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1.  Agenesis and not ectopia is common in North Indian children with thyroid dysgenesis 
Ectopic Thyroid Gland (ETG) is known to be the most common form of thyroid dysgenesis in children with permanent congenital hypothyroidism (CH). Recent reports indicate that agenesis or hypoplasia of thyroid gland may be commoner as compared to ETG in thyroid dysgenesis (TD). There is limited information available on the proportion of different variants of TD in Indian children.
To characterize the different TD variants in a cohort of North Indian children with TD.
Settings and Design:
Endocrinology Unit of a large Multispecialty Pediatrics Center located in North India. Retrospective review of clinical records of children with CH due to TD diagnosed between April 2004 and March 2014.
Diagnoses of TD in 94 children (48 boys and 46 girls) were based on combined scanning with high-resolution ultrasonography, and technetium-99m pertechnetate thyroid scintigraphy. Thyroid agenesis, ectopia and hypoplasia were diagnosed in 74 (78.7%), 14 (14.8%) and 6 (6.4%) patients respectively. The mean initial serum total T4 and thyroid stimulating hormone concentrations at diagnosis were 3.03 ± 2.88 μg/dL (range 0.01–8.9) and 284.52 ± 300.67 mIU/L (range 10.03–1159.0) respectively. Patients with ETG were older at the time of diagnosis as compared to patients with hypoplasia or ectopia. The mean duration of follow-up was 3.7 ± 2.85 years (range 3 months–10 years).
Thyroid agenesis was the most common form of TD in our children with permanent CH. Hypoplasia and ectopia were uncommon. Female preponderance, noted in many previous reports, was not seen in our patients with TD.
PMCID: PMC4266877  PMID: 25538886
Agenesis; congenital hypothyroidism; ectopic thyroid gland; thyroid dysgenesis
2.  Combined ultrasound and isotope scanning is more informative in the diagnosis of congenital hypothyroidism than single scanning 
Archives of Disease in Childhood  2006;91(12):972-976.
Thyroid imaging is helpful in confirming the diagnosis of congenital hypothyroidism and in establishing the aetiology. Although isotope scanning is the standard method of imaging, ultrasound assessment may be complementary.
To determine the strengths and weaknesses of thyroid ultrasound and isotope scanning in neonates with thyroid stimulating hormone (TSH) elevation.
Babies from the West of Scotland with raised capillary TSH (>15 mU/l) on neonatal screening between January 1999 and 2004 were recruited. Thyroid dimensions were measured using ultrasonography, and volumes were calculated. Isotope scanning was carried out with a pinhole collimator after an intravenous injection of 99m‐technetium pertechnetate.
40 infants (29 female) underwent scanning at a median of 17 days (range 12 days to 15 months). The final diagnosis was athyreosis (n = 11), ectopia (n = 12), hypoplasia (n = 8; 3 cases of hemi‐agenesis), dyshormonogenesis (n = 5), transient hypothyroidism (n = 2), transient hyperthyrotropinaemia (n = 1) and uncertain status with gland in situ (n = 1). 6 infants had discordant scans with no isotope uptake but visualisation of thyroid tissue on ultrasound. This was attributed to TSH suppression from thyroxine (n = 3); maternal blocking antibodies (n = 1); cystic degeneration of the thyroid (n = 1); and possible TSH receptor defect (n = 1).
Isotope scanning was superior to ultrasound in the detection of ectopic tissue. However, ultrasound detected tissue that was not visualised on isotope scanning, and showed abnormalities of thyroid volume and morphology. We would therefore advocate dual scanning in newborns with TSH elevation as each modality provides different information.
PMCID: PMC2082992  PMID: 16864597
3.  Role of color Doppler in differentiation of Graves' disease and thyroiditis in thyrotoxicosis 
World Journal of Radiology  2013;5(4):178-183.
AIM: To evaluate the role of thyroid blood flow assessment by color-flow Doppler ultrasonography in the differential diagnosis of thyrotoxicosis and compare it to technetium pertechnetate thyroid scanning.
METHODS: Twenty-six patients with thyrotoxicosis were included in the study. Clinical history was taken and physical examination and thyroid function tests were performed for all patients. Thyroid autoantibodies were measured. The thyroid glands of all patients were evaluated by gray scale ultrasonography for size, shape and echotexture. Color-flow Doppler ultrasonography of the thyroid tissue was performed and spectral flow analysis of both inferior thyroid arteries was assessed. Technetium99 pertechnetate scanning of the thyroid gland was done for all patients. According to thyroid scintigraphy, the patients were divided into two groups: 18 cases with Graves’ disease and 8 cases with Hashimoto’s thyroiditis. All patients had suppressed thyrotropin. The diagnosis of Graves’ disease and Hashimoto’s thyroiditis was supported by the clinical picture and follow up of patients.
RESULTS: Peak systolic velocities of the inferior thyroid arteries were significantly higher in patients with Graves’ disease than in patients with thyroiditis (P = 0.004 in the right inferior thyroid artery and P = 0.001 in left inferior thyroid artery). Color-flow Doppler ultrasonography parameters demonstrated a sensitivity of 88.9% and a specificity of 87.5% in the differential diagnosis of thyrotoxicosis.
CONCLUSION: Color Doppler flow of the inferior thyroid artery can be used in the differential diagnosis of thyrotoxicosis, especially when there is a contraindication of thyroid scintigraphy by radioactive material in some patients.
PMCID: PMC3647210  PMID: 23671754
Doppler; Thyrotoxicosis; Thyroid scintigraphy; Graves’ diseases; Thyroiditis
4.  Permanent and Transient Congenital Hypothyroidism in Fayoum, Egypt: A Descriptive Retrospective Study 
PLoS ONE  2013;8(6):e68048.
