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PubMed1985

Immunohistological phenotyping of thyroid infiltrating lymphocytes in Graves' disease and Hashimoto's thyroiditis.

Subsets of lymphocytes in the thyroid were immunophenotyped by their surface antigens in frozen tissues of Hashimoto's thyroiditis and Graves' disease. Using triple layer immunoperoxidase staining (IP), monoclonal antibodies (T3, Leu 3, T8, anti-Tac and Leu 7) were employed to detect markers of T cell subsets, activated T cells, and a natural killer associated antigen. B cells were identified by 2 step IP with anti-IgD antisera. Excluding those cells forming lymphoid follicles, the density of lymphocytes infiltrating between thyroid epithelial cells was much higher in Hashimoto's thyroiditis than in Graves' disease. However, relative proportions of subsets were similar in both diseases. Most of the infiltrating cells were T3 positive T cells (T3+), with more T8+ (suppressor/cytotoxic T) than Leu 3+ (inducer/helper T). Some Leu 7+ were occasionally seen, but surface IgD positive mature B cells (IgD+) were almost absent. In contrast, IgD+ cells were densely aggregated in primary lymphoid follicles and mantle zones of secondary follicles. In these regions, Leu 3+ cells were about twice as frequent as T8+ cells. Some Leu 7+ and scarce Tac+ cells were also found. The present study indicates a major involvement of immunoregulatory T cells in autoimmune thyroid disease, and also suggested intrathyroidal maturation of B cells.

Adult↗

PubMed1985

Thyroid function during the spontaneous course of subacute thyroiditis.

A study of changes in serum T4, T3, and Tg as well as of serum TSH response to TRH was done in ten patients with subacute thyroiditis, from the acute phase up to 56 mo. All patients had symptoms of thyrotoxicosis. The mean +/- s.e.m. serum T4 (21.6 +/- 8.2 micrograms/dl), T3 (315 +/- 191 ng/dl) and Tg (149 +/- 52 ng/ml) concentrations were significantly higher than in normal subjects (8.5 +/- 1.7 micrograms/dl, 136 +/- 34 ng/dl, and 10.5 +/- 1.0 ng/ml, respectively). The basal TSH concentrations failed to increase in response to TRH. Mean serum T3 and serum Tg levels remained higher than in normal subjects until 4 to 5 mo after the acute phase. However, normalization of clinical status and serum thyroid hormone levels did not coincide with the normalization of serum Tg levels. Thyroid autoantibodies were absent during the whole period of study. An exaggerated response of TSH to TRH in six out of seven patients was observed from a 2 to 3 mo period until the end of follow-up. All patients with T3 to T4 ratio above the normal range (7-24 ng/micrograms) showed also an exaggerated response of TSH to TRH. These data suggest that the spontaneous course of subacute thyroiditis may lead to a low thyroid reserve detectable even 5 yr following the acute phase of the disease.

Adult↗

PubMed1974

Thyroid nodules and thyroid cancer.

A review of clinical and laboratory features of thyroid cancer, designed to help in a more precise selection of patients for operation, showed that factors contributing to a high index of suspicion of cancer include previous exposure to low doses of radiation, the presence of a firm, solitary thyroid nodule clearly different from the rest of the gland, a young patient, nodules that are "cold" on scan with radioiodine, and nodules that fail to regress after an adequate trial of thyroxine therapy. Factors contributing to a low index of suspicion of thyroid cancer include soft or cystic lesions, multinodular goiters, nodules that are "hot" on (131) I scan, and those that regress during thyroxine treatment. When these factors are used to select patients for surgical operation, about 30 percent are found to have thyroid cancer. Until more precise methods for preoperative diagnosis are established, it is suggested that this type of clinical selection may be very helpful in the management of patients with thyroid nodules or nontoxic goiter.

Adolescent↗

PubMed1978

[Lymphocytic infiltrations in normal and pathological thyroid glands (so-called focal lymphocytic thyroiditis) (author's transl)].

A series of 1004 goitres removed surgically before (1959) and after (1970, 1975) the introduction of the iodine prophylaxis reveals an impressive increase in lymphocytic infiltration of the thyroid gland parenchyma. So-called focal lymphocytic thyroiditis is closely associated with the functional state of the organ. Furthermore, there is an increase in focal thyroiditis, especially in younger persons, after the introduction of iodine prophylaxis. Autoantibodies or clinical signs of inflammation were not found in these cases. Focal lymphocytic thyroiditis is seen as the expression of a regulatory function of the immunological system over the thyroid gland.

