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Radioiodine therapy in Graves' disease patients with large diffuse goiters treated with or without carbimazole at the time of radioiodine therapy.

We sought to ascertain how high the success rates of radioiodine therapy are for Graves' disease patients with large diffuse goiters when aiming for a constant absorbed dose of 250 Gy. Thirty-six patients with a thyroid volume of 50-110 mL were evaluated for changes in thyroid function and appearance 3, 6, and 12 months after radioiodine therapy. Success was defined as definitive elimination of hyperthyroidism following therapy (hypothyroidism corrected with thyroxine on diagnosis); failure as persistent/recurrent hyperthyroidism after 12 months. Overall success rate was 50%. However, a subgroup of 20 patients without simultaneous carbimazole (carbimazole-off) showed a highly significantly larger success rate (85%) than the 16 patients with simultaneous carbimazole (carbimazole-on) at the time of radioiodine therapy (6.3%, p < 0.000005). Successful cases showed a significantly higher volume reduction after radioiodine than failures (75.5% vs. 35.4%, p < 0.00005). Stepwise logistic regression showed that therapy failure was related to administration of carbimazole during radioiodine therapy (p < 0.0250 and absorbed dose (p < 0.05), but not thyroid function (free triiodothyronine [FT3] and free thyroxine [FT4]), initial thyroid volume or thyrotropin-receptor antibody (TRAb) value. However, a significant correlation of therapy success to absorbed dose (r = 0.69, p < 0.005) could be shown only for carbimazole-off patients, but not for the others. Finally, multivariate factor analysis consistently showed that therapy success was correlated only to absorbed dose and antithyroid drugs, not to initial thyroid volume, TRAb value, or thyroid function. Thyroid volume per se is not responsible for the lower success rate in Graves' disease patients with large goiters because even a comparable group of 32 Graves' disease patients with small thyroid glands (< or =20 mL) and without simultaneous carbimazole showed a success rate of 87.5%. The high failure rate in the carbimazole-on patients (absorbed dose comparable to carbimazole-off) is due to the simultaneous administration of carbimazole. Therefore, if clinically feasible, we recommend discontinuing carbimazole at least one day before beginning radioiodine therapy.

Adult↗

The yield of adequate and conclusive fine-needle aspiration results in thyroid nodules is uniform across functional and goiter types.

Relatively little is known about the cytological characteristics of hyperfunctioning (hot) thyroid nodules. Concern has been expressed that fine-needle aspiration (FNA) identifies hot nodules as follicular tumors or indeterminate, and as a consequence patients could be unnecessarily referred for surgery. Between 1979 and 1996, thyroid FNA was performed on 829 patients. Result of thyroid scan was available in 326; 69 (21%) patients had hot, and 257 (79%) had warm or cold thyroid nodules. Nodules in each of these major groups were divided into 2 subgroups: clinically solitary nodules and dominant nodules in multinodular goiters (MNG). The frequencies of adequate versus inadequate FNA samples, and of conclusive versus indeterminate FNA results were determined separately for each of the groups and subgroups. In addition, patients with hot nodules and overt hyperthyroidism were identified and evaluated separately. Bivariate analyses were performed for the frequency of adequate versus inadequate smears and conclusive versus indeterminate results between hot, toxic, and cold-warm nodules, and between solitary nodules and MNG. The frequency of adequate aspirations and conclusive results in the various groups and subgroups was found to be statistically indistinguishable. In conclusion, the yield of adequate samples and the rate of conclusive results of FNA in thyroid nodules is similar, irrespective of the functional state or of goiter presentation. Hot thyroid nodules do not seem to produce an increase in the rate of inadequate or indeterminate FNA results, and therefore, do not affect the overall performance of thyroid FNA.

Adolescent↗

Evaluation of routine basal serum calcitonin measurement for early diagnosis of medullary thyroid carcinoma in seven hundred seventy-three patients with nodular goiter.

