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Biomedical subjects

A Pinchera

Publications and source records attributed to A Pinchera.

At least 163 records · Page 9Linked to original sources
PubMed1997

Skeletal integrity in men chronically treated with suppressive doses of L-thyroxine.

We measured bone mineral density (BMD) (lumbar spine, femoral neck, Ward's triangle, and trochanter) in 34 men given suppressive doses of levothyroxine (L-T4) for a mean of 10.2 years. Indications for treatment were nontoxic goiter (n = 5) or thyroidectomy for differentiated thyroid cancer (n = 6) or nontoxic goiter (n = 3). Patients were followed at our institution and treated with the minimal amount of L-T4 able to suppress thyroid-stimulating hormone (TSH). At the time of evaluation, free T3 was normal in all cases, whereas free T4 was increased in 14 men (41.2%). The mean daily dose of L-T4 was 172 +/- 6 microg, and the cumulative dose of L-T4 was 673 +/- 71 mg. We found no significant difference between patients and age- and weight-matched controls in BMD (g/cm2) at any site of measurement (lumbar spine 1.144 +/- 0.12 vs. 1.168 +/- 0.15; femoral neck 0.979 +/- 0.13 vs. 1.001 +/- 0.13; Ward's triangle 0.854 +/- 0.17 vs. 0.887 +/- 0.15; and trocanther 0.852 +/- 0.13 vs. 0.861 +/- 0.13). BMD was not correlated with the duration of therapy, cumulative or mean daily dose of L-T4, serum levels of free T4, free T3, osteocalcin, and bone alkaline phosphatase. Serum calcium and osteocalcin were slightly but significantly elevated in patients compared with controls, whereas there was no difference in intact parathyroid hormone, bone alkaline phosphatase, and sex hormone-binding globulin (marker of thyroid hormone action). Our data suggest that L-T4 suppressive therapy, if carefully carried out and monitored, using the smallest dose necessary to suppress TSH secretion, has no significant effects on bone metabolism and bone mass in men.

Absorptiometry, Photon↗
PubMed1997

Neuropsychological development in a child with early-treated congenital hypothyroidism as compared with her unaffected identical twin.

OBJECTIVE: Neonatal screening for congenital hypothyroidism (CH) prevents the serious neuropsychological features of CH, but the question remains whether intelligence and motor skills of CH children treated early are completely normal. DESIGN: In this report we describe the rare case of two genetically identical twins, only one of whom was affected by CH due to thyroid agenesis. L-Thyroxine (9 microg/kg body weight/day) therapy was initiated at 27 days of age and was adequate throughout the follow-up. METHODS: Neuropsychological evaluation was performed on the twins in parallel from 3 months to 8 years of age. RESULTS: The CH twin (NB) did not show major neuromotor impairments but, compared with the unaffected twin (EB), she had a slight delay in postural/motor achievements and in language development that completely disappeared at 8 years of age. On standardised tests of intelligence, NB was indistinguishable from control children but, compared with her twin, she had lower IQ scores in most testing occasions up to 7 years of age (NB = 108 vs EB = 115). School achievements of NB did not significantly differ from those of her classmates but, compared with her twin, she scored worse in writing, mechanical reading, verbal memory, and possibly in arithmetic. CONCLUSIONS: Because the twins were genetically and phenotypically identical, were raised in the same environment, and received a similar education, it is concluded that hypothyroidism in utero and in the first neonatal month was responsible for the lower neuropsychological achievements of the CH twin. While foetal hypothyroidism is at present unavoidable, earlier diagnosis and initiation of treatment in neonates with CH are important and highly recommended.

Aging↗
PubMed1997

Identification and characterization of a novel de novo mutation (L346V) in the thyroid hormone receptor beta gene in a family with generalized thyroid hormone resistance.

We have investigated an Italian family with generalized resistance to thyroid hormone (RTH), consisting of two individuals with elevated serum thyroid hormones (TH) and a non-suppressed TSH, together with unaffected family members, for a mutation in the thyroid hormone receptor beta gene (hTR beta). We have identified a single nucleotide substitution (1321 CTT to GTT) corresponding to a leucine to valine substitution at codon 346 (L346V) in the predicted protein. The index case and her affected child are heterozygous for the receptor defect, with normal sequence in unaffected family members. Furthermore, both parents of the index case were unaffected, suggesting that the mutation had arisen de novo. When expressed in vitro, the L346V mutant receptor showed a marked reduction in its affinity for tri-iodothyronine (T3), impaired ligand-dependent transactivation and potent dominant negative activity. Its functional impairment could not be alleviated, even at supraphysiological concentrations of T3, suggesting that the mutation might interfere with the intrinsic ligand-dependent transactivation function (AF-2) located in the hormone binding domain of hTR beta. Finally, the presence of the L346V mutation in the son of the propositus, who died from complications associated with congenital heart disease, raises the possibility that RTH might have contributed to the pathogenesis or severity of the latter.