Autoantibodies↗

PubMedDate not supplied

Association of autonomous thyroid adenoma with chronic thyroiditis.

Coexistence of an autonomous thyroid adenoma (ATA) with chronic thyroiditis suggests a complex pathogeny pointing to the autonomous character of the nodule and to the presence of immunitary disorders. The rarity of this association and the paucity of data prompted us to present 4 cases of a series of 71 thyroidectomized ATA cases. The rarity of ATA associated with chronic thyroiditis, accumulation of radioiodine under the conditions of euthyroidism only at the adenoma level as well as the possibility for the disease to occur in hypopituitarism, all support the hypothesis of an initial thyreotropic deficiency, with subsequent hyperplasia "of necessity". Later on there is an autonomous hyperfunction increasing pituitary depression, with total extinction of the thyroid tissue outside the adenoma. When the two lesions are associated, we consider that initially there was the TSH-dependent thyroiditis that developed during which, by accidental depression of TSH secretion a local hyperplasia occurs which later becomes autonomous.

Adenoma↗

PubMed1984

Prediction of malignancy in the solitary thyroid nodule by physical examination, thyroid scan, fine-needle biopsy and serum thyroglobulin. A prospective study of 100 surgically treated patients.

A prospective study was made of 100 consecutive patients selected for surgical treatment of a clinically solitary thyroid nodule. Anamnestic data and findings at physical examination, thyroid scan, fine-needle aspiration biopsy and measurement of serum thyroglobulin were correlated with the postoperative histologic diagnoses. The histologic findings were malignant in 18 cases and benign in 82. Familial occurrence of benign goiter was reported more frequently by patients with benign than by those with malignant histology (46 and 11%). Of the 11 nodules that were hard at palpation, 7 were malignant. All 12 scintigraphically "hot" nodules were benign, but 13 of 59 "solitary, cold" nodules were malignant. The cytologic specimens were reviewed and reclassified. The needle aspirate was insufficient for cytologic diagnosis in 11 cases. Papillary carcinoma was cytologically recognized in four cases. Of 36 lesions cytologically reported to be neoplasm of unspecified type, 12 were histologically shown to be malignant, 20 were follicular adenomas and 4 were colloid goiter. Benign lesion was the cytologic diagnosis in 47 cases. One diagnosis was false negative, but the cancer lay beneath the index nodule. The thyroglobulin level was significantly higher in patients with thyroid cancer than in those with benign disorders, but the test's predictive value was low. Thyroglobulin levels more than tenfold the upper limit of normal were found only in three patients with thyroid cancer and two with thyrotoxicosis. Although all of the mentioned investigative data were helpful in the management of solitary thyroid nodule, fine-needle biopsy was the best single method. When cytologic examination shows malignancy or unspecified neoplasm, surgery is indicated. For most patients with cytologically benign lesions, careful follow-up will suffice.

Adult↗

PubMed1984

The thyroid-system function in preterm infants of postmenstrual ages of 31 weeks or less: evidence for a "transient lazy thyroid system".

A prospective study was conducted in order to evaluate thyroid function in 20 healthy and 18 sick preterm infants with postmenstrual ages of 31 weeks or less. The clinical condition of both groups was compared using a "Neonatal Special Care Evolution Score". The effect of thyroid hormone treatment, given from D10 on to the sick infants, was also studied. TSH, thyroid hormone levels (TG, T4, T3, rT3, FT4 and FT3) and TBG were measured by radioimmunoassays at D0, D10, D20, D30 and D40. Healthy preterm infants on D0 have a median TSH level of 22 microU/ml and a high TG level of 200 ng/ml; thereafter, median serum levels decrease to 6 microU/ml and 35 ng/ml respectively. During the same period, median serum T4 is maintained at a low level of about 6-8 micrograms/dl, median serum T3 gradually increases from 80 ng/dl on D0 to 150 ng/dl on D40, and median serum rT3 decreases beyond D10 from a plateau of 200 ng/dl to about 100 ng/dl. In the sick preterm infants before treatment, serum TSH is as in the control group but serum T4, T3 and rT3 on D10 are well below the control values (P = 0.005). In all conditions, there is a significant correlation between serum T4 and FT4, and between serum T3 and FT3. Thyroxine, given to the sick preterm infants from D10 on, brings median serum T4 values closely to the ones of the control group whereas serum levels of TSH and TG are unaffected and similar to those of the healthy preterm infants. Furthermore, thyroxine brings serum rT3 within the range of the control group but leaves median serum T3 at a low level of about 50 ng/dl. On T3 treatment, serum T3 normalizes but rT3 and particularly T4 tend to decline further. In the conditions of this study a significant difference in TBG level is not proven. Although an untreated sick group was not enrolled in the study, thyroid hormone treatment brought the "Neonatal Special Care Evolution Score" of the treated sick infants closer to that of the healthy preterm infants. In the sick preterm infant with failure to thrive on D10, there is an impaired thyroid discharge of T4 in spite of serum TSH values not different from those of the control group.(ABSTRACT TRUNCATED AT 400 WORDS)

