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Biomedical subjects

L Chiovato

Publications and source records attributed to L Chiovato.

At least 73 records · Page 4Linked to original sources
PubMed1996

Study of serum 3,5,3'-triiodothyronine sulfate concentration in patients with systemic non-thyroidal illness.

Sulfation is an important pathway of triiodothyronine (T3) metabolism. Increased serum T3 sulfate (T3S) values have been observed during fetal life and in pathological conditions such as hyperthyroidism and selenium deficiency. Similar variations have also been reported in a small number of patients with systemic non-thyroidal illness, but the underlying mechanisms have not been elucidated. In this study, serum T3S concentrations have been measured by a specific radioimmunoassay in 28 patients with end-stage neoplastic disease (ESND) and in 44 patients with chronic renal failure (CRF); 41 normal subjects served as controls. Both ESND and CRF patients had lower serum total T4 (TT4) and total T3 (TT3) than normal controls, while serum reverse T3 (rT3) was increased significantly in ESND (0.7 +/- 0.5 nmol/l; p < 0.001 vs. controls) but not in CRF (0.3 +/- 0.1 nmol/l). The TT3/rT3 ratio, an index of type I iodothyronine monodeiodinase (type I MD) activity, was reduced significantly in both groups of patients. Serum T4-binding globulin (TBG) was decreased in CRF but not in ESND patients. Serum T3S was significantly higher both in ESND (71 +/- 32 pmol/l) and CRF (100 +/- 24 pmol/l) than in controls (50 +/- 16 pmol/l, p < 0.001). Serum T3S values showed a positive correlation with rT3 values and a negative correlation with both TT3 and FT3 values in ESND, but not in CRF. In the latter group a positive correlation was observed between T3S and TBG values. The T3S/FT3 ratio was higher both in CRF (18 +/- 5) and in ESND (23 +/- 18) as compared to controls (10 +/- 4). Serum inorganic sulfate was increased and correlated positively with T3S values in CRF patients. In conclusion, the results of this study in a large series of patients confirm that patients with systemic non-thyroidal illness have increased serum T3S levels. The mechanisms responsible for these changes appear to be different in ESND and CRF patients. In ESND the increase in serum T3S levels is mainly related to reduced degradation of the hormone by type I MD, whereas in CRF it might be driven by the enhanced sulfate ion concentration, and could be partially dependent on the impaired renal excretion of T3S. Because T3S can be reconverted to T3, it is possible that increased T3S concentrations contribute to maintenance of the euthyroid state in systemic non-thyroidal disease.

Adult↗
PubMed1996

Autoimmune hypothyroidism and hyperthyroidism in patients with Turner's syndrome.

A high prevalence of autoimmune thyroid disease (AITD) has been described in Turner's syndrome (TS) but the extent of this association is controversial for the prevalence of thyroid autoantibody and the clinical impact of thyroid dysfunction. In this study we searched for thyroid disease and thyroid autoantibodies in patients with TS. Seventy-five unselected TS patients (age range 3-30 years) were studied. Sera were tested for thyroid hormones, thyrotropin (TSH), thyroglobulin (TG-ab) and thyroperoxidase (TPO-ab) antibodies. The TSH-receptor antibodies with thyroid-stimulating (TS-ab) or TSH-blocking activity (TSHB-ab) were measured in the IgG fraction using a bioassay. Ten out of 75 (13.3%) TS patients had AITD: eight had autoimmune thyroiditis (AT) (six with subclinical and two with overt hypothyroidism and one with euthyroidism) and one had Graves' disease. The prevalence of AITD increased significantly (p < 0.05) from the first (15%) to the third (30%) decade of life. The prevalence of TPO-ab and/or TG-ab (20%) was higher (p < 0.05) in TS than in age-matched female controls and increased from the first (15%) to the third (30%) decade of life. Clinical AITD was diagnosed in 46% of TS patients with TPO-ab and/or TG-ab. Thyroid-stimulating antibody was detected in the hyperthyroid patient, and TSHB-ab was found in one of eight patients with hypothyroid AT. It was concluded that: TS patients are at higher than average risk of developing AITD not only in adolescence and adult age but also in childhood; hypothyroidism, mainly subclinical, is the most frequent thyroid dysfunction; elevated TPO-ab and/or TG-ab alone do not imply thyroid dysfunction; TS-ab or TSHB-ab are always associated with thyroid dysfunction although most cases of autoimmune hypothyroidism are not due to the latter antibody.