Congenital hypothyroidism (CH) is one of the most common preventable causes of mental retardation. One important challenge in understanding the epidemiology of CH is that some newborns will have transient CH, a temporary depression of thyroid hormone concentrations that can last from several days to several months. Studies from other countries have reported that 10 to 15% of children treated for CH ultimately prove not to need treatment past 3 years of age to maintain normal hormone concentrations, and thus have transient hypothyroidism. The purpose of this study was to determine the prevalence of permanent and transient congenital hypothyroidism in Fayoum, Egypt.
Cases detected by Fayoum neonatal screening program (NSP) between January 2003 and December 2011, and followed up at health insurance center were included. Permanent or transient CH was determined using results of thyroid function tests.
Of the 248 patients diagnosed primarily with CH by NSP; 204 (82.3%) patients were diagnosed to have permanent CH (prevalence 1/3587 live birth), and 44 (17.7%) patients were diagnosed to have transient CH (prevalence 1/16667 live birth). Initial TSH levels were higher in permanent CH cases than transient cases (p<0.004). Female to male ratio was 0.8 and 0.7 in permanent and transient CH respectively. 161 (65%) patients had thyroid dysgenesis (107 ectopic thyroid gland, 28 athyreosis and 26 thyroid hypoplasia). 87 (35%) patients had intact gland in thyroid scan and were considered to have dyshormonogenesis. Of these 87 patients 44 proved to have transient CH and 43 had permanent CH.
The preliminary data from our study revealed that the incidences of CH as well as the permanent form were similar to worldwide reports. Although the high incidence of transient CH in our study could be explained by iodine deficiency further studies are needed to confirm the etiology and plan the treatment strategies.
PMCID: PMC3695950  PMID: 23840807
5.  Evaluation of Congenital Hypothyroidism in Fars Province, Iran 
Iranian Journal of Pediatrics  2012;22(1):107-112.
In Iran thyroid-stimulating hormone (TSH) based neonatal screening program is included in health care services from 2005 for detection of patients with primary congenital hypothyroidism (CH). This study was performed for a critical evaluation of the screening program primary congenital hypothyroidism in Fars province, Iran.
From November 2006 to September 2007, TSH serum concentrations of 63031 newborns, 3 to 5 days old born in Fars province, were measured by heel prick. The newborns with TSH ≥5mIU/L were recalled for measurement of serumT4 and TSH in venous blood samples
Of 127 recalled subjects, 43 were confirmed to be hypothyroid, showing a prevalence of 1:1465 with F:M ratio of 1.05:1. The most common clinical and radiological findings were prolonged jaundice (73%), large anterior fontanel (56%), wide posterior fontanel (55%), absence of distal femoral epiphysis (20%), and umbilical hernia (11%). Scintigraphy of the thyroid with 99mTC revealed eutopia (67.4%), hypoplasia (23.3%), agenesis (4.7%) and ectopia (2.3%).
It is concluded that a cut off value of TSH≥5mIU/L overestimates recalling the number of patients with CH. The most common cause of congenital hypothyroidism is not dysgenesis of the gland and perhaps dyshormonogenesis in Iran is more common than what is reported in other countries.
PMCID: PMC3448225  PMID: 23056868
Congenital Hypothyroidism; Thyroxin; Thyroglobolin; Thyroid Dysgenesis; Fars province
6.  Preoperative localization and minimally invasive management of primary hyperparathyroidism concomitant with thyroid disease*  
The coexistence of thyroid diseases with primary hyperparathyroidism (PHPT) can present a challenge in the clinical diagnosis and management for these patients. This study aims to determine the frequency of coexisting thyroid gland lesions in a consecutive series patients with PHPT, and to analyze the clinical features, diagnosis and treatment of these patients. Twenty-two cases of a total of 52 PHPT patients who had synchronous thyroid and parathyroid pathology were surgically managed in this study. Thirteen patients had ipsilateral thyroid nodules, and 9 patients had thyroid nodules in contralateral or bilateral side. Seven patients underwent direct parathyroidectomy and hemithyroidectomy via a mini-incision (about 3 cm), while other 15 procedures were converted to Kocher incision. Seventeen nodular goiter (32.7%), 2 thyroiditis (3.8%), 2 thyroid adenoma (3.8%) and 1 thyroid carcinoma (1.9%) coexisting with parathyroid adenoma were pathologically diagnosed. The sensitivity of preoperative ultrasonography (US) and methoxy-isobutyl-isonitrile (MIBI) scintigraphy for parathyroid lesions was 63.6% and 85.7%; and the overall positive predictive values for MIBI and US were 100% and 95.5% respectively. A high incidence of thyroid diseases that coexisted with PHPT in literatures was briefly reviewed. Our study illustrated the need for clinical awareness of concomitant PHPT and thyroid disease. A combination of US, computed tomography (CT) and MIBI scintigraphy would be recommended for preoperative localization of enlarged parathyroid adenoma and for evaluation of thyroid lesions. Synchronous treatment of associated thyroid abnormalities is desirable, and open minimally invasive surgical approach with additional resection of isolated ipsilateral thyroid nodules is possible in some of these patients.
PMCID: PMC1963428  PMID: 17726743
Hyperparathyroidism; Thyroid diseases; Imaging diagnosis; Surgical treatment
7.  Thyroglobulin Gene Mutation with Cold Nodule on Thyroid Scintigraphy 
Case Reports in Endocrinology  2012;2012:280319.
Thyroglobulin gene mutation is a rare cause of congenital hypothyroidism, but thyroglobulin gene mutations are thought to be associated with thyroid cancer development. A 21-year-old Japanese man treated with levothyroxine for congenital hypothyroidism had an enlarged thyroid gland with undetectable serum thyroglobulin despite elevated serum TSH level. The patient was diagnosed with thyroglobulin gene mutation, with compound heterozygosity for Gly304Cys missense mutation and Arg432X nonsense mutation. Ultrasonography showed a hypovascular large tumor in the left lobe that appeared as a cold nodule on thyroid scintigraphy. He underwent total thyroidectomy, but pathological study did not reveal findings of thyroid carcinoma, but rather a hyperplastic nodule with hemorrhage. Strong cytoplasmic thyroglobulin immunostaining was observed, but sodium iodide symporter immunostaining was hardly detected in the hyperplastic nodule. The clinical characteristics of patients with thyroglobulin gene mutations are diverse, and some patients are diagnosed by chance on examination of goiter in adults. The presence of thyroid tumors that appear as cold nodules on thyroid scintigraphy should consider the potential for thyroid carcinoma, if the patient has relatively low serum thyroglobulin concentration in relation to the degree of TSH without thyroglobulin autoantibody.
