Prognostic value of serial serum thyroglobulin determinations after total thyroidectomy for differentiated thyroid cancer.

Serial weekly serum samples (for 3 weeks) were obtained from 42 patients with differentiated thyroid cancer (DTC, papillary no.=35, follicular no.=6, Hurthle cell no.=1) for serum thyroid hormone, TSH and TG before and after total thyroidectomy. Serum specimens were also obtained one month after radioiodine (131I) therapy followed by suppressive dose of L-thyroxine (L-T4, 2.5 microg/kg). The patients were subdivided into four groups: group I: the DTC was confined to a single solid nodule (no.=1 2); group II: thyroid malignancy invaded local cervical structures but there were no lymph node metastases (no.=8); group III: DTC with lymph node metastases (no.=6); and group IV: DTC with distant metastases (no.=16). In all group I patients serum TG remained undetectable in spite of elevated serum TSH levels at the 3rd week post-surgery (PS). Only one of group II patients had a detectable serum TG value of 5.2 ng/ml (3rd week PS). By contrast, 37.5% of group III patients had detectable serum TG levels, ranging from 3.4 to 16.8 ng/ml (3rd week PS). Lymph node metastases were detected in 5 of these patients by whole body scan (WBS) and removed surgically in 3. As expected, group IV patients had elevated serum TG values ranging 33.0-958.0 ng/ml and distant metastases were confirmed in all of them by WBS. From the calculations through univariate logistic regression comparing TG concentrations at the 3rd week PS from groups I and II vs groups III and IV, we obtained a cut-off value of 2.3 ng/ml with the following efficacy features: sensitivity=74.5%; specificity=95%; positive predictive value=92.3%; negative predictive value=65.5%; and accuracy=73.8%. After 131I and L-T4 suppressive therapy, only 5 out of 36 patients of groups I, II and III had detectable serum TG levels (3.1-7.0 ng/ml) whereas serum TG was detectable in all group IV patients (ranging 2.5-8.6 ng/ml). We concluded that serum TG concentrations above 2.3 ng/ml at the 3rd week PS could be suggestive of lymph node or distant metastases in patients with DTC. Patients with serum TG above this limit could be considered at risk for metastatic disease and higher doses of diagnostic iodine-131 (131I) may be indicated for actinic ablation.

Prevalence and characteristics of postpartum thyroid dysfunction in São Paulo, Brazil.

OBJECTIVE: Postpartum thyroid dysfunction (PPTD) is an autoimmune disorder characterized by the development of transient hyperthyroidism and, more frequently, hypothyroidism (or both) during the first six months of the puerperal period. A variable incidence has been reported in part because of differences in the number of women studied, the frequency of thyroid assessment postpartum, diagnostic criteria and methodology. The aim of this study was to evaluate thyroid function, ultrasound images and titre of autoantibodies against thyroid antigens in a cohort of pregnant women who met the criteria of 'normal' thyroid gland structure on clinical examination and imaging and normal thyroid function tests without a significantly positive anti-thyroid peroxidase (TPO) antibody titre (i.e. < 100 U/ml) in the first trimester. DESIGN AND PATIENTS: Eight hundred nulliparous or multiparous (one to seven previous pregnancies) pregnant women (age 26.1 +/- 4.8 years, mean +/- SD), were submitted to clinical, laboratory and ultrasonographic examination in the first trimester of pregnancy. Among these forty-six patients were excluded because of thyroid dysfunction, ultrasound structural abnormalities or a positive anti-TPO antibody titre (> 100 U/ml). A total number of 754 women were available for further studies in the postpartum period. A relatively large number of these patients (386) were lost for follow-up either before or after delivery. MEASUREMENTS: A cohort of 368 puerperal women was followed up regularly at 3, 6, 12 and 24 months after delivery, with periodic thyroid function tests, random urine iodine measurements, assays for serum autoantibodies against thyroid antigens and imaging by ultrasound. RESULTS: The provisional diagnosis of PPTD was established in 78 out of 368 who had positive anti-TPO levels and ultrasonographic thyroid structural changes. Twenty-nine of these patients had a transient rise of anti-TPO autoantibodies characterizing an autoimmune reaction. These autoantibodies levels progressively declined or became negative. Moreover none of these patients had evidence for altered thyroid function during the 18-24 months of follow-up. The remaining 49 patients (13.3%) progressively developed thyroid function abnormalities (mainly hypothyroidism) indicating the presence of thyroid gland changes due to PPTD. Further follow-up studies indicated that at 18-24 months, 42 patients had serum levels of anti-TPO-Ab that were more elevated, as compared with the first year values. Predictive factors found during pregnancy for developing PPTD were: (1) relatively low levels of anti-TPO, between 60 and 100 U/ml (odds ratio 3.1 : 1), and (2) ultrasonographic thyroid structural changes in the first trimester (odds ratio 6.4 : 1). CONCLUSIONS: We conclude that the prevalence of postpartum thyroid dysfunction in our geographical area ranges from 6.7% to 13.3%, considering, respectively, all pregnant women that were examined (n = 754) or only the number of puerperal women actually followed-up (n = 368). A transient form of thyroid autoimmune reaction characterized by elevated serum levels of anti-TPO that progressively declined or disappeared was observed in 29 puerperal women. Sonographic structural and echogenicity changes in the thyroid gland and borderline positive anti-TPO levels (between 60 and 100 U/ml) during pregnancy were considered to be of predictive value for development of postpartum thyroid dysfunction.

