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The adaptation of the human thyroid gland to a physiological regimen of iodide intake: evidence for a transitory inhibition of thyroid hormone secretion modulated by the intrathyroidal iodine stores.

The effects of iodide on thyroid function were so far only studied after administration of pharmacological or small continuous doses. We were interested to know how the human thyroid gland would react to a more physiological situation: small doses taken in intermittently. Ten normal male volunteers were given weekly doses of iodide: 1 mg for the first 6 weeks and 2 mg afterwards for another 6 weeks period. Intrathyroidal iodine stores were evaluated by the X-Ray-Fluorescence method. The following thyroid parameters were estimated during the 3 months period: total thyroxine, total triiodothyronine, free thyroxine, free triiodothyronine, reverse triiodothyronine, plasma inorganic iodide, thyroid stimulating hormone and thyrotropin-releasing hormone tests. The following observations were made: i) a steady increase of intrathyroidal iodine (p less than 0.01); ii) no changes in free thyroxine, free triiodothyronine, thyroid stimulating hormone, thyrotropin-releasing hormone test or plasma inorganic iodide. iii) a decrease of total thyroxine (and total triiodothyronine) with a nadir at about 3 weeks and a spontaneous rise afterwards; repetition of this phenomenon by doubling the dose of iodide. It is concluded that 1 mg or 2 mg iodide a week does not inhibit incorporation into the normal human thyroid gland and suggested that these physiological doses of iodide cause a transitory inhibition of thyroxine secretion, representing a form of autoregulation of the thyroid cell, since it was modulated by the intrathyroidal iodine stores and no evidence of pituitary mediation could be evidenced in the experimental protocol.

Adult↗

Accumulation of identical T cell clones in the right and left lobes of the thyroid gland in patients with Graves' disease: analysis of T cell clonotype in vivo.

To elucidate the involvement of intrathyroidal T cells in the thyroid antigen-specific immune response in Graves' disease (GD), we investigated whether identical T cell clonotypes accumulate clonally in the right and left lobes of thyroid glands of GD patients. mRNAs extracted from thyroid glands of five females patients with GD were reverse-transcribed to cDNA and then the genes coding the T cell receptor B chain variable (V-NDN-J) region were amplified using polymerase chain reaction. Single strand conformation polymorphism analysis and subsequently nucleotide sequencing were also performed to determine the clonotype of accumulating T cells. T cells infiltrating the thyroid glands showed oligoclonal expansion. The expanded T cell clonotypes were not detected in peripheral blood of the same patients. Importantly, the majority of expanding T cell clonotypes in the two lobes of the thyroid glands were identical. Our findings suggest that the clonal expansion of identical T cell clonotypes in the two lobes is driven by factors common to both lobes, such as thyroid-specific antigens, in patients with Graves' disease.

Adult↗

Acid thyroglobulin protease activities in human diseased thyroid glands.

The lysosomal acid protease is thought to be a main enzyme in hydrolysis of thyroglobulin. The protease activity of lysosome-rich fractions of various diseased thyroid glands were assayed by the sensitive and reproducible method developed in our laboratory. They included 78 diseased thyroid glands; 37 thyrotoxic goitres, five irradiated thyroids, five Hashimoto's thyroiditis, one granulomatous thyroiditis, six multinodular goitres, 14 'cold' adenomas, four 'hot' adenomas with three paranodular tissues, and six carcinomas. Fifteen paranodular tissues of cold and solitary thyroid nodules were served as controls. The protease activities were significantly increased in thyroid tissues of thyrotoxic goitres, Hashimoto's thyroiditis, adenomas and adenocarcinomas. In thyrotoxic goitres, the protease activity correlated well with the mean area size of colloid follicles. The 'hot' adenomas had higher protease activity than 'cold' ones. The protease activity of multinodular goitres was nearly normal. Only the irradiated thyroid glands had low protease activities. Therefore the high protease activities in hyperfunctioning goitres seem to reflect hormone secretory activities. On the other hand, cold neoplastic goitres seem to have lysosomal protease activities which are not associated with thyroidal secretory process. The assay of acid protease activity will be useful to understand the pathophysiology of lysosomal system in diseased thyroid glands.