PMCID: PMC3420384  PMID: 22934199
8.  Scintigraphic Detection of Dual Ectopic Thyroid Tissue: Experience of a Chinese Tertiary Hospital 
PLoS ONE  2014;9(4):e95686.
To assess scintigraphic pattern, clinical indication and relevance of dual ectopic thyroid tissue (ETT). Literature is reviewed for such cases.
In this 5-year retrospective study, we reviewed all thyroid scintigraphies in our data base. Patients diagnosed with suspected ETT were identified. Literature is reviewed. Statistics were done by one-way analysis of variance and least significant difference test.
From 11905 thyroid scintigraphies during the 5-year period, we retrieved 121 patients eligible for analysis. The top two indications were assessing a palpable front neck mass to determine whether it was an ETT, and primary hypothyroidism. Patients were divided into 3 groups. Group 1 with single ETT (83 cases); group 2 with dual ETT (6 cases) and group 3 with athyroid (32 cases). Age and thyroid hormones were highest in group 2, and lowest in group 3. Thyrotropin was highest in group 3, and lowest in group 2. Thyroxine was given to hypothyroid patients, while no surgery was performed. There were 42 published cases with dual ETT, most of whom were under 30 years old. 38.10% of them were euthyroid, 33.33% hypothyroid, and 21.43% subclinical hypothyroid. Most frequent ectopic positions included lingual (33.73%), sublingual (27.71%) and subhyoid (22.89%).
In our cohort, incidence of dual ETT was 0.05% if the denominator was total number of thyroid scintigraphies. The incidence was 4.96% if the denominator was the number of patients with suspected ETT. Important clinical indication is a front neck palpable mass suggestive of an ETT. Important clinical relevance of recognizing the dual ETT pattern is to avoid inappropriate surgery. After reviewing all published cases, we find dual ETT is often seen in young patients. Most of such patients are euthyroid or mildly hypothyroid. Thyroid ectopia often resides in lingual, sublingual and subhyoid areas.
PMCID: PMC3991721  PMID: 24748408
9.  Thyroid diseases in pregnancy: The importance of anamnesis 
Pakistan Journal of Medical Sciences  2013;29(5):1187-1192.
Objective: Primary objective of our study was to evaluate the efficiency of detailed medical history and thyroid examination of the pregnant women presenting to our clinic from Rize province and nearby which was an endemic goiter region. It was aimed to investigate the frequency of thyroid diseases, pregnancy outcomes and the efficiency of screening with thyroid function tests during the first trimester of pregnancy as secondary endpoint.
Methodology : A prospective clinical study was conducted with 998 pregnant women between the ages of 17-48 years. In the first step of our study, a detailed medical history was obtained and a detailed thyroid gland examination was performed in all the patients (n=998). In the patients diagnosed with thyroid disease or considered to have thyroid disease with these results (n=107), thyroid diseases were evaluated with thyroid function tests and imagining methods. Analyses of socio-demographic data and nutrition were also made. In the second step, thyroid stimulating hormone (TSH), free T3 and free T4 tests were performed in the first antenatal examination of the pregnant cases considered not to have thyroid disease after medical history and examination (n=891). Parameters of thyroid peroxidase antibodies (TPOAb), thyroglobulin antibodies (TgAb) and TSH receptor auto antibodies (TRAb) were investigated in the cases whose TSH, sT3 and sT4 levels were different than the reference values after examination of the endocrinologist. Thyroid ultrasonography was performed. Urinary iodine levels in 24 hour urine were investigated.
Results: During pregnancy, the incidence of hyperthyroidism and hypothyroidism in the whole study group were 2.8% (28/998) and 4.3% (43/998), respectively, 6.7% of the patients (67/998) had a diagnosis of thyroid disease before pregnancy. Hyperthyroidism and hypothyroidism depending on the TSH screening results were 1.9% (17/891) and 1.1% (10/891) respectively and the incidence of overt hyperthyroidism and overt hypothyroidism were 0.2% (2/891) and 0.2% (2/891) in the pregnant cases considered not to have thyroid disease with medical history and examination.
Conclusion: Detailed medical history and family history obtained during the first trimester of pregnancy helped us to identify 6.7% of thyroid diseases among the pregnant women. This result effectively emphasizes the importance of detailed first prenatal examination regarding the thyroid.
PMCID: PMC3858910  PMID: 24353717
Hyperthyroidism; Hypothyroidism; Thyroid diseases in pregnancy; Goiter
10.  Diffuse Metastasis to the Thyroid: Unique Ultrasonographic Finding and Clinical Correlation 
Journal of Korean Medical Science  2014;29(6):818-824.
Cases of metastases to the thyroid gland seem to be increasing in recent years. The clinical and ultrasonographic findings of diffuse metastases have been sparsely reported. Thirteen cases of diffuse metastases to the thyroid gland were documented by thyroid ultrasonography-guided fine needle aspiration cytology between 2004 and 2013. We retrospectively reviewed the patients with diffuse thyroid metastases. The most common primary site was the lung (n=9), followed by unknown origin cancers (n=2), cholangiocarcinoma (n=1), and penile cancer (n=1). Eleven patients were incidentally found to have thyroid metastases via surveillance or staging FDG-PET. Other 2 patients were diagnosed during work-up for hypothyroidism and palpable cervical lymph nodes. On ultrasonography, the echogenicity of the enlarged thyroid gland was heterogeneously hypoechoic or isoechoic, and reticular pattern internal hypoechoic lines were observed without increased vascularity found by power Doppler ultrasonography (3 right lobe, 2 left lobe, and 8 both lobes). In the 8 patients who had involvement of both lobes, 3 had hypothyroidism. In conclusion, ultrasonographic finding of diffuse metastasis is a diffusely enlarged heterogeneous thyroid with reticular pattern internal hypoechoic lines. Thyroid function testing should be performed in all patients with diffuse thyroid metastases, especially those with bilateral lobe involvement.
