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PubMedDate not supplied

Lack of reported mutations in a Japanese case of toxic multinodular goiter.

We describe a toxic multinodular goiter that was subjected to genomic sequencing of the thyroid-stimulating hormone receptor and the alpha-subunit of the stimulatory guanine nucleotide-binding protein. No mutation was detected in either gene. While frequent occurrence of thyroid-stimulating hormone receptor gene mutations in toxic multinodular goiters has been reported in areas such as part of Europe with a relatively high prevalence of iodine deficiency, toxic multinodular goiters in areas with an abundance of dietary iodine such as Japan seem unlikely to involve mutations of this gene.

Aged↗
PubMed2005

Effects on bone mineral density by treatment of benign nodular goiter with mildly suppressive doses of L-thyroxine in a cohort women study.

OBJECTIVES: Thyroid diseases and their treatment may influence the osseous system. The influence that prolonged suppressive L-thyroxine (LT4) therapy may have on inducing subclinical hyperthyroidism on bone metabolism is still a matter of debate. The aim of the present study was to assess the effects of chronic LT4 treatment at mildly inhibiting serum thyroid-stimulating hormone (TSH) doses on bone mineral density (BMD) and biochemical bone remodeling markers in a cohort of women with benign nodular goiter, and to verify the efficacy of the treatment on nodule size. SUBJECTS AND STUDY DESIGN: A total of 200 euthyroid Caucasian women with nodular goiter (age 52.1 +/- 9; 80 pre- and 120 postmenopausal) were enrolled: 96 had been treated with LT4 for at least 3 years and a matched group of 104 had untreated goiter. LT4 therapy was given at a dose sufficient to reduce TSH under the lower limit of the normal range (0.27-4.20 microIU/ml) without suppressing it below the limit of assay sensitivity (0.005 microIU/ml) and maintaining normal serum values of free triiodothyronine (FT3) and free thyroxine (FT4). The adequacy of the dose was evaluated on the basis of serum TSH levels. The osteopenic effect of LT4 treatment was evaluated directly by total body and lumbar spine dual-energy X-ray absorptiometry (DEXA) and indirectly by biochemical parameters (alkaline phosphatase, osteocalcin, calcium, parathyroid hormone) at the baseline and throughout the follow-up. The efficacy of LT4 schedule on thyroid nodule size was assessed on the basis of the ultrasonographic evaluation. RESULTS: Mineralometric data showed no significant difference between BMD values for treated and untreated patients in both pre- and postmenopausal status. In all patients, serum markers of bone turnover were in the normal range, with no differences in the treated and control groups. The TSH concentrations were significantly lower in treated than in untreated patients (p < 0.0001); FT3 and FT4 were in the normal range for all patients. Evaluation of nodule size during follow-up showed a reduction of > or = 30% in 32 of 96 treated patients (33.3%) versus none in those untreated, whilst nodule size remained unmodified in 60 treated patients (62.5%) versus 35 (33.6%) in those untreated, and an increase in nodule size and/or development of new nodules was found in 4 treated patients (4.2%) versus 69 of the 104 untreated patients (66.3%). CONCLUSIONS: This study suggests that at slightly suppressing TSH doses, LT4 therapy has no adverse effects on BMD in both pre- and postmenopausal women, while having an efficacy on nodule size comparable with that reported using an LT4 schedule able to maintain TSH near or below the assay sensitivity limit.

Absorptiometry, Photon↗
PubMed1991

Intrauterine treatment of thyroid goiters.

A fetal thyroid goiter detected by ultrasonography at 20 weeks of amenorrhea (WA) was diagnosed at 23 WA by a second ultrasound examination and a TSH assay in amniotic fluid. Since a sample of fetal blood at 27 WA showed that hypothyroidism was compensated and that goiter size and amniotic fluid volume were stable, intra-amniotic injection of 300 micrograms of L-thyroxine was delayed until 36 WA. This injection was performed before delivery to avoid potential perinatal complications (dystocia and neonatal respiratory distress) caused by large goiters.

Amniocentesis↗
PubMedDate not supplied

Solitary nodular goiter. Review of cytomorphologic features in 441 cases.

