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Iodine deficiency in Azerbaijan after the discontinuation of an iodine prophylaxis program: reassessment of iodine intake and goiter prevalence in schoolchildren.

The goal of this study was to assess the prevalence of iodine deficiency (ID) in Azerbaijan after the discontinuation of an iodine prophylaxis program by assessing the prevalence of goiter, iodine intake, and thyroid function. The study included 942 schoolchildren (475 boys and 467 girls) ages 8-14 years, from 13 distinct regions. The survey included the following: (1) clinical evaluation; (2) assessment of thyroid volume both by ultrasound and by palpation; (3) determination of iodide in a morning urine specimen using the classic Sandel-Kolthoff reaction in 347 schoolchildren; (4) determinations of thyrotropin (TSH), triiodothyronine (T3), thyroxine (T4), thyroglobulin (Tg), and anti-thyroid peroxidase (TPO) in serum (n = 165) and TSH in whole blood spotted on filter paper (n = 942). The prevalence of goiter for the whole country was determined by ultrasound (US) to be 86% and by palpation 66%, reaching 100% in the mountainous regions of Caucasus. The median urinary iodine excretion (UIE) was 54 microg/L, reaching level of 26 and 39 microg/L in the Caucasus region. In conclusion, according to the World Health Organization (WHO) classification, Azerbaijan now has mild to moderate ID (median UIE, 54 microg/L) and in the mountainous regions with severe ID. The high prevalence of goiter and the low UIE emphasizes the need for urgent medical reintervention. An iodination program is now implemented by our team in the mountainous regions under the auspice of the government of Azerbaijan.

Adolescent↗

Aggressive metastatic follicular thyroid carcinoma with anaplastic transformation arising from a long-standing goiter in a patient with Pendred's syndrome.

In this article we describe detailed pathological and molecular genetics studies in a consanguineous kindred with Pendred's syndrome. The index patient was a 53-year-old female patient with congenital deafness and goiter. Her parents were first-degree cousins. She had a large goiter (150 g) that had been present since childhood. One of her sisters and a niece are also deaf and have goiter as well. The presence of Pendred's syndrome was confirmed by a positive perchlorate test and the demonstration of a Mondini malformation. Thyroid function tests (under levothyroxine [LT4] therapy) were in the euthyroid range with a thyrotropin [TSH] level of 2.8 microU/mL (0.2-3.2), a serum total thyroxine (T4) of 90 nmol/L (54-142), and a serum total triiodothyronine (T3) of 2.7 nmol/L (0.8-2.4). Total thyroidectomy was performed, and the mass in the right lobe was found to have invaded adjacent tissues. The histopathological findings were consistent with a follicular carcinoma with areas of anaplastic transformation and lung metastasis. The patient was treated twice with 100 mCi 131iodine (3,700 MBq) and received suppressive doses of LT4. Postoperatively, the serum thyroglobulin (Tg) levels remained markedly elevated (2,352 to 41,336 ng/mL). The patient died of a sudden severe episode of hemoptysis. Sequence analysis of the PDS gene performed with DNA from the two relatives with Pendred's syndrome revealed the presence of a deletion of thymidine 279 in exon 3, a point mutation that results in a frameshift and a premature stop codon at codon 96 in the pendrin molecule. We concluded that prolonged TSH stimulation because of iodine deficiency or dyshormonogenesis in combination with mutations of oncogenes and/or tumor suppressor genes, may result in the development of follicular thyroid carcinomas that undergo transformation into anaplastic cancers. It is likely that these pathogenetic mechanisms have been involved in the development of aggressive metastatic thyroid cancer in this unusual patient with Pendred's syndrome.

Adult↗

Different growth control of the two human thyroid cell lines of adenomatous goiter and papillary carcinoma.

