The thyroid reserve in children with chronic lymphocytic thyroiditis revealed by the thyrotropin-releasing hormone and thyroid-stimulating hormone tests

Serum thyroid hormone and TSH concentrations were measured before and after the administration of TRH (10 micrograms/kg body weight) and bovine TSH (10 IU) in 14 children with chronic lymphocytic thyroiditis. The TRH test showed that the responsiveness of TSH was positively correlated with the basal TSH (P less than 0.001) and inversely with the increase in serum thyroid hormones, for delta T3 (P less than 0.05) and for delta T4 (P less than 0.001). Overall, the patients had significantly lower mean values for basal T4, but not for T3. The TSH test revealed that the delta T3 was positively correlated with delta T4 (P less than 0.05). delta T3 after TSH administration was positively correlated with it after TRH (P less than 0.05). The patients were divided into three groups on the basis of their peak TSH values after TRH administration. In Group 1 (peak value below 40 microU/ml; N = 5); T3 increased significantly after TRH and TSH administrations (P less than 0.05 and P less than 0.025, respectively). In addition, delta T4 was significant after TSH administration. In Group 2 (peak TSH above 40 and less than 100 microU/ml; N = 6); only delta T3 after TRH was significant (P less than 0.05). In Group 3 (peak TSH above 100 microU/ml; N = 3); the response of thyroid hormones was blunted. Thus, the thyroid hormone responses to endogenous TSH coincided with that to exogenous TSH, and the exaggerated TSH response to TRH indicates decreased thyroid reserve.     

The prediction of thyroid function in infants born to mothers with chronic thyroiditis

To elucidate the relationship between the mother's TSH-receptor antibody activities and the status of thyroid dysfunction in their offspring, blood was taken from 5 mothers with chronic thyroiditis with potent thyrotropin (TSH)-receptor blocking activity, and the potency of TBII and TSBAb activity was assayed more quantitatively. In those mothers whose infants suffered from neonatal hypothyroidism, the 50% inhibition of binding of labeled TSH to its receptors was obtained at more than 30 to 50-fold dilution, while in those mothers whose infants had transiently increased TSH or were euthyroid, the titers were of less than 30-fold dilution. Similarly, in those mother whose infants suffered from neonatal hypothyroidism, the 50% inhibition of TSH-induced cAMP accumulation was obtained at approximately 400 to 3000-fold dilution, while in those mothers whose infants had transiently increased TSH or were euthyroid, the titers were of less than 50-fold dilution. On the other hand TBII activity was much less potent in serum from patients with Graves' disease. These results suggested that the titration of serum with dilution to obtain 50% inhibition of labelled TSH binding to its receptor may be the simplest way to predict thyroid dysfunction of the newborn infants born to mothers with chronic thyroiditis.     

Comparative findings of lymphocytic thyroiditis and thyroid lymphoma

OBJECTIVE: To compare the cytologic features of histologically proven lymphocytic (Hashimoto's) thyroiditis (Hashimoto's thyroitidis) and primary thyroid lymphomas (TL). STUDY DESIGN: Clinical histories, smears (stained with Diff-Quik, Papanicolaou stain or hematoxylin and eosin [HE]) and surgical specimens (HE slides) were reviewed in 25 cases of lymphocytic thyroiditis and 12 of thyroid lymphomas. RESULTS: Surgical specimens of thyroiditis were obtained for other medical reasons: goiter and compressive symptomatology in 21 cases and neoplasms in 4 (2 papillary carcinomas, 1 follicular carcinoma and 1 oncocytic adenoma). Seven cases were primary lymphomas, and 5 were secondary. Histologically there were 6 large B-cell lymphomas, 2 mantle cell lymphomas, 1 Burkitt lymphoma, 2 mucosal-associated lymphoid tissue lymphomas in blastic transformation and 1 of unknown type. Sensitivity for the diagnosis was 67.5% for HT and 92.3% for lymphoma. CONCLUSION: A heterogeneous population of small and large lymphocytes was the most frequent pattern in both diseases. The presence of a monotonous population of large lymphocytes or, more rarely, of small cells indicates a probable TL. Plasma cells favor HT. Other techniques are mandatory for the differentiation of cases with inconclusive diagnoses.     