Graphical Abstract
PMCID: PMC4055816  PMID: 24932084
Thyroid; Diffuse; Metastasis; Ultrasonography; Fine Needle Aspiration Cytology
11.  Role of ultrasonography in the management of patients with primary hyperparathyroidism: retrospective comparison with technetium-99m sestamibi scintigraphy 
Journal of Ultrasound  2014;17(1):1-12.
Primary hyperparathyroidism (PHPT) is a common endocrine disorder that can be cured only by parathyroidectomy. Cervical ultrasonography and scintigraphy are the imaging studies most widely used for preoperative localization of the affected glands. The aim of this retrospective comparative study was to define the respective roles of ultrasonography and parathyroid scintigraphy in these cases.
Materials and methods
We analyzed 108 patients who had undergone parathyroidectomies for PHPT following cervical ultrasonographic and scintigraphic examinations. The ultrasound examinations were carried out by an expert physician sonographer in 61 cases and by various physician sonographers with different levels of experience in 47 cases. Sonographic and scintigraphic findings were compared with surgical findings and the diagnostic performance of the two imaging methods was evaluated by means of statistical analysis.
The operator dependency of ultrasonography was confirmed by marked variations in sensitivity related to the experience of the sonographer. When sonography was performed by an expert, the sensitivity of combined use of the two methods was not significantly higher than that of sonography alone.
In expert hands, the diagnostic yield of ultrasound is appreciably superior. It can therefore be used as the main and possibly sole method for preoperative localization of pathological parathyroid tissues. Combined use of ultrasound and scintigraphy is not cost-effective in these cases. Scintigraphy is indicated only when the ultrasound examination produces negative results.
PMCID: PMC3945200  PMID: 24616746
Primary hyperparathyroidism; Parathyroid adenoma; Ultrasonography; Localization
12.  Comparing results of clinical versus ultrasonographic examination in developmental dysplasia of hip 
Developmental dysplasia of hip (DDH) is one of the congenital anomalies in newborns that if not diagnosed and treated on time can lead to a severe disability. Although clinical examination is a very useful way for screening, but in some patients, a confirmatory diagnostic method such as ultrasonography is needed. The aim of the present study is to compare the sensitivity and specificity of clinical examination and ultrasonography in early detecting of DDH.
Materials and Methods:
A total of 5800 of newborns were examined by orthopedic surgeon as a screening method. The newborns with risk factors or suspicious on clinical examination were introduced to repeat clinical and ultrasonographic examination of hip. The results were collected and recorded by a check list and then the sensitivity and specificity of clinical examination were calculated.
Of 5701 newborns (11402 hips) who were studied by two methods of clinical examination and ultrasonography (by Graf method), the overall incidence of DDH was 29 per 1000. Only 94 hips (13.5%) of 694 disordered ones according to clinical examination were involved on ultrasonographic evaluation. A total of 240 hips of 334 (72%) involved hips according to ultrasonography (Graf type IIb or more) were diagnosed normal on clinical examination, considering ultrasonography as a gold standard method of evaluating DDH, the sensitivity and specificity of clinical examination were calculated 28.1% and 94.5%, respectively.
According to the present study, ultrasonogeraphic examination has a high valuable in screening of DDH and the clinical examination done by an experienced orthopedic surgeon has an acceptable value in primary screening of DDH in developing countries for detecting of healthy neonates, but if the newborn has a risk factor or is suspicious on clinical examination, it will be necessary to get assistance from ultrasonography by an experienced sonographer.
PMCID: PMC3908525  PMID: 24523795
Developmental dysplasia of hip (DDH); instability; dislocation; subluxation; ultrasonography
13.  Etiology of congenital hypothyroidism in Isfahan: Does it different? 
Considering the higher prevalence of congenital hypothyroidism (CH) in Iran and the importance of determination of the etiology of CH for assessing appropriate treatment strategies, understanding the pathogenesis of CH and the implications of its inheritance and prognosis, the aim of this study was to determine the etiology of CH 7 years after initiation of the program in Isfahan province.
Materials and Methods:
In this cross-sectional study, children with a primary diagnosis of CH studied. They clinically examined and their medical files were reviewed by a Pediatric Endocrinologist. Considering screening and follow-up lab data and radiologic findings the etiology of CH was determined. Screening properties of different etiologies of CH was compared.
In this study, 437 patients with permanent CH (PCH) were studied. Etiology of PCH in 316 (72.3%) and 121 (27.7%) of cases was thyroid dyshormonogenesis and thyroid dysgenesis, respectively. Prevalence of agenesis, ectopia, hypoplasia and hemiagenesis in thyroid dysgenetic patients was 13.3%, 6.4%, 4.3% and 3.7% respectively. Mean of thyroid stimulating hormone in screening, recall and after discontinuing treatment at 3 years of age was significantly lower in dyshormonogenetic CH patients than dysgenetic ones(P < 0.01).
Seven years of our experiences in CH screening program indicated that the etiology of CH in Isfahan, with a higher rate of CH, with a predominance of thyroid dyshormonogenesis is different from most of the studies world-wide and similar to other reports from Iran. The findings of the current study provide us baseline information for determination of CH pathogenesis in this region.
PMCID: PMC3929017  PMID: 24600601
Congenital hypothyroidism; dysgenesis; dyshormonogenesis; permanent
14.  Hyperfunction Thyroid Nodules: Their Risk for Becoming or Being Associated with Thyroid Cancers 
Korean Journal of Radiology  2013;14(4):643-652.