To study the growth control of human thyroid cells in different stages of differentiation, we established two human thyroid cell lines of adenomatous goiter and papillary carcinoma. A 59-year-old female patient with adenomatous goiter was operated in September 1991, and a 27-year-old female patient with papillary carcinoma in May 1990. The thyroid cell lines were established by successive passage without cellular or genetic manipulations such as fusing other cell lines or oncogenic viral infection. These cell lines, human adenomatous goiter cells (hAG) and human papillary thyroid carcinoma cells (hPTC), exhibited a flattened polygonal shape and proliferated as a monolayer in cell culture. The doubling time of the hAG cells was 60 h in Ham's F12 medium supplemented with 10% fetal bovine serum, and that of the hPTC cells, 18 h in the same medium. Both cell lines expressed mRNA for TSH receptor and secreted cAMP into the medium during incubation with thyrotropin (TSH) at concentrations as low as 0.01 mU/mL. The effects of activators of protein kinase A (PKA), protein kinase C (PKC), tyrosine kinase (TK), and estradiol (E2) on proliferation of the hAG cells and the hPTC cells were assessed by measuring cellular DNA content in 24-well plates with diaminobenzoic acid. TSH stimulated proliferation of the hAG cells, but it inhibited proliferation of the hPTC cells. Since TSH activates two signaling pathways, the adenyl cyclase-PKA system and phospholipase C-PKC system, we tested effects of dibutylyl cAMP (dBC) and phorbol myristate 13-acetate (PMA), separately. dBC stimulated proliferation of the hAG cells, but it inhibited that of the hPTC cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗

The effect of oral administration of iodine to patients with goiter and hypothyroidism due to defective synthesis of thyroglobulin.

The effects of administration of iodine (1 mg/day orally, 64 days) were studied in three siblings with congenital goiter and hypothyroidism due to defective thyroglobulin (Tg) synthesis. The patients presented very large goiters, elevated RAI uptake, negative perchlorate discharge test, low serum T4, and elevated TSH concentrations. Immunoassayable Tg was low and failed to increase after stimulation with exogenous bovine TSH. Analysis of individual thyroid extracts by gel filtration failed to reveal a Tg component; the immunoassayable Tg antigens in these goitrous tissues were 0.12 and 0.21 mg/g tissue, respectively (normal 70-90 mg/g tissue). The histological pattern of their thyroids was compatible with defective Tg synthesis. The administration of iodine caused a rise in the mean serum T4, T3, and free T4 concentrations in all three siblings, but did not alter the serum Tg concentration. TSH concentrations rose in the terminal period of observation in the three subjects and this was considered to be due to a possible effect produced by the iodine load in the thyroperoxidase system (Wolff-Chaikoff effect). One patient showed an increase in goiter size during the period of observation. These results suggest that iodine administration enhanced the ability of the dyshormonogenetic gland to synthesize iodothyronines.

Adolescent↗

Long-standing goiter and hypothyroidism: an unusual presentation of a TSH-secreting adenoma.

A 63-year-old female patient was referred to our hospital in February 1994 for a pituitary tumor. On a previous examination, in 1973, she had a goiter, nonspecific symptoms and only an elevated serum T3. In 1984 she had become hypothyroid, her goiter had increased, serum T4 was 69 nmol/L, TSH 34.4 mU/L, and TPO antibodies were positive. Hypothyroidism due to autoimmune thyroiditis was diagnosed and she received L-T4 100 micrograms/day. In 1985 and 1986, serum TSH had decreased but remained slightly elevated, while T4 was at the upper limits of normal. From 1987 to 1989 her serum TSH rose from 9 to 20 mU/L and remained at that level for the ensuing 4 years in spite of increasing L-T4 up to 150 micrograms/day. In October 1993, after discontinuing L-T4 for 6 weeks, TSH was 23.7 mU/L, T4 170 nmol/L, 131I thyroid uptake 52%, and the CT scan showed a large pituitary tumor with suprasellar extension. On preoperative investigation TSH was 40-51 mU/L with no response to TRH or GnRH. The alpha-subunit was increased at 6.33 micrograms/L with the alpha-TSH/TSH molar ratio of 1.23. Prolactin was elevated, but plasma cortisol, FSH, and LH were low. At surgery, we found a large chromophobe adenoma with few PAS-positive granules and with immunostaining positive for TSH and prolactin. From the clinical and biological data, we can conclude that the patient had probably a TSH-secreting adenoma since the goiter was first detected. The development, however, of autoimmune thyroiditis with hypothyroidism considerably modified the presentation of the disease and may have accelerated the growth of the tumor.