Adolescent↗
PubMed1996

Use of cells expressing the human thyrotropin (TSH) receptor for the measurement of thyroid stimulating and TSH-blocking antibodies.

A clone of Chinese hamster ovary cells (CHO) transfected with the cDNA of the human thyrotropin (TSH) receptor (CHO-R) was used to optimise assays for TSH receptor antibodies with either thyroid stimulating (TSAb) or TSH blocking (TSH-blocking Ab) activity. The study group included 89 patients with Graves' disease, 38 patients with goitrous Hashimoto's thyroiditis (HT) and 47 subjects with atrophic thyroiditis (AT). In the HT group, 8 patients had subclinical hypothyroidism (HT-SH) and 30 had overt hypothyroidism (HT-H). In the assay for TSAb, CHO-R cells were incubated with 1mg/ml of the immunoglobulin G (IgG) from patients with Grave's disease, while in the assay for TSH-blocking Ab cells were incubated with IgGs from patients with HT or AT alone (1mg/ml), or IgGs plus TSH (10 mU/L). After 2 h of incubation the extracellular cAMP was measured by a RIA. In these conditions a significant stimulation by Graves' IgG was obtained in patients with active hyperthyroidism (33/35, 94% untreated; 21/23, 91% relapsed after a course of medical treatment), in 12/20 (60%) patients euthyroid under methimazole and in 4/11 (36%) euthyroid after a course of antithyroid drugs. TSH-blocking Ab were detected in 1/8 (12.5%) patients with HT-SH, in 7/30 (23.3%) with HT-H and in 16/47 (34.0%) patients with AT. TSAb and TSH-blocking Ab coexisted in 4 IgGs that belonged to patients in whom spontaneous hypothyroidism developed after hyperthyroidism, or viceversa. TSAb and TSH-blocking Ab were also tested on FTRL-5 cells. TSAb were positive in both assays in 43/58 (74%) patients with active Graves' disease, negative in both assays in 3 (5%), negative in FRTL-5 and positive in CHO-R in 11 (19%), negative in CHO-R and positive in FRTL-5 in 1 (1.7%). In FTRL-5 cells TSH-blocking Ab were detected in 1/8 (12.5%) patients with HT-SH, in 5/30 (16.6%) with HT-H and in 15/47 (31.9%) with AT. The results of cAMP stimulation in FRTL-5 and CHO-R showed a fairly good correlation in TSAb (r = 0.60, p < 0.0001) and in TSH-blocking Ab (r = 0.74, p < 0.0001) assays. In conclusion, CHO cells transfected with the cloned human TSH receptor are suitable for the clinical assay of TSAb and TSH-blocking Ab. The sensitivity of this assay is higher than that obtained using FRTL-5 cells, having the additional advantages of expressing the human TSH receptor and requiring less cumbersome procedures for cell culture.

Animals↗
PubMed1995

The location and the regulation of the type I-iodothyronine 5'-monodeiodinase (type I-MD) in the rat thyroid: studies using a specific anti-type I-MD antibody.

Type I-iodothyronine monodeiodinase (type I-MD) is abundant in thyroid tissue and contributes to the generation of T3 secreted by the gland. The availability of a specific antibody against rat type I-MD (type I-MD Ab) allowed us to directly identify this enzyme in rat thyroid glands, and in a differentiated strain of rat thyroid cells maintained in continuous culture (FRTL-5 cells). FRTL-5 cells maintain many differentiated functions of thyroid cells, including the expression of TSH receptor and thyroid peroxidase. Using an immunohistochemical technique on rat thyroid sections, a clear staining for type I-MD was demonstrated in follicular cells. The degree of immunoreactivity was greater in small follicles containing little amounts of colloid compared to large follicles lined by functionally inactive cells. Using immunofluorescence (IFL), a strong staining for type I-MD was observed in FRTL-5 cells grown in medium containing TSH. Both in vivo and in culture the staining for type I-MD was localised in the cytoplasm of thyroid cells, while nuclei were negative. Interestingly, no surface staining was shown when viable FRTL-5 cells were submitted to the same IFL procedure. TSH deprivation for 7 days was followed by the disappearance of type I-MD. Immunoreactivity for type I-MD was recovered by addition of TSH, forskolin or thyroid stimulating antibody (TSAb) to TSH-deprived FRTL-5 cells. The effect of TSH was prevented by cycloheximide. There was no induction of type I-MD when IGF-I was added to FRTL-5 cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Mild iodine deficiency during fetal/neonatal life and neuropsychological impairment in Tuscany.

