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Radioiodine uptake as a function of stored iodine and thyroglobulin in thyroid follicles: in vitro quantitative imaging approach with secondary ion mass spectrometry (SIMS) microscopy in human nontoxic goiter.

We studied by an imaging technique, secondary ion mass spectrometry (SIMS) microscopy, the ability of thyroid follicles to pick-up and organify radioiodine (125I) according to the amounts of iodine (127I) and sulfur previously stored in thyroglobulin (Tg). After incubation with radioiodine in miniorgan culture, the SIMS analysis of 14 fragments from 12 goitrous patients permitted the observation of 3 iodine distribution profiles. In group 1 125I and 127I were easily detected by imaging; 125I concentration in follicular lumen was 80-fold lower than that of 127I. In group 2 125I images were obtained after long-term exposure and image processing. 125I concentration was not measurable while that of 127I was about 1.7-fold higher than that observed in group 1. In group 3 it was not possible to detect 125I while only traces of 127I were detected. This last profile can coexist with profile 1 in the same specimen. Tg sulfur concentration was 2-fold lower in group 3 than in the other 2 groups in which they were almost the same and significantly correlated with those of 127I. These data provide new insight into Tg and 127I traffic in the development of nonfunctioning goiters.

Adult↗

Increased urinary excretion of sulfated 3,3',5-triiodothyronine in patients with nodular goiters receiving suppressive thyroxine therapy.

Increased serum 3,3',5-triiodothyronine sulfate (T3S) levels have been detected in various pathophysiologic states. However, little is known about T3S concentrations in other biological fluids. By employing a highly sensitive, specific, and reproducible radioimmunoassay (RIA), we measured T3S in the serum and urine of 20 premenopausal women with benign nodular goiters before and after administration of thyroxine for 6 months (T4; 3.2 micrograms/kg/day). Serum T3 concentrations did not change significantly after treatment (2.0 vs. 1.7 nmol/L; p > 0.05). However, the mean serum T4 and free T4 concentrations were significantly higher after treatment (138 vs. 88 nmol/L and 28 vs. 17 pmol/L; p < 0.01, respectively). Serum thyroid stimulating hormone (TSH) levels were significantly reduced after T4 treatment (0.13 vs. 0.66 mU/L, p < 0.01) and the serum levels of T3S were significantly increased after treatment (82 vs. 45 pmol/L; p < 0.01). A good correlation was observed between increased serum T3S and T4 concentrations (r = 0.66; p < 0.001). The sulfoconjugate of T3 was significantly increased in creatinine-corrected urine after treatment (606 vs. 253 pmol/umol Cr.; p < 0.01). There was a significant correlation between increased creatinine-corrected urine T3S and increased serum free T4 (r = 0.65; p < 0.001). In summary, significant increases in serum and urine T3S levels were noted in T4-treated patients with subnormal serum TSH and borderline elevated T4. We thus conclude that the sulfation pathway may play a role in the homeostasis of thyroid hormone metabolism in T4-treated subjects with relative hyperthyroxinemia. In addition, the creatinine-corrected urine concentrations of T3S may serve as an index for the evaluation of T4-treated patients with elevated levels of T4.

Adult↗

Autonomy in endemic goiter.

The occurrence of hyperthyroidism in many individuals after introduction of iodine prophylaxis in endemic goiter areas can have dramatic consequences for the affected individuals. It indicates that in such individuals the increase of serum thyroid hormone level in response to iodine supplementation does not exert its normal negative feedback on thyroid activity, ie, that in such individuals some thyroid tissue has become autonomous. In this short review we summarize what is known about the possible mechanisms, cause, diagnosis, and consequences of thyroid autonomy.

Goiter, Endemic↗

Treatment of patients with toxic multinodular goiter.

