Biotin Interference in Assays for Thyroid Hormones, Thyrotropin and Thyroglobulin.

Background: Biotin has been reported to interfere with several commonly used laboratory assays resulting in misleading values and possible erroneous diagnosis and treatment. This report describes a prospective study of possible biotin interference in thyroid-related laboratory assays, with a comparison of different commonly used assay platforms. Materials and Methods: Thirteen adult subjects (mean age 45 ± 13 years old) were administered biotin 10 mg/day for eight days. Blood specimens were collected at three time points on day 1 and on day 8 (baseline, two, and five hours after biotin ingestion). Thyrotropin (TSH), free triiodothyronine (fT3), free thyroxine (fT4), total triiodothyronine (TT3), total thyroxine (TT4), thyroxine binding globulin (TBG), and thyroglobulin (Tg) levels were analyzed with four different platforms: Abbott Architect, Roche Cobas 6000, Siemens IMMULITE 2000, and liquid chromatography with tandem mass spectrometry (LC-MS/MS). TSH, fT3, fT4, TT3, and TT4 were measured with Abbott Architect and Roche Cobas 6000. fT3, fT4, TT3, and TT4 were also measured by LC-MS/MS. Tg was measured by Siemens IMMULITE 2000. TBG was assessed with Siemens IMMULITE 2000. Results: Significant changes in TSH, fT4, and TT3 measurements were observed after biotin exposure when the Roche Cobas 6000 platform was used. Biotin intake resulted in a falsely lower Tg level when measurements were performed with Siemens IMMULITE 2000. At the time points examined, maximal biotin interference was observed two hours after biotin exposure both on day 1 and day 8. Conclusions: A daily dose of 10 mg was shown to interfere with specific assays for TSH, fT4, TT3, and Tg. Physicians must be aware of the potential risk of erroneous test results in subjects taking biotin supplements. Altered test results for TSH and Tg can be particularly problematic in patients requiring careful titration of levothyroxine therapy such as those with thyroid cancer.

Low intake of iodized salt and iodine containing supplements among pregnant women with apparently insufficient iodine status - time to change policy?

BACKGROUND: Iodine is an essential nutrient for human health throughout the life cycle, especially during early stages of intrauterine life and infancy, to ensure adequate neurocognitive development. The growing global reliance on desalinated iodine-diluted water raises the specter of increased iodine deficiency in several regions. The case of Israel may be instructive for exploring the link between iodine status and habitual iodine intake in the setting of extensive national reliance on desalinated water. The aim of this study was to explore the relationship between iodine intake, including iodized salt and iodine-containing supplements intake, and iodine status among pregnant women residing in a sub-district of Israel that is highly reliant on desalinated iodine-diluted water. METHODS: A total of 134 consecutive pregnant women were recruited on a voluntary basis from the obstetrics department of the Barzilai University Medical Center during 2018. Blood was drawn from participants to determine levels of serum thyrotropin (TSH), thyroid peroxidase antibodies (TPOAb), thyroglobulin antibodies (TgAb) and thyroglobulin (Tg). An iodine food frequency questionnaire (sIFFQ) was used to assess iodine intake from food, IS and ICS. A questionnaire was used to collect data on demographic and health characteristics. RESULTS: A total of 105 pregnant women without known or reported thyroid disease were included in the study. Elevated Tg values (≥ 13 µg/L), were found among 67% of participants, indicating insufficient iodine status. The estimated iodine intake (median, mean ± SD 189, 187 ± 106 µg/d by sIFFQ) was lower than the levels recommended by the World Health Organization and the Institute of Medicine (250 vs. 220 µg/day respectively). The prevalence of iodized salt intake and iodine containing supplement intake were 4 and 52% (respectively). Values of Tg > 13 µg/L were inversely associated with compliance with World Health Organization and Institute of Medicine recommendations. CONCLUSIONS: While the Israeli Ministry of Health has recommended the intake of iodized salt and iodine containing supplements, this is apparently insufficient for achieving optimal iodine status among Israeli pregnant women. The evidence of highly prevalent probable iodine deficiency in a sample of pregnant women suggests an urgent need for a national policy of iodized salt regulation, as well as guidelines to promote iodine containing supplements and adherence to them by caregivers. In addition, studies similar to this one should be undertaken in additional countries reliant on desalinated iodine-diluted water to further assess the impact of desalinization on maternal iodine status.

Type of fish consumed and thyroid autoimmunity in pregnancy and postpartum.

