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Is residence in areas of endemic goiter a risk factor for thyroid cancer?

The association between an indicator of iodine deficiency and differentiated thyroid cancer has been investigated in a population-based case-control study. This included all incident cases (N = 484) of papillary and follicular thyroid cancer diagnosed during the years 1980-1992 in a Swedish Health Care Region among residents born in Sweden, and as many individually matched controls. Cases were included after a uniform review of their histopathological specimens. Residence in areas where goiter had been severely endemic in the 1930s was used as exposure indicator. Odds ratios (OR) and 95% confidence intervals as estimates of relative risk were calculated as a measure of association using logistic regression. A trend toward an association was found with a duration of residence in goiter areas between 21 and 40 years, most prominent among follicular cancer cases and in the group diagnosed at age > or = 50 years compared to not exposed. Exposure for the first time during adolescence (between 11 and 20 years) was associated with an increased risk of papillary cancer. This was especially evident among women, both when compared to not exposed and to those exposed during the first year of life; the association was strengthened after adjustment for duration of residence. These findings support the hypothesis of distinct causation patterns from iodine deficiency to the 2 most common histological types of thyroid cancer.

Adolescent↗

Microcephalic cerebrum with hypomyelination in the congenital goiter mouse (cog).

2',3'-Cyclic nucleotide 3'-phosphohydrolase activity in the cerebrum of the congenital goiter mouse (cog/cog) is reduced in comparison with the normal heterozygote (cog/+). The weight of the cog/cog cerebrum and cerebellum were significantly less than those of the normal controls, 89.0% less for the cerebrum, and 81.1% less for the cerebellum. However, no differences were observed with regard to DNA and RNA content and the RNA/DNA ratio. The results of this study indicate that hypomyelination in the congenital goiter mouse is restricted to the cerebrum, and is not related to arrested glial proliferation.

Animals↗

[Thyroidal autoregulation in nontoxic goiter patients: normalization of the T3/T4 ratio in serum by treatment with potassium iodide (author's transl)].

In iodine deficiency areas, an increased T3/T4 ratio in serum was reported earlier. In this study the influence of potassium iodide on the T3/T4 ratio was investigated. Treatment with 200 mug KI per day for only 4 weeks normalized the initially elevated T3/T4 ratio in 16 nontoxic goiter patients (24.6 plus or minus 9.9 times 10-3, mean plus or minus S.D., before, respectively 18.9 plus or minus 5.5 times 10-3 after KI treatment, p smaller than 0.0025). The mean basal TSH levels (1.42 plus or minus 0.68 before, respectively 1.29 plus or minus 0.52 mugU/ml after KI), and the TSH increase 30 min after 200 mug TRH i.v. (5.54 plus or minus 4.22 and 6.50 plus or minus 5.09 mugU/ml, respectively) did not change significantly. Since the normalization of the T3/T4 ratio in nontoxic goiter patients was independent from changes in the TSH levels, this effect of KI obviously represents an example of thyroidal autoregulation.

Goiter, Endemic↗

Iodine vs thyroxine. A changing concept of therapy in endemic goiter?

The hypothesis that goitrogenesis in iodine deficiency can be attributed to the stimulatory effect of thyrotropin (TSH) on the thyroid gland and has long been held to be valid. The task of this review is to describe the reasons why this concept is being challenged. In addition, we report on the autoregulation of the thyroid gland and on in vitro investigations dealing with TSH as a growth factor, which have yielded conflicting results. Finally, we summarize preliminary studies comparing the therapeutic effect of thyroxine and iodine on goiter size. In comparison to thyroxine, iodine application in doses of 300-500 micrograms/day may represent an equally effective way of treatment in areas of endemic goiter, especially in younger patients. In this age group, the risk of side-effects, e.g., iodine-induced thyrotoxicosis, should be low.

Diiodotyrosine↗

Ectopic goiters of the mediastinum: presentation of two cases and review of the literature.

Two cases of ectopic goiters located in the anterior mediastinum are presented. These comprise 5.1 per cent of our cases of intrathoracic goiters and 1.3 per cent of mediastinal tumors. These benign tumors have been rarely reported in the literatures, however, excision by thoracotomy is the surgical procedure advocated for these cases and the diagnosis is generally established operatively. Angiography and tomography have proved useful in diagnosing and localising these lesions prior to the surgical procedure.

Aged↗

Adenomatous goiter with hyperthyroidism.