To retrospectively evaluate the risk of thyroid cancer in patients with hyperfunctioning thyroid nodules through ultrasonographic-pathologic analysis.
Materials and Methods
Institutional review board approval was obtained and informed consent was waived. From 2003 to 2007, 107 patients consecutively presented with hot spots on thyroid scans and low serum thyroid-stimulating hormone levels. Among them, 32 patients who had undergone thyroid ultrasonography were analyzed in this study. Thyroid nodules depicted on ultrasonography were classified based on size and categorized as benign, indeterminate, or suspicious malignant nodules according to ultrasonographic findings. The thyroid nodules were determined as either hyperfunctioning or coexisting nodules and were then correlated with pathologic results.
In 32 patients, 42 hyperfunctioning nodules (mean number per patient, 1.31; range, 1-6) were observed on thyroid scans and 68 coexisting nodules (mean, 2.13; range, 0-7) were observed on ultrasonography. Twenty-five patients (78.1%) had at least one hyperfunctioning (n = 17, 53.1%) or coexisting (n = 16, 50.0%) nodule that showed a suspicious malignant feature larger than 5 mm (n = 8, 25.0%), or an indeterminate feature 1 cm or greater (n = 20, 62.5%) in diameter, which could have been indicated by using fine needle aspiration (FNA). Seven patients were proven to have 11 thyroid cancers in 3 hyperfunctioning and 8 coexisting nodules. All of these had at least one thyroid cancer, which could have been indicated by using FNA. The estimated minimal risk of thyroid cancer was 6.5% (7/107).
Patients with hyperfunctioning nodules may not be safe from thyroid cancer because hyperfunctioning nodules can coexist with thyroid cancer nodules. To screen out these cancers, ultrasonography should be performed.
PMCID: PMC3725360  PMID: 23901323
Hyperfunctioning nodule; Radionuclide imaging; Thyroid cancer; Ultrasonography; Guideline
15.  The role of the resistive index in Hashimoto's thyroiditis: a Sonographic pilot study in children 
Clinics  2012;67(11):1253-1257.
The role of Doppler ultrasonography in the diagnosis of diffuse thyroid diseases is not well established. In particular, Doppler ultrasonography findings in children with Hashimoto's thyroiditis are very limited. We examined gray-scale and Doppler ultrasound findings in Hashimoto's thyroiditis in children in an attempt to understand the feasibility of future prospective controlled studies.
Twenty-one children with newly diagnosed Hashimoto's thyroiditis were recruited in the study. The patients were euthyroid or had subclinical hypothyroidism at the time of the ultrasonography examination. According to the color Doppler scale developed by Schulz et al., thyroid glands were classified into four patterns based on visual scoring and the mean resistive index (RI), which was calculated via measurements from both lobes, and these results were compared with gray-scale findings.
The mean RI value, calculated as the mean of the RI values of both lobes obtained from each patient, was found to be 0.57±0.05 (range 0.48-0.67) cm/sn. The distribution of thyroid classifications was as follows: Pattern 0, n = 7; Pattern I, n = 6; Pattern II, n = 4; and Pattern III (“thyroid inferno”), n = 4. The mean RI values in patients with normal or near-normal gray-scale findings (n = 10) and patients with more substantial gray-scale changes (n = 11) were not significantly different and were lower than the values in normal children previously presented in the literature.
The results indicated that the RI may be more sensitive than other ultrasound parameters for the diagnosis of Hashimoto's thyroiditis.
PMCID: PMC3488981  PMID: 23184199
Doppler Ultrasound; Hashimoto's Thyroiditis
16.  Neonatal Thyroid Function in Seveso 25 Years after Maternal Exposure to Dioxin 
PLoS Medicine  2008;5(7):e161.
Neonatal hypothyroidism has been associated in animal models with maternal exposure to several environmental contaminants; however, evidence for such an association in humans is inconsistent. We evaluated whether maternal exposure to 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), a persistent and widespread toxic environmental contaminant, is associated with modified neonatal thyroid function in a large, highly exposed population in Seveso, Italy.
Methods and Findings
Between 1994 and 2005, in individuals exposed to TCDD after the 1976 Seveso accident we conducted: (i) a residence-based population study on 1,014 children born to the 1,772 women of reproductive age in the most contaminated zones (A, very high contamination; B, high contamination), and 1,772 age-matched women from the surrounding noncontaminated area (reference); (ii) a biomarker study on 51 mother–child pairs for whom recent maternal plasma dioxin measurements were available. Neonatal blood thyroid-stimulating hormone (b-TSH) was measured on all children. We performed crude and multivariate analyses adjusting for gender, birth weight, birth order, maternal age, hospital, and type of delivery. Mean neonatal b-TSH was 0.98 μU/ml (95% confidence interval [CI] 0.90–1.08) in the reference area (n = 533), 1.35 μU/ml (95% CI 1.22–1.49) in zone B (n = 425), and 1.66 μU/ml (95% CI 1.19–2.31) in zone A (n = 56) (p < 0.001). The proportion of children with b-TSH > 5 μU/ml was 2.8% in the reference area, 4.9% in zone B, and 16.1% in zone A (p < 0.001). Neonatal b-TSH was correlated with current maternal plasma TCDD (n = 51, β = 0.47, p < 0.001) and plasma toxic equivalents of coplanar dioxin-like compounds (n = 51, β = 0.45, p = 0.005).
Our data indicate that environmental contaminants such as dioxins have a long-lasting capability to modify neonatal thyroid function after the initial exposure.
Andrea Baccarelli and colleagues show that maternal exposure to a dioxin following the industrial accident in Seveso, Italy in 1976 is associated with modified neonatal thyroid function even many years later.