Fish consumption or supplementation with omega-3 fatty acids was reported to cure and/or prevent autoimmune and nonautoimmune disorders. Serum positivity for thyroid autoantibodies is a predictive marker of postpartum thyroiditis and postpartum depression. We hypothesized that stable consumption of the omega-3-rich oily fish was associated with a more favorable profile of serum thyroid antibodies throughout pregnancy and early postpartum compared with stable consumption of swordfish, a predator that concentrates pollutants. We prospectively measured serum thyroglobulin antibodies and thyroperoxidase antibodies in pregnancy (first, second trimesters) and postpartum (day 4), in 236 thyroid disease-free, nonsmoker Caucasian women with stable dietary habits. We did not measure thyroid autoantibodies prior to pregnancy. Women were divided into groups A (n = 48; swordfish), B (n = 52; oily fish), C (n = 68; swordfish + other fish, not necessarily oily fish), and D (n = 68; fish other than swordfish and oily fish). Major endpoints were positivity rates and serum concentrations of the two autoantibodies. We resorted to previous studies for the estimated content of fatty acids and microelements in the consumed fish. Positivity rates and serum concentrations of both antibodies were the greatest in group A and the lowest in group B (P < 0.001 and P < 0.05 to < 0.001, respectively). Relationship between monthly fish consumption and serum concentrations of either antibody was direct in group A but inverse in group B. The estimated content of omega-3 fatty acids in fish consumed by group B was the greatest (P < 0.001 vs. any other group). These data reinforce recommendations that pregnant women should avoid consuming swordfish and indicate consumption of oily fish as a favorable alternative. Because thyroid autoantibodies are markers of autoimmune-related postpartum problems, our data suggest a dietary prophylaxis of such problems.

[Diagnostics and treatment of differentiated thyroid cancer using nuclear medicine]. / Nuklearmedicinsk billeddiagnostik og behandling ved differentieret thyroideacancer.

Differentiated thyroid cancer (DTC) is a rare cancer with excellent prognosis for most patients. Primary treatment is surgery. Adjuvant radioiodine is used after surgery and in case of residual radioiodine positive disease. Measurements of serum thyroglobulin levels and neck ultrasound (US) are the primary follow-up procedures. For suspected recurrence, US, computed tomography (CT), radioiodine single photon emission computed tomography/CT, and FDG positron emission tomography/CT will be appropriate choices for restaging and further treatment planning. Multidisciplinary collaboration is crucial for optimal management of patients with DTC.

Mucoepidermoid carcinoma of the thyroid: a report of three cases and postulated histogenesis.

BACKGROUND: Primary mucoepidermoid carcinoma (MEC) of the thyroid is a rare clinical and pathological entity that accounts for <0.5% of all thyroid malignancies. Although the histogenesis has been controversial, most investigators now favor it as arising from either metaplasia of thyroid follicular epithelium or heterologous de-differentiation from papillary thyroid carcinoma (PTC). We report three cases of thyroid MEC found in continuity with, and clearly arising from de-differentiation of, well-differentiated thyroid carcinomas (WDTCs). PATIENT FINDINGS AND SUMMARY: The cases presented here included two women (aged 22 and 52) and one man (aged 58). One of these cases arose in conjunction with PTC, one with follicular thyroid carcinoma (FTC), and one with Hurthle cell carcinoma (HCC). In all three cases, there was a gradual transition in morphology between the areas of typical WDTC and the areas showing MEC differentiation. In addition, immunohistochemistry demonstrated a gradual loss of thyroid specific markers (thyroid transcription factor-1, thyroglobulin) mirroring the change in morphology. CONCLUSION: We conclude that thyroid MEC can arise from metaplastic de-differentiation of WDTC, including FTC or HCC in addition to PTC. Currently, we recommend that after excision, each of the WDTC and MEC components of these tumors be treated with targeted adjuvant therapies, which may involve radioactive-iodine ablation, thyrotropin suppression, and external beam radiotherapy.

Identification of a neck lump as a lymph node metastasis from an occult contralateral papillary microcarcinoma of the thyroid: key role of thyroglobulin assay in the fine-needle aspirate.