The neuropsychological performance of schoolchildren living in areas with present and past iodine deficiency in Tuscany was investigated. Children were submitted to: a) block design subtest of the Wechsler Intelligence Scale for Children-Revised (WISC-R) and a modified version of the WISC-R coding subtest which evaluate the general neuropsychological and cognitive performance, independently from familial cultural background; b) simple reaction time (RT) session which evaluates the efficiency of the whole information processing and nervous transmission mechanisms. Neuropsychological performance was tested in 107 children living in Borgo a Mozzano, an area of mild iodine deficiency (IDA) with a median urinary iodine excretion (UIE) of 64 micrograms/L (mean +/- SD: 80.1 +/- 57). One hundred and six sex and age-matched children living in Marina di Pisa, an iodine sufficient coastal village of Tuscany (ISA) with a median UIE of 142 micrograms/L (mean +/- SD: 173 +/- 95) were used as controls. Tests for neuropsychological performance were performed in 57 children living in the village of Vagli, an area with past iodine deficiency (PIDA): 30 children born before iodine prophylaxis (Group 1), when the median UIE was 32 micrograms/L (mean +/- SD: 47 +/- 22), 27 children born after the institution of iodine prophylaxis (Group 2), when the median UIE was 109 micrograms/L (mean +/- SD: 130 +/- 73). Sex and age-matched ISA-children were used as controls for each group. RTs were significantly delayed (p < 0.05) in IDA than in ISA children, while block design and coding subtests showed no significant difference.(ABSTRACT TRUNCATED AT 250 WORDS)

Child↗
PubMed1995

Humoral thyroid autoimmunity is not involved in the pathogenesis of myxedematous endemic cretinism.

A role of thyroid autoimmunity in the pathogenesis of myxedematous endemic cretinism was suggested by reports indicating the presence of thyroid growth-blocking antibodies in the sera of these patients. To check this hypothesis, we searched for TSH receptor antibodies with thyroid growth-blocking or adenylate cyclase (AC)-inhibiting (TSH-blocking) activity in immunoglobulin G (IgG) from 18 euthyroid and 21 hypothyroid endemic cretins living in Italy and Peru. Among hypothyroid cretins, 12 had no palpable goiter. Stages I-III goiters were present in 12 of 18 euthyroid cretins. Controls included 25 euthyroid nongoitrous subjects living in the same endemic regions as cretins, and 10 normal subjects from an iodine-sufficient area. IgG from 4 selected patients with autoimmune atrophic thyroiditis and from 2 neonates with sporadic transient congenital hypothyroidism due to maternal TSH-blocking antibodies were included in the study. The blocking effect of the IgG was assessed in FRTL-5 cells by measuring TSH-stimulated [3H]thymidine incorporation, DNA accumulation, and AC activation. A radioreceptor assay was used to detect TSH-binding inhibiting antibodies (TBIAb). No IgG from hypothyroid endemic cretins without goiter contained TBIAb or inhibited TSH-stimulated cell growth or AC activation. The effect of IgG from hypothyroid nongoitrous cretins did not differ from that produced by IgG from hypothyroid cretins with goiter, euthyroid cretins with or without goiter, or normal controls. In contrast to these results, IgG from patients with autoimmune atrophic thyroiditis and from neonates with sporadic transient congenital hypothyroidism contained TBIAb that inhibited both TSH-stimulated cell growth and AC activation. In conclusion, our results indicate that, similar to other types of endemic cretinism, hypothyroid endemic cretins without goiter do not have TSH receptor antibodies able to inhibit TSH-stimulated thyroid cell growth or function. These observations argue against a role of humoral thyroid autoimmunity in the development of myxedematous endemic cretinism.

Adolescent↗
PubMed1994

Detection of antibodies blocking thyrotropin effect using Chinese hamster ovary cells transfected with the cloned human TSH receptor.