Psammoma bodies in fine needle aspirate of the thyroid in lymphocytic thyroiditis

Psammoma bodies are concentric, laminated microcalcifications that are regarded as nearly specific markers in the thyroid gland for the presence of papillary carcinoma. While psammoma bodies have been seen rarely in some benign thyroid diseases, there appear to be no reports of psammoma body formation in lymphocytic or Hashimoto's thyroiditis. We report a case of Hashimoto's thyroiditis in which psammoma bodies were identified in a fine needle aspiration specimen of the thyroid and in histologic sections of the right thyroid lobectomy; papillary carcinoma was not found in either specimen. We conclude that psammoma bodies may be seen in any benign process, such as nodular goiter or lymphocytic thyroiditis, that produces reactive papillary hyperplasia of thyroid epithelium, as well as in papillary carcinoma. However, the finding of psammoma bodies in a fine needle aspirate without corroborating cytologic evidence of papillary cancer is still an indication for surgical removal of the thyroid nodule since these structures are reliable markers for occult papillary carcinoma of the thyroid, despite the rarity of their formation in benign diseases.     

High incidence of chronic lymphocytic thyroiditis in apparently healthy school children: epidemiological and clinical study.

An epidemiological survey on the incidence of juvenile chronic lymphocytic thyroiditis was performed in 10,220 apparently healthy school children in Ishikawa district, Japan. The subject of present study included 6,244 school children (2,831 boys and 3,413 girls, ages 6-18 yrs.) in Kanazawa City and 3,976 children (2,055 boys and 1,921 girls, ages 6-18 yrs.) in Wajima City. The first group was selected as a representative of urban area and the second group as that of seaside area. Children who have goiter or firm thyroid were selected for testing antithyroglobulin and anti-microsomal antibodies in sera. Final diagnosis of chronic lymphocytic thyroiditis was made on histological specimen obtained by needle biopsy on the antibody positive subjects. The overall incidence of chronic lymphocytic thyroiditis in these children was 3.0 per 1,000, whereas the incidence in adolescent girls was as high as 8.2 per 1,000. There was a considerable sex difference in the prevalence, the ratio of female to male was 6.5:1, and the incidence increased with age. The incidence in seaside area was 5.3 per 1,000 that was significantly higher than in urban area, 1.4 per 1,000 (p less than 0.005). Histologically, 26 of 30 cases (87%) were classified as focal thyroiditis and 4 cases (13%) were diffuse thyroiditis. Serum T4-I and T3 values within normal range in all patients, but resting TSH was elevated in 1 of 23 cases and TSH response to TRH was exaggerated in 3 of 23 cases. Impaired organification of iodide was observed in 6 of 32 cases by iodide-perchlorate discharge test. The present study demonstrates that juvenile chronic lymphocytic thyroiditis is highly prevalent among apparently healthy school children and early recognition of the disease with preventive care for hypothyroidism in future should be stressed.     

Hyalinizing trabecular tumor in a background of lymphocytic thyroiditis: a challenging neoplasm of the thyroid

ObjectiveTo describe a case of hyalinizing trabecular tumor (HTT) in a background of lymphocytic thyroiditis that was misdiagnosed as papillary thyroid carcinoma (PTC) based on fine-needle aspiration (FNA) cytologic findings and overtreated with total thyroidectomy.MethodsWe present a case report, including the imaging and pathologic findings, of a 68-year-old woman who presented with a multinodular goiter that was suspicious for PTC.ResultsOn the basis of FNA cytologic findings, she underwent a total thyroidectomy, and histologic examination of the thyroid gland revealed HTT in a background of lymphocytic thyroiditis. Radioiodine treatment was not administered because of the tumor’s low risk profile. No metastatic foci were established under nonsuppressive levothyroxine therapy after 3 years of follow-up.ConclusionsHTT is a challenging entity because of the uncertainty of its nature, the diagnostic challenges,and the mimicry of other types of thyroid tumors. In order to avoid overtreatment, endocrinologists and thyroid surgeons should be aware of the features of HTT, and suspicious cases should be evaluated by experienced cytopathologists. (Endocr Pract. 2011;17:e140-e143)     

Tall cell variant of papillary carcinoma coexisting with chronic lymphocytic thyroiditis. A case report.