BACKGROUND: Thyroglobulin (Tg) assay of material from fine-needle aspiration of neck masses can help distinguish neck masses of thyroid origin from other masses. We describe its utility in a patient with an unusual constellation of findings, a neck lump identified as a lymph node metastasis from a contralateral occult papillary thyroid carcinoma (PTC). SUMMARY: A 56-year-old woman was referred to our center for evaluation of a 15-mm right lateral cervical neck mass which was strongly hypoechoic, not homogenous and contained several microcalcifications. There was no family history of thyroid disease, the patient was euthyroid and was not taking medications for thyroid disorders. On physical examination the thyroid was slightly enlarged and was normal on ultrasound except for a 1 x 3 mm hypoechoic nodule in the middle of the left lobe. Ultrasound-guided fine-needle aspiration biopsy (FNAB) of the right lateral cervical mass was performed with the Tg concentration of the FNAB washout liquid being >300 ng/mL and the cytology showing lymphoid elements mixed with polymorphous epithelial cells with atypical nuclei, suggesting lymph node metastasis from a cancer of epithelial origin. A lymph node metastasis from a papillary thyroid microcarcinoma (micro-PTC) was the presumptive diagnosis with the preoperative staging being Tx N1b. The patient underwent total thyroidectomy and bilateral lymph node dissection. At pathology, the right cervical mass was confirmed as lymph node metastasis of a PTC, and a unifocal micro-PTC was found in the middle left lobe. The patient was readmitted for a therapeutic (131)I dose (4810 MBq). At the time of (131)I administration, the whole-body scan showed only minimal thyroid bed uptake and serum Tg was <1 ng/mL. She was maintained on l-thyroxine treatment (150 microg/d). Five year later she did not have evidence of recurrent or residual PTC. CONCLUSIONS: We describe the first case of contralateral lymph node metastasis from a unifocal micro-PTC identified by the detection of high Tg levels in the wash-out liquid of FNAB.

Cáncer diferenciado de tiroides. Metástasis pulmonares y cerebrales / Pulmonary and brain metastases from well-differentiated thyroid carcinoma

La tiroidectomía total es el tratamiento de elección en el cáncer diferenciado de tiroides. A pesar de esta intervención, pueden aparecer metástasis regionales y a distancia. El control posterior de la enfermedad se realiza con la determinación de los valores de tiroglobulina, y el rastreo corporal con 201Tl y 131I. Éstos son más fiables en los pacientes a los que se ha practicado una tiroidectomía total. Queremos enfatizar en la importancia del seguimiento médico tras el tratamiento quirúrgico, incluso en ausencia de síntomas (AU)

Total thyroidectomy is the surgical treatment of choice for differentiated thyroid carcinoma. Despite this surgical treatment, locoregional and distant metastases can develop. Postoperative follow-up should include determination of serum thyroglobulin levels and radioactive iodine (131I) and thallium (201Tl) whole body scans. These techniques are more reliable in patients who have undergone total thyroidectomy. We stress the importance of routine medical follow-up after surgical treatment of thyroid cancer, even in the absence of symptoms (AU)

Effect of the traditional Korean immunomodulating formulation, Gamguntang (GGT), on experimental thyroiditis model.

The crude herbal formulation, Gamgungtang (GGT), is an immunomodulator showing marked down-regulation of several experimental autoimmune diseases. In this study, its effect on different experimental models of thyroid disease was investigated. Although very effective at preventing thyroid infiltrates in mice immunized with mouse deglycosylated thyroglobulin and complete Freund's adjuvant and in spontaneous models of thyroiditis, it completely failed to modify experimental autoimmune thyroiditis (EAT) induced in mice immunized with mouse thyroglobulin and lipopolysaccharide. There was no significant shift in the observed isotypes of anti-mouse thyroglobulin antibodies and only anti-mouse thyroglobulin antibodies in the spontaneous model were completely down-modulated by the GGT. One surprising fact to emerge was that GGT-treated donor mice, although protected from thyroid lesions themselves, were still able to transfer EAT showing that they must have been effectively primed while being treated with GGT. It is possible that the drug down modulated EAT by interfering with the trafficking of primed effector cells.

Usefulness of recombinant human TSH aided radioiodine doses administered in patients with differentiated thyroid carcinoma

The published studies confirming the safety and efficacy of rhTSH for diagnostic purposes have ledto an increased interest in its use for preparation for radioiodine (RI) dose administration in patientswith recurrent or persistent differentiated thyroid carcinoma (DTC). In order to establish the efficacy of RItherapy after rhTSH, we have reviewed 39 rhTSH-aided radioiodine treatment in a series of 28 DTC patients.Patients were divided into two groups: GI (n=17), with previous thyroid bed uptake and undetectable thyroglobulin(Tg) levels under levothyroxine treatment and GII (n=11), with proven metastatic local or distant disease.Median follow-up after the first rhTSH-aided radioiodine treatment was 32 ± 13 months (range 8 to 54 months).Sixteen patients (94%) in GI were rendered disease free and one patient was shown to have persistent disease.In GII, the post therapy whole body scan showed pathological uptakes in all cases: in four patients in lungs, infour in mediastinum and in three in lateral neck. In two patients with mediastinum uptake, Tg levels wereundetectable after rhTSH. In the follow-up, two patients with lateral neck uptake were rendered disease free,four patients died (three due to thyroid cancer) and five out of the remaining patients have persistent disease. Inconclusion, rhTSH aided therapy was helpful to eliminate normal thyroid bed remnants in 16/17 (94%) patients(GI). rhTSH stimulated Tg was undetectable in two patients with mediastinal metastasis. We believe that rhTSHis a good alternative to levothyroxine withdrawal for the treatment of DTC with radioactive iodine, increasing thequality of life in these patients. Caution should be recommended in the follow-up of unselected DTC patientsonly with stimulated Tg levels. (AU)