Adenomatous goiter with hyperthyroidism is a rare disease entity in Japan. Over a five-year period, we operated on 20 patients with this disease. Pre-operatively, basal thyrotropin was not necessarily suppressed and the thyrotropin-binding inhibiting immunoglobulin activity, which had been recently measured in five patients, showed normal values. Uneven patches of cold areas were noted on 131I thyroidal scintigrams. Thyroid function tests carried out three years after surgery in one lobectomy case and in eleven subtotal thyroidectomy cases revealed hypothyroidism in seven, hyperthyroidism in two and euthyroidism in only three cases. These results suggest that the pathogenesis and clinical features of adenomatous goiter with hyperthyroidism are quite different from those of Graves' disease, and that routinely performing near-total thyroidectomy may be considered as the treatment of choice.

Adenoma↗

Prolactin secretion and nodular goiter. (Hypothetical correlations).

In a group of 129 female patients with nodular goiter, Graves' disease and primary hypothyroidism, the PRL and TSH secretions were studied in parallel. Concurrent changes in the two hormones were evident only in conditions of marked hyper- or hypothyroidism. In the patients with non-toxic nodular (single or multiple) goiter the TSH showed low or normal values, while the PRL appeared normal or elevated. From these results two important conclusions can be drawn: 1. the T3 and T4 levels interact with PRL secretion concomitantly with TSH only when they undergo a huge deviation from the normal range; 2. the goitrogenic action of PRL that has been reported in experimental animals cannot be excluded in man.

Adolescent↗

Side-effects of iodized oil administration in patients with simple goiter.

The objective of this study was to determine side-effects associated with iodized oil injection in patients with simple goiter. In an iodine-deficient population, 3420 patients with simple goiter, who were not taking supplemental iodine, were chosen for this study. They received a single intramuscular injection of 1 ml iodized oil, containing 480 mg iodide. Clinical and laboratory evaluations were performed every 3 months for one year and every 6 months for the next 4 years. The incidence of hypo- and hyperthyroidism was 0.6% each, with equal prevalence in both sexes. Most cases of hypo- and hyperthyroidism were observed during the first 5 months after the injection. Eight cases of hyperthyroidism were asymptomatic. A further 8 patients had overt thyrotoxicosis and required treatment with methimazole for 18 months. Recurrence of hyperthyroidism was observed in one patient. Five hypothyroid patients were diagnosed only by abnormal thyroid function tests, and 4 cases needed no treatment. Others received T4 treatment for a mean of 14.5 months. Among 14 T4-treated patients, recurrence of hypothyroidism occurred in 7 patients after treatment was discontinued. Twenty-nine patients (0.8%) were afflicted with dermatologic complications. The most common dermatologic side-effect was urticarial reaction. In 15 subjects, skin lesions appeared 8 to 14 days after injection. It is concluded that side-effects of iodized oil injection are rare, and in most cases the complications are transient and self-limited. The occurrence of iodine induced hyperthyroidism following iodized oil administration is close to the ratio observed in spontaneous thyrotoxicosis.

Adolescent↗

Amyloid goiter in a case of systemic amyloidosis secondary to ankylosing spondylitis.

Infiltrative diseases of the thyroid include systemic sclerosis, hemochromatosis, sarcoidosis, chondrocalcinosis and amyloidosis. Only rarely does thyroid amyloidosis result in clinically palpable goiter. Classically, amyloidosis is associated with tuberculosis, rheumatoid arthritis, multiple myeloma or inflammatory bowel disease. Only rarely does clinical amyloidosis develop in the setting of ankylosing spondylitis. We describe a case of amyloid goiter in a patient with ankylosing spondylitis-associated amyloidosis.

Adult↗

Differential levels of thyroid peroxidase and thyroglobulin messenger ribonucleic acids in congenital goiter with defective thyroglobulin synthesis.

The biosynthesis of thyroid hormones requires iodide, thyroid peroxidase (TPO), thyroglobulin (Tg) and H2O2. We have studied two sisters with congenital large goiters and hypothyroidism. Perchlorate tests were negative. Serum T3 and T4 were decreased, TSH was increased and Tg was within the lower limit of normal. Biochemical and molecular studies were performed on goiter samples obtained after surgery. Tg content in both tissues was negligible. Paper chromatography of labeled iodocompounds showed a decrease in T4, and the presence of a pronase/pancreatin-resistant iodoprotein. TPO activity was normal in the tissues. Sephacryl S-300 gel filtration demonstrated labeled iodoalbumin-like protein and the absence of a Tg peak. Salting out studies of soluble protein fraction gave an abnormal pattern. Agarose gel electrophoresis showed the presence of an iodoalbumin-like protein and the absence of Tg in the tissues. This last finding was confirmed by immunoelectrophoresis. The Tg and TPO mRNAs levels were also analyzed. Dot-blot hybridization studies with pM5 (TPO cDNA) and phTgM2 (Tg cDNA) probes showed increased and decreased signals, respectively. The increase in TPO mRNA can be explained as a compensatory mechanism vis a vis an increase in serum TSH caused by decreased serum T3 and T4 due to the impairment in Tg mRNA. The Tg mRNA of both patients was further studied with four different probes covering 5' and 3' regions (phTgM1, phTgB1, phTgB2 and phTgB3). Hybridization was observed with all four probes, thus excluding a dramatic deletion defect. Northern transfer showed a clear signal of hybridization with the phTgB1 probe in the 8-9 Kb range. We may conclude that the biochemical and molecular abnormality of these patients is characterized by a decrease of Tg mRNA and of Tg translation.