BACKGROUND: Recent studies have shown a correlation between lymphocytic thyroiditis and papillary carcinoma of the thyroid. It is thought that autoimmune thyroiditis could be a risk factor for the development of thyroid carcinoma, mainly for the papillary variant. CASE: A 59-year-old female presented with a history of enlargement in the neck and five months of dysphagia. Clinical examination showed generalized expansion and an increase in the hardness of the thyroid gland. Hormonal outline showed subclinical hypothyroidism with serum levels of TSH slightly elevated (5 micrograms/dL; range, 0.25-4). Thyroglobulin antibodies and thyroperoxidase titers were moderately positive. Given these results, a diagnosis of chronic thyroiditis was made. Thyroid ultrasound scan showed diffuse gland irregularity and the presence of a solitary nodule (2.3 cm in diameter) localized in the right lobe. Fine needle aspiration biopsy (FNAB) of the nodule was performed under ultrasound guidance. CONCLUSION: Although clinical and laboratory results supported the diagnosis of autoimmune thyroiditis only, FNAB of the nodular lesion provided evidence of a rare case of papillary carcinoma, tall cell variant, confirmed by histologic results.     

Anomalies in thyroid function in children with trisomy 21

Thyroid function of 60 children with Down (DS) aged 3 months to 16 years was studied by evaluation of serum concentration of ultra-sensitive thyroid stimulating hormone (TSH), free T4 and T3 (FT4, FT3), total T4 and T3 (T4 and T3) and reverse T3 (rT3). Each DS child was matched to a control of the same age. The concentration of TSH was increased in DS children while the concentration of rT3 of the DS children was significantly decreased compared to the controls as was the ratio rT3/TSH. These results showed that thyroid function of DS children is abnormal.     

Effects of chronic hemodialysis on thyroid function in chronic renal failure

Thyroid function was studied in 54 patients undergoing chronic hemodialysis. Serum thyroxine, triiodothyronine and free thyroxine and the free thyroxine index were significantly lower than normal. The levels of both serum thyroxine and the free thyroxine index tended to fall progressively the longer the patients were on hemodialysis. These findings, in association with low serum TSH levels and normal increase in radioactive iodine uptake by the thyroid after TSH injection, suggest that a defect in pituitary secretion of TSH may be responsible. Although some patients experienced symptomatic improvement after treatment with L-thyroxine the efficacy of this form of treatment in patients on chronic hemodialysis has not yet been established.     

Surfactant function in children with chronic airway inflammation.

Pulmonary surfactant is necessary to keep the terminal conducting airways patent. It is unknown whether mild to moderate airway inflammation may influence surfactant function and thus contribute to the pathogenesis of chronic airway inflammation in children. To answer this question, 21 children with chronic obstructive bronchitis and 19 asymptomatic children with long-term tracheostomy and increased numbers of neutrophils in their airways were compared with 15 healthy controls. Bronchoalveolar lavage fluid was separated into large surfactant aggregates (LA) and a supernatant containing inhibitory constituents. Surfactant function of LA, recombinations of LA and supernatant, and recombinations of a defined bovine surfactant and supernatant was assessed in a capillary surfactometer. Compared with controls, the function of the LA surfactant was reduced and there was no difference between children with tracheostomy and chronic obstructive bronchitis. The function of LA-supernatant recombinations was poor in all subjects. This may be explained by the well-known protein influx during the lavage procedure. The activity of bovine surfactant-supernatant reconstitutions was impaired in children with tracheostomy. In all surfactant mixtures assessed, surfactant function was inversely correlated to the number of neutrophils in the lavage fluid. Chronic lower airway inflammation with mild or no clinical symptoms is associated with impaired surfactant function. The dysfunction may contribute to airflow restrictions frequently observed in these children.     

Fludarabine modulates composition and function of the T cell pool in patients with chronic lymphocytic leukaemia

The combination of cytotoxic treatment with strategies for immune activation represents an attractive strategy for tumour therapy. Following reduction of high tumour burden by effective cytotoxic agents, two major immune-stimulating approaches are being pursued. First, innate immunity can be activated by monoclonal antibodies triggering antibody-dependent cellular cytotoxicity. Second, tumour-specific T cell responses can be generated by immunization of patients with peptides derived from tumour antigens and infused in soluble form or loaded onto dendritic cells. The choice of cytotoxic agents for such combinatory regimens is crucial since most substances such as fludarabine are considered immunosuppressive while others such as cyclophosphamide can have immunostimulatory activity. We tested in this study whether fludarabine and/or cyclophosphamide, which represent a very effective treatment regimen for chronic lymphocytic leukaemia, would interfere with a therapeutic strategy of T cell activation. Analysis of peripheral blood samples from patients prior and during fludarabine/cyclophosphamide therapy revealed rapid and sustained reduction of tumour cells but also of CD4⁺ and CD8⁺ T cells. This correlated with a significant cytotoxic activity of fludarabine/cyclophosphamide on T cells in vitro. Unexpectedly, T cells surviving fludarabine/cyclophosphamide treatment in vitro had a more mature phenotype, while fludarabine-treated T cells were significantly more responsive to mitogenic stimulation than their untreated counterparts and showed a shift towards T_H1 cytokine secretion. In conclusion, fludarabine/cyclophosphamide therapy though inducing significant and relevant T cell depletion seems to generate a micromilieu suitable for subsequent T cell activation.     