Adenoma↗

Body mass and body composition after total thyroidectomy for benign goiters.

To date there are no data available as to whether postmenopausal women who undergo total thyroidectomy for benign euthyroid goiter demonstrate changes in body mass or body composition. We prospectively evaluated 8 postmenopausal women (mean age 57 +/- 7; range 48 to 70 years) who underwent total thyroidectomy for benign goiter. All patients were euthyroid preoperatively (serum free thyroxine [FT4] 12.7 +/- 0.6 pmol/L and serum thyrotropin [TSH] 0.98 +/- 0.2 mU/L) and were commenced on adequate thyroxine replacement immediately postoperatively in order to maintain a serum TSH within the normal range (0.5-4 mU/L). Body mass, body composition, and thyroid function were assessed preoperatively, and at 4 and 12 months postoperatively. Body composition was assessed by anthropometry and dual energy x-ray absorptiometry (Lunar DPX-L scanner). Eight healthy postmenopausal women without evidence of thyroid disease matched for age, weight, and estrogen therapy who were followed over the same period were used as controls. All patients were maintained in a euthyroid status throughout the study. No significant changes in body mass or any parameter of body composition were demonstrated at 4 and 12 months postoperatively. Similar findings were recorded in our control group. We conclude that total thyroidectomy in euthyroid postmenopausal women with benign goiter does not result in a significant change in either body mass or body composition if adequate thyroxine replacement is maintained.

Aged↗

Resolution of fetal goiter after discontinuation of propylthiouracil in a pregnant woman with Graves' hyperthyroidism.

We report a case of Graves' hyperthyroidism in a 34-year-old pregnant woman treated with propylthiouracil (PTU) complicated by the development of a fetal goiter. Because of the fetal goiter and normal maternal thyroid function tests, the PTU was discontinued. Over the next 10 weeks, there was a progressive decrease in the fetal thyroid volume as documented by ultrasonography. The fetal neck returned to a normal flexed position, fetal growth and amniotic fluid remained normal, and the patient remained asymptomatic. A normal infant was delivered at term. This is the first report to demonstrate that noninvasive management may be appropriate for fetuses with goiter caused by antithyroid drug therapy.

Adult↗

Intrauterine diagnosis and management of fetal goitrous hypothyroidism: a report of an Iranian family with three consecutive pregnancies complicated by fetal goiter.

The diagnosis and treatment of hypothyroidism during the fetal period may decrease perinatal morbidity and are believed to be important to optimize growth and intellectual development. Herewith a case report of fetal goitrous hypothyroidism is presented in a euthyroid mother, detected at 34 weeks' gestation by ultrasonography, and treated with intra-amniotic levothyroxine injections. The mother had two previous consecutive pregnancies (13 and 8 years ago), also complicated by the occurrence of fetal goiter, resulting in tracheal compression, asphyxia, and early neonatal death in the first and in an emergency cesarean section delivery, because of fetal malpresentation, in the second neonate affected by congenital hypothyroidism (CH). The present male newborn, although born without observable goiter, had a large thyroid on ultrasonography and an early rise of his peripheral venous blood thyrotropin confirmed the diagnosis of CH. Low serum thyroglobulin in the proband and his older brother and parental consanguinity was mostly compatible with a thyroglobulin defective synthesis and secretion as the cause of CH and fetal goiter. Despite apparently sufficient dose of intraamniotic levothyroxine injections repeated weekly from 34-37 weeks' gestation (i.e., four injections of 500 microg levothyroxine), neonatal bone age on the second day of life showed delayed skeletal maturation.

Adult↗

Lack of correlation between thyroid size and body growth in an area of endemic goiter.

