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Thyroid hemiagenesis with multinodular goiter: a case report and review of the literature.

Thyroid hemiagenesis is a very rare abnormality, in which one thyroid lobe fails to develop. Most of the patients diagnosed have an associated thyroidal disease. The true prevalence of thyroid hemiagenesis is not known, but it is estimated to be 0.02% in normal children. We report a forty-five year-old female patient with a multinodular goiter in left lobe, associated with hemiagenesis of right lobe and isthmus.

Female↗

Development of subclinical hyperthyroidism due to Graves' disease in a hypothyroid woman who had undergone hemithyroidectomy for adenomatous goiter and radiotherapy for nasopharyngeal cancer.

A variety of thyroid disorders develop following external radiation to head and neck cancers. Hypothyroidism is the most common clinical consequence of the radiotherapy and lifelong thyroid hormone replacement is required in many cases. Patients who received both hemithyroidectomy and the external radiation to the neck are at especially high risk for permanent hypothyroidism. Here we report an unusual case with radiation-induced hypothyroidism who had undergone hemithyroidectomy for adenomatous goiter 8 years before the radiotherapy for nasopharyngeal cancer and subclinical hyperthyroidism due to Graves' disease developed during thyroxine replacement therapy. Thus subclinical hyperthyroidism due to Graves' disease can develop in patients with radiation-induced hypothyroidism even if they have undergone hemithyroidectomy for thyroid nodules. Therefore careful and periodic evaluation of thyroid function is required even on adequate thyroxine replacement therapy.

Adult↗

Serum levels of cytokines in children and adolescents with Graves' disease and non-toxic nodular goiter.

It has been shown that human thyrocytes can synthesize cytokines which activate T and B lymphocytes. These immune cells play important roles in the initiation and continuation of thyroid autoimmunity. The aim of this study was to estimate serum concentrations of soluble interleukin-6 receptor (sIL-6R), interleukin-6 (IL-6) and interleukin-8 (IL-8) in patients with Graves' disease (GD) (n=44, mean age 14.8 years), in patients with nontoxic nodular goiter (NTNG) (n=36, mean age 15.6 years) and in a group of healthy controls (n=20, mean age 14.5 years). ELISA was used to determine the concentration of cytokines, antithyroglobulin and antithyroid peroxidase antibodies in patients with thyroid disease. Radio receptor assay (RRA) was performed to detect anti-TSH receptor autoantibodies (TRAb). Serum levels of IL-6, sIL-6R and IL-8 were markedly elevated in patients with GD before treatment with methimazole (p<0.0001 for IL-6, p<0.006 for sIL-6R, p<0.004 for IL-8) and after 8 weeks of therapy (p<0.011 for IL-6, p<0.04 for IL-8). However, following 24 months of treatment, normal serum concentrations of these cytokines were restored. Furthermore, patients with NTNG showed a slightly elevated concentration of cytokines (IL-6, IL-8). Serum levels of tri-iodothyronine in patients with GD positively correlated with serum concentrations of IL-6 (r = 0.35, p<0.025) and sIL-6R (r = 0.31, p<0.047), while no correlation was found between thyroxine and cytokines. Moreover, we observed a positive correlation between serum levels of TPO-Abs, TRAb and IL-6 (r = 0.43, p<0.008; r = 0.5, p<0.003) and between TPO-Abs and IL-8 (r = 0.67, p<0.0001). However, in patients with NTNG no correlation was observed between serum levels of antithyroid antibodies or thyroid hormones and serum levels of cytokines. We conclude that the cytokines (IL-6, sIL-6R, IL-8) could play an important role in the development of Graves' disease and that their levels are modulated by thyreostatic treatment.

Adolescent↗

Multinodular goiter in children.