Los estudios publicados que confirman la seguridad yeficacia de la TSH recombinante (rhTSH) llevaron a un incremento en el interés para su uso como adyuvanteterapéutico en el CDT (ablación o tratamiento de enfermedad metastática). Para evaluar la efectividad de laadministración de dosis terapéuticas de RI luego de la administración de rhTSH, realizamos un análisisretrospectivo en 28 pacientes con CDT que recibieron 39 dosis de RI. Los pacientes se dividieron en 2 grupos:GI (n=17) pacientes con captación en el lecho tiroideo y niveles indetectables de tiroglobulina (Tg) bajo tratamientosupresivo con levotiroxina y GII (n=11), pacientes con enfermedad metastática local o a distancia, previamentecomprobada. El seguimiento promedio luego de la primera dosis de RI fue de 32 ± 13 meses (rango 8 a 54meses). Dieciseis pacientes (94%) del GI fueron considerados libres de enfermedad y un paciente presentó unapersistencia local. En el GII, las captaciones patológicas fueron: en 4 pacientes en pulmones; en 4 en mediastinoy en 3 a nivel lateral cervical. Dos pacientes con captaciones mediastinales presentaron niveles indetectablesde Tg. En el seguimiento, dos pacientes con captaciones latero-cervicales se consideraron libres de enfermedad,cuatro pacientes murieron (tres debido al CDT avanzado) y cinco de los restantes tienen enfermedad persistente.En conclusión, la terapia con RI luego de rhTSH fue útil para ablacionar remanentes normales en el GI. Losniveles de Tg estimulados con rhTSH fueron indetectables en dos pacientes con metástasis mediastinales. Eluso de rhTSH parece ser una alternativa válida frente a la suspensión de la terapia hormonal en el tratamientode pacientes con CDT, incrementando la calidad de vida de estos pacientes. (AU)

Usefulness of recombinant human TSH aided radioiodine doses administered in patients with differentiated thyroid carcinoma

The published studies confirming the safety and efficacy of rhTSH for diagnostic purposes have ledto an increased interest in its use for preparation for radioiodine (RI) dose administration in patientswith recurrent or persistent differentiated thyroid carcinoma (DTC). In order to establish the efficacy of RItherapy after rhTSH, we have reviewed 39 rhTSH-aided radioiodine treatment in a series of 28 DTC patients.Patients were divided into two groups: GI (n=17), with previous thyroid bed uptake and undetectable thyroglobulin(Tg) levels under levothyroxine treatment and GII (n=11), with proven metastatic local or distant disease.Median follow-up after the first rhTSH-aided radioiodine treatment was 32 ± 13 months (range 8 to 54 months).Sixteen patients (94%) in GI were rendered disease free and one patient was shown to have persistent disease.In GII, the post therapy whole body scan showed pathological uptakes in all cases: in four patients in lungs, infour in mediastinum and in three in lateral neck. In two patients with mediastinum uptake, Tg levels wereundetectable after rhTSH. In the follow-up, two patients with lateral neck uptake were rendered disease free,four patients died (three due to thyroid cancer) and five out of the remaining patients have persistent disease. Inconclusion, rhTSH aided therapy was helpful to eliminate normal thyroid bed remnants in 16/17 (94%) patients(GI). rhTSH stimulated Tg was undetectable in two patients with mediastinal metastasis. We believe that rhTSHis a good alternative to levothyroxine withdrawal for the treatment of DTC with radioactive iodine, increasing thequality of life in these patients. Caution should be recommended in the follow-up of unselected DTC patientsonly with stimulated Tg levels. (AU)

Los estudios publicados que confirman la seguridad yeficacia de la TSH recombinante (rhTSH) llevaron a un incremento en el interés para su uso como adyuvanteterapéutico en el CDT (ablación o tratamiento de enfermedad metastática). Para evaluar la efectividad de laadministración de dosis terapéuticas de RI luego de la administración de rhTSH, realizamos un análisisretrospectivo en 28 pacientes con CDT que recibieron 39 dosis de RI. Los pacientes se dividieron en 2 grupos:GI (n=17) pacientes con captación en el lecho tiroideo y niveles indetectables de tiroglobulina (Tg) bajo tratamientosupresivo con levotiroxina y GII (n=11), pacientes con enfermedad metastática local o a distancia, previamentecomprobada. El seguimiento promedio luego de la primera dosis de RI fue de 32 ± 13 meses (rango 8 a 54meses). Dieciseis pacientes (94%) del GI fueron considerados libres de enfermedad y un paciente presentó unapersistencia local. En el GII, las captaciones patológicas fueron: en 4 pacientes en pulmones; en 4 en mediastinoy en 3 a nivel lateral cervical. Dos pacientes con captaciones mediastinales presentaron niveles indetectablesde Tg. En el seguimiento, dos pacientes con captaciones latero-cervicales se consideraron libres de enfermedad,cuatro pacientes murieron (tres debido al CDT avanzado) y cinco de los restantes tienen enfermedad persistente.En conclusión, la terapia con RI luego de rhTSH fue útil para ablacionar remanentes normales en el GI. Losniveles de Tg estimulados con rhTSH fueron indetectables en dos pacientes con metástasis mediastinales. Eluso de rhTSH parece ser una alternativa válida frente a la suspensión de la terapia hormonal en el tratamientode pacientes con CDT, incrementando la calidad de vida de estos pacientes. (AU)