Histocompatibility lymphocytic antigen (HLA) typing in patients with acute exacerbation of Hashimoto's thyroiditis

Histocompatibility lymphocytic antigen (HLA) typing was performed in 6 patients with acute exacerbation of Hashimoto's thyroiditis whose diagnoses were established on the basis of typical histological findings, and was compared with those of 12 with subacute thyroiditis, 33 with general Hashimoto's thyroiditis and also with a control group. There was a high incidence of BW35 in patients with subacute thyroiditis, although it was only seen in 1 of 6 patients with acute exacerbation. The difference was statistically significant (p less than 0.01). Four of 6 patients with acute exacerbation had DR2 and none of them had DR4, which was the reverse of the findings for Hashimoto's thyroiditis patients in general, and the difference in the incidence of DR2 was significant (p less than 0.001). None of the HLA types in patients with acute exacerbation was significantly different from those of the control group. In conclusion, HLA typing in patients with acute exacerbation was different from those of subacute thyroiditis and general Hashimoto's thyroiditis. Acute exacerbation was considered to involve quite a limited and rather unique population among patients with Hashimoto's thyroiditis.     

Immune defects in patients with chronic lymphocytic leukemia

Over the past decade, the introduction of nucleoside analogs and monoclonal antibodies into the treatment of patients with chronic lymphocytic leukemia (CLL) has resulted in higher rates and longer duration of response. This is a significant step towards achieving the ultimate goal of disease-eradication and improved survival. A continuing problem, however, is the susceptibility of these patients to infections. Profound dysregulation of the host immune system in patients with CLL and its impact on the clinical course of the disease are well established. A number of investigators have sought to identify the mechanisms underlying this innate immune dysfunction, which is further exacerbated by the actions of the potent therapeutic agents. The early recognition of infections as well as prophylactic administration of appropriate antibiotics has been the mainstay of managing infections in patients with CLL. Hopefully, increasing understanding of the molecular events underlying the neoplastic change in CLL will lead to more targeted and less immunosuppressive therapeutic modalities. Furthermore, the understanding of the mechanisms of immune dysfunction in CLL is of pivotal importance in the novel immune-based therapeutic strategies currently under development.     

Genetic alteration associated with chronic lymphocytic leukemia

The genetics of B-cell chronic lymphocytic leukemia (B-CLL) differ considerably from most other forms of hematologic malignancy which are usually characterized by chromosome translocations. B-CLL typically contains chromosomal deletions and chromosomes 13q14 and 11q22-->q23 are the most common. These two regions appear to share a common ancestral origin (Auer et al., 2007b). Overall, chromosomal abnormalities can be found in the majority of patients with B-CLL when using sensitive techniques (Dohneret al., 2000) and possibly reflects an underlying predisposition, with a small but significant number of familial cases. Although single and consistent abnormalities are most common, multiple rearrangements can occur, often with disease progression (Feganetal., 1995; Dohner et al., 2000). Regions of recurrent deletion suggest the presence of tumor suppressor genes if following Knudson's theoretical 2-hit model. However, despite extensive sequencing analysis over the last decade and lack of pathogenic mutations identified, there has been a move away from this suggested hypothesis and alternative mechanisms of gene inactivation involving epigenetic silencing or haploinsufficiency may be considered as more likely in this disease. This review focuses on the common genetic abnormalities in B-CLL and relates them to some of the more recent hypotheses on inactivation of genes within these regions of deletion.     

Karyotypes of 33 patients with clonal aberrations in chronic lymphocytic leukaemia. Review of 216 abnormal karyotypes in chronic lymphocytic leukaemia

We report on 33 unpublished patients with clonal anomalies in chronic lymphocytic leukaemia. The literature was thoroughly reviewed in order 1) to quantify the frequency of anomalies found in chronic lymphocytic leukaemia and to give new status to the rarest, 2) to determine whether a given anomaly was an additional anomaly and/or a primary anomaly, and 3) to find out whether strong associations between different anomalies exist in this disease.