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PubMed1992

Hyposialylated thyroglobulin in a patient with congenital goiter and hypothyroidism.

A large family (14 children) with congenital goiter whose parents are first cousins was studied. Thyroid tissue was obtained, after 125I in vivo labeling, from one of the siblings (JBM). Gel filtration of thyroid proteins indicated that thyroglobulin (Tg) eluted as a single symmetrical peak in the same position as authentic 19S Tg. Gel electrophoresis in a 7.5% sodium dodecyl sulfate-polyacrylamide gel revealed a major band with the same mobility and immunoreactivity as normal 19S Tg. Hydrolysis of the patient's Tg indicated that most of the radioactivity was mono- and diiodotyrosines. The yield of T4 from JBM Tg (26 pmol/mg protein) was 5-fold less than normal thyroid tissue (140 pmol/mg protein) and approximately half of that in thyroid tissue from endemic goiter (51 pmol/mg). Total T3 released from JBM Tg was similar to the other two tissues. When the carbohydrate content of normal and patient Tg was analyzed, there was no differences in glucosamine, galactose or mannose content. However, unlike normal and endemic-goiter Tg, that had a mean sialic acid content of 7.3 and 5.6 micrograms/mg protein, respectively, the sialic acid concentration of the patients Tg was only 0.3 microgram/mg. Sialyltransferase activity was readily demonstrated in homogenate from normal thyroid or endemic goiter, but no sialyltransferase activity was detectable in a homogenate of JBM-thyroid tissue. We conclude that the finding of severely hyposialylated Tg is linked to a defect in iodotyrosine coupling seen in this patient with a possibly abnormal migration of Tg into the follicular lumen.

Carbohydrate Sequence↗
PubMed1992

Histomorphological and immunohistochemical evidence that human nodular goiters grow by episodic replication of multiple clusters of thyroid follicular cells.

This study was aimed at dissecting the cellular mechanisms that underly the growth of actively expanding human goiter nodules. Thirty-two nodules from different patients, all removed because of steady recent growth, were serially sectioned and screened for 1) histomorphological signs of cell proliferation and 2) in situ expression of the immunohistochemically stained p21ras protooncogene product. Bovine, porcine, and rat thyroid glands (the latter from both T4- and perchlorate-treated animals) were used as controls. In normal glands, only a few follicular cells contain substantial amounts of stainable p21ras. Some of these cells are unusually large, but do not proliferate. In contrast, all goiter nodules contain areas where the epithelial cells are morphologically grossly altered and heavily loaded with p21ras. Cells of this type are mostly clustered in large cohorts coating whole follicles or entire groups of follicles. Only a small fraction of these activated cells actually proliferates at any one point in time. Actively replicating cells are scattered in tiny foci all over the nodules. The earliest proliferating buds are solid, but soon begin to generate microfollicles that enlarge by adding new cells to the follicular epithelium. Regionally heterogeneous p21ras content in morphologically identical cells suggests that growth occurs in bursts and waves. We conclude that goiter nodules grow by episodic proliferation of heterogeneous cohorts of epithelial cells from which new follicles are generated. Only a tiny fraction of all goiter cells proliferate at any one point in time. The molecular mechanisms governing these growth processes are unknown.

Adolescent↗
PubMed1997

Prevalence of goiter and urinary iodine excretion levels in children around Chernobyl.

The prevalence of goiter among children living in areas affected by the Chernobyl accident was investigated by analysis of data on approximately 120,000 children examined at five medical diagnostic centers in Belarus, Russia, and the Ukraine. Examinations of thyroid gland were conducted with an arch-automatic ultrasonographic instrument at the five centers under the same protocol. The diagnosis of goiter was established when the thyroid volume exceeded a limit calculated from age, height, and body weight of a child. A considerable variation by region was noted in the prevalence of goiter. Highest in the Kiev region, the prevalence in the five regions was 54% in Kiev, 38% in the Zhitomir regions of the Ukraine, 18% in Gomel, 22% in the Mogilev regions of Belarus, and 41% in the Bryansk region of Russia. Urinary iodine content was measured in approximately 5700 children, and an endemic iodine deficient zone was confirmed in the Bryansk, Kiev, and Zhitomir regions. A significant negative correlation was observed between the prevalence of goiter and the median level of urinary iodine content (Spearman's rank correlation coefficient was -0.35, P = 0.025).