Combined ultrasonographic and cytological studies in the diagnosis of thyroid nodules.

Many aspects of thyroid nodule evaluation and management remain controversial. Widespread application of ultrasonography has resulted in frequent discovery of incidental nodules in the general population which has created a management dilemma for physicians. In this paper we have introduced a novel approach for evaluation of solid nodules, using an index derived from ultrasonographic and cytologic studies. Briefly thyroid nodules were classified ultrasonographically into four grades, with increasing score numbers (1-4) as progression to malignantly suspicious lesions was present. Similarly, four grades of a cytologic classification of fine needle biopsy aspirates were introduced with scores of 1-6 (benign to malignant diagnosis). The sum of the ultrasonographic and cytologic scores were the basis of a diagnostic index: benign (2-4), doubtful (5), suspicious (6) and malignant (7-10). Sixty patients with an index equal or higher than 6 were submitted to thyroidectomy and the prevalence of thyroid cancer (n = 46) in the excised nodules was 76.6%. Most series report a 10% to 30% incidence of malignancy in excised nodules with suspicious diagnosis. We concluded that using an index derived from combined ultrasonographic and cytologic studies will result in a better patient selection for surgery.

Levothyroxine suppressive therapy is partially effective in treating patients with benign, solid thyroid nodules and multinodular goiters.

We prospectively evaluated the effect of thyrotropin (TSH)-suppressive therapy with levothyroxine (LT4) on the size of a benign, solitary, solid nodule and multinodular goiter in a relatively low iodine intake area. In this study, 101 euthyroid subjects with a benign, solitary, predominantly solid nodule (n = 54) confirmed by biopsy or multinodular goiter (n = 47) received 200 microg of levothyroxine daily as a single morning tablet for 12 months. Thirty-five receiving no therapy were considered as controls (solitary nodules, n = 20, multinodular, n = 15). Patients were admitted to the study after evaluation of thyroid biochemical parameters (thyroxine [T4], free thyroxine [FT4], triiodothyronine [T3], thyrotropin [TSH], and thyroglobulin [Tg]), thyroid scanning, ultrasound examination, and fine-needle aspiration biopsy. Every 3 months, thyroid function tests and every 6 months ultrasound examinations were repeated. Twelve months later 20 of 54 (37.1%) patients with single, solid nodules had 50% or more regression of the nodular volume (responders). Eleven of 54 (20.3%) patients had more than 20%, but less than 49.9% reduction of nodular volume (partial responders). Nonresponders were 23 of 54 (42.5%). One-third of subjects with multinodular goiter had 50% or more regression of the glandular volume, whereas 46.8% were considered as nonresponsive. The mean serum Tg levels decreased significantly only in responders with solitary nodular disease or multinodular goiter. In the control group only 1 patient (5% of total) with a solitary nodule had a 50% reduction in the nodular volume. Five others had a partial response (<49%, >20% reduction). None of the patients with multinodular goiter had a significant reduction (>50%) of the combined nodular volumes. We concluded that LT4 may be effective, among other factors, in arresting the growth or in reducing the volume of relatively small, benign, solitary, solid thyroid nodules or the combined nodular volume of multinodular goiter.

Prevalence of incidental thyroid disease in a relatively low iodine intake area.

An ultrasonographic survey of thyroid abnormalities was conducted in 547 consecutive apparently normal overweight subjects (380 females and 167 males), aged 27-58 years in an urban area with relatively low iodine intake (mean daily urinary iodine excretion: 10.6 micrograms/dL). Individuals with any previous thyroid disease or familial thyroid pathology were excluded. In 240 subjects (44%) high resolution ultrasonography of the thyroid was considered normal. In 307 individuals (56%) abnormalities of the echo structure (39%) or thyroid nodular disease (17%) were detected by ultrasonography. Marked heterogeneity of the echo structure that was considered suggestive of chronic autoimmune thyroiditis was present in 81 subjects (15%). In 72 of these patients the serum anti-TPO levels were positive by a sensitive RIA. Thyroid nodules either solid or predominantly cystic were present in 90 subjects (17%). Eighteen patients had a relatively large nodule (diameter 15-18 mm). Eleven of these nodules were missed at clinical examination. Fine needle aspiration cytology was performed in 14 patients and 7 individuals underwent thyroid surgery. In 6 subjects the pathologic diagnosis was benign adenomatous goiter and one patient had a follicular carcinoma. Thyroid function studies confirmed subclinical hypothyroidism in 27 patients (4.9%), all of them with elevated serum anti-TPO autoantibodies levels. It was concluded that the overall occurrence of thyroid disease is more common than suspected by clinical examination.