OBJECTIVE: As multinodular goiter (MNG) is an uncommon pediatric disorder, we decided to evaluate the children with this diagnosis at our center to try to delineate better its etiology, the risk of malignancy and appropriate management strategies. METHODS AND RESULTS: Eighteen patients (12 girls and 6 boys) were the subject of this retrospective review spanning a period of 20 years. All were previously well, except one, and none had had head or neck irradiation. Average age at diagnosis was 12.8 years. Four children belonged to two previously identified kindreds diagnosed with familial MNG. These families had members affected with multiple cases of non-medullary thyroid carcinoma (NMTC). All were euthyroid and had no symptoms. In eight of 18 patients, the clinical examination missed the presence of multiple nodules which were subsequently detected by ultrasound. Twelve patients had tissue diagnosis by fine needle aspirate cytology (FNAC) or surgery. Five of eight patients undergoing surgery had nodular hyperplasia, one had a follicular adenoma and one had a normal thyroid gland on histology. There was one patient with papillary carcinoma combined with nodular hyperplasia. Seven of the patients had evidence of antithyroid autoimmunity. CONCLUSION: The etiology of pediatric MNG appears multifactorial including autoimmune and familial factors. We believe that previously healthy children can usually be managed conservatively. Ultrasound at the time of diagnosis and in follow up seems beneficial. Familial forms appear to warrant close follow up, given the apparent increased risk of malignancy. The risk of malignancy while low remains real.

Adenoma↗

Earliest prevention of endemic goiter by iodine supplementation during pregnancy.

During pregnancy complex changes of maternal thyroid function occur and they are influenced by the maternal iodine supply. It has been demonstrated that with decreasing iodine supply maternal goiter and hypothyroxinemia as well as fetal and neonatal hypothyroidism become more prevalent. Therefore iodine supplementation during pregnancy is now strongly recommended also in areas of moderate iodine deficiency. To monitor the success of iodine supplementation and its theoretical risk of increasing the frequency of thyroid autoantibodies, we have investigated the thyroid volume, thyroid function, urinary iodine excretion and antibodies to thyroid peroxidase at 10-12 weeks of gestation and postpartum in 38 mothers receiving 300 micrograms potassium iodide/day and in 70 mothers without iodine supplementation. In all of their newborns thyroid volume was determined by ultrasound. The thyrotropin (TSH) levels and antibodies to thyroid peroxidase (TPO-ab) in the neonates were measured in dried blood spots on filter paper from their newborn screening. Urinary iodine excretion was increased significantly after iodine supplementation in mothers (p < 0.001) and their newborns (< 0.05). No hypo- or hyperthyroidism was observed in the mothers or newborns. Interestingly, no difference of maternal thyroid volumes was observed between the two groups after pregnancy, but the volumes of the thyroid glands in newborns of mothers who received iodine were significantly (p < 0.004) lower (0.7 +/- 0.4 ml) than in the control group (1.5 +/- 1.1 ml). There was no change in the frequency of TPO-ab in either group after pregnancy. In four mothers transplacental passage of these antibodies was documented by positive measurement in the blood sample of the newborn. This study documents that iodine supplementation during pregnancy in an area of moderate iodine deficiency results in a lower size of neonatal thyroid volume and that this supplementation was not accompanied by an increase in the frequency of TPO-ab.

Autoantibodies↗

Comparison of two different doses of iodide in the prevention of gestational goiter in marginal iodine deficiency: a longitudinal study.

OBJECTIVE: A prospective randomized trial was performed to assess the usefulness of iodine supplementation in the prevention of goiter in pregnant women living in marginally iodine-deficient areas. DESIGN: Eighty-six pregnant women were recruited and randomized in two groups and treated daily for up to six months after delivery with 200 microg iodide (group A) or 50 microg iodide (group B). Sixty-seven women (32 in group A and 35 in group B) completed the study. METHODS: Thyroid volume (TV), thyroid functional parameters and urinary iodine concentration were determined in all subjects at booking, at the 18th-26th, and the 29th-33rd week of gestation, and at the 3rd and 6th month after delivery. RESULTS: A slight but not significant increase in TV during gestation was observed only in group B. After delivery a progressive decrease in TV was documented in both groups, the final TV being significantly reduced with respect to the initial volume in group A. No significant changes in serum free thyroid hormones and TSH concentrations were found during gestation in either group. Postpartum thyroiditis was observed in 5 women (2 in group A, 3 in group B). No side effects were seen. CONCLUSION: The present data indicate that in marginally iodine-deficient areas, the administration of iodide is recommended in pregnancy and lactation. In the conditions of the present trial a dose of 50 microg iodide/day is a safe and effective measure in preventing an increase in TV during pregnancy but a dose of 200 microg iodide/day appeared to be more effective without inducing side effects and without enhancing the frequency of post-partum thyroiditis.

