Hashimoto's thyroiditis associated with Riedel's thyroiditis and retroperitoneal fibrosis

This article describe the case of a 38-year-old woman with simultaneous involvement of the thyroid by Hashimoto's thyroiditis and Riedels's disease, associated with retroperitoneal fibrosis and lipidic endarteritis. According to a large review of the literature on the occurrence of this rare condition the difficulty in sharply defining the two thyroid processes is discussed. The chronology of the events is analyzed, and etiopathogenic hypotheses are listed with emphasis on the relationship between the vascular lesions and the onset of the fibrosing process.     

Intrathyroidal lymphoepithelial cyst. A report of two cases not associated with Hashimoto's thyroiditis

Two cases of intrathyroidal lymphoepithelial cyst are described. Both of them were solitary, one being found incidentally in a patient operated on for a multinodular goiter, the other being clinically obvious as a cold nodule. They exhibited features of cysts of branchial cleft origin, i.e. squamous cell lining epithelium and abundant lymphoid tissue with reactive germinal centers. The thyroid gland parenchyma showed a discrete lymphoid infiltration consistent with the diagnosis of focal lymphocytic thyroiditis. In the first case a single epidermoid solid cell nest was found. The histogenesis of intrathyroidal lymphoepithelial cysts remains unclear, but their origin from cystically degenerated ultimobranchial body remnants (solid cell nests) seems to be most probable. This assumption is supported by a similar immunohistochemical profile of solid cell nests and epithelial cells lining the cysts and also by the presence of one solid cell nest in the proximity to the cyst in one of our cases.     

Hashimoto's thyroiditis and insulin-dependent diabetes mellitus: differences among individuals with and without abnormal thyroid function

Insulin-dependent diabetes mellitus probands from the Familial Autoimmune and Diabetes Study were evaluated for autoimmune thyroid disease (n = 265). The prevalence of Hashimoto's thyroiditis was 26.6%; 42.0% of these individuals were euthyroid, and 58.0% were hypothyroid. There was a female predominance among hypothyroid and euthyroid Hashimoto's cases compared to those with no thyroid disease (75% vs. 72.4% vs. 41.6%; P < 0.001). Insulin-dependent diabetes mellitus patients with hypothyroid Hashimoto's thyroiditis were more likely to report another autoimmune disease compared to euthyroid Hashimoto's patients or individuals with no thyroid disease (30.8% vs. 17.2% vs. 13.9%; P < 0.01). Sex-specific analysis revealed that this difference was significant for men but not for women. Both euthyroid and hypothyroid Hashimoto's cases were more likely to have a family history of the disease (66.7% vs. 69.2% vs. 47.7%; P < 0.05). No differences were observed in the prevalence of DQA1*0501-DQB1*0201 or DQA1*0301-DQB1*0302 across the three groups. Body mass index, lipid levels, glycemic control, and diabetes complications were also similar. However, euthyroid Hashimoto's women were more likely to report spontaneous abortions than those with hypothyroid Hashimoto's thyroiditis or no thyroid disease (23.8% vs. 61.5% vs. 29.1%; P < 0.05). These data suggest that gender-specific risk factors may be primary determinants of Hashimoto's thyroiditis and other autoimmune diseases among women. However, disease-specific determinants may also increase susceptibility to other autoimmune diseases.     

Coexistent thyroiditis is associated with lower tumour stage in thyroid carcinoma

BACKGROUND: Microsatellite instability (MSI) is a new mechanism described in carcinogenesis of several tumours and seems to predispose for cancer in some chronic inflammatory diseases. As thyroiditis is thought to be both the cause and the consequence of thyroid carcinoma, it was the aim of this retrospective study to investigate the epidemiology and the influence of a coexistent thyroiditis on prognosis and clinicopathological parameters in an iodine-deficient area. METHODS: The grade of lymphocytic infiltration (LI) of 153 thyroid carcinomas was determined in paraffin-embedded tissues: G0 = no LI, G1 = peritumoral LI, G2 = peritumoral LI with follicle, G3 = diffuse LI. A non-radioactive PCR-based screening method was used for detection of MSI. RESULTS: Twenty-seven (17.7%) out of 153 carcinomas were accompanied by thyroiditis (G1, 16; G2, 5; G3, 6). Ten cases fulfilled the criteria necessary for diagnosing Hashimoto's thyroiditis. Nine out of 10 (90%) Hashimoto's cases and 16 out of 17 (94%) other thyroiditis cases were associated with a significantly (chi2 < 0.01) lower pT stage (pT1, pT2) than cases without thyroiditis. No statistical association was found by comparing multifocality or sclerosing variants with the grade of lymphocytic infiltration. MSI was detected neither in patients with severe inflammation nor in the absence of thyroiditis. CONCLUSIONS: MSI does not seem to play a role in the pathogenesis of thyroid carcinoma. Coexistent thyroiditis is associated with a lower pT stage and thus could be an indicator of a better prognosis.     