Aspartic Acid Endopeptidases↗

[Etiology and pathogenesis of autoimmune diseases of the thyroid gland].

As for other autoimmune diseases it is discussed also for immune hyperthyroidism (Basedow's disease) and immune thyroiditis, whether factors such as stress and infections with viruses and bacteria may lead to a disturbance of the immune tolerance in persons genetically predisposed. In Basedow's disease antibodies against the TSH-receptor cause an uncontrolled stimulation of the function of the thyroid gland. One year after the end of an antithyroid drug treatment, e.g. with thiamazol, a recidivation rate of circa 50% develops. There are no criteria which may predict the clinical development of an individual after the end of the treatment with a sufficient reliability. This applies particularly also to the measurement of the TSH receptor antibodies and the suppression test at the end of treatment (Alexander's test). According to the experiences of author moreover patients with small and large goitres and with different degrees of Basedow's orbitopathy do not show any difference in the frequency of the recidivations. In the immune thyroiditis a series of antibody-dependent and lymphocyte-dependent processes may lead to a decreased function of the thyroid gland. This includes the interaction of antibodies with the complement system or with the killer cells (ADCC), the direct decomposition of the cells of the thyroid gland by certain subgroups of lymphocytes and the occurrence of blocking antibodies against the TSH receptor. In patients in whom antibodies were made evident may develop a hypothyroidism. But many patients also for ever remain euthyroid. These observations and experimental data suggest that the cell of the thyroid gland also itself must be "susceptible" to the destruction by the antibodies and lymphocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoantibodies↗

Lingual thyroid gland: clinical evaluation and comprehensive management.

Although lingual thyroid gland is the most common benign mass found at the junction of the anterior two-thirds and the posterior one-third of the tongue, it is still a rare clinical entity. This developmental anomaly is the result of an arrested descent of the gland anlage early in the course of embryogenesis. Patients may have symptoms of dysphagia due to obstruction or even hemorrhage. These symptoms can occur at any time from infancy through adulthood. The clinical findings, laboratory tests, and radiographic imaging studies employed in confirming the diagnosis and in planning appropriate treatment have been evaluated. The primary therapeutic goal is to restore thyroid function. We describe a case of lingual thyroid gland and summarize the current management principles for this condition.

Adult↗

[Dynamics of thyroxine and triiodothyronine concentration in the rat blood at early times after subtotal removal of the thyroid gland or under effects of different I-131 action].

The alterations of amount of thyroid hormones have the characteristic dynamics that manifest itself by initial reduction with following partial or complete restoration of T3 and T4 concentration in rat blood after surgical or radioactive injuries of thyroid gland. Through presence of threshold of several dozens Gy for early dose-dependent hypothyroidism, the thyroid gland seems to be relatively radioresistant organ. Thyroid hormones concentration in blood has restored to normal level after experimental injuries which shows high restoration potential of thyroid gland function.

Animals↗

Nonresponsiveness of the thyroid gland to goitrogen in the early neonatal period in the rat: light- and electron-microscopic observations.

The thyroid response of fetal and neonatal rats to propylthiouracil (PTU) as a goitrogen was studied with observation of the thyroid glands by light and electron microscopy. On day 19 of gestation and on days 1, 3, 5 and 8 after birth, fetal and neonatal rats were given a subcutaneous injection of PTU and were autopsied 2 days later. PTU induced conspicuous goiters in fetal rats but did not in neonatal rats aged up to day 5 after birth. Beyond that age, PTU again induced goiters. Histologically, the follicular cell height in goitrous thyroid glands was significantly increased. Ultrastructurally, follicular cells in goitrous thyroid glands often had colloid droplets and lysosomes. It seems that nonresponsiveness of the thyroid glands in early neonatal rats to goitrogen is due to a temporary decline of the pituitary activity of thyrotropin secretion. About 5 days or more after birth, the pituitary-thyroid system begins to operate again in response to goitrogen.

Aging↗

Arteriovenous fistula of the thyroid gland associated with spontaneous bleeding from a flow-induced aneurysm of the inferior thyroid artery.