The medical records of 253 patients evaluated for toxic multinodular goiter from 1975 through 1993 were reviewed to determine treatment trends, success, and complications. Of the 235 (93%) treated, 174 (74%) received surgical treatment and 61 (26%) received radioiodine (131I) treatment. Three months after initial treatment, 82% of surgically treated patients became euthyroid or hypothyroid compared with 21% of the 131I group. Among the 131I-treated patients, 20% required a second treatment, whereas none needed further treatment in the surgical group. At 2 years, the estimated probability of success was similar. The probability of post-treatment hypothyroidism was significantly higher for surgically treated patients, which is expected.

Adult↗

Screening of thyrotropin receptor mutations by fine-needle aspiration biopsy in autonomous functioning thyroid nodules in multinodular goiters.

Multinodular goiter (MNG) is characterized by nodules of different size and function. Areas of increased function may emerge, appearing as single, or more frequently, multiple autonomously functioning thyroid nodules (AFTN). The molecular mechanism for the autonomous growth and function of these nodules has been related to mutations in the thyrotropin receptor (TSHR) that constitutively activate the adenylyl cyclase. We searched for mutations in a limited area of the TSHR gene, covering the major mutational hotspot, in 38 AFTNs found in 37 patients with MNGs. We used reverse transcriptase-polymerase chain reaction (RT-PCR) and restriction enzyme analysis of fine-needle aspiration biopsy (FNAB) samples to rapidly identify 4 of the more frequently occurring TSHR mutations: D619G, F631C, T632I and D633E. Mutations were identified in 5 nodules (1 D619G mutation and 4 T632I mutations). Subsequently, the entire transmembrane portion of the TSHR gene was sequenced in a random sample of 12 AFTN samples that were free of mutations by RT-PCR and restriction enzyme analysis. By direct sequencing we identified a new mutation, F666L, in the seventh transmembrane domain in a sample from 1 nodule. Analysis of FMA samples of AFTN is an effective approach to identify TSHR gene mutations because individual mutations may be associated with different growth and function in vitro, our approach might, allow correlation of a given mutation with the clinical behavior in vivo.

Adult↗

Cathepsin B activity and protein levels in thyroid carcinoma, Graves' disease, and multinodular goiters.

Cathepsin B (CB) is involved in the hydrolysis of thyroglobulin (Tg) and thought to be regulated by thyroid stimulating hormone (TSH) in the normal thyroid. Our analyses of 91 thyroid tissues from 71 patients with Graves' disease (GD), multinodular goiter (MNG), papillary carcinoma (PC), or follicular carcinoma (FC), demonstrated a 2-fold increase in expression of CB in GD and an average increase of 1.5-fold in MNG (varying from 10-fold below normal to 6-fold above normal in MNG nodules), as might be predicted by the altered functional status of thyroid follicular cells in those diseases. However, CB activity was not downregulated in conjunction with the known "blocking effect" of malignancy on many thyroid functions, but rather increased on average 9-fold in papillary carcinomas (n = 33), and also showed a marked increase in 2 follicular carcinomas. Activity measurements were confirmed by CB protein detection on Western blot with moderately increased CB protein levels demonstrated in GD, variable expression in nodules of MNG, and markedly increased protein expression in carcinomas. In all diseased states, increased protein was detected primarily as overexpression of the 27 kd heavy chain of 2-chain mature CB and less frequently as overexpression of 31 kd single-chain mature CB. However, an additional 35 kd protein form was noted in 3 of 9 PCs, 1 of 2 FCs, and 1 of 4 GD cases but in none of 10 MNG cases. In conjunction with elevated CB activity plus additional protein bands on Western blots, altered patterns of CB immunohistochemical staining were observed, irrespective of the type of thyroid disease, suggesting certain common changes in CB expression, posttranslational processing, and vesicular trafficking. In summary, GD and MNG thyroid tissues demonstrated altered CB expression in keeping with predicted functional changes in thyroid follicular cells, while increased CB expression in carcinomas indicated a more pathological role for CB in thyroid cancers, possibly related to the processes of invasion or metastasis.

Blotting, Western↗

The use of fine-needle aspiration biopsy under ultrasound guidance to assess the risk of malignancy in patients with a multinodular goiter.