Chinese hamster ovary (CHO) cells transfected with the cloned human TSH receptor (CHO-R) were used to develop an assay to detect thyroid autoantibodies blocking the TSH-dependent cAMP production (TSHBAb). The study group included 38 patients with goitrous Hashimoto's thyroiditis (HT) and 47 subjects with atrophic thyroiditis (AT). In the HT group, 8 patients had subclinical hypothyroidism (HT-SH) and 30 had overt hypothyroidism (HT-H). Thirty normal subjects served as controls. Immunoglobulin G (IgG) was prepared from serum by double chromatography on DEAE-Sephadex. CHO-R cells were seeded in 96-well plates and were cultured for 48 h before the assay in RPMI-1640 medium plus 1 mmol/L glutamine, 10% fetal calf serum, and 0.4 g/L geneticin. In the assay for TSHBAb, CHO-R cells were incubated with IgG alone (0.5-2 mg/ml), TSH alone (0.2-625 mU/L), or IgG plus TSH; all samples were diluted in hypotonic medium containing 0.5 mmol/L isobutylmethylxanthine (IBMX). After 2 h of incubation at 37 degrees C in 5% CO2-95% air atmosphere, TSH-stimulation was quantified by measuring extracellular cAMP by a RIA. IgGs from normal subjects did not significantly modify the stimulation of adenylate cyclase produced by TSH, the results obtained ranging between -30% and +18% (mean +/- SD = -3 +/- 14%). All IgGs producing an inhibition greater than 2SD from the mean of controls (> 25%) were considered positive for blocking antibodies. TSHABAb were detected in 1/8 (12.5%) patients with HT-SH, in 7/30 (23.3%) with HT-H and 16/47 (34.0%) patients with AT.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Appearance of thyroid stimulating antibody and Graves' disease after radioiodine therapy for toxic nodular goitre.

A patient with toxic nodular goitre is described in whom radioiodine (131I) therapy paradoxically induced typical Graves' disease. This patient had a goitre with two autonomously functioning nodules suppressing uptake by the remainder of the gland. Circulating thyroid peroxidase antibody indicated the coexistence of focal lymphocytic thyroiditis. Radioiodine therapy was followed by the development of severe and persistent Graves' hyperthyroidism associated with diffuse 131I uptake by the gland. A second administration of 131I produced a further worsening of hyperthyroidism, and the appearance of ophthalmopathy. TSH-receptor antibody and thyroid stimulating antibody were undetectable before 131I, appeared after the first administration of radioiodine, and showed a further increase after the second dose of 131I. We suggest that, in a patient genetically susceptible to thyroid autoimmunity, the release of TSH-receptor antigenic components from follicular cells damaged by radioiodine therapy triggered an autoimmune response to the TSH-receptor, thus turning a toxic nodular goitre into Graves' disease.

Autoantibodies↗
PubMed1994

Studies on the in vitro cytotoxic effect of amiodarone.

Amiodarone, a potent antiarrhythmic drug, contains 37.2% iodine by weight and may induce either hypo- or hyperthyroidism. The high iodine content of amiodarone may be responsible for both complications, but a cytotoxic effect of the drug on the thyroid resulting in thyroiditis has been reported. In the present study the cytotoxic effect of amiodarone was evaluated in three culture systems with different biological properties: 1) a strain of rat thyroid cells (FRTL-5 cells) that maintains most differentiated functions of normal thyroid cells, including an active iodide pump, but an inability to organify iodide; 2) a line of Chinese hamster ovary (CHO) fibroblasts; and 3) freshly prepared primary cultures of human thyroid follicles (hTF) that trap and organify iodide. Cells were radiolabeled with 51Cr and incubated for 24 h with medium alone, medium plus amiodarone (3.75-200 microM), medium plus an iodinated radiographic contrast agent (sodium diatrizoate; 7.5-200 microM), or medium plus potassium iodide (7.5-300 microM). At concentrations ranging from 75-200 microM, amiodarone induced a significant and dose-dependent release of 51Cr in FRTL-5 cells. In contrast, diatrizoate or KI had no cytotoxic effect on FRTL-5 cells. In the same molar concentrations, amiodarone was also cytotoxic in CHO cells. In hTF, the release of 51Cr produced by amiodarone occurred at a lower concentration (37.5 vs. 75 microM) and was significantly greater than that in FRTL-5 cells. The cytotoxic effect of amiodarone in hTF was partially, but significantly, reduced by methimazole, an inhibitor of iodide organification. In the FRTL-5 cell culture system, amiodarone also produced a dramatic inhibition of TSH-stimulated cell growth. This growth-inhibiting effect of amiodarone was evident at low concentrations (3.75-7.5 mumol/liter) of the drug, which did not produce significant cytotoxicity. In conclusion, 1) amiodarone had a cytotoxic effect in CHO fibroblasts, a nonthyroid cell line; 2) this cytotoxic effect occurred in thyroid cells independent of their ability to organify iodide; 3) however, the toxic effect of amiodarone was greater and occurred at a lower molar concentration in freshly prepared human thyroid follicles that trap and organify iodide; and 4) in the latter culture system, methimazole, an inhibitor of iodide organification, partially, but significantly, reduced the cytotoxic effect of amiodarone. These data suggest that thyroid cytotoxicity produced by amiodarone is mainly due to a direct effect of the drug on thyroid cells, but excess iodide released from the drug may contribute to its toxic action.