Adult↗
PubMed1997

Influences of thyroid diseases in diabetic pregnant women.

Thyroid disorders are particularly frequent in women and, second to diabetes mellitus, are the most common endocrine diseases during pregnancy. An association between insulin-dependent diabetes mellitus and thyroid autoimmunity has long been recognized. Management of thyroid diseases in pregnancy is different than in non pregnant women, due to physiological changes of thyroid hormone economy in the childbearing period. Thyroid dysfunction may affect carbohydrate metabolism and worsen glucose control in diabetic patients. On the other hand, poorly compensated diabetes mellitus may cause alteration in the production and metabolism of thyroid hormones. Pregnant women with insulin-dependent diabetes mellitus have an increased risk of developing post partum thyroiditis. These observations have lead to the recommendation that thyroid function should be checked in diabetic women during pregnancy and in the post partum.

Adult↗
PubMed1996

Relevance of estrogen and progesterone receptors enzyme immunoassay in malignant, benign and surrounding normal thyroid tissue.

Several authors have demonstrated the presence of estrogen receptors (ER) and progesterone receptors (PR) in thyroid tissue, generally using dextran coated charcoal method (DCCA). The aim of the study was to measure ER and PR in thyroid specimens using an immunoenzymatic method, and to evaluate the meaning of different prevalence of ER and PR in malignant and benign thyroid disease, as compared with normal thyroid tissue. We have measured ER and PR in thyroid tissue from 28 benign and 20 malignant thyroid lesions, and in 38 samples of surrounding normal thyroid tissues. The sensitivity of ER-EIA and PR-EIA was 1.0 and 1.5 fmol/mg protein, respectively. In thyroid carcinoma the frequency of ER positivity (ER+) was 7/20 (35%); it was significantly higher in the surrounding normal tissue (15/20; 71%) (p = 0.03). In benign thyroid disease, the prevalence of ER+ was 11/28 (39%) and in the surrounding normal tissue it was 11/18 (61%) (p = not significant). PR+ was detected in 7/20 (35%) thyroid cancers and in 15/28 (53%) benign lesions without significant difference with the frequency detected in the surrounding normal tissues. ER and PR concentrations (mean +/- SD) in thyroid cancer was 2.2 +/- 2.2 and 2.2 +/- 2.9 respectively, similarly to that detected in benign thyroid disease and in normal tissue. The simultaneous presence of ER and PR (ER+PR+) was also evaluated. We have found that the frequency of ER+ PR+ was significantly higher in benign lesions (8/28; 28.6%) as compared with malignant samples (1/20; 5%) (p < 0.05); the frequency of ER+PR+ was significantly higher in normal tissue surrounding the malignant lesions (9/20; 45) (p = 0.003). Our data indicate i) EIA method is appropriate to detect ER and PR in thyroid tissue. ii) The frequency of ER+ and ER+PR+ specimens is significantly higher in normal thyroid tissue than in pathologic tissues. This indicates that ER and PR immunoassays may be useful tools to evaluate the normal biological activity of thyroid cells.

Adult↗
PubMed1996

Transfection with the cDNA of the human thyrotropin receptor of a poorly differentiated rat thyroid cell line (FRT).

A cell line derived from the Fisher rat thyroid (FRT), that does not have functional TSH receptor, was stably transfected with the cDNA of the human TSH receptor (h TSH-R). In wild FRT cells TSH (1-1000 mU/l) was unable to increase cAMP production, while 10-10000 nmol/l forskolin elicited a 10-30 fold cAMP stimulation. Two of the transfected clones were responsive to TSH in terms of cAMP production. In particular, the FRT-R3 transfected clone showed the highest sensitivity to the hormone with a 10 fold cAMP increase over the basal at 100 mU/l TSH. The Northern blot analysis using a 2.4 kbp cDNA probe for the hTSH-R showed a band corresponding to the mRNA of TSH receptor in FRT-R3 cells, but not in wild FRT cells. In both cell types TSH was ineffective in stimulating growth assayed by 3H-thymidine incorporation into DNA. Hybridization with a probe for thyroperoxidase on polymerase chain reaction products after reverse transcription of mRNA showed that FRT-R3, as well as FRT cells, do not have a transcript for thyroperoxidase. In conclusion, the data reported in this paper show that the insertion of the hTSH-R cDNA in the genome of poorly differentiated rat thyroid cells results in the recovery of TSH-dependent adenylate cyclase, but not other differentiated thyroid cell functions.

Adenylyl Cyclases↗
PubMed1996

Surgical treatment of Graves' disease: subtotal or total thyroidectomy?