PURPOSE: Fine-needle aspiration biopsy (FNAB) is a commonly performed procedure used in the evaluation of solitary thyroid nodules, in which the risk of malignancy is approximately 5% in most patients. Recently, the use of ultrasound (US) guidance in FNAB has been shown to enhance the diagnostic efficacy of this procedure. However, the risk of malignancy in thyroid nodules occurring within a multinodular goiter (MNG) has not been completely clarified, nor has the optimal means of investigating such nodules using FNAB. SUBJECTS AND METHODS: We performed a retrospective study of all patients seen over a 4-year period with a MNG that had one or more nodules who underwent FNAB under US guidance. The results from the history and physical examination, thyroid function and antibody tests, radionuclide studies, thyroid sonogram, cytology of aspirated nodules, and surgical pathology were recorded and analyzed. RESULTS: A total of 93 nodules were aspirated in 61 patients with MNG. Adequate material was obtained in 96% of aspirates on the first attempt. Sixty-seven aspirates in 44 patients yielded benign cytology and 22 aspirates in 15 patients yielded suspicious cytology. All patients with suspicious cytology underwent thyroid surgery. Thyroid cancer was found in 5 of these nodules, including 4 cases of papillary cancer and 1 case of Hürthle cell cancer, and 1 additional patient had occult papillary cancer discovered. The overall malignancy rate in thyroid nodules among the patients with MNG was approximately 5%. CONCLUSIONS: FNAB under US guidance is a useful diagnostic modality in the evaluation of thyroid nodules in selected patients with MNG. Because the risk of thyroid malignancy in these nodules is comparable to that which exists in solitary thyroid nodules, the possibility of thyroid malignancy should be considered in all patients with MNG.

Adenocarcinoma, Follicular↗

Human recombinant TSH preceding a therapeutic dose of radioiodine for multinodular goiters has no significant effect in the surge of TSH-receptor and TPO antibodies.

Radioiodine (RAI) treatment has increasingly been used mostly in elderly patients with multinodular goiter (MNG) as an alternative for surgery. Recombinant human thyrotropin (rhTSH) has been demonstrated to increase the uptake of RAI and also to promote a more even distribution of radionuclide among the various nodules. We have compared the surge of autoantibodies to thyroid peroxidase (anti-TPO) and to the TSH receptor (TRAb) in two groups of patients with MNG. Group RAI (n = 15) received only RAI, and Group RAI+rhTSH (n = 15) received RAI 24 h after 0.45 mg of rhTSH intramuscularly. At baseline, all 30 patients had negative anti-TPO antibodies. After RAI, 16 patients (eight in each group) exhibited a positive anti-TPO test (range, 70-2359 U/mL). In the rhTSH-treated group, anti-TPO values were significantly higher (as compared to basal levels; p < 0.02) after 3 months of RAI treatment. After 12 months, the anti-TPO values decreased to lower but still positive concentrations in nine patients (Group RAI: three patients; Group RAI+rhTSH: five patients). Only one patient had a positive TRAb test at baseline (67.5% inhibition of the TSH binding). After RAI, positive TRAb values were present in 21/30 patients. After 6 months of RAI treatment, there was a significant increase of the TRAb values in Group RAI+rhTSH patients. After 12 months, only four patients had positive TRAb (Group RAI: three patients; Group RAI+rhTSH: one patient). Two patients, one of each group, had an elevation of free T4 levels and suppressed serum TSH values, indicating hyperthyroidism (Graves' disease). Bioassay of TSH receptor (TSHR) indicated absence of a significant elevation of cAMP in the medium before and after RAI treatment in all patients. Moreover, predominantly blocking TSHR autoantibodies were detected in six of the 30 patients (three of each group). Sera from these patients were able to reduce the TSH-stimulated cAMP generation by CHO cells. We conclude that the autoantibodies to the TSHR and to TPO may occur after RAI treatment of patients, either with or without previous stimulation by rhTSH. The antibodies to the TSH comprised a combination of agonist (stimulating) and antagonist (blocking) antibodies, which in most patients did not induce clinical and laboratory evidence of active Graves' disease.