The aims of the study were to identify medullary thyroid cancer (MTC) in its earliest stages by screening patients with basal calcitonin measurements and to determine whether basal serum calcitonin measurements should be a part of the routine evaluation of a nodular goiter. Basal serum calcitonin levels were obtained from 75 patients (female:male 57:18, mean age 42.8 years, range with 18-76 years) with nonnodular thyroid disease as controls. Their mean basal calcitonin level was 7.8+/-0.4 pg/mL with a range of 5-27 pg/mL. Seven hundred seventy-three patients with nodular goiter were included in the study (female:male 586:187) with the mean age of 46.1 years (range 17-78). Four patients had elevated basal serum calcitonin levels ranging between 150-1000 pg/mL. These 4 patients underwent surgery. MTC was confirmed by histopathology in all 4. One patient's mother and brother were also diagnosed as MTC as a result of family screening. Basal serum calcitonin levels were higher than 150 pg/mL in these patients. Fine needle aspiration biopsy (FNAB) of 2 of 4 MTC patients were incorrectly diagnosed as papillary carcinoma; another had malignant cytology and the fourth had benign cytology. None were diagnosed as MTC on the basis of FNAB. In conclusion, calcitonin measurement is an effective method for the diagnosis of MTC. Measurement of basal calcitonin levels in patients with malignant or suspicious FNAB may be a cost-effective approach to screen for MTC. High basal serum calcitonin levels increase the chance of curative therapy by diagnosing MTC in the early stages. It is superior to FNAB for diagnosis of MTC.

Adolescent↗

Assessment of goiter in an area of endemic iodine deficiency.

Urinary iodone (UI) excretion and sonographically measured thyroid volume were investigated in 195 subjects living in 6 separate villages in the Casamance region of southeastern Senegal, West Africa. A comparison of goiter prevalence using thyroid palpation and volume measurement and of iodine excretion expressed as micrograms per gram (microg/g) creatinine or micrograms per deciliter (microg/dl) urine was undertaken, and possible pathogenetic factors were investigated. Ultrasound measured thyroid volumes were above the recommended upper limit of the reference range for an area replete in iodine in 83.1% or females, 52.3% of males, and 80.0% of children aged 13 years or younger. Overall sensitivity and specificity for palpation compared to sonographically demonstrated thyroid enlargement was 51.7% and 91.5%, respectively. Thyroid enlargement was not associated with ethnic origin, thiocyanate ingestion, HLA DR/DQ phenotype frequency, or thyroid growth-stimulating immunoglobulin (TGI) positivity. Median UI was 32 microg/g creatinine with 65.0% having values consistent with iodine deficiency (< 50 microg/g). When results were expressed as micrograms per deciliter, the percentage having values consistent with iodine deficiency (< 5.0 microg/dl) increased to 95.7%. The findings suggest a primary role for iodine deficiency in goitrogenesis in the study population. They demonstrate that classification of the severity of the endemia in this or other study populations in areas of iodine deficiency is dependent on the methods used to determine goiter prevalence (palpation or ultrasound measured thyroid enlargement), or dietary iodine status (iodine excretion expressed as micrograms per gram creatinine or micrograms per deciliter urine).

Adolescent↗

High incidence of thyroid cancer in long-standing goiters with thyroglobulin mutations.

In this paper, we report the high prevalence of thyroid malignancy in patients with thyroglobulin mutations in Japan. Mutations of the thyroglobulin gene cause defective thyroid hormone synthesis, resulting in congenital hypothyroidism. Since our report in 1999 on the thyroglobulin mutations C1264R and C1996S, we have identified 14 adult patients (7 males and 7 females) from 9 unrelated families. They visited hospitals for treatment of huge goiters that first appeared in childhood. Persistent growth of the thyroid gland, probably caused by thyrotropin (TSH) stimulation, partially compensated thyroid hormone production, resulting in lowered serum TSH concentrations in turn. Consequently, many patients had to undergo multiple operations. Of 11 patients who had undergone surgery, 7 had thyroid cancers. Of five patients whose thyroid tissue was available, we found a heterozygous activating mutation, either V599E or K600E, in cancerous tissue from each of 2 patients. From these observations, we conclude that goiter resulting from thyroglobulin mutations is associated with thyroid cancer.