A case of acute, spontaneous cervical hemorrhage caused by a ruptured aneurysm of the inferior thyroid artery is described. This lesion was accompanied by an arteriovenous fistula within the thyroid gland that caused a flow-induced aneurysm. Diagnosis and treatment were successfully performed by selective angiography with endovascular occlusion and embolization. Both diagnostic and therapeutic management are discussed, and the related literature is reviewed. To our knowledge, this is the first reported case of an aneurysm of a thyroid artery in conjunction with an intraparenchymatous arteriovenous fistula of the thyroid gland.

Aged↗

Expression and regulation of type II iodothyronine deiodinase in human thyroid gland.

We have studied the expression of type II iodothyronine deiodinase (DII) in human thyroid tumors and cultured human thyroid cells to elucidate the mechanisms involved in the regulation of DII expression in human thyroid gland. Three cases with hyperfunctioning thyroid adenoma, including a case that showed an activating mutation of G(s)alpha with a constitutive activation of cAMP production in cultured cells, and six cases with papillary thyroid carcinoma were analyzed in the present study. Free T(3) was increased, whereas free T(4) was within the normal range in all patients with hyperfunctioning thyroid adenoma. Thyroid tumor tissue and surrounding nontumor tissue were obtained at the time of surgery, and DII expression was compared between tumor tissue and nontumor tissue in each case. Northern analysis demonstrated the presence of DII messenger RNA (mRNA) approximately 7.5 kb in size in all of the tumor and nontumor tissues. DII mRNA and DII activity in hyperfunctioning thyroid adenoma were significantly increased compared with those in nontumor tissue in each case. In contrast, DII mRNA and DII activity in papillary thyroid carcinoma were decreased compared with those in nontumor tissue in each case. DII mRNA and DII activity in cultured human thyroid cells were significantly stimulated by TSH in a dose-dependent manner. The promoter activity of the human DII gene including the complete cAMP response element, transfected to cultured human thyroid cells, was stimulated by (Bu)(2)cAMP. In summary, these results suggest that DII expression in human thyroid gland is regulated at the transcriptional level through the TSH receptor-G(s)alpha-cAMP regulatory cascade, which may be related to the increase in circulating T(3) level in patients with Graves' disease and hyperfunctioning thyroid adenoma.

Adenoma↗

[The effect of emotional stressors on thyroid gland function].

Response of the normal and goiterous thyroid gland to the information on the forthcoming operation was studied in 12 patients with varicose veins of the lower limbs and in 67 patients with thyrotoxicosis; this was done by determination of protein-bound iodine (PBI). PBI proved to increase before the operation in both groups of the patients. Due to undesirable hyperfunction of the thyroid gland prior to the operation in thyrotoxicosis, the psychodepressive premedication component should be increased.

Goiter, Endemic↗

Demonstration of iodide transport defect but normal iodide organification in nonfunctioning nodules of human thyroid glands.

Benign and malignant nodules in human thyroid glands, which did not concentrate iodide in vivo, were also unable to accumulate iodide in vitro. The mean thyroid-to-medium ratio (T/M) in seven benign nodules was 0.8+/-0.2 compared with 7+/-2 in adjacent normal thyroid tissue. In four malignant thyroid nodules, the mean T/M was 0.5+/-0.1 compared with 11+/-4 in adjacent normal thyroid. Despite the inability of such nodules to concentrate iodide, iodide organification was present but was only one-half to one-third as active as in surrounding normal thyroid. Thyroid-stimulating hormone (TSH) increased iodide organification equally in both benign nodules and normal thyroid although it had no effect in three of the four malignant lesions. The reduction in organification is probably related to the absence of iodide transport, since incubation of normal thyroid slices with perchlorate caused similar diminution in iodide incorporation but no change in the response to TSH. Monoiodotyrosine (MIT) and di-iodotyrosine (DIT) accounted for most of the organic iodide in both the nodules and normal tissue. The MIT/DIT ratio was similar in normal and nodule tissue. The normal tissue contained much more inorganic iodide than the nodules, consistent with the absence of the iodide trap in the latter tissue. The thyroxine content of normal thyroid was 149+/-17 mug/g wet wt and 18+/-4 mug/g wet wt in the nodules. The transport defect in the nodules was not associated with any reduction in total, Na(+)-K(+)- or Mg(++)-activated ATPase activities or the concentration of ATP. Basal adenylate cyclase was higher in nodules than normal tissue. Although there was no difference between benign and malignant nodules, the response of adenylate cyclase to TSH was greater in the benign lesions. These studies demonstrate that nonfunctioning thyroid nodules, both benign and malignant, have a specific defect in iodide transport that accounts for their failure to accumulate radioactive iodide in vivo. In benign nodules, iodide organification was increased by TSH while no such effect was found in three of four malignant lesions, suggesting additional biochemical defects in thyroid carcinomas.