Amiodarone↗
PubMed1994

Failure to detect thyroid growth-promoting activity in immunoglobulin G of patients with endemic goiter.

The [3H]thymidine incorporation assay in FRTL-5 cells was used to measure thyroid growth-stimulating antibody in the purified immunoglobulin G (IgG) fraction of patients with endemic nontoxic goiter (grade I-III) living in Italy (n = 34) or Peru (n = 37). IgG of euthyroid nongoitrous subjects living in the same endemic area (n = 25) and from an area of sufficient iodine intake were used as controls. Bovine TSH (10 mU/L) and thyroid-stimulating antibody of Graves' disease produced a significant increase in [3H]thymidine incorporation and DNA content in FRTL-5 cells. IgG from Italian or Peruvian patients with endemic goiter produced a small increase in [3H]thymidine incorporation in FRTL-5 cells (131 +/- 54% and 165 +/- 57%, respectively), which was indistinguishable from that obtained with IgG from normal nongoitrous subjects residing in endemic or nonendemic areas (167 +/- 80% and 161 +/- 36%, respectively). For comparison 18 of 25 (72%) IgG of hyperthyroid patients with Graves' disease produced clear-cut increases in [3H]thymidine incorporation (1142 +/- 1065%) and DNA content (219%) in FRTL-5 cells. IgG from patients with endemic goiter, at variance with Graves' IgG, did not cause an increase in DNA in FRTL-5 cells. All Graves' IgG that stimulated [3H]thymidine incorporation in FRTL-5 cells also stimulated cAMP production in this culture system, whereas no adenylate cyclase stimulation was produced by IgG from patients with endemic goiter. The prevalence of thyroglobulin antibody and thyroperoxidase antibody in endemic goiter patients did not differ from that in control subjects residing in the same iodine-deficient area. Our data show that sera of endemic goiter patients are devoid of thyroid growth-stimulating antibody and thyroid-stimulating antibody activities. These observations argue against a direct role of thyroid autoimmunity in the development of goiter in iodine-deficient areas.

Adult↗
PubMed1994

Simultaneous expression of thyroid peroxidase and human leukocyte antigen-DR by human thyroid cells: modulation by thyrotropin, thyroid-stimulating antibody, and interferon-gamma.

Major histocompatibility class II molecules human leukocyte antigen-DR (HLA-DR) are abnormally expressed by human thyroid cells (HTC) in autoimmune thyroid glands. The simultaneous expression of HLA-DR and organ-specific autoantigens such as thyroid peroxidase (TPO) by HTC might enable these cells to function as antigen-presenting cells, thus perpetuating the autoimmune process. The aim of the present study was to clarify the interplay of endocrine (TSH) and immune [TSab or interferon-gamma (IFN gamma)] factors on the expression of HLA-DR and TPO in HTC. Thyrocytes were cultured with supernatants of T-cells cloned from the infiltrate of Hashimoto's glands, human recombinant IFN gamma, TSab, or TSH. These factors were added either alone or in different combinations and sequences. HLA-DR and TPO were identified in HTC by a double indirect immunofluorescence technique, using a monoclonal anti-HLA-DR antibody and human serum containing anti-TPO antibody, respectively. IFN gamma, either recombinant or produced by T-cell clones, induced HLA-DR appearance in thyrocytes, whereas TSH or TSab stimulated TPO expression. The appearance of HLA-DR induced by IFN gamma was accompanied by a progressive reduction of TPO despite stimulation by TSH or TSab. This decline reached a nadir after 9-10 days in different primary cultures. During this period, a percentage of cells ranging from 10-40% simultaneously expressed HLA-DR and TPO on their surface and in the cytoplasm. The inhibition of TPO expression and the appearance of HLA-DR induced by IFN gamma were rapidly reverted when TSH or TSab was substituted for interleukin in the culture medium and vice versa. We conclude that 1) the expression of TPO or HLA-DR in thyroid cells is a dynamic phenomenon that is differently influenced by TSH, TSab, and IFN gamma. It is the interplay of these factors in different follicles and during different periods of time that determines the expression of TPO alone, HLA-DR alone, or both molecules together in the same thyroid cell; 2) during exposure to TSH (or TSab) and IFN gamma, TPO and HLA-DR can be expressed simultaneously by thyroid cells for up to 7 days; and 3) the modulation of HLA-DR and TPO by supernatants of T-cells cloned from Hashimoto's glands is reproduced by IFN gamma alone.