Adolescent↗

The effects of oral iodized oil on intelligence, thyroid status, and somatic growth in school-age children from an area of endemic goiter.

One hundred goitrous school children received 475 mg iodized oil by mouth, while 100 controls received mineral oil, on a double-blind basis. On follow-up 22 months later the urinary iodine had increased and goiter size had decreased in both groups, more strikingly in the iodine-treated children. There were no consistent differences between the two treatment groups in rate of somatic growth or performance on the Stanford-Binet and Bender tests. Because of the complexities introduced by increases in urinary iodine in the controls, we compared goiter reduction with improvement in IQ score in all children, regardless of group, and found a significant relationship (p = 0.014), particularly in girls (p = 0.029). We conclude that oral iodized oil is an attractive alternative to its injection but we recommend an approximate doubling of the dose used here for more effective control. Also, while our data are not conclusive, they support the possibility that correction of iodine deficiency may improve mental performance in school age children, particularly girls.

Administration, Oral↗

Rapid relapse of thyroid dysfunction and goiter in school-age children after discontinuation of salt iodization.

BACKGROUND: In programs to control iodine deficiency disorders (IDD), sustainability is a major concern. IDD has recently recurred in countries where salt iodization programs have lapsed. OBJECTIVE: The objective of the study was to describe the evolution of thyroid dysfunction after the discontinuation of salt iodization in a cohort of children in an area of severe endemic goiter. DESIGN: Moroccan children (aged 6-16 y, n = 159) with severe IDD received iodized salt (IS) for 1 y. Because of practical and financial constraints, including a lack of infrastructure and electricity at the production site, salt iodization abruptly ceased. The children were followed for another 14 mo, and concentrations of urinary iodine, thyrotropin, total thyroxine, and thyroglobulin and thyroid volume were measured. RESULTS: Before iodization, median urinary iodine was 18 microg/L, 88% of children had elevated serum thyroglobulin concentrations, and 72% were goitrous. One year after the introduction of IS, median urinary iodine and thyroglobulin concentrations had normalized, mean thyroid volume had decreased by 34%, and median thyrotropin and mean total thyroxine concentrations were improved. Five months after the discontinuation of salt iodization, median urinary iodine had fallen to 20 microg/L. Fourteen months after the discontinuation of salt iodization, the rate of goiter was again similar to the rate before salt iodization; median thyrotropin and thyroglobulin concentrations were sharply higher than before the introduction of IS (P < 0.001); and the prevalence of hypothyroidism was 10%, compared with 3% before the introduction of IS (P < 0.001). CONCLUSIONS: In IDD-affected areas, cessation of salt iodization is associated with a rapid deterioration of thyroid function in school-age children. These findings underline the importance of sustainability in IDD control and the vulnerability of children to even short-term lapses in IS programs.

Adolescent↗

Role of goiter and of menstrual and reproductive factors in thyroid cancer: a population-based case-control study in New Caledonia (South Pacific), a very high incidence area.

Exceptionally high incidence rates of thyroid cancer have been reported for Melanesian women in New Caledonia (South Pacific). To investigate the occurrence of thyroid cancer in that country and to clarify the role of goiter and hormonal factors in that disease in women, a countrywide population-based case-control study was conducted in 1993-1999. The study included 293 cases, identified through pathology registers and whose thyroid cancer was verified histologically, and 354 population controls. Thyroid cancer was associated with goiter, age at menarche, irregular menstruation, and hysterectomy. There was a dose-response trend with number of full-term pregnancies (p = 0.01), with an odds ratio of 2.2 (95% confidence interval: 1.1, 4.3) for women with eight or more pregnancies. Miscarriage, particularly as an outcome of the first pregnancy, was also indicated as a risk factor. The association between voluntary abortion and thyroid microcarcinoma could be explained by enhanced medical surveillance and improved cancer detection in women undergoing abortion. Oral contraceptives and hormone replacement therapy were unrelated to thyroid cancer. The very high birth rate among Melanesian women in New Caledonia, as well as late age at menarche, may explain, in part, their elevated incidence of thyroid cancer.