There is conflicting information in the literature about the relationship between thyroid size and body growth in endemic goiter. This study reports data from highland Bolivia where 408 children were examined for thyroid size, height, weight, head circumference, and academic performance, the latter as measured by teacher evaluation. The presence or size of goiter showed no consistent correlation with height, weight, or head circumference. School performance was significantly correlated with all other variables in boys and not in girls, but there are severe limitations involved in the use of school grades alone for assessment of intelligence. Height and weight were less than for normals in the United States at each age level, but did not differ from those of other Quechuan children in neighboring Peru who were reportedly nongoitrous. Our data support the conclusion that there is no clear relationship between thyroid size and body growth in areas of endemic goiter.

Adolescent↗

Goiter problems in Ethiopia.

Survey studies have shown that there is wide-spread goiter in Ethiopia (mean incidence 25%). The occurrence of goiter is associated with low iodine intakes, but little information has been available on goitrogens. A program of distribution of iodized salt has been initiated to eliminate the goiter problem.

Adolescent↗

Goiter and deaf mutism.

The occurrence of deaf-mutism and goiter unassocaited with creatinism or mental retardation in euthyroid patients is known as Pendred's Syndrome. It is considered due to a single mutant recessive gene responsible for both the goiter and deafness. The penetrance is high, the intenseness of expressivity may vary within the same family and only one generation is affected. The extremely atypical hyperplasia seen in such goiters has been considered malignant. In 1956 the author reported a family in which 4 of 6 sibilings demonstrated Pendred's Syndrome. Three of the 4 had undergone thyroidectomy, two were considered to have carcinoma. Nineteen years later the family is again reported. The fourth sibling has recently undergone thyroidectomy. This thyroid demonstrated the same atypical hyperplasia as seen in the elder two siblings. The 19 year followup of this family has shown no evidence of recurrence or metastases, indicating that the atypical hyperplasia is probably not malignant. Pendred's Syndrome is described and certain suggestions are made for the counseling of the parents and the treatment and counseling of those children so afflicted.

Adolescent↗

Dosimetric determination of I-131 activity in the treatment of recurrent, nontoxic, multinodular goiter.

Although surgical treatment of nontoxic multinodular goiter remains the most effective therapy, I-131 is a reasonable alternative in cases where thyroidectomy is not appropriate. Selection of I-131 activity in the management of nontoxic multinodular goiter has largely been empirical. The use of dosimetric measurements in guiding I-131 therapy in the treatment of a patient with a recurrent, nontoxic, multinodular goiter is described.

Goiter, Nodular↗

Preoperative localization of a parathyroid adenoma with Tc-99m sestamibi imaging in a patient with concomitant nontoxic multinodular goiter.

Preoperative localization of parathyroid adenomas is useful in patients undergoing parathyroidectomy. The authors report a patient with hyperparathyroidism and an associated nontoxic nodular goiter. Technetium-99m sestamibi scintigraphy localized and differentiated the parathyroid adenoma from the multinodular goiter. Excellent correlation was found between preoperative radionuclide imaging and surgical pathology. Technetium-99m sestamibi parathyroid imaging may be a simple and helpful test in the surgical management of parathyroid adenomas, particularly in patients with nontoxic multinodular goiter.

Adenoma↗

Tc-99m pertechnetate scintigraphy before and after potassium perchlorate administration for the diagnosis of retrosternal goiter.

A 52-year-old woman was hospitalized because of dyspnea and dysphagia. Thoracic computed tomography revealed a retrotracheal mass. Tc-99m pertechnetate scintigraphy showed intense accumulation of radioactivity corresponding to the mediastinal mass detected by computed tomography. Repeated Tc-99m pertechnetate scintigraphy performed after oral administration of potassium perchlorate (KCLO4) revealed complete disappearance of the radioactive accumulation in the mediastinum, suggesting that the retrotracheal mass was a retrosternal goiter. Subsequent surgical removal and analysis of the mass showed it was indeed a retrosternal goiter. This case highlights the importance of Tc-99m pertechnetate thyroid scintigraphy with and without KCLO4 administration as a simple, accurate, and cost-effective imaging method to diagnose retrosternal goiter.