Usefulness of recombinant human TSH aided radioiodine doses administered in patients with differentiated thyroid carcinoma

The published studies confirming the safety and efficacy of rhTSH for diagnostic purposes have ledto an increased interest in its use for preparation for radioiodine (RI) dose administration in patientswith recurrent or persistent differentiated thyroid carcinoma (DTC). In order to establish the efficacy of RItherapy after rhTSH, we have reviewed 39 rhTSH-aided radioiodine treatment in a series of 28 DTC patients.Patients were divided into two groups: GI (n=17), with previous thyroid bed uptake and undetectable thyroglobulin(Tg) levels under levothyroxine treatment and GII (n=11), with proven metastatic local or distant disease.Median follow-up after the first rhTSH-aided radioiodine treatment was 32 ± 13 months (range 8 to 54 months).Sixteen patients (94%) in GI were rendered disease free and one patient was shown to have persistent disease.In GII, the post therapy whole body scan showed pathological uptakes in all cases: in four patients in lungs, infour in mediastinum and in three in lateral neck. In two patients with mediastinum uptake, Tg levels wereundetectable after rhTSH. In the follow-up, two patients with lateral neck uptake were rendered disease free,four patients died (three due to thyroid cancer) and five out of the remaining patients have persistent disease. Inconclusion, rhTSH aided therapy was helpful to eliminate normal thyroid bed remnants in 16/17 (94%) patients(GI). rhTSH stimulated Tg was undetectable in two patients with mediastinal metastasis. We believe that rhTSHis a good alternative to levothyroxine withdrawal for the treatment of DTC with radioactive iodine, increasing thequality of life in these patients. Caution should be recommended in the follow-up of unselected DTC patientsonly with stimulated Tg levels.

Los estudios publicados que confirman la seguridad yeficacia de la TSH recombinante (rhTSH) llevaron a un incremento en el interés para su uso como adyuvanteterapéutico en el CDT (ablación o tratamiento de enfermedad metastática). Para evaluar la efectividad de laadministración de dosis terapéuticas de RI luego de la administración de rhTSH, realizamos un análisisretrospectivo en 28 pacientes con CDT que recibieron 39 dosis de RI. Los pacientes se dividieron en 2 grupos:GI (n=17) pacientes con captación en el lecho tiroideo y niveles indetectables de tiroglobulina (Tg) bajo tratamientosupresivo con levotiroxina y GII (n=11), pacientes con enfermedad metastática local o a distancia, previamentecomprobada. El seguimiento promedio luego de la primera dosis de RI fue de 32 ± 13 meses (rango 8 a 54meses). Dieciseis pacientes (94%) del GI fueron considerados libres de enfermedad y un paciente presentó unapersistencia local. En el GII, las captaciones patológicas fueron: en 4 pacientes en pulmones; en 4 en mediastinoy en 3 a nivel lateral cervical. Dos pacientes con captaciones mediastinales presentaron niveles indetectablesde Tg. En el seguimiento, dos pacientes con captaciones latero-cervicales se consideraron libres de enfermedad,cuatro pacientes murieron (tres debido al CDT avanzado) y cinco de los restantes tienen enfermedad persistente.En conclusión, la terapia con RI luego de rhTSH fue útil para ablacionar remanentes normales en el GI. Losniveles de Tg estimulados con rhTSH fueron indetectables en dos pacientes con metástasis mediastinales. Eluso de rhTSH parece ser una alternativa válida frente a la suspensión de la terapia hormonal en el tratamientode pacientes con CDT, incrementando la calidad de vida de estos pacientes.

Administration of a single dose of recombinant human thyrotrophin enhances the efficacy of radioiodine treatment of large compressive multinodular goitres.