Adult↗

Effect of iodine or iopanoic acid on thyroid Ca2+/NADPH-dependent H2O2-generating activity and thyroperoxidase in toxic diffuse goiters.

OBJECTIVE: The aim of the present study was to compare the effects of iopanoic acid (IOP) or a saturated solution of potassium iodide (SSKI) administration to patients with toxic diffuse goiters (TDG). DESIGN: Patients with TDG are treated with thionamides and high doses of iodine preoperatively. In this study, two types of preoperative drug regimens were used: propylthiouracil or methimazole plus SSKI for 10-15 days (n=8) or IOP for 7 days (n=6). METHODS: Serum thyroid hormones (total and free thyroxine (T(4)), total tri-iodothyronine (T(3)) and reverse T(3) (rT(3)), were evaluated after 7 days of either SSKI or IOP treatment, and after 10-15 days of SSKI administration. During thyroidectomy, samples of thyroid gland were obtained to evaluate thyroperoxidase and thyroid H(2)O(2)-generating activities. RESULTS: Serum total T(3) was significantly decreased after 7 days of either treatment, and serum rT(3) was significantly increased in IOP-treated patients. Serum total and free T(4) were unaffected by 7 days of IOP treatment, but decreased after 7 days of SSKI treatment, although significantly diminished levels were only reached after a further 3-8 days of SSKI administration. During both drug regimens, serum TSH remained low (SSKI: 0.159+/-0.122; IOP: 0.400+/-0.109 microU/ml). Thyroperoxidase activity was significantly lower in thyroid samples from patients treated with SSKI for 10-15 days than in the thyroid glands from IOP-treated patients. However, thyroid H(2)O(2) generation was inhibited in samples from patients treated with either IOP or SSKI. CONCLUSIONS: We show herein that IOP treatment can be effective in the management of hyperthyroidism and that this drug inhibits thyroid NADPH oxidase activity, just as previously described for SSKI, probably due to its iodine content.

Adolescent↗

Low-dose recombinant human thyrotropin-aided radioiodine treatment of large, multinodular goiters in elderly patients.

OBJECTIVE: We aimed to assess low-dose recombinant human thyroid-stimulating hormone (rhTSH)-aided, fixed-activity radioiodine therapy of large, multinodular goiters (MNGs) in elderly patients with comorbidities. DESIGN: This was a short-term, observational study. METHODS: We measured 24-h thyroid radioiodine uptake (RAIU) of 2 microCi 131-iodine at baseline and 24 h after intramuscular injection of 0.03 mg rhTSH in 17 patients (aged 60-86 years, 12 women), who subsequently received 30 mCi 131-iodine 24 h after an identical rhTSH injection. TSH and free thyroxine (FT4) were measured at baseline and days 10, 30 and 90 after therapy. Thyroid volume was assessed by computed tomography at baseline and day 180. RESULTS: rhTSH, 0.03 mg, significantly increased mean 24-h thyroid RAIU from 25.8% +/- 10.3% to 43.3% +/- 8.4% (68% relative increase; t(16) = -8.43, P < 0.001). The proportion of patients overtly or subclinically hyperthyroid (TSH < 0.5 mU/l) decreased from 71% (12/17) at baseline to 19% (3/16) at 3 months. Mean serum FT4 peaked at slightly above normal range, 25.9 +/- 7.7 pmol/l (46% over baseline) and was 21% under baseline levels at 3 months. Mean estimated thyroid volume fell 34% from baseline to 6 months (170.0 +/- 112.8 to 113.1 +/- 97.5 ml; P < 0.01). Symptomatic relief, improved well-being, and/or reduction or elimination of antihyperthyroid medication were seen in 76% of patients. Three (18%) patients had transient neck pain or tenderness, or palpitations; one had transient asymptomatic thyroid enlargement; and three (18%) became hypothyroid by 3 months. CONCLUSIONS: Intramuscular rhTSH, 0.03 mg, followed 24 h later by 30 mCi 131-iodine, is a safe, effective and convenient treatment for MNG in elderly patients with comorbidities.