Editors' Summary
The thyroid, a butterfly-shaped gland in the neck, controls the speed at which the human body converts food into the energy and chemicals needed for life. In healthy people, the thyroid makes and releases two hormones (chemical messengers that travel around the body and regulate the activity of specific cells) called thyroxine (T4) and triiodothyronine (T3). The release of T4 and T3 is controlled by thyroid secreting hormone (TSH), which is made by the pituitary gland in response to electrical messages from the brain. If the thyroid stops making enough T4 and T3, a condition called hypothyroidism (an underactive thyroid) develops. Adults with hypothyroidism put on weight, feel the cold, and are often tired; children with hypothyroidism may also have poor growth and mental development. Because even a small reduction in thyroid hormone levels increases TSH production by the pituitary, hypothyroidism is often diagnosed by measuring the amount of TSH in the blood; it is treated with daily doses of the synthetic thyroid hormone levothyroxine.
Why Was This Study Done?
Although hypothyroidism is most common in ageing women, newborn babies sometimes have hypothyroidism. If untreated, “neonatal” hyperthyroidism can cause severe mental and physical retardation so, in many countries, blood TSH levels are measured soon after birth. That way, levothyroxine treatment can be started before thyroid hormone deficiency permanently damages the baby's developing body and brain. But what causes neonatal hypothyroidism? Animal experiments (and some but not all studies in people) suggest that maternal exposure to toxic chemicals called dioxins may be one cause. Dioxins are byproducts of waste incineration that persist in the environment and that accumulate in people. In this study, the researchers investigate whether exposure to dioxin (this name refers to the most toxic of the dioxins—2,3,7,8-Tetrachlorodibenzo-p-dioxin) affects neonatal thyroid function by studying children born near Seveso, Italy between 1994 and 2005. An accident at a chemical factory in 1976 heavily contaminated the region around this town with dioxin and, even now, the local people have high amounts of dioxin in their bodies.
What Did the Researchers Do and Find?
The researchers identified 1,772 women of child-bearing age who were living very near the Seveso factory (the most highly contaminated area, zone A) or slightly further away where the contamination was less but still high (zone B) at the time of the accident or soon after. As controls, they selected 1,772 women living in the surrounding, noncontaminated (reference) area. Altogether, these women had 1,014 babies between 1994 and 2005. The babies born to the mothers living in the reference area had lower neonatal blood TSH levels on average than the babies born to mothers living in zone A; zone B babies had intermediate TSH levels. Zone A babies were 6.6. times more likely to have a TSH level of more than 5 μU/ml than the reference area babies (the threshold TSH level for further investigations is 10 μU/ml; the average TSH level among the reference area babies was 0.98 μU/ml). The researchers also examined the relationship between neonatal TSH measurements and maternal dioxin measurements at delivery (extrapolated from measurements made between 1992 and 1998) in 51 mother–baby pairs. Neonatal TSH levels were highest in the babies whose mothers had the highest blood dioxin levels.
What Do These Findings Mean?
These findings suggest that maternal dioxin exposure has a long-lasting, deleterious effect on neonatal thyroid function. Because the long-term progress of the children in this study was not examined, it is not known whether the increases in neonatal TSH measurements associated with dioxin exposure caused any developmental problems. However, in regions where there is a mild iodine deficiency (the only environmental exposure consistently associated with reduced human neonatal thyroid function), TSH levels are increased to a similar extent and there is evidence of reduced intellectual and physical development. Future investigations on the progress of this group of children should show whether the long-term legacy of the Seveso accident (and of the high environmental levels of dioxin elsewhere) includes any effects on children's growth and development.
Additional Information.
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The MedlinePlus encyclopedia provides information about hypothyroidism and neonatal hypothyroidism; MedlinePlus provides links to additional information on thyroid diseases (in English and Spanish)
The UK National Health Service Direct health encyclopedia provides information on hypothyroidism
The Nemours Foundation's KidsHealth site has information written for children about thyroid disorders
Toxtown, an interactive site from the US National Library of Science, provides information on environmental health concerns including exposure to dioxins (in English and Spanish)
More information about dioxins is provided by the US Environmental Protection Agency and by the US Food and Drug Administration
Wikipedia has a page on the Seveso disaster (note: Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
PMCID: PMC2488197  PMID: 18666825
17.  Impact of concomitant thyroid pathology on preoperative workup for primary hyperparathyroidism 
The former standard surgical treatment in patients with primary hyperparathyroidism (pHPT) has been bilateral cervical exploration. New localization techniques and the possibility of intraoperative measurement of intact parathormone (iPTH) permit a focused, minimally invasive parathyroidectomy (MIP). The introduction of MIP without complete neck exploration leads to the potential risk of missing thyroid pathology. The aim of the present study is to evaluate the value of MIP in respect to coexisting thyroid findings and their impact on preoperative workup for primary hyperparathyroidism.
This is a prospective study including 30 consecutive patients with pHPT (median age 65 years; 17 females, 13 males). In all patients preoperative localization was performed by ultrasonography and 99mTc-MIBI scintigraphy-Intraoperative iPTH monitoring was routinely done.
Ten patients (33%) had a concurrent thyroid finding requiring additional thyroid surgery, and two patients (7%) with negative localization results underwent bilateral neck exploration. Therefore, MIP was attempted in 18 (60%) patients. The conversion rate to a four gland exploration was 6% (1/18). The sensitivities of 99mTc-MIBI scanning and ultrasonography were 83.3% and 76.6%, respectively. The respective accuracy rates were 83.3% and 76.6%. Of note, the combination of the two modalities did not improve the sensitivity and accuracy in our patient population. During a median follow-up of 40 months, none of the patients developed persistent or recurrent hypocalcaemia, resulting in a 100% cure rate.
Coexisting thyroid pathology is relatively frequent in patients with pHPT in our region. Among patients having pHPT without any thyroid pathology, the adenoma localization is correct with either ultrasonography or 99mTc-MIBI scintigraphy in the majority of cases. MIP with iPTH monitoring are highly successful in this group of patients and this operative technique should be the method of choice.