OBJECTIVE: Patients with very large multinodular goitres, frequently found among elderly people, often suffering from cardiovascular or other disabling disorders, may be considered as unsuitable for surgery. We have evaluated the feasibility of relatively high-dose 131I therapy in such patients. As subclinical or clinical hyperthyroidism is commonly found in these patients, associated with a low radioiodine (RAI) uptake at 24 h, we pretreated a group of patients with a single intramuscular injection of recombinant human TSH (rhTSH 0.45 mg) in order to increase the uptake of the therapeutic dose of RAI. DESIGN AND PATIENTS: Forty-one patients with large, long-standing multinodular goitres, were recruited for this study. After a careful and detailed clinical and laboratory evaluation, 34 patients (28 women, six men) were included and randomly assigned to group 1 (control, n = 17, 15 women, two men, age 63.1 +/- 11.2 years) receiving only RAI. Patients in group 2 (n = 17, 13 women, four men, age 63.6 +/- 12.3 years) received the therapeutic dose of RAI, having been pretreated (24 h) with 0.45 mg of rhTSH. Both groups of patients were submitted to a low iodine diet, 4-6 months before RAI treatment, while seven thyrotoxic patients also received methimazole (40 mg/day) until they reached euthyroidism. Ultrasonographic studies were performed for all patients and fine-needle aspiration biopsy (FNAB) were performed on one or two nodules before RAI treatment. RAI was given as a single oral dose to the hospitalized isolated patients. Blood samples for thyroid function tests and serum thyroglobulin (Tg) were collected daily during the first week following RAI treatment, and at 1, 3, 6, 9 and 12 months thereafter. MEASUREMENTS: Goitre volume was estimated by computed tomography scan. Thyroid function tests (total T3, free T4, TSH and serum Tg) were assayed with commercial kits. Urinary excretion of iodine was assayed by the Sandell-Kolthoff method. RESULTS: After the RAI therapeutic dose, serum thyroid function tests were carried out daily for the first week and then on a monthly basis (1, 3, 6, 9 and 12 months). Serum TSH levels rose to a peak level of 45.9 +/- 19.1 mU/l (24 h) in group 2 returning to normal at 72 h. Free T4 serum concentrations rose significantly to 59.35 +/- 21.61 pmol/l at 48 h (in group 2) returning to normal at 7 days. Similarly, serum TT3 also peaked above normal levels only in group 2 (6.12 +/- 1.89 nmol/l) at 24 h. Serum Tg increased in both groups (significantly higher in group 2) and remained elevated during the following 12 months. Both groups had a significant reduction in goitre volume at 12 months (group 2: 57.8%vs. group 1: 39.7%, P < 0.05). Hypothyroidism was detected after RAI treatment, respectively, in 21.4% (group 1) and 64.7% (group 2), of the patients at 12 months. CONCLUSIONS: Our results indicate that the use of hTSH increased the efficacy of the RAI therapeutic dose. This was basically due to an increased uptake of the radionuclide (as a consequence of the higher serum TSH levels) and a more extensive distribution of 131I within the nodules of the multinodular goitre. A more intense radiation effect was reflected in there being a higher output of serum Tg and thyroid hormones (group 2). As a consequence this group had a significantly higher reduction of the goitre volume. Also incidence of hypothyroidism post-RAI was significantly higher in group 2. We concluded that pretreatment with rhTSH in elderly patients with large multinodular goitres increases the uptake of the RAI therapeutic dose, thereby significantly reducing the multinodular goitre volume and relieving the compressive symptoms with relatively few side-effects.

Development of a dried whole-blood spot thyroglobulin assay and its evaluation as an indicator of thyroid status in goitrous children receiving iodized salt.

BACKGROUND: Serum thyroglobulin appears to be a sensitive marker of thyroid dysfunction in endemic goiter. However, its value as an indicator of thyroid status in children after the introduction of iodized salt has not been tested. OBJECTIVE: The objective was to optimize and validate a thyroglobulin assay on dried whole blood spots and to evaluate thyroglobulin as an indicator of thyroid response to iodized salt. DESIGN: A standardized, commercially available, sandwich fluoroimmunometric serum thyroglobulin assay was adapted for use on blood spots and validated in Swiss children. In a 1-y prospective study in 377 goitrous Moroccan children aged 6-15 y, the assay was used to measure thyroglobulin before and after the introduction of iodized salt. Urinary iodine, thyroid volume, thyrotropin, and thyroxine were measured, and regression was done with thyroglobulin as the dependent variable. RESULTS: Correlation between the blood spot and serum assays was excellent (r = 0.98). The SD of the difference between the blood spot and serum assays was 3.8 micro g/L; the median CVs for the blood spot assay in controls and samples were 6.3% and 14.4%, respectively. Median thyroglobulin was 24.5 (range: 0-328.8) micro g/L at baseline and fell significantly after the introduction of iodized salt to 6.2 (0-83.1) and 4.4 (0-47.1) micro g/L at 5 and 12 mo, respectively (P < 0.0001). Regression of urinary iodine and thyroid volume on thyroglobulin was highly significant at baseline and at 5 mo (P < 0.001). CONCLUSION: Thyroglobulin, measured in dried whole blood spots, may be a valuable indicator of improving thyroid function in children after supplementation with iodized salt.