Adolescent↗
PubMed1997

Identification of constitutively activating somatic thyrotropin receptor mutations in a subset of toxic multinodular goiters.

Constitutively activating mutations in the TSH receptor (TSHR) gene and in the Gs alpha gene are frequent molecular causes for solitary toxic nodules of the thyroid. However, the etiology of toxic multinodular goiter is still largely unknown. Therefore, DNA from nodular and quiescent surrounding tissue of six patients with toxic multinodular goiters was screened for mutations in exons 9 and 10 of the TSHR gene and exons 7-10 of the Gs alpha gene by direct automated sequencing. In one patient, two different somatic TSHR mutations were identified in two different toxic nodules (L632I and F631L). In another patient, two different toxic nodules harbored the same TSHR mutation (I630L), whereas only one TSHR mutation (F631L) was identified in one of the two toxic nodules of an additional patient. In the other three patients, no mutations could be found in exons 9 and 10 of the TSHR gene or in exons 7-10 of the Gs alpha gene. Our results demonstrate that not only solitary toxic adenomas but also toxic multinodular goiters can be caused by constitutively activating mutations of the TSHR. In addition to mutations in the TSHR and possibly in Gs alpha, there are probably other still unknown mechanisms that cause hot nodules in toxic multinodular goiters.

Amino Acid Sequence↗
PubMed1999

Phenocopies for deafness and goiter development in a large inbred Brazilian kindred with Pendred's syndrome associated with a novel mutation in the PDS gene.

Pendred's syndrome is an autosomal recessive disease characterized by goiter, impaired iodide organification, and congenital sensorineural deafness. The gene mutated in Pendred's syndrome, PDS (Pendred's syndrome gene), was cloned very recently and encodes the putative sulfate transporter pendrin. Pendred's syndrome may account for up to 10% of the cases with hereditary hearing loss, and pendrin mutations have also been found in a kindred with non-syndromic deafness. In this study, 41 individuals from a large, highly inbred pedigree from Northeastern Brazil were examined for features of Pendred's syndrome. Linkage studies and sequence analysis of the coding region of the PDS gene were performed with DNA from 36 individuals. The index patient, with the classical triad of deafness, positive perchlorate test, and goiter, was found to be homozygous for a deletion of thymidine 279 in exon 3, resulting in a frameshift and a premature stop codon at amino acid 96. This alteration resulted in truncation of the protein in the first transmembrane domain. Two other patients with deafness were found to be homozygous for this mutation; 19 were heterozygous and 14 were homozygous for the wild type allele. Surprisingly, 6 deaf individuals in this kindred were not homozygous for the PDS gene mutation; 3 were heterozygous and 3 were homozygous for the wild type allele, suggesting a probable distinct genetic cause for their deafness. All 3 homozygous individuals for the PDS mutation had goiters. However, goiters were also found in 10 heterozygous individuals and in 6 individuals without the PDS mutation and are most likely caused by iodine deficiency. In conclusion, we identified a novel mutation in the PDS gene causing Pendred's syndrome. The comparison of phenotype and genotype reveals, however, that phenocopies generated by distinct environmental and/or genetic causes are present in this kindred and that the diagnosis of Pendred's syndrome may be difficult without molecular analysis.

Adult↗
PubMed2000

Administration of a single low dose of recombinant human thyrotropin significantly enhances thyroid radioiodide uptake in nontoxic nodular goiter.