Fatal heatstroke in a young woman with previously undiagnosed Hashimoto's thyroiditis

Heatstroke represents the most severe form of the heat-related illnesses. Potentially fatal, heatstroke most often affects the elderly, obese, or chronically ill. Thyroid disease, which may interfere with the normal regulation of body temperature, has not previously been reported in cases of heatstroke. A fatal case is reported in a young woman discovered unconscious in a sauna who was found to have preexisting Hashimoto's thyroiditis on subsequent autopsy. The diagnosis of hypothyroidism in heatstroke rests on clinical information and morphologic observations. This case underscores the importance of evaluating the thyroid in unusual cases of heatstroke.     

Fas/Fas ligand-driven T cell apoptosis as a consequence of ineffective thyroid immunoprivilege in Hashimoto's thyroiditis

Hashimoto's thyroiditis (HT) is a chronic autoimmune disease resulting from Fas-mediated thyrocyte destruction. Although autocrine/paracrine Fas-Fas ligand (FasL) interaction is responsible for thyrocyte cell death during the active phases of HT, the role of infiltrating T lymphocytes (ITL) in this process is still unknown. Therefore, we investigated the expression and function of Fas and FasL in ITL. All ITL expressed high levels of Fas and CD69, an early marker of T cell activation associated with functional Fas expression in T cells in vivo. In contrast to thyrocytes that were found to produce high levels of FasL, ITL did not express significant amounts of FasL, suggesting that ITL are not directly involved in thyrocyte destruction. The analysis of ITL purified from HT thyroids showed that ITL were massively killed by Fas crosslinking and that a considerable number (24-36%) underwent spontaneous apoptosis within 36 h of culture. Accordingly, in situ TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) staining revealed that a significant number (10-15%) of ITL in proximity to FasL-producing thyroid follicles were apoptotic. Moreover, virtually all ITL in proximity to thyroid follicles were preapoptotic, as they expressed high levels of GD3 ganglioside, a killer glycolipid responsible for the generation of irreversible apoptotic signals that accumulate in hematopoietic cells shortly after Fas crosslinking. These data demonstrate that ITL are not directly involved in thyrocyte cell death during HT, suggesting that autocrine/paracrine Fas-FasL interaction is a major mechanism in autoimmune thyrocyte destruction.     

Agenesis of the pulmonary valve associated with interventricular defect

The association between ventricular septal defect and pulmonary valve atresia is a rare congenital disease, which can provoke the compression of bronchioles, that make a high mortality rate possible in the first years of life. If this syndrome is tolerated, using a convenient medical therapy, it is possible to wait for a more suitable age for a complete correction, which must provide, besides V.S.D. closing, pulmonary valvular substitution by porcine aortic heterograft. The authors also report on their own experience of five cases surgically treated and studied from a pre- and postoperative hemodinamic point of view.     

Autoimmune thyroiditis complicated with reversible changes of thyroid function

The purpose of this study was to determine whether warm ischemia (WIT) and cold storage preservation (CSP) impair endothelium-dependent vascular relaxation in the kidney. Twenty-four canine kidneys were harvested, preserved with CSP for 24 or 48 hours, and then perfused with canine blood at 37 C for the determination of glomerular filtration rate (GFR), perfusion flow rate, and renal vascular resistance (RVR). There were four experimental groups: Group I--no WIT followed by 24 hours CSP, Group II--30 minutes WIT followed by 24 hours CSP, Group III--no WIT followed by 48 hours CSP, Group IV--30 minutes WIT followed by 48 hours CSP. Endothelial function in each group was evaluated using acetylcholine (ACh, 1 mg. bolus) as an endothelial dependent vasodilator, and sodium nitroprusside (NP, 10 mg. bolus) as an endothelial independent vasodilator. Glomerular filtration rate was significantly less (P < .05) and RVR was significantly greater (P < .05) for kidneys from Groups II, III and IV compared to group I. The highest RVR was observed in kidneys from Groups II and IV. Nitroprusside administration caused an equivalent reduction in RVR among all four study groups. ACh administration caused a similar reduction in RVR in Groups I and III; however, the change in RVR was significantly less in Groups II and IV (P < .05). We hypothesize that the more severe ischemic insult in the latter groups led to vascular endothelial damage with a consequent loss of ability to secrete endothelium-derived relaxing factor in response to ACh administration.     