Abortion, Spontaneous↗

Flow volume loops in patients with goiters.

Plain radiology is the standard means of assessing upper airway obstruction in patients with goiters. Flow volume loop curves will provide additional information, because they allow a quantitative assessment of airflow dynamics in the respiratory cycle. Fifty-one patients had flow volume loops performed before and after thyroidectomy. There was a significant increase in the maximum inspiratory flow rate (3.9 +/- 0.2 versus 4.9 +/- 0.2 L/second, p less than 0.01) after thyroidectomy. Eight of twelve patients with normal tracheal radiology had improved airflow dynamics in the postoperative period. The flow volume loop curve is a simple noninvasive means of assessing airflow dynamics in patients with goiters and may be superior to conventional radiology.

Adolescent↗

Effect of neck position during radionuclide superior cavography. Its value in the diagnosis of superior vena cava obstruction due to retrosternal goiter.

In five patients with substernal goiter, three of whom presented with superior vena cava (SVC) syndrome, and in five normal subjects, radionuclide superior cavography (RNSC) was performed with extension and flexion of the neck during tracer administration (simultaneous bilateral injection of Tc-99m pertechnetate). When the tracer was injected during neck extension, venous flow pattern was abnormal in four of five patients, and transit time (TT) prolonged in three of five patients. In this posture, mean TT +/- 1 standard deviation (SD) was 6.3 +/- 2.6 s (range 3.5 to 9 s) for the five patients and 3.5 +/- 0.7 s (range 2.5 to 4.5 s) for a group of five control subjects. When the tracer was injected during neck flexion, all five patients showed abnormal flow patterns and prolonged TT (mean +/- 1 SD 10.1 +/- 4.1 s; range 4.4 to 16 s), in contrast to the control group where a slight decrease in TT was found (mean +/- 1 SD 3 +/- 0.6 s; range 2 to 3.5 s). In the presence of a substernal goiter, or any mobile mass at the thoracic inlet, impairment of venous flow through the SVC system appears to be a common occurrence, readily detectable by RNSC. RNSC should be performed with neck flexion during tracer injection, since in this posture its ability to detect compromised venous flow through the SVC system is enhanced, even in patients without a clinically apparent SVC syndrome.

Adult↗

A large substernal goiter as a cause of a pulmonary perfusion defect.

A pulmonary perfusion defect was caused by an extremely large anterior mediastinal mass subsequently proved by I-131 imaging to be an intrathoracic extension of a cervical goiter. Substernal goiter is not known to be reported previously as one of the causes of a perfusion defect in lung scanning.

Aged↗

Ga-67 citrate accumulation in adenomatous goiter.

An elderly woman with a diffusely enlarged goiter and multiple miliary nodular lesions on chest x-ray showed Ga-67 accumulation in the right thyroid lobe. Histologic findings obtained after total thyroidectomy and open lung biopsy revealed papillary carcinoma in the left lobe with pulmonary metastases and adenomatous nodules in the right lobe. This is the first report of Ga-67 accumulation in adenomatous goiter.

Adenoma↗

I-123 uptake by mediastinal goiter after recombinant human thyroid-stimulating hormone administration.