Radioiodine (131I) is increasingly used as treatment for volume reduction of nontoxic, nodular goiter. A high dose of 131I is often needed because of low thyroid radioiodide uptake (RAIU). We investigated whether pretreatment with a single, low dose of recombinant human TSH (rhTSH; Thyrogen, Genzyme Transgenics Corp.) enhances RAIU in 15 patients with nontoxic, nodular goiter (14 women and 1 man; aged 61+/-11 yr). Four patients were studied twice, and 1 patient was studied 3 times. RAIU was measured both under basal conditions and after pretreatment (im) with rhTSH, given either 2 h (0.01 mg; n = 7) or 24 h [0.01 mg (n = 7) or 0.03 mg (n = 7)] before 131I administration (20-40 microCi). Serum levels of TSH, free T4 (FT4), and total T3 were measured at 2, 5, 8, 24, 48, 72, 96, and 192 h after rhTSH administration. After administration of 0.01 mg rhTSH, serum TSH rose from 0.7+/-0.5 to a peaklevel of 4.4+/-1.1 mU/L (P < 0.0001), FT4 rose from 16.0+/-2.6 to 18.5+/-3.7 pmol/L (P < 0.0001), and T3 rose from 2.10+/-0.41 to 2.63 - 0.66 nmol/L (P < 0.0001). After administration of 0.03 mg rhTSH, TSH rose from 0.6+/-0.4 to 15.8+/-2.3 mU/L (P < 0.0001), FT4 rose from 15.2+/-1.5 to 21.7+/-2.9 pmol/L (P < 0.0001), and T3 rose from 1.90+/-0.43 to 3.19+/-0.61 nmol/L (P < 0.0001). Peak TSH levels were reached at 5-8 h and peak FT4 and T3 levels at 8-96 h after rhTSH administration. Administration of 0.01 mg rhTSH 2 h before 131I increased 24-h RAIU from 30+/-11% to 42+/-10% (P < 0.02), 0.01 mg rhTSH administered 24 h before 131I increased 24-h RAIU from 29+/-10% to 51+/-10% (P < 0.0001), and 0.03 mg rhTSH administered 24 h before 131I increased 24-h RAIU from 33+/-11% to 63+/-9% (P < 0.0001). After administration of 0.01 mg rhTSH 2 h before 131I, 24-h RAIU did not increase in 1 patient, whereas the increase in 24-h RAIU was less than 10% in 2 other patients. In contrast, administration of rhTSH 24 h before 131I increased 24-h RAIU by more than 10% in all 14 patients (by >20% in 10 and by >30% in 6). In conclusion, pretreatment with a single, low dose of rhTSH in patients with nontoxic, nodular goiter increased RAIU considerably. Our observations hold promise that administration of rhTSH before 131I therapy for nontoxic, nodular goiter will allow treatment with lower doses of 131I in these patients.

Adult↗
PubMed2001

Pretreatment with recombinant human TSH changes the regional distribution of radioiodine on thyroid scintigrams of nodular goiters.

In a recent study, we demonstrated that pretreatment with a single, low dose of recombinant human TSH (rhTSH) doubles 24-h thyroid radioactive iodine uptake in patients with nodular goiter. The purpose of the present study was to investigate whether rhTSH pretreatment induces changes in the regional distribution of radioiodine as visualized on thyroid scintigrams in these patients. Anterior planar thyroid 123I scintigrams were obtained in 26 patients with a nodular goiter (23 women and 3 men; age, 62 +/- 9 yr, mean +/- SD; thyroid weight, 165 +/- 72 g) 24 h after administration of a diagnostic dose of radioiodine. All patients were studied twice: first, without rhTSH pretreatment (baseline study), and second, after an im injection of 0.01 mg (n = 10) or 0.03 mg rhTSH (n = 16), given 24 h before radioiodine administration (rhTSH study). For quantification of regional differences in radioiodine uptake, a region of interest method was used. Upon visual inspection, baseline scintigrams showed a heterogeneous uptake of radioiodine. In general, rhTSH scintigrams also showed heterogeneous radioiodine uptake. In some patients, the distribution of radioiodine in the rhTSH scintigram was considerably more homogeneous than in the baseline scintigram. In a few patients, originally "cold" areas had changed into "hot" ones, whereas originally hot areas had changed into cold ones. Quantification of regional radioiodine uptake showed that pretreatment with rhTSH caused a larger increase in radioiodine uptake in relatively cold areas and a smaller increase in radioiodine uptake in relatively hot areas, compared with the increase in radioiodine uptake in the entire thyroid. In patients with a baseline serum TSH level of 0.5 mU/liter or lower, the increase in radioiodine uptake in relatively cold areas was significantly larger than in patients with a baseline serum TSH level higher than 0.5 mU/liter. In conclusion, a single, low dose of rhTSH not only doubled 24-h radioactive iodine uptake but also caused a more homogeneous distribution of radioiodine within the thyroid gland in patients with a nodular goiter by stimulating radioiodine uptake in relatively cold areas more than in relatively hot areas. This was most marked in patients with a low baseline serum TSH level. Our data suggest that pretreatment with rhTSH may improve the efficacy of radioiodine treatment for volume reduction of nodular goiters, especially in patients with a low baseline serum TSH level.