Aged↗

Congenital diffuse hyperplastic goiter associated with perinatal mortality in 11 captive-born bottlenose dolphins (Tursiops truncatus).

Diffuse hyperplastic goiter was diagnosed by histopathology in 11 perinatal bottlenose dolphins (Tursiops truncatus) that died at four separate zoos and aquaria. Thyroid morphology of these animals was compared with the histologically normal thyroids of two stranded wild bottlenose dolphin calves, a neonate and a 2-mo-old calf. Histologic changes included reduced follicular luminal diameter, markedly reduced or absent luminal colloid, hypertrophy of follicular epithelium, and follicular dysplasia. The etiology of the thyroid gland lesion was not identified. Cause of death was not determined for most of these animals, but they were presumed to have died from metabolic derangements associated with the thyroid lesion, drowning, or dystocia.

Animals↗

Prognostic factors of papillary and follicular thyroid cancer: differences in an iodine-replete endemic goiter region.

Papillary (PTC) and follicular thyroid carcinoma (FTC) are known as differentiated thyroid carcinoma (DTC). Nevertheless, according to the UICC/AJCC (TNM) classification PTC and FTC are frequently analyzed as one cancer. The aim of this study is to show differences in outcome and specific prognostic factors in an iodine-replete endemic goiter region. Six hundred and three patients with DTC treated within a 35-year-period were retrospectively analyzed with respect to carcinoma-specific survival. Prognostic factors were tested for their significance using univariate and multivariate analysis. The histological type (PTC versus FTC) was found to be a highly significant factor - carcinoma-specific survival both in univariate (P<0.001) and multivariate analyses (P=0.003) was significantly different. Univariate analysis revealed patients' age, extra-thyroid tumor spread, lymph node and distant metastases, increasing tumor size, and the tall cell variant to be significant prognostic factors for PTC patients. Age > or =45 years, positive lymph nodes and increasing tumor size were confirmed as independent prognostic factors. Univariate analysis of FTC patients revealed age at presentation, gender, extrathyroidal tumor spread, lymph node and distant metastases, increasing tumor size, multifocality, widely invasive tumor growth and oxyphilic variant to be factors bearing prognostic significance. The presence of distant metastases and increasing tumor size could be identified as independent prognostic factors for FTC patients. This study shows distinctive differences in prognostic factors of PTC and FTC: independent factors predicting poor prognosis are age > or =45 years, positive lymph nodes and increasing tumor size for PTC, and distant metastases and increasing tumor size for FTC. PTC and FTC patients should be analyzed and reported separately.

Adenocarcinoma, Follicular↗

Unfolded protein response is involved in the pathology of human congenital hypothyroid goiter and rat non-goitrous congenital hypothyroidism.

The unfolded protein response (UPR) is an intracellular signaling pathway that regulates the protein folding and processing capacity of the endoplasmic reticulum (ER). The UPR is induced by the pharmacological agents that perturb ER functions but is also activated upon excessive accumulation of the mutant secretory proteins that are unable to attain correct three-dimensional structure and are thus retained in the ER. Such defects in intracellular protein transport underlie the development of a number of phenotypically diverse inherited pathologies, termed endoplasmic reticulum storage diseases (ERSD). We have studied UPR development in two similar ERSDs, human congenital goiter caused by the C1264R and C1996S mutations in the thyroglobulin (Tg) gene and non-goitrous congenital hypothyroidism in rdw dwarf rats determined by the G2320R Tg mutation. In both cases, these mutations rendered Tg incapable of leaving the ER. A major ER chaperone immunoglobulin-binding protein (BiP), and a novel putative escort chaperone endoplasmic reticulum protein 29 KDa (ERp29) were found to be associated with Tg, which might be interpreted as the contribution of the quality control machinery to the previously shown retention of Tg in the ER. We have extended our earlier observations of ER chaperone induction with the identification of the additional ER (ERp29, ERp72, calreticulin, protein disulfide isomerase (PDI)), cytoplasmic (heat shock protein (HSP)70, HSP90) and mitochondrial (mtHSP70) upregulated chaperones and folding enzymes. Activation of the transcriptional arm of UPR, as judged by the appearance of the spliced (active) form of X-box binding protein (XBP1) and processed activating transcription factor 6 (ATF6) transcription factors was suggested to contribute to the overexpression of the ER chaperones. The processing of ATF6 was observed in both human and rat tissues with Tg mutations. Whereas, in human tissues, weak splicing of XBP1 mRNA was detected only in the C1264R mutant, all rat thyroids including wild-type contained significant amounts of the spliced form of XBP1 as opposed to human liver and rat brain tissues, implying the existence of a previously unknown tissue-specific regulation of XBP1 processing.