OBJECTIVE: To study the cytomorphologic features of solitary nodular goiters (SNG). STUDY DESIGN: May-Grünwald-Giemsa-stained smears in 441 SNG diagnosed by ultrasonography and fine needle aspiration (FNA) and found to have optimum cellular material at review were subjected to detailed cytologic assessment. The age of the patients ranged from 11 to 75 years, with a median of 35. Male: female ratio was 69:372. The parameters for cytologic assessment included cellularity, colloid content, acinar formation, papillary formation, intranuclear cytoplasmic inclusions, nuclear grooves, marginal vacuoles, Hürthle cells and various inflammatory cells. Histopathology reports on thyroidectomy specimens were available in 27 cases from two Delhi hospitals. RESULTS: Hyperplastic nodules (68 cases) differed significantly from colloid goiters (269 cases) by having more cases with excessive cellularity, acinar formation and marginal vacuoles (P < .001). There was also a significant difference with respect to papillary formation and moderate-to-excessive colloid content (P < .001). As compared to hyperplastic nodules, neoplasms (60 cases) had a significantly higher number of cases with papillary formation, intranuclear inclusions and nuclear grooves but lower number of cases with marginal vacuoles (P < .01-.001). Among neoplasms, usual papillary carcinoma (19 cases) differed from follicular neoplasms (20 cases) with respect to acinar formation, papillary formation and nuclear grooves (P < .001). A significant difference was also observed with respect to colloid content and nuclear inclusions. Follicular variant of papillary carcinomas (FVPC) (10 cases) emerged as a distinct cytologic entity following review and differed from usual papillary carcinomas in having a higher number of cases with acinar formation, tubular formation and marginal vacuoles (P < .01-.001) and lower number of cases with nuclear grooves (P = .05). FVPC also differed from follicular neoplasms with respect to papillary formation, tubular formation, intranuclear inclusions and nuclear grooves (P < .01-.001). Overall cytohistologic agreement was achieved in 24 of 27 (88.9%) cases. CONCLUSION: Detailed cytologic assessment of FNA smears-in SNG was helpful in highlighting parameters that differentiate between various types of goiters.

Adolescent↗
PubMedDate not supplied

Fine needle aspiration cytology of amyloid goiter. A report of four cases.

BACKGROUND: Amyloid goiter is a very rare clinical entity. It can be confused easily with a neoplastic goiter both clinically and cytologically. CASES: In four cases of amyloid goiter the diagnosis was established preoperatively by fine needle aspiration cytology. Abundant violet to pink amorphous material with staining characteristics of amyloid was obtained in all cases. This material was morphologically distinct from colloid. Abdominal fat aspiration was done in all four cases. Two of the four abdominal fat aspirates were positive for amyloid. CONCLUSION: Attention to the morphology of cells accompanying amyloid allows exclusion of medullary thyroid carcinoma, thereby avoiding unnecessary surgery. Moreover, aspirates from the abdominal pad of fat and the thyroid and salivary glands, when enlarged, are useful in the workup of suspected amyloidosis, especially since it is a safe, easily performed procedure.

Adipose Tissue↗
PubMed1987

Autonomy of growth and of iodine metabolism in hyperthyroid feline goiters transplanted onto nude mice.

Hyperthyroidism caused by nodular goiters is a common disease of aging cats. Growth and iodine metabolism were studied by autoradiography in normal and hyperfunctioning thyroid tissue obtained from cats injected with 125I before surgery, and in xenografts, grown in nude mice, after double-labeling with 131I and [3H]thymidine. Hyperthyroid cat goiters contain single or multiple hyperplastic nodules, consisting of highly cellular tissue with an iodine metabolism exceeding that of the surrounding normal tissue. Xenografts of hyperplastic hot tissue in thyroxine-treated nude mice retain their original histologic pattern and continue to accumulate radioiodine intensely. Autoradiographs assessed for [3H]thymidine incorporation reveal autonomously proliferating follicular cells within the hyperplastic foci but not within the normal tissue. Administration of sera from donor cats into host mice fails to stimulate the xenografts. Neither hyperfunction nor growth of toxic cat goiters depends on extrathyroidal stimulators. The basic lesion appears to be an excessive intrinsic growth capacity of some thyroid cells.

Animals↗
PubMed2003

Giant substernal goiter with chylothorax.