Aged↗
PubMed2001

Changes in serum thyroid hormone levels in newborn calves as a diagnostic index of endemic goiter.

Maximum serum thyroxine (T4) and triiodothyronine (T3) levels of healthy calves were seen at 1 day after birth, and thereafter rapidly decreased until 5 days after birth. They stabilized until 2 weeks after birth, then gradually decreased until 4 weeks after birth. Serum T4 levels of calves with endemic goiter tended to be lower than those of healthy ones, but showed similar levels to those of adult cows. T3 levels of calves with goiter were similar to those of healthy ones, but showed higher variation. T4/T3 ratio of calves with goiter were significantly lower than those of healthy ones and adult cows. While individual levels of serum T4 and T3 at just after birth could not be considered as a diagnostic index, the T4/T3 ratio could be adopted as a diagnostic index of endemic goiter.

Age Factors↗
PubMed1995

The prevalence of thyroid dysfunction among elderly subjects in an endemic goiter area of Central Anatolia.

The prevalence of thyroid dysfunction in the elderly is reported to be markedly high, at least in some Western countries in which iodine intake is sufficient or increased because of recent supplementation of iodine for public health. We therefore wished to investigate the prevalence of thyroid dysfunction among elderly people in an endemic goiter area. The study included 198 subjects over the age of 55 years. It was carried out in two towns 20-30 km, south of Kayseri, Central Anatolia. Questioning on medical history, physical examination and grading of thyroid gland size were performed. Serum TSH was measured by a sensitive immunoradiometric assay. Serum free thyroid hormones and thyroid autoantibodies were measured in the subjects with TSH concentrations below 0.4 mu IU/ml or above 4.5 mu IU/ml on the initial screen. Drinking water was also analysed for iodine content. Twenty-five (12.6%) subjects had either elevated (6.5%) or suppressed (6.1%) serum TSH levels. No patient had clinical hypothyroidism (high TSH and low free thyroxine and free triiodothyronine). Three (1.5%) subjects had clinical hyperthyroidism (low TSH and high free thyroxine and free triiodothyronine). Only one subject was positive for antimicrosomal and antithyroglobulin antibodies. The prevalence of goiter was 25.8%. The iodine level in drinking water was found to be 3 micrograms/L. In conclusion, we believe that the prevalence of thyroid dysfunction in the elderly may depend on the iodine status in the environment. We think that hyperthyroidism due to multinodular goiter is more important than hypothyroidism for elderly people living in an endemic goiter area, probably due to the low frequency of autoimmune thyroid disorders.

Age Factors↗
PubMed1998

Amyloid goiter presented as a subacute thyroiditis-like symptom in a patient with hypersensitivity vasculitis.

We present a 25-year-old woman with amyloid goiter due to hypersensitivity vasculitis, who developed transient thyrotoxicosis resembling subacute thyroiditis. She received prednisolone (20 mg/ day) for three years for hypersensitivity vasculitis, and was diagnosed as having secondary amyloidosis by biopsies of the stomach, rectum and kidneys. She noticed neck swelling with severe right neck tenderness, palpitation, hyperhidrosis and weight loss. An elastic firm diffuse goiter was palpable, and the upper pole of the right lobe was extremely tender. Her serum free T4 and T3 levels were high, and the serum TSH was suppressed to subnormal. She was positive for serum C-reactive protein. Anti-thyroidal autoantibodies were all negative. Her thyrotoxicosis subsided spontaneously within one week. Serum titers of antibodies to various viruses were unchanged during the clinical course for two weeks, but she was positive for HLA B35. Examination of a needle-biopsy specimen of the thyroid gland showed extensive amyloid deposition and no evidence of subacute thyroiditis. We considered her transient thyrotoxicosis to be associated with amyloid goiter. The clinical course of this case was similar to the subacute thyroiditis-like syndrome, first described by Ikenoue et al. When patients with primary or secondary amyloidosis have symptoms and signs of subacute thyroiditis, but develop an unusual course, amyloid goiter should be considered.

