Circadian rhythm of the thyroid mast cells in untreated and methylthiouracil-treated rats

Recent investigation have shown that mast cells of the rat thyroid participate in the regulation of thyroid function. Serotonin released from the mast cells influenced by thyrotropin promotes iodothyronine secretion by its effect on the thyroid follicle cells. The present histophysiological studies on the circadian rhythm in the normal rat thyroid reveal a close correlation between the number of the thyroid mast cells and the thyroid function. It has been shown that in the morning, when thyroid function is decreased, the number of the mast cells is low, but at noon it shows an increase an then is highest in the evening, when the thyroid activity is most intense. This phenomenon suggests a relationship between the mast cell function and the thyroid feedback mechanism. In methylthiouracil-treated rats inhibition of the thyroid iodothyronine production and change of the feedback mechanism function induce development of a hypertrophic goitre in which degranulation of the mast cells accompanied by release of their bioamines induce dilatation of blood vessels and increase in the thyroid blood flow. Simultaneously the circadian rhythm of the thyroid mast cell occurrence is changed, i.e. their number found in the morning gradually decreases by the evening.     

Blocking activity to action of thyroid stimulating hormone in serum from patients with primary hypothyroidism.

Spontaneous primary hypothyroidism in adults is usually associated with autoimmune thyroiditis. The hypothesis that hypothyroidism may result from the presence in serum of a factor that blocks stimulation of the thyroid by thyroid stimulating hormone was examined. Serum samples were collected from 28 patients with recently diagnosed primary hypothyroidism. After removal of endogenous thyroid stimulating hormone the effect of the serum on secretion of triiodothyronine induced by thyroid stimulating hormone or thyroid stimulating antibodies was examined in thyroid slices incubated in vitro. Serum samples from six of the patients demonstrated significant blocking of the stimulation by bovine thyroid stimulating hormone. Inhibition of the stimulatory action of thyroid stimulating antibodies was also exhibited by serum samples with blocking activity. It is concluded that in some patients with primary hypothyroidism a serum factor, which is probably an IgG, exists that can block the thyroid response to thyroid stimulating hormone and thyroid stimulating antibodies; it may represent an important mechanism in the pathogenesis of hypothyroidism.     

Age-related nuclear size variability of thyreocytes in thyroid aspirates

Variations in nuclear areas in thyroid aspirates may be caused by many different pathologic conditions of the thyroid gland. Our experience in routine thyroid cytology has suggested that the age of the patient could also be a factor that can influence the nuclear size of thyroid epithelial cells. Planimetric measurements of nuclear areas of cytologically normal thyroid nuclei from patients with normal thyroid glands and from those with cold thyroid nodules, with each category containing two different age groups, revealed both a significant increase in nuclear areas in normal thyroid tissue from older patients and a significant increase in nuclear size variability among older patients with nodular goiters. This finding seems to indicate that patient age is another factor that exercises an influence upon the variability of nuclear areas, even in histologically normal thyroid glands.     

不同性质甲状腺结节与微血管密度关系的研究

目的:探讨不同性质甲状腺结节与微血管密度关系,提高认识.方法:分别选取甲状腺乳头状癌、甲状腺腺瘤、结节性甲状腺肿及正常甲状腺组织,病理切片行常规HE染色及免疫组化SP染色.在高倍视野(×400)下选取5个血管着色密集区进行计数并取其平均数,MVD值=(n1 +n2+n3+n4+n5)/5.结果:(1)甲状腺乳头状癌、甲状腺腺瘤、结节性甲状腺肿及正常甲状腺组织平均MVD值分别为(65.54±19.21)个/HP、(54.54±11.76)个/HP、(47.85± 10.92)个/HP、(21.82±7.43)个/HP,甲状腺乳头状癌MVD值显著高于甲状腺腺瘤、结节性甲状腺肿及正常甲状腺组织(P＜0.05).甲状腺腺瘤、结节性甲状腺肿MVD值显著高于正常甲状腺组织(P＜0.05).(2)伴有淋巴结转移的甲状腺乳头状癌患者MVD值显著高于不伴有淋巴结转移者(P＜0.05);男性甲状腺乳头状癌患者MVD值显著高于女性患者(P＜0.05);＞40岁及≤40岁甲状腺乳头状癌患者MVD值间无统计学差异(P＞0.05).结论:甲状腺乳头状癌MVD值显著高于甲状腺腺瘤、结节性甲状腺肿及正常甲状腺组织,且伴有淋巴结转移的甲状腺乳头状癌患者MVD值显著高于不伴有淋巴结转移者.     

Role of the hypophysis in thyroid regeneration after partial thyroidectomy.