Increased serum concentration of soluble CD30 in patients with Graves' disease and Hashimoto's thyroiditis

This study investigated serum levels of the soluble form of CD30 (sCD30), which is mainly secreted from T helper 2(Th2) cells, in autoimmune thyroid diseases. The possible relationship of sCD30 to autoantibody production was also evaluated. Serum levels of sCD30 were determined by an enzyme-linked immunosorbent assay in 71 patients with Graves' disease, 37 patients with Hashimoto's thyroiditis, and 21 normal donors. Compared with normal subjects (7.1 +/- 4.5 U/mL), sCD30 was increased in patients with Graves' disease (29.2 +/- 25.2 U/mL, P < 0.0001) and in patients with Hashimoto's thyroiditis (29.9 +/- 26.9 U/mL, P < 0.0001). In Graves' disease, sCD30 levels were higher in thyrotoxic patients (41.7 +/- 31.2 U/mL, P < 0.001) than in remission patients (15.8 +/- 11.0 U/mL), and a significant correlation was observed between sCD30 levels and serum activities of TSH receptor antibody (r = 0.444, P < 0.0001). In Hashimoto's thyroiditis, sCD30 levels were higher in patients with transient destructive thyrotoxicosis caused by the aggravation of the disease (48.8 +/- 34.4 U/mL, P < 0.05) than in euthyroid patients (24.2 +/- 19.4 U/mL). These data suggest that serum sCD30 is a valuable marker of disease activity and support an important role of the Th2-type immune response in the pathogenesis in Graves' disease and Hashimoto's thyroiditis.     

Cardiovascular effects of long-term L-thyroxine therapy for Hashimoto's thyroiditis in children and adolescents

Morphology and function of the left ventricle were evaluated by echo and Doppler examination in 16 females affected by Hashimoto's thyroiditis, aged 13.3 (4.5) years (range 7.9-24.6). They were on L-thyroxine (L-T4) treatment for a period of 2.8 (2.8) years (range 0.8-7.6) with a mean daily dose of 77 (18) micrograms/m2. Left ventricular mass, systolic and diastolic function, cardiac output and systemic vascular resistance did not differ from a control group matched for age, sex and body size. A further analysis of the patients according to thyrotrophin serum levels (less or more than 0.1 mU/l) gave similar results. Moreover, no relationship was found between echocardiographic findings and age, L-T4 daily doses, duration of treatment and serum level of thyroid hormones. We can therefore conclude that chronic L-T4 treatment for Hashimoto's thyroiditis at the given doses did not affect cardiac function and morphology in children and adolescents; however, a longer follow-up is needed before confirming the safety of this therapy in the long term.     

Agenesis of the internal carotid artery associated with an aneurysm of the anterior communicating artery

We report a case of agenesis of the internal carotid artery which was revealed by a subarachnoid hemorrhage. Angiography showed a ruptured aneurysm of the anterior communicating artery and unilateral absence of the left internal carotid artery. Both the left anterior and middle cerebral arteries were perfused from the right carotid artery via the anterior communicating artery. Absence of the left carotid canal was proved on bone CT. Such an association is discussed. An hemodynamic stress on a congenital defect of the cerebral arterial wall could be the origin of the aneurysm development.     

Generalized amyloidosis associated with Hashimoto''s thyroiditis and hypothyroidism]

In uninephrectomized rats on 1% NaCl solution to drink, aldosterone (0.75 micrograms/h subcutaneously for 8 weeks) raises blood pressure and causes marked interstitial and perivascular cardiac fibrosis, effects not seen in animals on a low salt intake. In extending these initial findings, we have shown that cardiac fibrosis (i) is not reversed by correction of mineralocorticoid-induced hypokalemia; (ii) appears not to involve the plasma or tissue renin-angiotensin systems, as fibrosis is largely unaffected by concurrent administration of Losartan or Perindopril; (iii) is independent of cardiac hypertrophy, in that it is equally seen in right and left ventricles, and in rats rendered hypertensive without cardiac hypertrophy by the administration of 9 alpha-fluorocortisol; (iv) is independent of elevated blood pressure, in that it is found in normotensive animals infused peripherally with aldosterone and intracerebroventricularly with the mineralocorticoid receptor (MR) antagonist RU28318; (v) is via classical MR, in that it is blocked by concurrent administration of the MR antagonist potassium canrenoate; and (vi) may or may not be a direct cardiac effect, inasmuch as data for in vivo effects on collagen formation by cardiac fibroblasts are conflicting. Although there is a high probability that the action of aldosterone to cause cardiac fibrosis in this experimental model is an effect via non-epithelial MR, the locus of aldosterone action remains to be established, as do the molecular mechanisms linking MR occupancy by aldosterone and collagen deposition. In addition, and in particular, the mechanisms underlying the crucial contribution of high salt intake in this model of mineralocorticoid excess await exploration.     