Adult↗
PubMed1999

A case of amyloid goiter secondary to Crohn's disease.

We herewith report a case of amyloid goiter secondary to Crohn's disease. The patient had been diagnosed as having Crohn's disease at the age of 15, and underwent right hemicolectomy at age 20. When he was 26 years old he complained of swelling of the anterior neck. Both TSH and thyroid hormones were within the normal range, and anti-thyroglobulin and anti-microsomal antibodies were negative. Only thyroglobulin was noticeably above the normal range. During the next year his goiter enlarged further and because he had a feeling of pressure he underwent total thyroidectomy. The presence of amyloid A protein in his surgical specimen led to the diagnosis of amyloid goiter. Although most cases of secondary amyloidosis are known to develop in neoplasms or chronic inflammatory diseases, our patient had no illness other than Crohn's disease. Perusal of literature revealed that Crohn's disease is rarely a cause of amyloid goiter.

Adult↗
PubMed2004

Effect of iodine supplementation on goiter prevalence among the pediatric population in a severely iodine deficient area.

We evaluated goiter status and urinary iodine excretion (UIC) of 304 school-children (7-12 years old) 3 years after a law was passed for mandatory production of iodinated salt in an area previously characterized by severe iodine deficiency in Zonguldak, a mountainous city in the West Black Sea region in Turkey. We examined all the children for goiter by palpation, measured sonographic thyroid volumes (STV) and UIC. Eighty-two percent of families had been using iodinated salt. UIC was above 100 microg/l in 71.2% of the children and median UIC was sufficient (143.5 microg/l). The prevalence of goiter was lower at ultrasound (14.6%) than by palpation (19.4%). Median STV values were within recommended normal limits at all ages. Although Zonguldak had been a highly endemic region, it became mildly endemic 3 years after mandatory iodination of salt, with decrease of goiter prevalence.

Child↗
PubMed1993

Iodized salt prophylaxis of endemic goiter: an experience in Toscana (Italy).

It is well established that iodine supplementation is effective in correcting iodine deficiency and reducing goiter prevalence. In Italy, legislation has allowed the production of iodized salt since 1972, but its consumption is on a voluntary basis. In the present study, the efficacy of legislative measures that made compulsory the availability of iodized salt in foodstores has been evaluated. Urinary iodine excretion and thyroid size, scored according to Pan American Health Organization recommendations, were determined prior to (1981) and 10 years after (1991) the introduction of legislative measures in the whole schoolchildren population residing in a restricted area of the Tuscan Appennines. Moreover, in 1991, thyroid volume was determined by ultrasonography. In 1981, mean urinary iodine excretion was 47.1 +/- 22.4 mg/kg creatinine (0.412 mumol/l) and goiter prevalence was 60%, indicating a moderate iodine deficiency. Eighty of the families subsequently used iodized salt on a regular basis; as a result of this excellent compliance, in 1991 the mean urinary iodine excretion increased to 129.7 +/- 73 mg/kg creatinine (1.24 mumol/l) and goiter prevalence dropped to 8.1%. The results of this study underline the effectiveness of iodine prophylaxis in correcting iodine deficiency and abating endemic goiter in schoolchildren, and suggest that implementation of measures that make compulsory the availability of iodized salt in foodstores overcomes the fact that there is no law governing the exclusive production and trading of iodized salt.

Adolescent↗
PubMed1999

Sonomorphologic evaluation of goiter in an iodine deficiency area in the Ivory Coast.

OBJECTIVES: This study evaluated the extent of thyroid abnormalities in a remote iodine-deficient area of the Ivory Coast. METHODS: Ultrasonography was used in detecting the presence of goiter. RESULTS: The overall prevalence rates of goiter were 64.7% among females and 53.3% among males. In children aged 6 to 15 years (n = 314), the prevalence of goiter was 62% regardless of sex. Thyroid volume increased steadily with age, with significantly larger goiters in women 25 years and older. Frequency of cysts and calcifications did not correlate with sex. CONCLUSIONS: Especially in developing countries, prophylaxis of iodine deficiency disorders must be improved in iodine-deficient areas to prevent substantial morbidity, which is more severe in women and elderly persons.