Age Factors↗

PubMed1983

Immunohistochemical study of substance P-like immunoreactivity in human thyroid and medullary carcinoma of the thyroid.

Substance P-like immunoreactivity (SPL-IR) was identified by the indirect peroxidase anti-peroxidase (PAP) method in normal thyroid glands as well as in medullary thyroid carcinoma. The SPL-IR cells were visualized intrafollicularly in the thyroid, within cells which resembled the parafollicular C cells which contain calcitonin immunoreactivity. The SPL-IR cells distributed differently in the normal thyroid and in thyroid with secondary C cell hyperplasia.

Calcitonin↗

PubMed1984

Women on thyroid hormone therapy: pregnancy course, fetal outcome, and amniotic fluid thyroid hormone level.

Thirty-four hypothyroid women on thyroid hormone substitution were followed through 37 pregnancies, and 16 women having previous surgery for thyroid carcinoma and thereafter placed on suppressive thyroxine treatment were followed through 19 pregnancies. The thyroxine treatment needed readjustment in 13 pregnancies (23%) to maintain euthyroidism. At delivery, the maternal free thyroxine index was 126 nmol/L in the group of patients treated for hypothyroidism and 146 nmol/L in the patients with treated thyroid carcinoma. The amniotic fluid thyroxine level in normal pregnancies was 6.7 nmol/L, in hypothyroid patients 6.7 nmol/L, and in patients with thyroid carcinoma 5.6 nmol/L. The amniotic fluid reverse triiodothyronine level in normal pregnancies was 0.51 nmol/L, in hypothyroid patients 0.66 nmol/L, and in patients with thyroid carcinoma 0.70 nmol/L. All infants were euthyroid.

Adenocarcinoma↗

PubMed1994

Growth hormone and thyroid function: is secondary thyroid failure underdiagnosed in growth hormone deficient patients?

Thyroid hormones and the GH/IGF-1 system show considerable mutual interference which may have physiological, pathophysiological and clinical importance. GH therapy of children and adults may induce a fall in serum T4, which seems to be due to an effect on the deiodination of T4 to T3. Animal studies suggest that the alterations in thyroid hormones in tissue may be much more prominent than the changes observed in serum. It is possible that the GH deficiency seen in the majority of patients with pituitary/hypothalamic disorders may mask secondary hypothyroidism in some patients by giving a relatively high serum T4. GH therapy may then unmask the hypothyroidism. In accordance with such a mechanism GH deficient children evaluated thoroughly to exclude secondary thyroid failure before GH administration do not develop thyroid insufficiency during GH substitution therapy. It is suggested that thyroid insufficiency should be considered in GH deficient patients with low normal serum T4.

Adult↗

PubMed1993

Experimental thyroiditis in guinea pigs and rabbits. Immunization with thyroglobulin and bovine thyroid gland suspension.