Animals↗

Estrogen receptor (ER)-beta, but not ER-alpha, is present in thyroid vessels: immunohistochemical evaluations in multinodular goiter and papillary thyroid carcinoma.

OBJECTIVE: Estrogen receptors (ERs) have been demostrated in the vessel structures of several systems. Little is known on the presence of ERs in the thyroid vessels. DESIGN: We immunohistochemically evaluated both ER-alpha and ER-beta immunoreactivity (IR) in both vascular and follicular thyroid cells in tissue samples from 17 cases of multinodular goiter (MNG) and 17 cases of papillary thyroid carcinoma (PTC). MAIN OUTCOME: ER-alpha IR was undetectable in either tissue examined. In 100% of MNG samples, nuclear ER-beta IR was detected in both endothelial and follicular cells. In PTC samples, endothelial nuclear ER-beta IR was found in 100% of cases, whereas the nuclear staining of follicular cells was found in 83% of cases. The intensity of staining of the endothelial ER-beta IR was comparable between MNG and PTC. However, when follicular cells were considered, a tendency toward a decrease in nuclear staining and a significant increase in cytoplasmic staining were found in PTC lesions as compared to MNG. CONCLUSIONS: This study demonstrated that ER-beta, but not ER-alpha, IR is present in the endothelium of thyroid vessels. Furthermore, although data need to be confirmed in larger observations, these results suggest the lack of differences in the pattern of vascular ER-beta IR between MNG and PTC.

Adult↗

Urgent thyroidectomy for acute airway obstruction caused by a goiter in a euthyroid pregnant woman.

Pregnancy constitutes a significant factor for thyroid enlargement. However, acute respiratory failure as a result of airway obstruction from an enlarged thyroid gland is an unusual incident. The case presented here concerns a 27-year-old black woman in her 20th gestational week who underwent an urgent operation for removal of a nontoxic, multinodular, mildly substernal goiter that was causing severe upper airway obstruction leading to acute life-threatening respiratory failure. Diagnosis of an extrathoracic tracheal stenosis was based on spirometry with analysis of the flow volume curve and was confirmed by magnetic resonance imaging of the neck. Despite operational risks to the mother as well as the fetus during gestation, an urgent thyroidectomy was carried out successfully. The postoperative period progressed normally and the patient completed her pregnancy with no further respiratory symptoms.

Adult↗

A critical appraisal of goiter assessment and the ratio of urinary iodine to creatinine for evaluating iodine status.

Iodine status can be evaluated by goiter assessment and measurement of urinary iodine concentration in either 24-h urine collections or in casual samples. It is often impossible to make 24-h collections. Therefore, iodine concentration in casual samples is often expressed in terms of urinary creatinine, assuming creatinine excretion to be constant between and within individuals. In this study large inter- and intraindividual variations were observed in the creatinine content of casual samples ranging from 0.6 to 9.87 mmol/L. Further, the urinary iodine-creatinine ratio correlated significantly with the creatinine concentration; Spearman's rank-order correlation coefficient, rs = 0.39 (P < 0.001). If creatinine is a suitable index to correct for variations in iodine excretion, no correlation would be expected. We conclude that the iodine-creatinine ratio in casual urine samples is an unsuitable indicator for evaluating iodine status in areas where large inter- and intraindividual variations in urinary creatinine excretion exist.

Child↗

Amyloid goiter. A clinicopathologic study of 14 cases and review of the literature.