Adolescent↗
PubMed1987

Efficacy of thyroid scintigraphy in the diagnosis of intrathoracic goiter.

For evaluation of the usefulness of thyroid scintigraphy in the diagnosis of intrathoracic goiter, we analyzed the results of radionuclide thyroid scintigraphy in 54 consecutive cases with suspected upper mediastinal masses. Intrathoracic goiters were found in 42. The sensitivity, specificity, and accuracy of the scintigraphy for intrathoracic goiter were 93% (39/42), 100% (12/12), and 94% (51/54), respectively. Scintigraphic morphology, scanning technique, and pitfalls are discussed. The results show that most intrathoracic goiters do have thyroid function and that radioiodine scintigraphy is a definitive and cost-effective diagnostic procedure for this disease.

Adult↗
PubMed1998

[Endemic goiter: clinical picture and evolution].

The goiter is the most frequent clinical manifestation of the nutritional deficiency of iodine. If present in more than 5% of the general population or more than 10% of the children in school of a defined geographic area, goiter is defined endemic. Endemic goiter is an adaptive disease produced by the persistent stimulation of the thyroid gland as consequence of the thyrotropin increased secretion due to the iodine deficiency. If iodine deficiency is severe or persistent, other manifestations can be observed in the clinical picture of the iodine deficiency disorders (IDD), such as cretinism. In general goiter is not associated to other manifestations during the initial state of the disease, but nodular and toxic evolution are frequent complication of long standing disease.

Deficiency Diseases↗
PubMed1998

[Epidemiologic investigation on the prevalence of goiter and urinary excretion of iodine in the school population of the province of Reggio Emilia].

The prevalence of goiter was evaluated in a sample from the schoolchildren population of Reggio Emilia district. 1020 children underwent physical examination of thyroid gland and thyroid ultrasonography for determination of thyroid volume. Urinary iodine excretion (UIE) was measured in 837/1020 (82.1%). Iodine content was measured in water samples collected from 65 wells and 12 springs all around the district. The prevalence of goiter according to thyroid gland palpation was 26.2%. Thyroid volume was 4.74 +/- 1.87 ml, and the median UIE value 85 micrograms/l. According to the UIE classes as defined by WHO, 57.8% of all subjects showed a UIE less than 100 micrograms/l. In 57 out of 65 wells and in all the 12 springs examined, iodine was completely absent. In the remaining 8 wells, only iodine traces were found. Based on the results of physical examination of the thyroid gland, Reggio Emilia district should be regarded as an endemic goiter area. Nevertheless, thyroid volume measurement by ultrasound indicates that goiter prevalence may be markedly overestimated by palpation. The high prevalence of subjects featuring an increased thyroid volume, the low median UIE value and the poor iodine content in the local reservoirs of drinkable water suggest the opportunity for iodine prophylaxis in the Reggio Emilia district.

Adolescent↗
PubMed1998

[Prevalence of goiter and urine iodine in a school population in an area of the Bolognese Apennines].

We evaluated goiter prevalence and urinary iodine excretion (UIE) in schoolchildren living in three villages of the Appennines in the Bologna district-Castel d'Aiano (CA), Gaggio Montano (GM) and Pietracolora (PC). 175 age-matched schoolchildren living in the urban area of Bologna were considered as control group. In the control area the presence of goiter was documented in 11 out of 175 subjects (6.3%). In the mountain area the presence of goiter was documented in 42 out of 233 subjects (18%) (p < 0.0001 vs control area). In the urban control area the UIE was 159 micrograms/l (median; range 19-298). In the mountain area the UIE was 119 micrograms/l (median; range 10-286) (p < 0.001 vs control area). We observed the highest prevalence of goiter and UIE levels < 100 micrograms/l only in the village of PC, which is still characterized by geographical isolation and rural economy.

Biomarkers↗