A 60-year-old woman presented with a huge goiter extending from the lower jaw to the diaphragm. Right pleurocentesis produced chylous fluid. A cervicothoracic incision was used to totally excise the substernal goiter, with near-total excision of the cervical goiter, and repair of the lymphatic leakage.

Chylothorax↗
PubMed2004

Posterior mediastinal goiter.

Most mediastinal goiters are retrosternally situated in the anterior mediastinal compartment. Posterior mediastinal goiters, either retrotracheal or retroesophageal, are rare. We herein describe a case involving a retrotracheal goiter in the right posterior mediastinum, which was excised using a combined cervico-partial sternotomy and right thoracotomy approach.

Cough↗
PubMed2006

Multinodular goiter compressing the trachea following open heart surgery.

Acute hemorrhage into an adenomatous goiter following cardiac surgery is a rare cause of acute upper airway obstruction. We report an unusual presentation of respiratory distress in a patient with goiter recovering from open heart surgery, which was successfully treated by left hemithyroidectomy. A mandatory evaluation of the upper trachea in patients with long-standing benign goiter is recommended prior to cardiac surgery.

Airway Obstruction↗
PubMedDate not supplied

Toxic intrathoracic goiter and mediastinal lymphadenopathy: an unusual presentation of systemic primary AL amyloidosis.

Mediastinal lymphadenopathy and goiter have been associated with primary amyloidosis, although not in the same patient. One previous case report described the association of an amyloid goiter and hyperthyroidism (due to Graves' disease) with primary amyloidosis. Till now no case reports of patients presenting simultaneously with mediastinal lymphadenopathy, intrathoracic amyloid goiter and hyperthyroidism as the first manifestation of systemic primary (idiopathic) amyloidosis have been described. The present case report describes the clinical, biological radiological and histological features in such a male patient.

Aged↗
PubMed1978

Thyroid hormone analogs and fetal goiter.

Transfer of iodothyronine across the placenta in most species occurs only with difficulty. Recently, biologically active, nonhalogenated thyroid hormone analogs have been synthesized with properties which might favor placental transfer. To test this possibility, we compared the doses of T4, T3, and thyroid hormone analogs necessary to prevent propylthiouracil-induced goiter formation in rat fetuses. T4 and T3 prevented fetal goiter, but in doses that caused maternal hyperthyroidism; in contrast, the thyroid hormone analogs prevented fetal goiter in doses that were not thyrotoxic to the mother.

Animals↗
PubMed2003

Pretreatment with a single, low dose of recombinant human thyrotropin allows dose reduction of radioiodine therapy in patients with nodular goiter.

In patients with nodular goiter, radioiodine ((131)I) therapy results in a mean reduction in thyroid volume (TV) of approximately 40% after 1 yr. We have demonstrated that pretreatment with a single, low dose of recombinant human TSH (rhTSH) doubles 24-h radioactive iodine uptake (RAIU) in these patients. We have now studied the safety and efficacy of therapy with a reduced dose of (131)I after pretreatment with rhTSH. Twenty-two patients with nodular goiter received (131)I therapy, 24 h after im administration of 0.01 (n = 12) or 0.03 (n = 10) mg rhTSH. In preceding diagnostic studies using tracer doses of (131)I, 24-h RAIU without and with rhTSH pretreatment (either 0.01 or 0.03 mg) were compared. Therapeutic doses of (131)I were adjusted to the rhTSH-induced increases in 24-h RAIU and were aimed at 100 micro Ci/g thyroid tissue retained at 24 h. Pretreatment with rhTSH allowed dose reduction of (131)I therapy by a factor of 1.9 +/- 0.5 in the 0.01-mg and by a factor of 2.4 +/- 0.4 in the 0.03-mg rhTSH group (P < 0.05, 0.01 vs. 0.03 mg rhTSH). Before and 1 yr after therapy, TV and the smallest cross-sectional area of the tracheal lumen were measured with magnetic resonance imaging. During the year of follow-up, serum TSH, free T(4) (FT(4)), T(3), and TSH receptor antibodies were measured at regular intervals. TV before therapy was 143 +/- 54 ml in the 0.01-mg group and 103 +/- 44 ml in the 0.03-mg rhTSH group. One year after treatment, TV reduction was 35 +/- 14% (0.01 mg rhTSH) and 41 +/- 12% (0.03 mg rhTSH). In both groups, smallest cross-sectional area of the tracheal lumen increased significantly. In the 0.01-mg rhTSH group, serum FT(4) rose, after (131)I treatment, from 15.8 +/- 2.8 to 23.2 +/- 4.4 pM. In the 0.03-mg rhTSH group, serum FT(4) rose from 15.5 +/- 2.5 to 23.5 +/- 5.1 pM. Individual peak FT(4) levels, reached between 1 and 28 d after (131)I treatment, were above the normal range in 12 patients. TSH receptor antibodies were negative in all patients before therapy and became positive in 4 patients. Hyperthyroidism developed in 3 of these 4 patients between 23 and 25 wk after therapy. In conclusion, in patients with nodular goiter pretreatment with a single, low dose of rhTSH allowed approximately 50-60% reduction of the therapeutic dose of radioiodine without compromising the efficacy of TV reduction.