Antibodies, Monoclonal↗
PubMed1994

[Transient neonatal hypothyroidism and iodine deficiency].

Iodine is the essential constituent of thyroid hormones. Iodine deficiency disorders, ranging from endemic goiter to cretinism, result from low dietary intake of iodine. The fetus and the newborn are more sensitive than adults to a reduced environmental iodine supply, and in iodine-deficient areas, transient neonatal hypothyroidism is frequently observed. This transient thyroid failure may be associated with neonatal goiter. Border-line elevated neonatal TSH levels frequently occur in iodine deficient areas, and result in a higher recalling rate in the screening for congenital hypothyroidism. Iodine prophylaxis is highly effective in preventing the development of iodine deficiency disorders including transient neonatal hypothyroidism. Since iodine prophylaxis in Italy is inadequate, variable degrees of iodine deficiency are still present all-over the Country, and are responsible of a higher incidence of transient neonatal hypothyroidism or hyperthyrotropinemia. Educational programs for the general population, health professionals, and decision makers are essential for a successful iodine prophylaxis. Elimination of iodine deficiency by the year 2000 has been recently pledged by WHO/UNICEF. This goal is feasible if pursued with sufficient vigor and resources.

Congenital Hypothyroidism↗
PubMed1994

[Thyroid autoimmunity and congenital hypothyroidism].

The involvement of thyroid autoimmunity in the pathogenesis of sporadic congenital hypothyroidism is still incompletely understood. While antithyroglobulin and anti-thyroperoxidase antibodies are harmless, the transplacental passage of TSH receptor antibodies with blocking activity from a mother with autoimmune thyroiditis to the fetus is responsible of transient neonatal hypothyroidism in the baby. This is however a rare condition. Thyroid growth blocking antibodies have been described in healthy mothers of children with permanent congenital hypothyroidism due to thyroid dysgenesis, but this observation was not confirmed in other studies including our own. Antibodies producing cell mediated cytotoxicity (ADCC), either transferred from the mother or due to an autoimmune thyroiditis developing in utero, might be involved in the pathogenesis of permanent congenital hypothyroidism. However, this hypothesis requires confirmation in more extensive studies.

Autoimmune Diseases↗
PubMed1993

Thyroid autoimmunity and female gender.

Sexual dimorphism exists in regard to the immune response between women and men, and it accounts for the greater prevalence of thyroid autoimmunity in women. Similarly to the human situation a sex-related susceptibility to autoimmune thyroiditis is evident in animal models. A direct influence of genes on sex chromosomes (X or Y) on the immune response has been postulated in some models of autoimmune thyroiditis in rats. On the other hand sex hormones have been implicated to explain the majority of sex differences in the autoimmune response against the thyroid. A state of immune suppression during pregnancy influences the clinical course of autoimmune thyroid diseases, in that a typical amelioration during pregnancy is accompanied by aggravation following delivery. This immunologic rebound phenomenon may also underly the post partum thyroid dysfunction in otherwise healthy women with a genetic predisposition to autoimmune thyroid disease. Thyroid autoimmunity also interferes with the female reproductive function. Hypothyroidism and less frequently hyperthyroidism due to thyroid autoimmune disorders may produce menstrual dysfunction, anovulation and eventually infertility. Maternal hyper- or hypothyroidism can affect the outcome of pregnancy, producing a higher incidence of miscarriages, maternal complications, and congenital malformations. Untreated maternal hypothyroidism produced by Hashimoto's disease during pregnancy can impair the neurological development of the fetus due to a reduced availability of maternal thyroxine during early gestation.2+ More specifically, fetal and/or neonatal hypo- or hyperthyroidism produced by the transplacental passage of maternal thyroid autoantibodies can impair growth and neuropsychological development of affected children.

Female↗
PubMed1993

Detection of thyroid-stimulating antibody using Chinese hamster ovary cells transfected with cloned human thyrotropin receptor.