Activating Transcription Factor 6↗

Expression of the endothelin-1 gene in the rat thyroid gland and changes in its peptide and mRNA levels in goiter formation and iodide-induced involution.

Endothelin-1 (ET-1) is a major vasoconstrictor peptide, first found in endothelial cells, and later in many other tissues, including the thyroid gland. We analysed the expression of the ET-1 gene in the rat thyroid gland and changes in ET-1 mRNA and peptide levels in goiter development and involution, two circumstances characterised by vascular changes. Thyroid hyperplasia was induced in adult Wistar rats by feeding a low iodine diet (LID) supplemented with 0.25% thiouracil for 10 days, and LID alone for 2 further days (H.12 group). Involution was induced by injecting 100 micrograms iodide and refeeding a normal diet during 6 h, 12 h, and 24 h (I.6h, I.12h, I.24h groups). Rats fed a normal iodine diet were used as controls. A specific 488 bp cDNA corresponding to the known sequence of pre-pro ET-1 was found by RT-PCR from RNA extracts in all thyroid experimental groups, as well as in lung and kidney which were used as positive controls. RP-HPLC analysis showed that ET-1 immunoreactivity eluted similarly as mature ET-1. During hyperplasia, ET-1 mRNA and peptide levels were increased 3.5- and 5-fold respectively. The relative volume of the vascular bed was more than doubled. During iodide-induced involution, the glandular ET-1 mRNA level remained elevated. The concentration of ET-1 peptide increased and was significantly greater at 12 h involution than in the H.12 group. At this time, the capillary reticulum reverted to individual capillaries and the vascular bed was significantly reduced. These data demonstrate that the ET-1 gene is expressed in the rat thyroid gland and that the ET-1 mRNA and peptide levels are increased during thyroid hyperplasia and remain elevated during a phase of rapid iodide-induced involution. These data suggest that changes in ET-1 production may play a role in control of thyroid gland trophic regulation and vascularity.

Animals↗

Congenital hypothyroidism with goiter in toy fox terriers.

Congenital hypothyroidism with goiter was observed to segregate as a simple autosomal recessive trait in Toy Fox Terriers (TFTs). Neonatal affected pups exhibited inactivity, abnormal hair coat, stenotic ear canals, and delayed eye opening. Palpable ventrolateral cervical swellings were evident by 1 week of age. Serum thyroid hormone and thyroid-stimulating hormone concentrations were low and high, respectively. Histologic examination of the cervical masses disclosed cuboidal to columnar follicular epithelial cell hyperplasia with widely varying follicular size, shape, and amount of colloid. Oral thyroid hormone replacement therapy restored near-normal growth and development. At 8 weeks of age, radioiodine uptake and perchlorate discharge testing indicated an iodine organification defect. Biochemical analysis of thyroid tissue from affected dogs demonstrated enzymatic iodine oxidation deficiency and lack of sodium dodecyl sulfate-resistant thyroglobulin dimers, suggesting thyroid peroxidase deficiency. A nonsense mutation in the thyroid peroxidase gene of affected dogs was discovered and demonstrated to segregate with the disease. A DNA-based carrier test was developed and currently is used by TFT breeders to prevent this disorder.

Animals↗

Endemic goiter associated with high iodine intake.