Case report: Hashimoto''s thyroiditis associated with Wegener''s granulomatosis

Wegener's granulomatosis is a well-defined systemic vasculitic syndrome that primarily affects the upper and lower respiratory tracts and the kidney. Hashimoto's thyroiditis is another autoimmune syndrome with the thyroid as its primary target organ. The relation between Hashimoto's thyroiditis and Wegener's granulomatosis is not reported in the English literature. In this article, the authors describe a patient with Hashimoto's thyroiditis in whom fulminant Wegener's granulomatosis subsequently developed. The immunologic similarities between these two diseases leads to the consideration that Wegener's granulomatosis possibly may be another immunologic disorder associated with Hashimoto's thyroiditis.     

TSH receptor antibody-associated thyroid dysfunction following subacute thyroiditis

The variation in the range of services provided by general practitioners (GPs) is not only related to personal characteristics and features of the country's health care system but also to the geographical circumstances of the practice location. In conurbations health services are more widely available than in the countryside, where GPs often are the only providers. With highly mobile populations and a plentiful supply of doctors, in cities the prevailing regulations for access and use of services are more difficult to maintain. It is also more difficult to control access and thus opportunities for inappropriate use are greater. Against this background an international study was conducted on variation in task profiles of GPs, especially focusing on differences between urban and rural practices. In 1993 standardised questionnaires in the national languages were sent to samples of GPs in 30 countries. Various aspects of service provision were measured as well as practice organisation, location of the practice and personal backgrounds of the GP. Completed questionnaires were received from 7,233 respondents, an overall response rate of 47%. Sources of variation have been analysed by using a two-level model. Rural practices provided more comprehensive services regardless of the health care system. Approximately half of the variation was explained by features of a country's health care system. The GP's position at the point of access to health care was strongly associated with the gatekeeper function controlling access to secondary care. In western countries where the GPs were self employed they had greater involvement in technical procedures and chronic disease management. There was a considerable gap between the task profiles of GPs in eastern and western Europe. We found evidence of a reduced gatekeeper role in inner cities in those countries where GPs held this position. GPs with an estimated overrepresentation of socially deprived people and elderly in the practice population reported a wider range of services. Differences also appeared to be related to factors which are largely controlled by the individual doctor, such as level of training and education, availability of equipment and practice staff. The results have important implications for education, policy development and health care planning both in eastern and western Europe.     

Fas/Fas ligand up-regulation and Bcl-2 down-regulation may be significant in the pathogenesis of Hashimoto's thyroiditis

Hashimoto's thyroiditis (HT) is an autoimmune disorder characterized by diffuse thyroid lymphocytic infiltration and follicle destruction. Cross-linking of the Fas receptor with its own ligand (FasL) triggers apoptosis in various systems, whereas the Bcl-2 protooncogene inhibits apoptotic cell death. The involvement of Fas, FasL, and Bcl-2 in the apoptotic process in HT was evaluated in 15 thyroid tissue samples from patients with HT stained for apoptosis and for Fas, FasL, and Bcl-2 protein expression. Eight samples from healthy thyroid tissue were used for comparison. Thyroid follicles in HT samples exhibited strong staining for Fas and FasL and a high percentage of apoptosis (30.3 +/- 14.5%, mean +/- SD), in contrast to normal control follicles that exhibited moderate Fas, minimal or no FasL, and hardly any apoptosis. Immunostaining for Bcl-2 was high in normal, and weak in involved, thyroid follicles. Infiltrating lymphocytes stained weakly for FasL and strongly for Bcl-2. We conclude that follicular cells in HT undergo apoptosis by concomitant up-regulation of FasL and Fas and down-regulation of Bcl-2 protein. The lymphocytes do not seem to be directly engaged in the process with their own FasL, but they may provide the appropriate cytokine milieu that, in turn, up-regulates Fas and/or FasL leading to apoptosis.     

Increased serum vascular endothelial growth factor levels and intrathyroidal vascular area in patients with Graves' disease and Hashimoto's thyroiditis

Vascular endothelial growth factor (VEGF) is one of the angiogenic factors. We examined both thyroid volume and intrathyroidal vascular area by color flow Doppler ultrasonography in patients with Graves' disease (GD), Hashimoto's thyroiditis (HT), and subacute thyroiditis. The serum concentrations of thyroid hormones, TSH, TSH receptor antibodies, and VEGF were also examined. There was a significant increase in serum VEGF levels in patients with untreated GD and goitrous HT compared with those in healthy subjects. The serum VEGF levels in untreated patients with subacute thyroiditis were significantly higher than those in patients with untreated GD or HT. There was a significant correlation between serum VEGF levels and the ratio of intrathyroidal vascular area and thyroid area in untreated patients with GD who had a goiter larger than or equal to 40 cm3. There was also a significant correlation between serum VEGF and TSH levels in patients with HT who were hypothyroid and had a goiter. Serum VEGF levels decreased significantly in these patients after treatment; this was accompanied by a significant decrease in intrathyroidal vascular area and thyroid volume. Our study demonstrates that VEGF appears to play an important role in intrathyroidal angiogenesis in patients with GD and goitrous HT.