A clone of Chinese hamster ovary (CHO) cells transfected with the cloned human TSH receptor (CHO-R) was used to optimize an assay for thyroid-stimulating antibody (TSAb), measuring adenylate cyclase stimulation by purified immunoglobulin G from patients with Graves' disease. Optimal sensitivity to bovine TSH (1 mU/L) and TSAb was obtained using hypotonic buffer and measuring extracellular cAMP. In time-response experiments, TSAb stimulation was maximal after 2 h of incubation in hypotonic buffer. Under these conditions, a significant stimulation by Graves' immunoglobulin G was obtained with 33 of 35 (94%) samples from patients with untreated Graves' disease and with 21 of 23 (91%) from patients who relapsed after a course of antithyroid drugs. On the other hand, TSAb was detected in only 12 of 20 (60%) patients who were euthyroid during methimazole treatment and in 4 of 11 (36%) who were euthyroid after a course of antithyroid drugs. All samples from Graves' patients were also tested for TSAb activity on FRTL-5 cells. The results of cAMP stimulation in FRTL-5 and CHO-R showed a fairly good correlation (r = 0.60; P < 0.0001). In particular, of the 58 patients with active Graves' disease (35 with untreated hyperthyroidism and 23 relapsed after methimazole), 43 (74%) were positive in both assays, 3 (5%) were negative in both, 11 (19%) were negative in FRTL-5 and positive in CHO-R, and 1 (1.7%) was negative in CHO-R and positive in FRTL-5. In conclusion, CHO cells transfected with the cloned human TSH receptor are suitable for the clinical assay of TSAb. The sensitivity of this assay is higher than that obtained using FRTL-5 cells, having the additional advantages of expressing the human TSH receptor and requiring less cumbersome procedures for cell culture.

Adenylyl Cyclases↗
PubMed1993

Antibodies producing complement-mediated thyroid cytotoxicity in patients with atrophic or goitrous autoimmune thyroiditis.

Thyroid-cytotoxic antibodies (thyroid-cytotoxic Abs) have been described in patients with autoimmune thyroiditis, but their role in the development of hypothyroidism remains to be clarified. In this study, we evaluated the pathogenetic role of thyroid-cytotoxic Abs in 20 patients with atrophic thyroiditis (idiopathic myxedema; AT) and 94 patients with goitrous Hashimoto's thyroiditis (HT). Among patients with HT, 27 were euthyroid (HT-E), 27 had subclinical hypothyroidism (HT-SH), and 40 had overt hypothyroidism (HT-H). Seventeen normal subjects and 8 patients with nonthyroidal illnesses were used as controls (C). To detect thyroid-cytotoxic Abs, human thyroid cells expressing thyroid peroxidase (TPO) were labeled with 51Cr and challenged with the immunoglobulin G (IgG) fraction of serum plus rabbit complement. The cytotoxic effect of IgGs was calculated as the percent specific lysis (% SL), taking into account the lytic effect of complement alone and the maximal lysis produced by a detergent. Most C-IgGs decreased the cytotoxic effect of complement (median % SL, -3.3). IgGs from hypothyroid patients with thyroiditis had a greater cytotoxic effect than C-IgGs, either as a whole group (P < 0.001), or when subdivided according to clinical diagnosis: HT-SH (median % SL, 4.8; P < 0.005), HT-H (%SL, 2.2; P < 0.0001), or AT (%SL, 0.9; P < 0.01). Among patients with HT, the lytic activity of IgGs from patients with subclinical and overt hypothyroidism was higher than that of IgGs from euthyroid patients (P < 0.05). The results of IgGs from euthyroid patients with HT (median % SL, -0.9) did not significantly differ from those of C-IgGs. By taking a cut-off over the upper range of % SL produced by C-IgGs (> 2), the prevalence of thyroid-cytotoxic Abs was 30% in AT, 59% in HT-SH, and 55% in HT-H. However, 37% of euthyroid patients with HT also had thyroid-cytotoxic Abs. No IgG containing TPO antibodies (TPOAb) at low titer (< 40(2)) was cytotoxic. However, the levels of thyroid-cytotoxic Abs did not correlate with TPOAb titers, and preabsorption with TPO only partially abolished the lytic effect of some HT-IgG. These findings suggest that TPO is a target of thyroid-cytotoxic Abs, but other thyroid antigens are also involved in the cytotoxic reaction.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