The role of the hypophysis in thyroid regeneration was investigated by measuring the mitotic activity of the thyroid remnant in hemithyroidectomized rats as well as the blood levels of thyroid hormone at various time-intervals after hemithyroidectomy. Mitotic activity underwent a significant increase to reach a peak (a 5- to 8- fold increase) 2 days after hemithyroidectomy. The thyroid hormone level in blood was lower than in controls. Histologically, the thyroid gland showed signs of an elevated rate of functional activity, as indicated by losses of colloid and cell hypertrophy. In a second approach, the mitotic activity of the thyroid remnant was estimated in hypophysectomized and in thyroxine treated rats. Both hypophysectomy and thyroxine injection prevented occurrence of the mitotic peak at 2 days. The regeneration of the thyroid after hemithyroidectomy, as it occurred in the present work, may be explained by a release of thyroid stimulating hormone from the pituitary, brought about by the low level of circulating thyroid hormone, itself resulting from a loss of thyroid tissue.     

Stable high level expression of human thyroid peroxidase in cultured Chinese hamster ovary cells

An expression plasmid containing both human thyroid peroxidase and mouse dihydrofolate reductase cDNAs was transfected into chinese hamster ovary cells. The stably transformed cells constitutively expressed immunoreactive thyroid peroxidase on the cell surface. These cells were further used to establish a subline producing a large amount of thyroid peroxidase by selecting clones resistant to methotrexate. The molecular weight of the expressed thyroid peroxidase was the same as purified human thyroid peroxidase. This expressed protein had peroxidase activity when determined by guaiacol oxidation. Furthermore, the expressed thyroid peroxidase was immunoreactive to sera of patients with autoimmune thyroid disease in which autoantibodies to thyroid peroxidase appeared.     

Arteries define the position of the thyroid gland during its developmental relocalisation

During vertebrate development, the thyroid gland undergoes a unique relocalisation from its site of induction to a distant species-specific position in the cervical mesenchyme. We have analysed thyroid morphogenesis in wild-type and mutant zebrafish and mice, and find that localisation of growing thyroid tissue along the anteroposterior axis in zebrafish is linked to the development of the ventral aorta. In grafting experiments, ectopic vascular cells influence the localisation of thyroid tissue cell non-autonomously, showing that vessels provide guidance cues in zebrafish thyroid morphogenesis. In mouse thyroid development, the midline primordium bifurcates and two lobes relocalise cranially along the bilateral pair of carotid arteries. In hedgehog-deficient mice, thyroid tissue always develops along the ectopically and asymmetrically positioned carotid arteries, suggesting that, in mice (as in zebrafish), co-developing major arteries define the position of the thyroid. The similarity between zebrafish and mouse mutant phenotypes further indicates that thyroid relocalisation involves two morphogenetic phases, and that variation in the second phase accounts for species-specific differences in thyroid morphology. Moreover, the involvement of vessels in thyroid relocalisation sheds new light on the interpretation of congenital thyroid defects in humans.     

Postpartum thyroid dysfunction in Mid Glamorgan

A high prevalence of postpartum thyroid dysfunction has been reported in several countries, but there have been no systematic studies of its prevalence in Britain. Among a group of 901 consecutive, unselected pregnant women thyroid autoantibodies were detected in 117 (13%) at booking. The clinical course of postpartum thyroid dysfunction, factors associated with its development, and its likely prevalence were defined in 100 of these women with thyroid antibodies and 120 women with no such antibodies who were matched for age. None of the women had a history of autoimmune thyroid disease. Normal reference ranges for thyroid function during pregnancy and post partum were established in the 120 women negative for thyroid antibodies. On the basis of these observations postpartum thyroid dysfunction was observed in 49 (22%) of the 220 women studied, and the prevalence in the total group of 901 women was estimated to be 16·7%. Thyroid dysfunction, mainly occurring in the first six months post partum, was usually transient and included both destruction induced hyperthyroidism and hypothyroidism. The development of the syndrome was significantly related to smoking more than 20 cigarettes a day and the presence of thyroid microsomal autoantibodies at booking. Of the 16 women with a family history of thyroid disease in whom thyroid microsomal autoantibody activity was detectable at booking, 11 developed thyroid dysfunction. Age, parity, presence of goitre at presentation, duration of breast feeding, and the sex and birth weight of the infant were not associated with the development of postpartum thyroid dysfunction.The mood changes experienced by women post partum may in part be associated with altered thyroid function during this time.     

Papillary carcinoma in an ectopic thyroid

Ectopic thyroid tissue can be seen anywhere from the foramen caecum to the lower neck. Most frequently it presents as a thyroglossal duct cyst associated with a normal thyroid gland. Less common is total ectopia, which can occur as a lingual thyroid or occasionally in non-lingual locations. Malignant transformation of such ectopic tissue is extremely uncommon. Only 21 cases of lingual thyroid carcinomas have been reported until 1971. We present, to our knowledge, the first case of a papillary carcinoma in a non-lingual ectopic thyroid in the absence of an orthotopic thyroid.     