Adenoma↗

Radiologic assessment of metastases to the thyroid gland.

PURPOSE: We reviewed the radiologic and clinical data in patients with metastatic disease to the thyroid gland and assessed the role of radiologic techniques in this disorder. METHOD: The findings on US (n = 11), CT (n = 7), MRI (n = 6), palpation or US-guided fine needle aspiration (FNA) biopsy, and clinical records were reviewed in 11 cases of pathologically verified metastatic tumors of the thyroid gland. RESULTS: Five patients had palpable thyroid nodules and six had nonpalpable nodules discovered incidentally with imaging procedures. Three patients had no known malignancies at the time of diagnosis of thyroid tumors. Correct diagnosis was obtained in 10 of the 11 cases with FNA biopsy. Thyroid metastases were detected in all of the cases with US and MRI and six of the seven cases with CT. Thyroid metastases were solitary (n = 5) or multiple (n = 6), and about half of them measured <2 cm in diameter. These tumors typically had well defined margins and no calcification and sometimes had cystic portions. Multiple nodules within the same patient were radiologically quite similar to each other. On US, metastases appeared as hypoechoic or markedly hypoechoic areas without halo, on CT as low density areas, and on MRI as areas of varying signal intensities. Half of the metastases showed hypointensity on either T2-weighted images or gadolinium-enhanced T1-weighted images. The tumors involved lymph nodes in 10 cases and other remote organs in 5. Level I or II or parotid nodes were involved in six cases. CONCLUSION: These radiologic features may alert clinicians to a possibility of metastatic thyroid cancer. US combined with US-guided FNA biopsy is suitable for early diagnosis of metastases to the thyroid gland.

Adult↗

Shape, measurements and weight of the thyroid gland in northwest Indians.

The shape of the thyroid gland, its extension as the pyramidal lobe (PL) and attachments of the levator glandulae thyroideae (LGT) were studied in 410 male and 160 female adults from the Chandigarh zone in northwest India during medicolegal autopsies performed in the department. Whereas the measurements of the gland were recorded in 210 subjects, the weights were taken only in 160 instances. The shapes of the glands were: lateral lobes (LL) with isthmus (50.2%), horseshoe-shaped gland (36.8%), gland with separate lobes (7.9%) and irregularly shaped gland (5.1%). No sexual dimorphism was seen in the incidence of various shapes of the gland. The incidence of the PL and LGT was 28.9% and 19.5%, respectively. Neither a PL nor LGT was present in irregularly shaped glands. The mean weight of the gland was 15.01+/-7.69 g in males and 13.16+/-5.64 g in females. Sexual and age-wise differences in weights were found to be statistically insignificant. A survey involving 152 subjects in 2 villages in Chandigarh showed that it is an iodine sufficient zone. The size and weight of thyroid glands in adults of the two genders were found to be smaller than in western Caucasian and Japanese subjects.

Adult↗

Hemiagenesis of the thyroid gland.

Three cases of hemiagenesis of the thyroid gland are reported and the literature reviewed. It is emphasized that this rare congenital anomaly is seldom diagnosed except by thyroid scanning or at surgery. If the clinician is aware of it, the diagnosis presents little difficulty and an unnecessary operation may be avoided. All our cases were discovered as a result of an associated thyroid disorder. In 2 cases there was an adenoma and in 1 a papillary adenocarcinoma.

Adenocarcinoma, Papillary↗

Quantitative morphologic study of the pituitary and thyroid glands of dogs administered L-thyroxine.