Morphological changes in the thyroid glands of the guinea pigs with autoimmune thyroiditis (EAT) experimentally induced by thyroglobulin (TGL) or immunization by the suspension of thyroid gland cells with CFA manifested mainly by atrophy and alterations of follicular cells, fibrotic tissue changes, formation of inflammatory lymphoplasmocytic infiltrations, multiplication of C-cells and by the increase in the proportion of lymphocytes with activated nucleoli in the tissue. The antigenic effects of TGL differed from those of the cell suspension; the effects of TGL participated especially in the formation of the infiltrates, the effects of cell suspension participated in the diapedesis of mononuclears and in the multiplication of C-cells. The findings correspond to the principal findings in human autoimmune lymphocytic thyroiditis. In an electron microscope, strongly dilated cisterns of endoplasmic reticulum (ER) and multiplied mitochondria in the cytoplasm of altered follicular cells were found. The wall of the follicles exhibited fully intact or altered C-cells. The latter had a large number of granules in cytoplasm with an unusually clear medullary substance. In the rabbit thyroid glands no morphological changes were observed following the immunization with both antigens. TGL antibodies examined immunohistochemically in the sera were present in all the sera of guinea pigs immunized with TGL and CFA. The antibodies determined by dot immunodetection were present in the sera of all guinea pigs immunized with TGL+CFA, the titres reached the level of 1:81 to 1:729; the highest titres were observed in the guinea pigs following the immunization by dose of 7.7 mg/kg after 12 weeks of immunization.

Animals↗

PubMed1994

[Diffuse sclerosing papillary carcinoma of the thyroid gland. Apropos of a pediatric case of association of an unilateral tumor with diffuse lymphocytic thyroiditis].

A 11-year-old girl presented in 1990 with bilateral goiter, hypothyroidism and thyroid auto-antibodies and was treated for Hashimoto's thyroiditis. In 1991, a cervical lymph node metastasis revealed diffuse sclerosing papillary carcinoma (DSPC) of the right thyroid lobe and chronic lymphocytic thyroiditis of the left lobe. The patient is in remission in 1993 (total follow-up, 39 months). The review of 60 previously reported cases of DSPC shows a predilection for young people, a high incidence of lymph node and pulmonary metastases; however the mortality rate is quite low, reflecting either the good prognosis linked to a young age in papillary thyroid carcinomas, or the short duration of the follow-up preventing assessment of the behaviour of DSPC.

Carcinoma, Papillary↗

PubMed1993

Chromatographic identification in serum of endogenously radioiodinated thyroid hormones after iodine-131 whole-body scintigraphy in the follow-up of patients with differentiated thyroid carcinoma.

Patients with differentiated thyroid cancer (DTC) are conventionally followed with serial 131I whole-body scintigraphy (WBS) and serum thyroglobulin (hTg) assay. Given the 15%-20% incidence of discordant results, we developed a sensitive and specific procedure for monitoring such patients, based on the assumption that 131I uptake, even if too low to be detected by 131I WBS, could be assayed in serum as thyroid products (hTg, T3 and T4) endogenously labeled with 131I. Our study included 125 patients routinely monitored for tumor recurrence or for the persistence of functioning thyroid tissue after complete primary treatment for DTC (surgery and 131I ablation of remnants). A plasma sample, taken 72 hr after administering 131I for WBS was fractionated on a Sephadex-G25 superfine column by first eluting all of the radioactive species except the thyroid hormones and then the radioiodothyronines. The sensitivity and specificity of chromatography in detecting functioning thyroid tissue after primary treatment for DTC were 98.4% and 100% (accuracy 99.2%), respectively, versus 90.6% and 95.1% for 131I WBS (accuracy 92.8%) and 60.9% and 100% for hTg (accuracy 80%). Combining chromatography with serum hTg gave the highest gains in diagnostic performance (100% for all parameters). This chromatographic method can be used in addition to conventional procedures in the follow-up of patients with DTC and represents a highly sensitive test for assessing the results of 131I ablation of postsurgical remnants.

Adolescent↗

PubMed1996

Inappropriate thyroid gland ablation in patients with generalized resistance to thyroid hormone. A common sequela of a rare disorder.

Generalized resistance to thyroid hormone is one of several rare disorders of thyroid metabolism that can be associated with confusing symptoms and signs. Five cases of generalized resistance to thyroid hormone that were misdiagnosed with thyrotoxicosis, leading to unnecessary thyroid gland ablation and iatrogenic hypothyroidism, are reviewed herein. These cases illustrate the point that a careful review of the history, physical examination, and laboratory data, as well as an understanding of hormonal feedback relationships, will greatly benefit the practitioner in evaluating the patients with thyroid dysfunction. Consultation with an endocrinologist may be helpful to establish the correct diagnosis and avoid unnecessary treatments.

Adult↗

PubMed1998

Multiple isoforms of thyroid hormone receptor: an analysis of their relative contribution in mediating thyroid hormone action.