PMCID: PMC3352203  PMID: 19258209
Primary Hyperparathyroidism; parathyroid imaging; parathormone monitoring; surgery; thyroid pathology
18.  Familial congenital hypothyroidism due to inactivating mutation of the thyrotropin receptor causing profound hypoplasia of the thyroid gland. 
Journal of Clinical Investigation  1997;99(12):3018-3024.
Thyroid gland agenesis is the most common cause of congenital hypothyroidism and is usually sporadic. We investigated a brother and sister from consanguineous parents, ascertained through systematic newborn screening, and initially diagnosed with thyroid agenesis. Careful cervical ultrasonography in both patients revealed a very hypoplastic thyroid gland. By direct sequencing of the thyrotropin receptor gene, we identified the substitution of threonine in place of a highly conserved alanine at position 553, in the fourth predicted transmembrane domain. The mutation was found homozygous in the affected siblings, and heterozygous in both parents and two unaffected siblings. Functional analysis in transfected COS-7 cells showed that it resulted in extremely low expression at the cell surface as compared with the wild-type receptor, in spite of an apparently normal intracellular synthesis. The small amount of mutated receptor expressed at the surface of transfected cells bound thyrotropin with normal affinity and responded in terms of cAMP production, but the in vivo significance of these data from overexpressed receptor in transfected cells is unclear. Of note, blood thyroglobulin was unexpectedly elevated in the patients at the time of diagnosis, a finding that might prove useful in refining etiologies of congenital hypothyroidism.
PMCID: PMC508154  PMID: 9185526
19.  Characteristics of thyroid nodules in infant with congenital hypothyroidism 
Korean Journal of Pediatrics  2014;57(2):85-90.
This study aimed to assess the characteristics of thyroid nodules among infants diagnosed with congenital hypothyroidism.
A retrospective study of 660 infants (374 males, 286 females) diagnosed with congenital hypothyroidism was carried out at the Pediatric Endocrine Clinic in Soonchunhyang University Hospital, Korea, between May 2003 and February 2013. The average age at diagnosis was 1.16±1.68 months.
Of the 28 patients (4.2%) with thyroid nodules, 17 (2.6%) had cystic thyroid nodules and 11 (1.6%) had solid thyroid nodules. There were no significant differences in gender or age between congenital hypothyroidism patients who hadthyroid nodules and those who did not. All nodules were asymptomatic. The average age at diagnosis of congenital hypothyroidism with nodules was 1.42±1.39 months. All detected nodules measured less than 1 cm in diameter. Twenty-two of the 28 infants (78.6%) had only one nodule, while multiple nodules were found in 6 infants (21.4%). Of the 28 infants diagnosed with nodules, 16 underwent thyroid ultrasonography during follow-up and 8 of them (50%) showed no signs of nodules at thyroid ultrasonography.
The prevalence of thyroid nodules in infants with congenital hypothyroidism was 4.2%. Most thyroid nodules were small in size and benign, disappearing during follow-up observation. We therefore conclude that thyroid nodules in infants with congenital hypothyroidism can simply be observed and do not require direct treatment.
PMCID: PMC3965800  PMID: 24678333
Thyroid nodule; Congenital hypothyroidism; Ultrasonography; Infant
20.  Radionuclide Imaging of Dual Ectopic Thyroid in a Preadolescent Girl 
Ectopic thyroid is a congenital defect in which the thyroid gland is located away from the usual pretracheal location. Dual ectopic thyroid, which consists of two foci of thyroid tissue, is very rare. In this case dual ectopic thyroid with subclinical hypothyroidism in a 10-year-old-girl was reported. The absence of the thyroid gland in the pretracheal location was revealed by ultrasonography (USG). Two foci of ectopic thyroid tissue located at the base of the tongue and infrahyoid region were determined by Technetium-99m pertechnetate thyroid scintigraphy. It can be concluded that if the thyroid gland is not visible by USG, ectopic thyroid tissue should be evaluated with scintigraphy.
PMCID: PMC4288225  PMID: 25541934
Thyroid; scintigraphy; congenital hypothyroidism
21.  Hypothyroidism Due to Hepatic Hemangioendothelioma: A Case Report 
Although hemangioendothelioma (HHE) is a commonly encountered hepatic tumor during infancy, HHE−related hypothyroidism is rare. We present a patient who developed HHE−related hypothyroidism during the neonatal period and showed marked improvement in hypothyroidism by regression of HHE. A 28−day−old boy with TSH level of 77 mIU/mL on neonatal screening and diagnosed as congenital hypothyroidism was started on L−thyroxine (L−T4) (11 μg/kg/day) therapy on the 21th day of life. On physical examination, the liver was palpable 5 cm below the right costal margin, and the thyroid gland was nonpalpable. Thyroid ultrasonography was normal. Although L−T4 dose was increased to 15 μg/kg/day, TSH was not suppressed and free T3 level remained low. HHE in both lobes of the liver was detected by abdominal ultrasonography and magnetic resonance imaging. Treatment was started with prednisolone 2 mg/kg/day and alpha−interferon 3 million U/m2/3 times per week. Thyroid dysfunction was thought to be due to type 3 iodothyronine deiodinase activity expressed by HHE. L−T4 therapy was changed to Bitiron® tablet, which includes both T4 and T3, and euthyroidism was attained within 1 month. Thyroid hormone requirement was reduced and treatment was discontinued after regression of the HHE. At the most recent visit, the patient was 21 months old and off treatment. His growth and neurological development were normal for age and he was euthyroid. HHE should be considered in cases with severe hypothyroidism resistant to high−dose thyroid hormone replacement. The treatment of HHE in combination with T4 and T3 therapy results in euthyroidism.
Conflict of interest:None declared.