Isolation and characterization of mononuclear cells from various thyroid tissue specimens

Extensive studies of humoral and cell mediated autoimmune responses to thyroid antigens have been performed in order to understand the underlying mechanisms of autoimmune thyroid disorders. Very little is known, however, about the nature of the lymphocyte subpopulations in the thyroid gland and their possible involvement in the pathogenesis of thyroid diseases. We have developed a Percoll gradient technique to separate mononuclear cells from thyroid cells of resected thyroid glands. Thyroid tissue was minced, incubated with Dispase and passed through a tissue sieve. The filtrate was layered onto a four step discontinuous Percoll gradient (densities 1.140, 1.077, 1.061, 1.030 g/ml). Thyroid cells appeared in band II and mononuclear cells in band III. Mononuclear cells were characterized using the monoclonal antibodies OKT-3, OKT-8, OKI-a and OKM-1, and the levels of these populations in peripheral blood and thyroid tissue compared. Patients have been classified by conventional clinical, immunological and histological criteria. The studies involved thyroid tissues from 8 patients with euthyroid nodular goitre, 7 patients with Graves' disease and 1 with Hashimoto's thyroiditis. In the thyroid tissue of non-autoimmune thyroid diseases we find significantly less OKT-3+ cells compared to peripheral blood. In thyroid tissue of autoimmune thyroid diseases there are significantly less OKT-8+ cells compared to peripheral blood. These preliminary results might be linked to the hypothesis of decreased suppressor T-cell activity in autoimmune thyroid disease.     

Graves' disease presented as painful goiter

Pain in the thyroid gland is rarely present in Graves' disease. We describe a 32-year-old female hyperthyroid Graves' disease patient with an initial manifestation of painful goiter. On physical examination, the thyroid gland was diffusely enlarged and tender. The laboratory examinations showed high serum thyroid hormone and low thyrotropin values. Serum inflammatory markers, including C-reactive protein and erythrocyte sedimentation rate, were elevated. Thyroid ultrasound revealed multiple focal hypoechoic areas. All these findings gave an initial impression of an acute inflammatory and destructive process in the thyroid gland. However, subsequent thyroid scintigraphy demonstrated a diffuse radioactive iodide uptake pattern with positive serum thyrotropin receptor antibodies. Fine-needle aspiration cytology showed only the presence of lymphocytes. She was diagnosed as having Graves' disease and was treated with propylthiouracil, and prednisolone was given for neck pain. Within a few days, the thyroid tenderness dramatically improved, and the erythrocyte sedimentation rate progressively normalized. However, follow-up thyroid function tests still showed high serum thyroid hormone levels. The possible etiologies of a painful thyroid gland in Graves' disease will be discussed.     

Measurement of thyroid hormone in the rat thyroid gland by radioimmunoassay

The present paper describes (i) a hydrolysis technique with Pronase and leucine aminopeptidase using one rat thyroid gland, resulting in maximum release of thyroid hormones and minimum deiodination, and (ii) a simple and rapid procedure for thyroid hormone radioimmunoassays in thyroid hydrolysates using commercial kits intended for serum thyroid hormone determinations. The procedure is used to determine T4, T3, and rT3 concentrations and hormonal molar ratios in a thyroid gland from a male Wistar rat. The reliability of the method is also studied.     

PHYSIOLOGY OF THE THYROID GLAND IN BIRDS: A REVIEW.

A brief introductory account of the structure of the thyroid gland and the general effects of its hormone are given.
There is sufficient experimental evidence to warrant the conclusion that in birds, as in other vertebrates, the level of thyroid function is regulated by a hormone of the anterior lobe of the pituitary gland, the thyrotrophic hormone.
Increased thyroid activity during the cooler period of the year is found in a number of species, and this is probably widespread.
For all species so far tested, feathers grown during thyroid deficiency show abnormally loose texture and become elongated and narrow. Reverse changes can be produced by thyroid administration to normal birds.
The relationship between the thyroid and migratory behaviour, though probable, needs further investigation.
Feather pigmentation is in some species unaffected by the thyroid, but is increased in others.
There is undoubtedly a relationship between the moult and increased thyroid activity since a phase of high thyroid function preceding the moult is of widespread occurrence. In some gallinaceous birds the moult can be precipitated by thyroid administration, but not in ducks. In some species complete suppression of the moult has been claimed if thyroidectomy is performed sufficiently far ahead of the next moult due. Complete dependence of moulting on a raised output of thyroid hormone has, however, not yet been proved for any species.
So far there is experimental evidence, which requires comfirmation, from one species only that return of the gonad to the resting condition following the breeding-season recrudescence is to a considerable extent dependent on the thyroid.
In Domestic Fowls thyroid hormone affects the spur.     