To determine the effects of long-term thyroxine treatment, histomorphometric analysis was performed on the pituitary and thyroid glands of healthy dogs, dogs treated for 9 weeks with a replacement dose of L-thyroxine, and dogs at 6 weeks after cessation of thyroxine treatment. In treated dogs, the volume density of thyrotropes decreased during thyroxine treatment and increased 6 weeks after cessation of treatment, compared with thyrotropes of healthy nontreated dogs. The activity of the thyroid gland was decreased in dogs during thyroxine treatment, as evidenced by decreases in epithelial volume density, epithelial height, and follicular area, and increase in colloid volume density, compared with thyroid gland activity in nontreated dogs. After cessation of thyroxine treatment, the thyroid gland had decreased colloid area, follicular area, and epithelial volume density, and increased interstitial volume density, compared with the thyroid gland of healthy nontreated dogs. Thyroxine treatment resulted in suppression of pituitary thyrotropes and thyroid follicular activity.

Animals↗

Direct extension of malignant lesions to the thyroid gland from adjacent organs: report of 17 cases.

OBJECTIVE: To characterize malignant tumors with direct extension to the thyroid gland from adjacent organs. METHODS: We retrospectively studied 17 patients with direct extension of malignant tumor to the thyroid from primary lesions in the head and neck who had been examined at Mayo Clinic Rochester between 1985 and 1994. The origin of the primary tumor was identified in all cases. Thyroid involvement was confirmed histologically. Data were analyzed for the frequency and types of malignant lesions, the clinical course, and the follow-up after thyroid involvement. RESULTS: All 17 study patients had a diagnosis of a primary malignant tumor before detection of thyroid involvement. Of the 17 patients, 12 had squamous cell carcinoma (SCC) of the larynx, 2 had SCC of the tongue base, 2 had SCC of the proximal and the cervical esophagus, respectively, and 1 had synovial cell sarcoma of the proximal esophagus. The time between diagnosis of the primary tumor and detection of thyroid invasion in the patients with SCC of the larynx or tongue base ranged from 1 to 196 months (mean, 38). Only 1 of these 14 patients had thyroid gland involvement clinically evident before surgical exploration. Thyroid invasion was diagnosed after surgical intervention. All three patients with esophageal malignant tumors had thyroid involvement clinically. CONCLUSION: SCC of the larynx, tongue base, or proximal esophagus may invade the thyroid gland directly. SCC of the larynx may have the greatest tendency to extend to the thyroid. In patients with SCC, extension of the primary malignant tumor to the thyroid gland should be considered despite lack of clinical evidence.

Journal Article↗

[Diagnosis of metastasis of malignant melanoma in the thyroid gland with f18-FDG PET scan].

Metastases in the thyroid gland are very rare. When they occur, long-term survival is dismal; thus an early diagnosis is critical. Malignant melanoma is one of the tumors which may metastasize to the thyroid gland. Therefore we wanted to demonstrate F18-Fluorodeoxyglucose-Positron emission tomography (F18-FDG-PET) is a sensitive and reliable method to identify such metastases. We report about a 51-year-old man, who had an inguinal lymph node metastasis of a malignant melanoma with unknown primary tumor site. He came to us for an a follow-up F18-FDG-PET investigation. In the PET there was a pathologic FDG-uptake in the left lobe of the thyroid gland. The nodule was removed and showed a malignant melanoma metastasis. This unusual scenario underscores the value of the PET in the oncologic follow-up of patients with malignant melanoma.

Diagnosis, Differential↗

[Effect of heparin on the thyroid gland].

Effect of heparin on the white rat thyroid gland has been studied in vivo and in vitro by means of light microscopy, electron microscopy and radiometry methods. Heparin is injected subcutaneously (1,000 units per 100 g of the body mass) once in 24 h. In the in vitro experiments heparin contents in medium is 10 units/ml and 10 units/ml. Heparin produces a decrease in thyrocyte height (control--12.6 +/- 0,5, experiment--10.4 +/- 0.6 mcm), a decrease in the number of folds on the basal surface of thyrocytes, changes in Golgi complex and an increase in electron density of the mitochondrial matrix. In endotheliocytes of the perifollicular blood capillaries the number of fenestrae decreases. Iodine accumulation in the thyroid is lowered under the effect of heparin. The thyroid gland blood stream (estimated by accumulation of 86Rb) decreases by 35%. The data obtained support the previous suggestion of the authors on a system-forming role of the tissue basophils in the thyroid micro-region.

Animals↗