Aged↗
PubMed2004

Genome-wide linkage analysis reveals evidence for four new susceptibility loci for familial euthyroid goiter.

Euthyroid goiter is characterized by diffuse or nodular enlargement of the thyroid gland. Iodine deficiency and cigarette smoking have been identified as important environmental factors. However, family and twin pair studies suggest a strong genetic predisposition. Therefore, we performed the first extended genome-wide scan to identify susceptibility loci that predispose for euthyroid goiter using 450 microsatellite markers in 18 extended Danish, German, and Slovakian families. Parametric and nonparametric multipoint linkage analyses were performed. The highest nonparametric LOD scores were obtained for chromosomes 2q and 3p with values of 2.54 at D2S1363 and 2.25 at D3S3038, respectively. Assuming heterogeneity and dominant inheritance, heterogeneity LOD scores (HLOD) of 2.71 and 1.94 were calculated for 2q and 3p, respectively. Furthermore, nonparametric LOD scores of 1.87 (HLOD 1.39) at D7S1808 on 7q and 1.79 (HLOD 1.80) at D8S264 on 8p were obtained. Haplotyping of families contributing to the linkage signals revealed four families compatible with a putative locus on 3p and one family each showing strict cosegregation with the loci on 2q, 7q, and 8p. The four novel candidate loci corroborate the assumed heterogeneity in the etiology of euthyroid familial goiter. For the first time, a more prevalent putative locus, present in 20% of the families investigated, was identified.

Adult↗
PubMed2004

Intrafamilial variability of the deafness and goiter phenotype in Pendred syndrome caused by a T416P mutation in the SLC26A4 gene.

Pendred syndrome (PS) is the most common cause of syndromic deafness, accounting for more than 5% of all autosomal-recessive hearing loss cases. It is characterized by bilateral sensorineural hearing loss and by goiter with or without hypothyroidism. Mutations in the SLC26A4 gene cause both classical PS and deafness associated with an enlarged vestibular aqueduct without goiter. To investigate a possible genotype-phenotype correlation in PS, we performed a detailed clinical and genetic study in three adult German sibs with typical PS caused by a common homozygous SLC26A4 mutation, T416P. An audiological long-term follow-up of 23 yr showed that the mutation T416P is associated with a distinct type of hearing loss in each of the three sibs: moderate-to-profound progressive deafness, profound nonprogressive deafness, and a milder but more rapidly progressing form. We show that these phenotypic differences are not caused by either different degrees of inner ear malformations or sequence variations in the GJB2/connexin 26 gene. Because the thyroid phenotype was also highly variable within the family, with thyroid sizes ranging from normal to large goiters requiring thyroidectomy, this study leads to the conclusion that other environmental and/or genetic factors have an impact on the PS phenotype.

Adolescent↗
PubMed2004

Management of the nontoxic multinodular goiter in Latin America: comparison with North America and Europe, an electronic survey.

