improvement of upper airway obstruction after 131I-treatment of multinodular nontoxic goiter evaluated by flow volume loop curves.

Symptoms of tracheal-esophageal compression are often related to a large nontoxic goiter. The aim of the present study was to evaluate to what degree upper airway obstruction, as measured by flow volume loops, FIF50% and FEF50%/FIF50% (Forced Expiratory Flow at 50% of the vital capacity/ Forced Inspiratory Flow at 50% of the vital capacity) exists in nontoxic multinodular goiter, and whether changes occur after 131I-treatment. Thirteen patients with large multinodular nontoxic goiters were evaluated by estimation of FIF50%, FEF50%/FIF50% ratio and a graphic plot of the flow volume loop curve before and three, six and 12 months after treatment with 131I. FIF50% increased over 12 months from median 1.79 l/sec (range 1.46-3.02) to 2.84 l/sec (1.13-5.69) (p = 0.01). A progressive increase was seen over time (p = 0.001, trend analysis). The FEF50%/FIF50% ratio decreased from in 1.45 (0.32-2.26) to 1.03 (0.43-2.13) 12 months after treatment (p < 0.001). A progressive decrease was seen over time (p = 0.001, trend analysis). By visual evaluation 11 had a flow volume loop curve typical for an upper airway obstruction and in 9 patients the FEF50%/FIF50% ratio was > 1.2. In conclusion we found that upper airway obstruction is present in patients with multinodular nontoxic goiter, and seems to be reduced after 131I-treatment. Flow volume loop curves and measurement of FEF50% and FIF50% are important estimates for upper airway obstruction in these patients.

Thyroid volume and morphology and urinary iodine excretion in a Danish municipality.

In order to throw light upon the eventual need for iodine supplementation in Denmark, four age groups of women (15, 30, 45 and 60 years) from the Holbaek municipality were invited for a clinical and ultrasound study of thyroid volume, structure and function. Of the 570 women invited, 391 accepted and were divided into the following groups: group I: 15 years, N = 113; group II: 30 years, N = 100; group III: 45 years, N = 98; group IV: 60 years, N = 80. The results were as follows the thyroid gland was palpable in 39% and visible in 16% of the entire group; 19% had a family history of thyroid disorders and 7.6% had a previous thyroid disorder. Thyroid volumes (median (range)) as measured by ultrasound were 12 ml (4-29 ml), 18 ml (5-47 ml), 18 ml (7-64 ml) and 18 ml (9-51 ml) in groups I-IV, respectively. The calculated 24-h iodine excretion was 65 micrograms (19-365 micrograms), 88 micrograms (15-274 micrograms), 97 micrograms (40-737 micrograms) and 83 micrograms (50-999 micrograms) in groups I-IV, respectively. An abnormal echo structure was present in 3, 10, 21 and 30%, respectively. Defining a goitre as a thyroid volume above 28 ml indicated a goitre prevalence of 17% in females aged 30-60 years in the Holbaek area of Denmark. Among the 60-year-old women, 3% had a clinically significant goitre (WHO grade III). Thyroid volume did not correlate with iodine excretion. The benefit of iodine supplementation is discussed.

Serum thyroid hormones and blood folic acid during monotherapy with carbamazepine or valproate. A controlled study.

Studies investigating the influence of antiepileptic drugs on thyroid hormones usually have compared patients chronically treated with antiepileptic drugs to controls. To date, this type of designs has produced divergent results both with regard to individual drugs and individual thyroid hormones. The present study comprised 31 patients with newly diagnosed epilepsy, commencing treatment with either carbamazepine or valproate. T3, T4, FT4, FT3, rT3, TSH, T3 resin uptake and blood folic acid, were determined before and during antiepileptic monotherapy, thus making the patient his own control. During treatment with carbamazepine, a significant decrease in T4, FT4, FT3, rT3 and TBG was observed. Valproate caused a decrease in T4, FT4 and T3. Neither of the drugs caused any changes in blood folic acid concentrations or persistent increases in the TSH values. None of the patients developed overt symptoms of hypothyreoidism. Conceivable mechanisms underlying these hormonal changes are reviewed.