BACKGROUND: The extent of thyroidectomy in Graves' disease is still controversial. We compared the outcome of two groups of patients with Graves' disease who underwent total and subtotal thyroidectomy, respectively. METHODS: One hundred forty patients were treated by subtotal (ST, n = 80) or total thyroidectomy (TT, n = 60) between 1988 and 1994 for a large goiter or recurrence of hyperthyroidism after antithyroid drugs. Surgical complications, relapse of hyperthyroidism, and serum levels of antibodies were evaluated. RESULTS: Thyroid-stimulating hormone receptor and thyroperoxidase antibodies significantly decreased in 44 of 60 and in 27 of 60, respectively, of TT patients and in 65 of 80 and 8 of 80, respectively, of ST patients. Thyroid-stimulating hormone antibody levels increased in three ST patients who had relapse of hyperthyroidism and in no TT patients; thyroperoxidase antibodies increased in nine ST patients (four with relapse of hyperthyroidism) and in no TT patients. Vocal cord palsy occurred in two ST (2.5%) and in 1 TT (1.7%) patients; hypoparathyroidism occurred in three ST (3.8%) and in two (3.3%) TT patients. CONCLUSIONS: Total thyroidectomy does not present more complications with respect to subtotal thyroidectomy, but it avoids the worsening of thyroid humoral autoimmunity and the relapse of hyperthyroidism. Thus it could represent the treatment of choice in Graves' disease.

Adolescent↗
PubMed1996

Relationship between breast cancer and thyroid disease: relevance of autoimmune thyroid disorders in breast malignancy.

The relationship between thyroid dysfunction and breast cancer (BC) is debated. To clarify this controversial issue, a prospective study on thyroid function in BC was performed. The prevalence of thyroid disease was examined in 102 consecutive BC patients with ductal infiltrating carcinoma after surgery and before starting any chemohormonal or x-ray therapy and in 100 age-matched control healthy women living in the same borderline iodine-sufficient geographic area. All subjects were submitted to clinical ultrasound thyroid evaluation and serum free T4, free T3, TSH, thyroperoxidase antibody, and thyroglobulin antibody determination. Fine needle aspiration was performed in all thyroid nodules. Estrogen and progesterone receptors (ER and PR, respectively) were assayed in 92 and 55 BC specimens, respectively. The overall prevalence of thyroid disease was 47 in 102 (46%) in BC patients and 14 in 100 (14%) in controls (P < 0.0001). The prevalence of nontoxic goiter was 27.4% in BC patients and 11% in controls (P = 0.003). Hashimoto's thyroiditis was found in 13.7% of BC patients and in only 2% of the controls (P < 0.005). Other thyroid disorders found in the BC group included 2 cases of Graves' disease, 2 of thyroid carcinoma, and 1 of subacute thyroiditis, whereas in the control group only 1 case of Graves' disease and none of the other disorders were found. Mean free T3, free T4, and TSH concentrations showed no difference between BC patients and controls. The prevalence of thyroperoxidase antibody was higher in BC patients than in controls (23.5% vs. 8%; P < 0.005), whereas the prevalence of thyroglobulin antibody was not different. In BC patients the presence of thyroid antibodies was more frequently associated with clinically detectable autoimmune thyroiditis (14 of 26, 51.8%; P = 0.03) and was more common in the younger group. The positivity of ER was found in 51 of 92 (55.43%) and that of PR was found in 26 of 55 (47.27%) BC specimens. No relationship was found among ER, PR status, and the presence of serum thyroid antibodies. In conclusion, 1) the present study provides evidence that the overall prevalence of thyroid disorders is increased in patients with breast cancer, and 2) thyroid autoimmune disorders, especially Hashimoto's thyroiditis, account to a large extent for the increased prevalence of thyroid disease in patients with breast cancer. This feature is independent from the ER and PR status of the primary tumor. The present findings call attention to the usefulness of screening for thyroid disease in any patient with breast cancer.

Adult↗
PubMed1996

Somatic mutations of the ret protooncogene in sporadic medullary thyroid carcinoma are not restricted to exon 16 and are associated with tumor recurrence.