Adolescent↗

Dyshormonogenetic goiter: presence of an inhibitor of normal human thyroid peroxidase.

A dialyzable, thermostable inhibitor of normal thyroid peroxidase (TPO), with UV absorption maximum at 250-260 nm, was found in the digitonized, washed particulate fraction of two dyshormonogenetic goiters. No intrinsic TPO iodide-oxidation activity was detectable in either of these goiters, and their TPO iodination activity was below the method sensitivity threshold, even after dialysis. These findings could be explained by an absent or abnormal TPO associated with the synthesis of a TPO-inhibitor, or by the irreversible inhibition of a normal enzyme by the inhibitor.

Dialysis↗

[The LISA trial-a- randomized, double-blind, placebo-controlled four-arm study of 1,000 patients with nodular goiter in Germany. Study Design and first results of feasibility].

BACKGROUND: Although levothyroxine is the mostly prescribed medicament in Germany, its therapeutic effectiveness in nodular goiter was never studied in a randomized, double-blind trial with sufficient power. Thus, in May 2004 a TSH-adapted (TSH: thyroid-stimulating hormone), randomized, doubleblind, placebo-controlled four-arm (placebo [P] vs. levothyroxine [T] vs. iodine [I] vs. levothyroxine + iodine [TI]) multicenter study was started in Germany (LISA study). PATIENTS AND METHODS: Based on former retrospective and prospective studies, it was calculated that a sufficient statistical power (> 80%) would be achieved with 250 patients in each arm. The primary endpoint of the trial is the 1-year change of ultrasonographically measured total volume of all nodules. Secondary criteria are volume of goiter, number of nodules, and echogenic structure of nodules. While the study is kept strictly double-blind, the dose of levothyroxine in the T and TI groups is adapted once according to 3-month TSH measurements (target range 0.2-0.8 mU/l). RESULTS: Up to now (1 year after beginning), 305 patients have been included. TSH adaptation could be performed without compromising the double-blind character of the study with good results: about 90% of the patients reached the TSH target range. CONCLUSION: Unblinded results are to be expected in 2007.

Adolescent↗

[The role of intraoperative ultrasound in surgery for benign nodular goiter].

BACKGROUND: In treating benign nodular goiter, selective surgery taking into account morphology and function is better than standard subtotal resection for reducing the frequency of nodules in the thyroid remnant. Intraoperative ultrasound (IOPUS) may additionally influence operative radicality and also the incidence of remaining nodules. METHODS: One hundred consecutive patients with benign nodular goiter were operated on with IOPUS; the specimens were compared with results of preoperative ultrasound and intraoperative palpation. Of these patients, 80 were reinvestigated after 3+/-1.6 years. A series of 80 patients with the same operative strategy but without IOPUS was used as control group, having been reinvestigated sonographically 1 year postoperatively, and was compared to the IOPUS group with respect to operative procedures, size of remnants, and sonography of lesions in thyroid remnants. RESULTS: In 35% of the thyroid lobes, preoperatively undetected nodules could be identified additionally by IOPUS, which also provided information on extent and structure in a further 20%. It resulted in the indication for more radical surgery in 24% and greater tissue preservation in 10%. Compared to surgery without IOPUS, IOPUS-guided surgery was more radical (total lobectomy in 40% vs 24%, nonresected lobes in 16% vs 26%, P<0.05) and showed a lower incidence of nodules in remnants at follow-up (2.5% vs 12.5%, P<0.05). CONCLUSIONS: With IOPUS, more nodules are detectable, size and structure of the remnants are optimized, and the number of nodular lesions in thyroid remnants is lower. Thus, an even lower risk of recurrence can be expected for long-term follow-up. All in all, the routine use of IOPUS can be advocated, with maintenance of the selective operative strategy.

Follow-Up Studies↗

Iodide or L-thyroxine to prevent recurrent goiter in an iodine-deficient area: prospective sonographic study.