Radioiodine scintigraphy is useful to confirm the presence of mediastinal thyroid tissue. However, the degree of iodine avidity of mediastinal goiters varies. Recombinant human thyroid-stimulating hormone given to stimulate iodine uptake by thyroid remnants and thyroid cancer metastases can now replace thyroid hormone withdrawal scanning of selected patients who have well-differentiated thyroid carcinoma. A case of mediastinal goiter visualized with I-123 after the administration of recombinant human thyroid-stimulating hormone is reported.

Aged↗

Acute respiratory failure and tracheal obstruction in patients with intrathoracic goiter.

Four cases of acute life-threatening tracheal obstruction due to intrathoracic goiter are reported. Acute respiratory insufficiency caused by an upper airway obstruction in patients with intrathoracic goiter is exceptional. In 3 of 4 cases reported, the histologic study showed multiple foci of recent hemorrhage, the mechanism probably responsible for these episodes.

Adult↗

Retropharyngeal mass as a rare presentation of a goiter: CT findings.

When sufficiently large, goiters often extend into the mediastinum. Less often, there is extension into the tracheoesophageal groove and the retroesophageal space, and, rarely, there may be growth into the retropharyngeal space. In the latter instance the goiter will present clinically as an oropharyngeal mass in a patient with stridor. We report two similar cases documented with CT studies that clearly show that the origin of the retropharyngeal mass was the thyroid gland.

Aged↗

Retrotracheal goiter.

Retrotracheal extension of a goiter, though rare usually causes respiratory compromise, dysphagia or vascular obstruction. We have described an asymptomatic patient with a large retrotracheal goiter resected via a collar incision.

Adult↗

Clonality of thyroid nodules in sporadic goiter.

Clonality studies have suggested that neoplasms are monoclonal and hyperplasias are polyclonal. To investigate this question in thyroid, we analyzed the clonality of 26 morphologically characterized hyperplastic nodules from 19 patients with sporadic goiters. For comparison we studied six thyroid carcinomas. We used the highly informative M27 beta probe that maps to the X-chromosome DXS255 locus (X cen-p11.22). Material was obtained from 52 nodules; tissue from nine nodules was rejected because of contamination with normal elements, five patients (eight nodules) were homozygous at Pst I sites in nonnodular thyroid tissue, and three nodules were excluded for technical reasons. Methylation patterns after Hpa II digestion confirmed polyclonality in all nontumorous thyroids of informative patients. Seven hyperplastic nodules were polyclonal, and 18 were monoclonal; one showed loss of heterozygosity. One nodule exhibited aberrant methylation. Multiple nodules were obtained from four patients; in three, all were monoclonal with activation of the same allele. Three papillary carcinomas were monoclonal; two exhibited aberrant methylation. One follicular carcinoma showed loss of heterozygosity. Our data indicate that morphologically indistinguishable hyperplastic thyroid nodules may be monoclonal or polyclonal. These findings suggest that variable molecular mechanisms are involved in the pathogenesis of nodules in sporadic goiter. Future studies will need to explore the biological significance of nodules of variable clonal origin.

Adult↗

Uses for recombinant human TSH in patients with thyroid cancer and nodular goiter.

Recombinant human TSH (rhTSH) has revolutionized the care of patients with differentiated thyroid cancer. Since its approval for clinical use in 2001 in Europe (1998 in the USA), rhTSH has greatly enhanced the surveillance of these patients by allowing the avoidance of hypothyroidism for TSH stimulation. Previously, a hypothyroid state was required for TSH stimulated diagnostic whole-body radio-iodine scans (DxWBS) and thyroglobulin (Tg) levels. Patients generally prefer rhTSH as a mechanism for TSH stimulation because symptoms of hypothyroidism can be completely avoided. Currently, rhTSH is only approved for diagnostic monitoring of differentiated thyroid cancer patients. There are many other potential uses for rhTSH, including facilitation of treatment of patients with thyroid cancer and nodular goiter. The diagnostic and therapeutic role of rhTSH in patients with differentiated thyroid cancer and nodular goiter will be discussed in this review.

Adjuvants, Pharmaceutic↗