Primary ectopic thyroid papillary carcinoma in the floor of the mouth and tongue: a case report.

We report a rare case of papillary carcinoma in the tongue and floor of the mouth with metastasis in cervical lymph nodes. Treatment was by total thyroidectomy with right radical lymph node dissection of the neck, followed by 60 Gy of radiotherapy and 100 mCi (131)I. Pathological examination of the thyroid gland showed no primary cancer. We review publications about ectopic thyroid and the value of antithyroglobulin immunostaining for diagnosis and treatment of the tumour.

Lack of impact of radioiodine therapy in tg-positive, diagnostic whole-body scan-negative patients with follicular cell-derived thyroid cancer.

Several reports have suggested a benefit from radioactive iodine (RAI) therapy in Tg-positive, whole-body scan-negative patients with follicular cell-derived thyroid cancer, who were said to have high rates of visualization of uptake in metastases after therapeutic doses of RAI. We sought to evaluate the rate of visualization of RAI uptake in these patients and determine the effect of such therapy on tumor progression and Tg levels. We studied 24 consecutive patients who had been treated with high-dose RAI, four of whom had no evidence of metastasis or persistent cancer. Our results showed that four patients had some uptake in posttherapy scans: in the neck, lung, and mediastinal metastases in one patient, in the thyroid remnant in two, and in a possible neck microrecurrence in one. In 13 patients with macrometastases-tumors 1 cm or greater-tumors progressed and serum Tg increased; five have died of thyroid cancer. The disease remained stable in the seven patients with micrometastases. We concluded that in high-risk patients with follicular cell-derived thyroid cancer with high Tg levels and negative diagnostic whole-body scans, only a small number showed meaningful uptake after high doses of RAI. Therefore, widespread use of empiric RAI therapy for such patients who have a large tumor burden should not be encouraged.

Ascidian homologs of mammalian thyroid peroxidase genes are expressed in the thyroid-equivalent region of the endostyle.

The endostyle is a pharyngeal organ for the internal filter feeding of urochordates, cephalochordates, and larval lamprey. This organ is also considered to be homologous to the follicular thyroid gland of higher vertebrates. Thyroglobulin (Tg) and thyroid peroxidase (TPO) are specifically expressed in the thyroid gland of higher vertebrates, and they play an important role in iodine metabolism for the synthesis of thyroid hormones. Previous histochemical observations showed that iodine-concentrating and peroxidase activities were detected in zones 7, 8, and 9 of the ascidian endostyle, suggesting that these zones contains cells that are equivalent to those in the vertebrate follicular thyroid. In order to investigate the molecular developmental mechanisms involved in the formation and function of the endostyle, with special reference to the evolution of the thyroid gland, in the present study, we isolated and characterized cDNA clones for TPO genes, CiTPO from Ciona intestinalis and HrTPO from Halocynthia roretzi. Northern blot and in situ hybridization analyses revealed that the expression of the ascidian TPO genes was restricted to zone 7, one of the elements equivalent to the thyroid. These results provide the first evidence at the gene expression level for shared function between a part of the ascidian endostyle and the vertebrate follicular thyroid gland. J. Exp. Zool. ( Mol. Dev. Evol. ) 285:158-169, 1999.

Thyroid papillary carcinoma of columnar cell type: a clinicopathologic study of 16 cases.