PMCID: PMC3005683  PMID: 21274327
Hepatic hemangioendothelioma; consumptive hypothyroidism; type 3 iodothyronine deiodinase
22.  Solitary Fibrous Tumor of Neck Mimicking Cold Thyroid Nodule in 99m Tc Thyroid Scintigraphy 
Case Reports in Endocrinology  2013;2013:805745.
A 68-year-old man had a rapidly growing, painless neck mass, thought to be nodular goiter. Ultrasonography showed a giant, heterogeneous mass occupying the middle and superior poles and protruding outside of the left thyroid lobe. The results of the thyroid function tests were normal. Thyroid scintigraphy revealed a large hypoactive nodule in the left thyroid lobe. Complete surgical removal of tumor was performed and macroscopically demonstrated a well-demarked lesion outside the thyroid gland. Microscopically, the lesion was composed of fibroblast-like spindle cells in a patternless architecture and extensive stromal hyalinization. Immunohistochemistry showed positive reaction for CD34 in spindle cells and diffuse bcl-2 staining. The pathology was confirmed as solitary fibrous tumor. In the follow-up period after surgery, thyroid scintigraphy showed normal left thyroid lobe. Solitary fibrous tumor originated from or associated with thyroid gland is extremely rare. According to our knowledge, this is the first reported solitary fibrous tumor presenting like a cold thyroid nodule. This pathology must be considered for differential diagnosis of neck masses in the thyroid region.
PMCID: PMC3806406  PMID: 24194989
23.  Parathyroid adenoma Localization 
Bilateral neck exploration is the gold standard for parathyroid adenoma localization in primary hyperparathyroidism. But surgeons do not have adequate experience for accurate surgical exploration and new methods are developed for surgery like unilateral exploration and minimally invasive surgery, thus, preoperative localization could reduces time and stress in surgical performance.
80 patients with documented primary hyperparathyroidism and with raised serum calcium and parathyroid hormone (PTH) were selected. The results of ultrasonographic localization for each patient were compared with findings of surgery and 99m technetium sestamibi scintigraphy. Also variables such as preoperative serum calcium, PTH level and adenoma weight were compared between patients who had localized and non-localized adenoma with ultrasonography or Sestamibi scan. The data was compared with student's t-test.
In a prospective diagnostic tests accuracy study, 80 patients with primary hyperparathyroidism were enrolled. Ultrasonography images detected enlarged parathyroid glands in 61 of 80 patients (76.3%) with sensitivity of 83.5% and positive predictive value (PPV) of 89.7%. Sestamibi scintigraphy detected adenoma in 63 patients (78.8%) with sensitivity of 85% and PPV of 91.3%. There was no significant deference between ultrasonography and scintigraphy in localization of adenomas. Both ultrasonography and scintigraphy used for determining localization, and they located 73 adenomas (91.3%) with sensitivity of 97.3% and PPV of 93.5%.
Ultrasonography as an accurate method for localization of enlarged parathyroid glands in primary hyperparathyroidism, is comparable in overall utility with sestamibi scintigraphy. This study suggests a strategy for initial testing with one method, followed by the alternate imaging test if the first test happens to be negative.
PMCID: PMC3587906  PMID: 23482497
Primary hyperparathyroidism; Scintigraphy; Ultrasonography; Localization
24.  Congenital Hypothyroidism Caused by a PAX8 Gene Mutation Manifested as Sodium/Iodide Symporter Gene Defect 
Journal of Thyroid Research  2009;2010:619013.
Loss-of-function mutations of the PAX8 gene are considered to mainly cause congenital hypothyroidism (CH) due to thyroid hypoplasia. However, some patients with PAX8 mutation have demonstrated a normal-sized thyroid gland. Here we report a CH patient caused by a PAX8 mutation, which manifested as iodide transport defect (ITD). Hypothyroidism was detected by neonatal screening and L-thyroxine replacement was started immediately. Although 123I scintigraphy at 5 years of age showed that the thyroid gland was in the normal position and of small size, his iodide trapping was low. The ratio of the saliva/plasma radioactive iodide was low. He did not have goiter; however laboratory findings suggested that he had partial ITD. Gene analyses showed that the sodium/iodide symporter (NIS) gene was normal; instead, a mutation in the PAX8 gene causing R31H substitution was identified. The present report demonstrates that individuals with defective PAX8 can have partial ITD, and thus genetic analysis is useful for differential diagnosis.
PMCID: PMC2956980  PMID: 21048839
25.  Earlier re-evaluation may be possible in pediatric patients with eutopic congenital hypothyroidism requiring lower L-thyroxine doses 
The incidence of congenital hypothyroidism (CH) has increased in several countries. Lower cut-off in screening programs have led to an increase in the proportion of transient hypothyroidism (TH) cases diagnosed, leading to debate on the associated clinical and economic impact. This study aimed to identify factors that would allow discrimination between TH and permanent CH (PH) in patients with a eutopic thyroid gland.
Sixty-six patients with CH from 3 different hospitals were studied: 26 cases of TH, and 40 cases of PH. Laboratory findings and clinical parameters were analysed in 56 patients with eutopic thyroid gland.
Initial serum thyroid stimulating hormone levels and L-thyroxine dose at 12 and 24 months of age were significantly higher in PH than TH patients with a eutopic thyroid gland. The area under the curve for the 12-month and 24-month dose for the prediction of TH in eutopic CH was 0.799 (95% confidence interval [CI], 0.678-0.919; P<0.001) and 0.925 (95% CI, 0.837-1.000; P<0.001), respectively. The optimum 12-month and 24-month dose in predicting TH is 3.25 µg/kg (12-month: sensitivity, 87.1%; specificity, 68.0%; 24-month: sensitivity 93.5%, specificity 88%).
Infants with CH requiring lower L-thyroxine doses (<3.25 µg/kg) are likely to have TH, and thus might be re-evaluated at 12 months or 24 months rather than 3 years of age.
PMCID: PMC4208263  PMID: 25346918
Congenital hypothyroidism; Thyroxine; Thyroid gland

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