To assess diagnostic and therapeutic approaches to nontoxic multinodular goiter and to compare them with previously reported American Thyroid Association (ATA) and European Thyroid Association (ETA) surveys, an online questionnaire was distributed to Latin American Thyroid Society (LATS) members. An index case was presented (42-yr-old woman with an enlarged, irregular, nontender, 50- to 80-g thyroid and no clinical suspicion of malignancy or dysfunction), and 11 variations were proposed to evaluate how each alteration would affect management. We obtained 148 responses (response rate, 50%). In the index case, the most used blood tests were TSH (96%), antithyroid peroxidase antibodies (76%), and free T(4) (64%); 5% included a calcitonin assay. Nearly 90% would perform ultrasound, and only 16% used scintigraphy. Fine needle biopsy was indicated by 88%, with ultrasound guidance in 75% of times. For treatment, observation was preferred by 39%, surgery by 28%, levothyroxine by 21%, and radioiodine by 7% (60% with recombinant TSH prestimulation). A suppressed TSH level prompted 45% of the respondents to recommend radioiodine, whereas 70-78% indicated surgery in the presence of a large goiter or suspicion of malignancy. In conclusion, no consensus exists concerning the ideal management of nontoxic goiter among LATS members, in agreement with previous ATA and ETA surveys. Levothyroxine therapy is less used by LATS than by ATA or ETA members, and a more aggressive therapeutic strategy is generally preferred by members of LATS and ETA compared with ATA.

Adult↗
PubMed2005

A new case of congenital goiter with hypothyroidism caused by a homozygous p.R277X mutation in the exon 7 of the thyroglobulin gene: a mutational hot spot could explain the recurrence of this mutation.

Identification of thyroglobulin (TG) gene mutations may provide insight into the structure-function relationship. In this study, we have performed molecular studies in a patient with congenital goiter, hypothyroidism, and impairment of TG synthesis. Genomic DNA sequencing revealed a homozygous c.886C-->T mutation in exon 7, resulting in a premature stop codon at amino acid 277 (p.R277X). The same nonsense mutation had been reported previously in two Brazilian families with multiple occurrence of congenital hypothyroidism with goiter. We compared the insertion/deletion polymorphism in intron 18, microsatellites (Tgm1, Tgm2, TGrI29, and TGrI30), and exonic single-nucleotide polymorphism haplotypes identified in the patient with a member of the previously reported family, who also carry the mutation as a compound heterozygous mutation. The single-nucleotide polymorphism and microsatellite analysis revealed that the two affected individuals do not share a common TG allele. This suggests that the p.R277X mutation is a mutational hot spot. No difference in either splicing or abundance of the amplified product was detected by RT-PCR, excluding that an alternative splicing mechanism, by skipping of exon 7, would restore the normal reading frame. In conclusion, we report a new case of congenital goiter and hypothyroidism caused by a p.R277X mutation in the TG gene. Moreover, we show that nucleotide 886 is a mutational hot spot that explains the recurrence of this mutation.

Amino Acid Sequence↗
PubMed1976

The acute thyroidal response to iodixed oil in severe endemic goiter.

The acute changes in serum thyrotropin (TSH) triiodothyronine (T3) and thyroxine (T4), were measured in 14 subjects, 4 to 10 (mean = 6) days following intramuscular iodized oil injection. In 8 subjects with small or absent goiter there was a significant fall in T3 and a rise in TSH concentrations, suggesting an acute inhibitory effect of the iodine. In 6 subjects with large multinodular goiters there was a marked rise in both T3 and T4, and reduction in the elevated basal TSH. Biochemical hyperthyroidism occurred in 3 of these subjects. The acute thyroid hormone response to iodized oil, whether inhibitory or stimulatory in a particular subject, depends both on goiter size and on the serum concentration of TSH.

Adolescent↗
PubMed1976

Similar serum IgM concentrations in Greek endemic goiter and control populations: failure to confirm previous experience.

Circulating immunoglobulin M (IgM) concentrations were determined in 47 nontoxic goiter patients from four Greek endemic goiter areas, and in 13 patients from Athens, a non-goitrous area; and compared with 38 control non-goitrous subjects from the same goiter regions, and 23 more controls from Athens. The values in both goitrous and non-goitrous groups were indistinguishable. Current techniques for single radial immunodiffusion were employed. The results are expressed in standardized international units/ml serum, instead of the formerly used mg/dl. The present findings are in disagreement with the earlier observation from this laboratory that 40 per cent of goitrous patients had elevated IgM values compared with 10 per cent of control subjects.

Adolescent↗