BACKGROUND: Thyroid papillary carcinoma of columnar cell type is considered an uncommon histologic subtype of papillary carcinoma characterized by its morphologic features and purportedly aggressive biologic course. METHODS: Sixteen cases of thyroid papillary carcinoma of columnar cell type were identified from the Endocrine Tumor Registry at the Armed Forces Institute of Pathology and the Washington Hospital Center. Clinical records and follow-up were available in all cases. Paraffin blocks were available for histochemical and immunohistochemical studies in 15 of the 16 cases. RESULTS: Of the 16 cases reported, 13 patients were female and 3 were male. The ages ranged from 16-76 years (average, 47 years; median, 40 years). An asymptomatic neck mass was the most common clinical presenting symptom. Macroscopically, the tumors varied from circumscribed or encapsulated to infiltrative, ranging in size from 1.5-6.5 cm. Histologically, the tumors had diverse growth patterns, including papillary, solid, microfollicular, and cribriform. A common pattern was the presence of markedly elongated follicles arranged in parallel cords. Colloid-filled follicles could be found, at least focally, in all cases. The characteristic histologic appearance included the presence of elongated cells showing nuclear stratification. Other features included the presence of vacuolated-appearing cells, spindle-shaped cells, and squamoid nests. Limited areas in the tumors showed morphologic features typical of thyroid papillary carcinoma. In 14 of the cases, the tumor was encapsulated, showed limited invasive growth, or was a microscopic tumor. In two of the cases, there was extrathyroidal invasion. Immunohistochemical studies showed consistent reactivity with cytokeratin and vimentin; varied reactivity with thyroglobulin, epithelial membrane antigen, carcinoembryonic antigen, and LeuM1; and no reactivity with calcitonin or chromogranin. Treatment was by surgical resection; supplemental radioactive iodine therapy was administered in eight patients. Follow-up was available for all patients, 13 of whom (81%) were alive and free of disease or had died of unrelated causes over periods ranging from 2-11 years (average, 5.8 years). All 13 of these patients had tumor confined completely to the thyroid gland. One patient died 4 months after diagnosis secondary to sepsis. Two patients (17%) had aggressive biologic courses. In both patients there was extrathyroidal invasion. One of these patients died of metastatic disease to the lungs 3 years after diagnosis; the other was alive with bilateral pulmonary metastases 9 years after the diagnosis. CONCLUSIONS: The findings of the current study indicate that thyroid papillary carcinoma of columnar cell type is a distinct morphologic type but not a distinct clinical type of thyroid papillary carcinoma. The biologic behavior of this tumor is predicated on clinical stage, with the presence or absence of extrathyroidal invasion being the single most important parameter. Treatment of patients with these tumors should be based on the clinical stage and not on the morphologic appearance.

[Value of thyroglobulin determination in the follow up treatment of patients with thyroid cancer]. / Thyreoglobulin meghatározások értéke differenciált pajzsmirigycarcinomában szenvedö betegek utókezelésében.

Tg measurements were performed regularly in 96 thyroid carcinomas in order to evaluate metastases and local recurrencies. Elevated Tg level was detected in 11 patient. 7 of them were operated on because of local recurrencies and lymph node metastases. All patients that needed reoperation had elevated Tg level. During the follow up period no patient needed reoperation who had elevated Tg level or metastases detected by other diagnostic procedures. Summarising the results they found the Tg level measurements valuable in the follow up of patients with differentiated thyroid cancer. The Tg level measurements can supplement or sometimes replace 131J thyroid scanning.

Primary structure of bovine thyroglobulin deduced from the sequence of its 8,431-base complementary DNA.

In mammals, an adequate supply of thyroid hormones is essential for normal growth and neurological development. The biosynthesis of thyroid hormones involves an iodinated precursor protein, thyroglobulin, which may be considered an extreme example of a pro-hormone. Thyroglobulin is a dimeric glycoprotein of relative molecular mass (Mr) 660,000 (660K), which is secreted by the thyrocyte and stored in the lumen of the thyroid follicle. The hormonogenic reaction is extracellular, and involves iodination of tyrosyl residues of thyroglobulin and the intramolecular coupling of a subset of these into thyroxine (T4) and triiodothyronine (T3), which remain part of the polypeptide chain. Secretion of hormones results from the endocytosis of thyroglobulin followed by its complete hydrolysis in lysosomes. Considering that the maximum yield of hormones is approximately 6-8 per 660K protein, the whole process is apparently wasteful. However, the efficiency of thyroglobulin as a thyroid hormone precursor is extremely high when the supply of iodine is short; in such conditions, almost all the iodine incorporated is found in iodothyronine. Hence it is suggested that the thyroglobulin structure has evolved to allow for the preferential and efficient iodination and coupling of the hormonogenic tyrosines. Here we report the complete primary structure of bovine thyroglobulin, derived from the sequence of its 8,431-base-pair complementary DNA. The 2,769-amino-acid sequence is characterized by a pattern of imperfect repeats derived from three cysteine-rich motifs. Four hormonogenic tyrosines have been precisely localized near the amino and carboxyl ends of the protein.

Effects of fluoride on thyroid hormone biosynthesis. Studies in a highly sensitive test system.

In view of the recommendation that fluoride supplements via drinking water or table salt prevent dental caries, we analyzed whether fluoride had antithyroid properties in a sensitive experimental model. Rats were given either 60 or 200 micrograms/ml fluoride in the drinking water. This raised the serum fluoride concentration from 0.165 to 0.246 in the first and to 0.576 micrograms/ml in the second instance. Although the higher fluoride dose was near the toxic range, no antithyroid effect was observed. Neither organification of iodine, nor any subsequent step of thyroid hormone biosynthesis (transformation of monoiodotyrosine to diiodotyrosine and then to thyroxine) were affected. Fluoride had no effect on thyroglobulin content of the thyroid gland or on the degree of iodination of thyroglobulin.