Administration, Oral↗

CT demonstration of isolated mediastinal goiter.

A substernal goiter is a common mediastinal mass that can usually be recognized as contiguous with the body of the thyroid. We report the rare occurrence of a mediastinal goiter that demonstrated no connection with the cervical thyroid on either CT or at thoracotomy. Pathologic examination confirmed this to be an intrathoracic goiter.

Diagnosis, Differential↗

MR imaging findings in fetal goiter caused by maternal graves disease.

Antenatal diagnosis of fetal goiter should be appropriately managed to avoid perinatal complications. Here, we present the MR imaging features of a fetal goiter caused by maternal Graves disease. Diffusely enlarged fetal thyroid gland was seen showing homogeneously elevated signal on T1-weighted images and intermediate signal on T2-weighted images. To our knowledge, this is the first MR imaging documentation of fetal goiter.

Adult↗

Application of staging systems for differentiated thyroid carcinoma in an endemic goiter region with iodine substitution.

OBJECTIVE: To evaluate and compare staging systems for differentiated thyroid carcinoma and predicted outcome in an endemic goiter region with iodine substitution and to examine the risk profile of differentiated thyroid carcinoma and compare it against nongoiter regions. SUMMARY BACKGROUND DATA: Differentiated (papillary or follicular) thyroid carcinoma has a favorable prognostic outcome. In numerous studies prognostic factors have been identified and staging systems created, particularly in Anglo-American centers (nonendemic goiter regions), to evaluate individual prognostic outcome. METHODS: In a retrospective study, the authors assessed 440 patients with differentiated thyroid carcinoma (papillary, n = 293; follicular, n = 147) and a long-term follow-up of median 10.6 years to determine the predictive accuracy of nine staging systems applicable to the study population; the systems were compared by calculating the proportion of variation explained. RESULTS: With regard to cause-specific mortality, the difference between the respective stages and/or risk groups was highly significant for every staging system. By means of calculating the proportion of variation explained, MACIS scoring supplied the most reliable prognostic information for differentiated thyroid carcinoma (relative importance 16.93%). EORTC and UICC/AJCC systems had a relative importance of 16.34% and 13.96%, respectively, also a high level of accuracy; this implies that they are superior to the other six staging systems. If we separate papillary and follicular carcinoma, for the former the MACIS score with a relative importance of 15.05% is clearly superior to the other staging systems, whereas for the latter the EORTC score and the UICC/AJCC staging system, with relative importance of 17.04% and 16.58%, respectively, yield the best prognostic information. CONCLUSIONS: By applying staging systems in an endemic goiter region with iodine substitution, the best prognostic information for papillary thyroid carcinoma has been achieved with the MACIS score, while for follicular thyroid carcinoma the EORTC score and the UICC/AJCC system have the best prognostic accuracy. Because of the individual factors, which are easy to obtain and generally available (age, T, N, M classification), the uncomplicated handling, and the widespread use and the good predictive accuracy, the UICC/AJCC classification is the staging system of choice for comparing published results.

Adenocarcinoma, Follicular↗

Thyroid ultrasonography consistently identifies goiter in adults over the age of 30 years despite a diminished response with aging of the thyroid gland to the effects of goitrogenesis.

Iodine deficiency is a national health problem in India and we have recently reported on the severity of IDD in adults and children in Gujarat province. The aim of this study was to determine the utility of thyroid ultrasonography to detect goiter in adults from an iodine-deficient population of Gujarat. We studied 472 adults selected by random household surveys. Data were collected on height, body weight, mid-upper arm circumference, thigh circumference, triceps skinfold thickness, thyroid size (palpation and ultrasonography), and diet. Casual urine samples for iodine (UI) and blood spots for TSH estimation were obtained. Endemic goiter is a major public health problem in Gujarat State, India and is probably caused by multiple factors including iodine deficiency, malnutrition, and other dietary goitrogens. These results indicate that thyroid US consistently detects goiter in adults despite a diminished thyroidal response to variable goitrogenic stimuli.

Adult↗