Thyroid hormone is essential for normal development and maintaining metabolic homeostasis. In mediating the thyroid hormone action, the thyroid hormone receptor (TR) plays a key role. Almost one decade ago, the cloning of TR was achieved, revealing the existence of at least two genes, TR alpha and TR beta, which encode TR. From these genes several TR isoforms can be generated by alternative splicing. They are designated as TR alpha 1, TR alpha 2 (inactive form), TR beta 1 and TR beta 2. Since the discovery of these TR isoforms, many studies have attempted to demonstrate their relative contribution to mediate thyroid hormone in various tissues. The distinct tissue distribution and the ontogenic expression of the TR isoforms, and the fact that TR gene abnormalities associated with the syndrome of resistance to thyroid hormone (RTH) have been found only in the TR beta gene, indicate that products of TR alpha and TR beta have distinct roles. However, no direct evidence of the distinct roles of the TR isoforms has been shown. Gene knockouts of either TR isoform would provide important information to understanding their specific roles. In this review, the history of the TR isoform discovery and studies attempting to demonstrate the specific roles of TR isoforms are summarized, and recent reports dealing with knockouts of TR isoforms are comprehensively presented.

Humans↗

PubMed2002

Specificity of thyroid hormone receptor subtype and steroid receptor coactivator-1 on thyroid hormone action.

Isoforms of the thyroid hormone receptor (TR)alpha and TRbeta genes mediate thyroid hormone action. How TR isoforms modulate tissue-specific thyroid hormone (TH) action remains largely unknown. The steroid receptor coactivator-1 (SRC-1) is among a group of transcriptional coactivator proteins that bind to TRs, along with other members of the nuclear receptor superfamily, and modulate the activity of genes regulated by TH. Mice deficient in SRC-1 possess decreased tissue responsiveness to TH and many steroid hormones; however, it is not known whether or not SRC-1-mediated activation of TH-regulated gene transcription in peripheral tissues, such as heart and liver, is TR isoform specific. We have generated mice deficient in TRalpha and SRC-1, as well as in TRbeta and SRC-1, and investigated thyroid function tests and effects of TH deprivation and TH treatment compared with wild-type (WT) mice or those deficient in either TR or SRC-1 alone. The data show that 1) in the absence of TRalpha or TRbeta, SRC-1 is important for normal growth; 2) SRC-1 modulates TRalpha and TRbeta effects on heart rate; 3) two new TRbeta-dependent markers of TH action in the liver have been identified, osteopontin (upregulated) and glutathione S-transferase (downregulated); and 4) SRC-1 may mediate the hypersensitivity to TH seen in liver of TRalpha-deficient mice.

Animals↗

PubMed2003

Prevalence of autoimmune thyroiditis and non-immune thyroid disease in multiple sclerosis.

Since multiple sclerosis (MS) and autoimmune thyroiditis (AIT) are presumed to be of autoimmune origin the correlation of these two diseases is of special interest. The aim of this study was to determine whether there are differences in the prevalence of thyroid disease with special emphasis on AIT compared with MS and normal subjects and whether the presence of thyroid disease correlates with disability, disease course, age, and disease duration. 353 consecutive patients with clinically definite MS, without interferon-beta treatment and 308 patients with low back pain or headache were extensively examined for the presence of non-immune or autoimmune thyroid disease. We found a significantly higher prevalence of AIT in male MS patients (9.4 %) than in male controls (1.9 %; p = 0.03). The prevalence of AIT in female MS patients (8.7 %) did not differ from female controls (9.2 %). Hypothyroidism, caused by AIT in almost all cases, showed a tendency to be more severe and more often present in patients with MS. There was no association between relapsing-remitting and secondary progressive disease course of MS and the prevalence of AIT. MS patients with AIT were significantly older but did not differ in disease duration and expanded disability status scale (EDSS). Further studies are warranted, to see if there is a difference in sex-hormone levels between MS patients with and without AIT and healthy controls. Longitudinal studies comparing MS patients with or without AIT could show whether there is an influence of AIT on the disease course or progression.

Adult↗

PubMed1988

Hashimoto's thyroiditis simulating De Quervain's thyroiditis.

A 13-year-old adolescent girl with Hashimoto's thyroiditis presented with a painful, diffuse goiter. The clinical features simulated those of subacute, or De Quervain's, thyroiditis. The markedly elevated titers of thyroid antibodies together with clinical and biochemical evidence of hypothyroidism resulted in a diagnosis of Hashimoto's thyroiditis with a subacute exacerbation.

Adolescent↗