妊娠期甲状腺疾病诊断及治疗的研究进展

妊娠期妇女体内激素水平会发生变化,使妊娠妇女甲状腺激素水平的测定和判断存在一定的困难,应选择适用于妊娠妇女的甲状腺激素水平特异值,进而正确评估甲状腺功能状态及对母体和胎儿的影响。孕前及妊娠期测定促甲状腺素和游离甲状腺激素有很大的必要性,因为甲状腺疾病以及单纯性甲状腺抗体阳性会导致多种妊娠不良结局,尤其是甲状腺功能减退对胎儿智力发育和认知功能具有非常大的影响。孕期甲状腺激素的监测对评估甲状腺功能状态及疾病预后具有非常大的作用,可以提示临床医师是否给予药物干预及如何调整药量。对于孕期甲状腺激素补充治疗后应达到的目标值以及甲状腺抗体阴性的亚临床甲状腺功能降低的妊娠患者是否给予干预,目前仍有异议。     

Pax2.1 is required for the development of thyroid follicles in zebrafish

The thyroid gland is an organ primarily composed of endoderm-derived follicular cells. Although disturbed embryonic development of the thyroid gland leads to congenital hypothyroidism in humans and mammals, the underlying principles of thyroid organogenesis are largely unknown. In this study, we introduce zebrafish as a model to investigate the molecular and genetic mechanisms that control thyroid development. Marker gene expression suggests that the molecular pathways of early thyroid development are essentially conserved between fish and mammals. However during larval stages, we find both conserved and divergent features of development compared with mammals. A major difference is that in fish, we find evidence for hormone production not only in thyroid follicular cells, but also in an anterior non-follicular group of cells. We show that pax2.1 and pax8, members of the zebrafish pax2/5/8 paralogue group, are expressed in the thyroid primordium. Whereas in mice, only Pax8 has a function during thyroid development, analysis of the zebrafish pax2.1 mutant no isthmus (noi(-/-)) demonstrates that pax2.1 has a role comparable with mouse Pax8 in differentiation of the thyroid follicular cells. Early steps of thyroid development are normal in noi(-/-), but later expression of molecular markers is lost and the formation of follicles fails. Interestingly, the anterior non-follicular site of thyroid hormone production is not affected in noi(-/-). Thus, in zebrafish, some remaining thyroid hormone synthesis takes place independent of the pathway leading to thyroid follicle formation. We suggest that the noi(-/-) mutant serves as a new zebrafish model for hypothyroidism.     

Pituitary resistance to thyroid hormones.

Pituitary thyroid hormone resistance (PRTH) refers to a particular form of thyroid hormone refractoriness that is accompanied by peripheral hyperthyroidism, as only the TSH-secreting pituitary cells appear to be resistant to the effects of thyroid hormones. The presence of PRTH is suspected and diagnosed on the basis of the finding of high free thyroid hormone levels along with unsuppressed TSH, clinical signs and symptoms of hyperthyroidism and values of at least one of the parameters evaluating peripheral thyroid hormone action in the hyperthyroid range. However, most patients with PRTH present with clinical signs and symptoms of thyroid dysfunction, particularly goiter and tachycardia, overlapping those recorded in patients with generalized thyroid hormone resistance (GRTH), i.e. refractoriness to thyroid hormones at both pituitary and peripheral tissue level. Moreover, most of them display normal values of other parameters evaluating the peripheral effects of thyroid hormones and bear mutations in the gene encoding for T3 nuclear receptors similar to those found in patients with GRTH. These findings are questioning the existence of PRTH as a separate clinical entity and support the view that the various forms of thyroid hormone resistance may be part of a spectrum of disease with variable expression in different issues.     

Thyroid cancer in patients with hyperthyroidism

Thyroid cancer can be associated with thyrotoxicosis caused by Graves' disease, toxic multinodular goiter, or autonomously functioning thyroid adenoma. The objective of this study was to summarize current evidence regarding the association of thyroid cancer and hyperthyroidism, particularly with respect to the type of hyperthyroidism found in some patients, and whether this affects the outcome of the patient. A PubMed search was performed up to August 2011. Articles were identified using combinations of the following keywords/phrases: thyroid cancer, papillary thyroid cancer, follicular thyroid cancer, medullary thyroid cancer, anaplastic thyroid cancer, hyperthyroidism, Graves' disease, auto-nomous adenoma, toxic thyroid nodule, and toxic multinodular goiter. Original research papers, case reports, and review articles were included. We concluded that the incidence, as well as the prognosis of thyroid cancer associated with hyperthyroidism is a matter of debate. It seems that Graves' disease is associated with larger, multifocal, and potentially more aggressive thyroid cancer than single hot nodules or multinodular toxic goiter. Patients with Graves' and thyroid nodules are at higher risk to develop thyroid cancer compared to patients with diffuse goiter. Every suspicious nodule associated with hyperthyroidism should be evaluated carefully.