In a randomized study, prevention of goiter recurrence with L-thyroxine was compared with pure iodide substitution after thyroid surgery for nodular goiter in an iodine-deficient area. Altogether 107 patients were followed up for 52 weeks after thyroid resection. The thyroid volume was determined sonographically. Free thyroxine, total thyroxine, thyrotropin, thyroglobulin, and antibodies to thyroglobulin and thyroid peroxidase were measured. The thyroid volume decreased slightly over the course of a year in the two therapy groups. There was no significant difference between the two groups. Recurrences were seen with both L-thyroxine medication and iodide substitution. The thyroglobulin levels fell significantly over the 52-week follow-up period in the iodide group. Antibody formation was not observed under iodine substitution. In an area of iodine deficiency, substitution with iodide is just as effective as medicating the patients with L-thyroxine for preventing recurrences.

Female↗

Indications, risks, and acceptance of total thyroidectomy for multinodular benign goiter.

Selective morphology- and function-adapted resection is generally regarded as the surgical treatment of choice for benign goiter causing iodine deficiency. This procedure aims to reduce the need for patients to undergo reoperations for recurrence by completely removing all nodules. However, to achieve this sometimes requires a total thyroidectomy, the option of which is often rejected because of a presumed higher rate of complications. In this study, 324 patients who underwent total thyroidectomy were evaluated retrospectively. The patients were interviewed about their postoperative course and their acceptance of the procedure performed. The complications were compared with those associated with subtotal resection or hemithyroidectomies performed in our collective experience. The rate of complications associated with total thyroidectomy, namely, recurrent nerve palsy in 0.9%, hypocalcemia in 0.9%, wound infection in 0.9%, and secondary hemorrhage in 0.6%, did not differ significantly from that associated with subtotal resections/ hemithyroidectomies. Moreover, 88.3% of the patients who underwent total thyroidectomy were satisfied with the results of surgery. These findings indicate that total thyroidectomy is an acceptable surgical alternative for benign multinodular goiters.

Adult↗

Hormone-containing peptides from normal and goiter human thyroglobulins.

A series of low iodine human thyroglobulin samples derived from colloid-rich goiter tissue was examined by HPLC mapping of tryptic digests and compared to normal human thyroglobulin. These samples ranged in iodine content from 2 to 8 gram-atoms of iodine (g.a. I) per mole and were not further iodinated in vitro. Peptides containing the principal hormonogenic sequence were detected using the long wavelength absorbance of the iodotyrosine derivatives at 325 nm. Two such peptides were isolated and sequenced. Their thyroxine content was confirmed by radioimmunoassay. The number of 325-nm-absorbing peaks was significantly lower in the normally iodinated human thyroglobulin than that observed the thyroglobulins of cattle and dog. This suggests a more restricted iodination in the human protein. Sodium dodecyl sulfate gel patterns of the reduced and alkylated proteins showed significant molecular size heterogeneity in all of the samples. Polypeptide fragments ranged in molecular size from approximately 330 to 45 kDa in the goiter derived material and from approximately 330 to 15 kDa in the normal human material. This difference between the proteins is consistent with earlier observations that peptides less than 45 kDa appear concomitantly with hormone formation. These data confirm that the human thyroglobulin molecule is capable of forming at least limited amounts of thyroid hormone at iodine levels as low as 4 g.a. I per mole. The hormone detected in this study was located at residue 5 near the amino terminus of the thyroglobulin molecule.

Chromatography, High Pressure Liquid↗

Afrikander cattle congenital goiter: size heterogeneity in thyroglobulin mRNA.

The mRNA coding for thyroglobulin in cattle homozygous for an autosomal recessive defect of thyroglobulin synthesis was investigated using a recombinant plasmid containing bovine mRNA coding sequence. Total RNA preparations from goiter contained one third of the thyroglobulin mRNA sequences found in normal thyroid tissue. This mRNA was not translated into thyroglobulin by Xenopus oocytes. Northern transfer analysis revealed both a normal sized and a smaller thyroglobulin mRNA in the goiter.

Animals↗

Studies on the goiter inhibiting action of iodolactones.

The thyroid gland synthesizes 6-delta-iodolactone, a compound shown to inhibit goiter growth in vivo and cell proliferation in culture. The present studies were performed to characterize this effect further with the aim of exploring the possible therapeutic action of iodolactones. Prevention assay: rats were treated simultaneously with a goitrogen, methylmercaptoimidazole, and either 6-delta-iodo-lactone or 14-iodo-omega-lactone, a synthetic derivative, given either i.p. or p. o. Both compounds caused a significant decrease in thyroid weight irrespective of the route of administration, but oral administration was less effective. A dose-response relationship was observed, the minimal effective dose (i.p.) being 3 micrograms/day. Involution assay: goiter was first induced with methylmercaptoimidazole and then the iodolactones were injected. Both compounds caused a significant involution, which was dose-related. Acute (10 days) administration of the iodolactones did not produce significant changes in several serum parameters (total T3 and T4, cholesterol, total protein, urea and acetylcholinesterase). These results give further support to the potential therapeutic application of iodolactones.

Administration, Oral↗