The authors report the clinicopathologic features of 14 cases of amyloid goiter (AG). Eleven patients were males and three females with ages ranging from 23 to 75 years (median, 54 years). Eight patients had secondary amyloidosis and six had primary amyloidosis. Nine cases were identified at autopsy. In symptomatic patients (n = 5), the clinical presentation included a nontender, rapidly enlarging neck mass with associated dysphagia, dyspnea or hoarseness. Clinical or laboratory evaluation failed to detect evidence of thyroid dysfunction. The histologic appearance of the thyroid predominantly consisted of diffuse amyloid deposition surrounding thyroid follicles. In two cases, a nodular pattern of amyloid deposition was seen resulting in compression and distortion of the follicular architecture. Areas of mature adipose tissue and focal lymphocytic thyroiditis with or without foreign-body type-giant cells were seen in approximately one third of the cases. Confirmation of amyloid was made by the presence of congophilia and apple-green birefringence under polarized-light microscopy. Immunohistochemical evaluation demonstrated the presence of amyloid A immunoreactivity. No Immunoreactivity was seen with calcitonin or thyroglobulin. Fine-needle aspiration may facilitate the diagnosis, as occurred in one the patients. In symptomatic patients, thyroidectomy is warranted to alleviate pressure symptoms.

Adult↗

Alpha heavy-chain disease presenting as goiter.

A patient with alpha heavy-chain disease (alpha HCD) originally had presented with a goiter from an extramedullary plasmacytoma. Alpha HCD was diagnosed by both standard laboratory procedures and high-resolution two-dimensional gel electrophoresis. The fragment of the alpha chain had a molecular weight of 38,000 and consisted of seven major charge forms, with an isoelectric point range of 5.2-5.6. Since alpha HCD usually involves the gastrointestinal tract, the thyroidal involvement in this case is unusual.

Adult↗

Alimentary tract ganglioneuromatosis-lipomatosis, adrenal myelolipomas, pancreatic telangiectasias, and multinodular thyroid goiter. A possible neuroendocrine syndrome.

Diffuse, alimentary tract ganglioneuromatosis-lipomatosis, bilateral adrenal myelolipomas, pancreatic telangiectasias, and a multinodular thyroid goiter were found at autopsy in a 56-year-old, white male with a history of insulin-dependent diabetes, hypertension, peptic ulcer, and remote cerebral infarction. The degree of atherosclerosis, arterionephrosclerosis, and cardiac disease found at autopsy did not correlate with the patient's history or his sudden death. The typical features of the multiple endocrine neoplasia syndrome, type II-B, were not identified. The findings in this patient may represent a variant of the multiple endocrine neoplasia complex, or a separate, previously unrecognized syndrome.

Adrenal Gland Neoplasms↗

Amyloid goiter and arthritides after kidney transplantation in a patient with systemic amyloidosis and Muckle-Wells syndrome.

A case of hereditary AA amyloidosis with Muckle-Wells syndrome is described. After a successful kidney transplantation for chronic renal failure due to renal amyloid deposits at age 21, the patient, a white female now 26 years of age, developed a large amyloid goiter as a manifestation of the systemic amyloidosis and recurrent monarthritides. Both observations are novel for this disease. Subtotal thyroidectomy and oral colchicine administration, known to be effective in preventing complications of familial Mediterranean fever, another hereditary type of AA amyloidosis, proved highly effective in the management of this unusual case.

Adult↗

Geologic implications in the distribution of endemic goiter in Colombia, South America.

A survey of 37 communities supplied by stream water and receiving iodised salt for the last 10-20 years indicates that the presence of sedimentary rocks in the watersheds of streams more closely correlates with goiter prevalence than 12 other possible causative variables. These results support the hypothesis that sedimentary rocks rich in organic matter are the main source of water-borne goitrogens.

Child↗

Autosomal recessive inheritance of congenital goiter in Afrikander cattle.

Congenital goiter was reported in a number of herds of Afrikander cattle in the 1950's. Some affected animals were assembled and maintained as a closed herd. Although considerable biochemical research into the nature of the disease has been conducted, no definitive report has described the mode of inheritance of the defect. This paper presents the results of breeding studies that indicate the defect is inherited as an autosomal recessive. Southern blot analysis of the thyroglobulin gene confirms this finding. In addition, serum levels of TSH (thyroid stimulating hormone, thyrotropin), T3 (3,4,3'-tri-iodothyronine), T4 (thyroxine), rT3 (3,3',5'-tri-iodothyronine), and DIT (diiodotyrosine) of goitrous animals are compared with normal animals.

Africa, Southern↗