OBJECTIVES: This study assessed the relation of iodine content of household water to thyroid size and urinary iodine excretion in an area with high iodine concentration in the water. METHODS: The iodine content of household water and indicators of iodine status (thyroid size and urinary iodine level) were assessed in selected villages in Jiangsu Province, China. RESULTS: Water iodine levels were positively correlated with urinary iodine levels and indicators of thyroid size at the township level. CONCLUSIONS: Excess iodine in household water was the likely cause of endemic goiter and elevated urinary iodine levels in the study area. This finding affects public health policy on the institution of universal salt iodization for the elimination of iodine deficiency disorders.

China↗

An unusual cause of hematemesis: Goiter.

Downhill varices are located in the upper part of the esophagus and are usually related to superior vena cava obstruction. Bleeding from these varices is extremely rare. We describe a 77-year-old patient with hematemesis due to downhill varices as a result of recurrent goiter. A right lobe thyroidectomy was carried out with disappearance of the varices.

Aged↗

Schwannoma of the left brachial plexus mimicking a cervicomediastinal goiter in a young Nigerian lady.

The schwannoma is thought to arise from the schwann cells of the nerve sheath. This tumor is usually solitary and may arise from any cranial or peripheral nerve. It is encapsulated and appears to arise focally on a nerve trunk so that the nerve itself is stretched over the tumor rather than running through it as in neurofibroma. This report is unusual as the tumor started as a cervical swelling which subsequently grew into the mediastinum simulating a retrosternal goiter. The patient, a 25 year-old female was referred to the University College Hospital, Ibadan, 24 hours after an attempted thyroidectomy at a private hospital. The history was of a painless anterior neck swelling of 4 years duration devoid of symptoms of hyperthyroidism with associated dysphagia and weakness of the left hand. Examination showed an asthenic young woman. Her voice was hoarse but there were no eye signs suggestive of thyrotoxicosis. On the anterior neck was a sutured skin-crease scar over a diffuse anterior neck swelling which one could not get below. The left hand showed wasting of the thenar and hypothenar eminences. Thyroid function test results were within normal limits, indirect laryngoscopy showed a left vocal cord paralysis, packed cell volume was 38%. Her chest x-ray showed a huge left retrosternal and apical soft tissue mass displacing the trachea to the right (figure 1). A fine needle aspiration cytology was reported as a chronic lymphocytic thyroiditis. A presumptive diagnosis of thyroid carcinoma with retrosternal extension was made. At surgery, manipulation of the mass was difficult as the tissue was soft, slimy and ruptured easily. Severe hemorrhage was encountered necessitating a median sternotomy to control the bleeding vessels. Her post-operative period was stormy, however she thereafter made gradual progress to warrant her discharge six weeks post surgery.

Adult↗

Superior vena cava syndrome caused by a benign retrosternal multinodular goiter.

Retrosternal thyroid accounts for a significant percentage of anterior mediastinal masses, but has been described very rarely as the cause of superior vena cava (SVC) syndrome. Most cases of SVC syndrome occur as a complication of malignancy. The authors report the case of a patient with few respiratory symptoms, mild upper airway obstruction, and SVC syndrome caused by a benign retrosternal multinodular goiter.

Aged↗

[Goiter prevalence and urinary excretion of iodine in a sample of school age children in the city of Rome].

The aim of the study was the assessment of the urinary iodine excretion and the evaluation of thyroid volume compared with clinical examination in 1040 schoolchildren (6-14 years old), living in Rome. Mean urinary iodine excretion was 98.52 +/- 49.81 micrograms/l (median 92 micrograms/l). Thyroid enlargement, as assessed by palpation, was found to be grade 1A in 35.4% of the children, grade 1B in 9.6% and grade 2 in 0.2%. Thyroid volume, determined by ultrasound, increased with age, was significantly correlated with body surface area and was significantly higher in females, as compared to males, in the 11 and 12 years old group. Eleven children (1.9%) were negative at palpation (grade 0) but showed thyroid enlargement by ultrasound. The prevalence of goiter determined by ultrasound resulted to be 4.7%.

Adolescent↗