Germline point mutations in exons 10, 11, and 16 of the ret protooncogene have been identified as causative in multiple endocrine neoplasia type 2 and in familial medullary thyroid carcinoma (MTC). Somatic point mutations of the same gene, exclusively associated with codon 918 of exon 16, have also been reported in few cases of sporadic medullary thyroid carcinoma. We analyzed the blood and tumor DNA of 19 patients with sporadic MTC and 6 patients with primary parathyroid adenoma for point mutations at exons 10, 11, and 16 of the ret protooncogene by restriction analysis of the PCR-amplified product and by sequence analysis of exons 10 and 11. A Cys634-->Tyr mutation was found in both the tumoral and blood DNA of one patient, indicating that he was affected by an hereditary form of MTC, erroneously considered sporadic. In the other 18 patients with MTC, somatic point mutations of ret were found in 8 cases (44.4%). In 5 cases the mutation affected exon 16 (Met918-->Thr), and in 3 cases it affected exon 11 (Cys634-->Arg in 1 and Cys634-->Trp in 2); these 3 mutations were confirmed by sequence analysis. The remaining 10 patients had no mutation in exon 10 by either restriction analysis or sequence analysis. Clinical data showed that 75% of the patients whose tumor carried ret mutation had tumor recurrence and/or increased serum calcitonin concentrations during the postsurgical follow-up period as opposed to 10% of the patients without mutations (P < 0.02, by chi2 analysis). No ret mutation was found in the tumoral DNA from parathyroid adenomas. Our findings indicate that the somatic ret point mutation frequently found in sporadic MTC may affect not only exon 16 but also exon 11 and is associated with less favorable clinical outcome.

Adult↗
PubMed1996

Age-related activation of the tyrosine kinase receptor protooncogenes RET and NTRK1 in papillary thyroid carcinoma.

Oncogenic rearrangements of RET and NTRK1 proto-oncogenes are frequently detected in papillary thyroid carcinomas. Several studies have shown an association between ionizing radiation and development of this tumor type. In addition in vitro irradiation of tumor cell lines induced rearrangements of RET similar to those observed in human papillary thyroid carcinomas. These two observations could be related to the reported increased incidence of papillary thyroid carcinomas in children living in contaminated areas around Chernobyl, given that it has been demonstrated that about 60% of them presents a RET oncogenic activation. However, this high frequency of RET positivity in radiation exposed children does not rule out the possibility that age could also play a role in the development of RET positive tumors. To assess this possibility we looked for a relationship between the presence of RET and NTRK1 oncogenic rearrangements and age at surgery in a sample of 92 consecutive patients. Our results show that, in papillary thyroid carcinoma, the frequency of RET and NTRK1 activation is significantly higher in the group of patients aged 4-30 years, thas supporting the concept that age could be contributing to this thyroid specific carcinogenic process.

3T3 Cells↗
PubMed1996

Treatment of solitary autonomous thyroid nodules by percutaneous ethanol injection: results of an Italian multicenter study. The Multicenter Study Group.

Percutaneous intranodular ethanol injection (PEI) has been proposed for the therapy of autonomously functioning thyroid nodules. In 1992, an Italian multicenter study was undertaken to confirm the usefulness and the feasibility of this procedure. The study included 429 patients: 242 (56.4%) were affected by a toxic adenoma (TA) and 187 (43.5%) by pretoxic adenoma (PTA). Free thyroid hormone levels (FT4, FT3) and thyroid stimulating hormone (TSH) were measured before and 3, 6, 12 months after the end of treatment; thyroid ultrasound and thyroid scintiscan were performed in the majority of patients before and after treatment. Patients underwent 2-12 sessions of ethanol injection under sonographic guidance (median 4). The total amount of ethanol administered per patient (1.5 mL/mL nodular volume) was 2-50 mL (mean +/- SD, 17 +/- 9 mL), and the amount per each injection was 1-8 mL (3.2 +/- 1.3 mL). The treatment was judged successful when both TSH and free thyroid hormone serum levels returned within the normal range and recovery of tracer uptake in extranodular tissue was observed at scintiscan, at any time during the follow-up period. The treatment was considered unsuccessful when no change was observed at scintiscan and/or serum TSH levels remained less than 0.4 mU/L. A successful treatment was achieved in 66.5% of patients with TA and in 83.4% of patients with PTA, when assessed after a 12-month follow-up. In all cases a reduction of the nodular size was observed. Almost all positive results were obtained in nodules whose initial volume was less than 15 mL; large nodules responded less favorably. The treatment was generally well tolerated, only transient side-effects, mainly local pain at the time of injection, were observed. Once normalization of scintigraphic image and of FT4, FT3 and TSH serum concentrations was achieved, no recurrence of hyperthyroidism nor development of hypothyroidism were observed for the length of the study. In conclusion, percutaneous ethanol injection for treatment of autonomously functioning thyroid nodules is effective and safe. Better results are obtained in patients with PTA than in patients with TA, particularly when the initial volume of the nodule is less than or equal to 15 mL. PEI may be considered as an alternative to surgery and to radioiodine for treatment of autonomously functioning thyroid nodules.

Adenoma↗
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

Exposure to radioactive iodine-131 for scintigraphy or therapy does not preclude pregnancy in thyroid cancer patients.

UNLABELLED: Radiation is known to be mutagenic. The aim of the present study was to ascertain whether exposure to 131I induces genetic damage, as assessed by pregnancy outcomes and the health status of offspring of women previously exposed to 131I during thyroid carcinoma treatment. METHODS: Data on 2113 pregnancies were obtained by interviewing female patients treated for thyroid carcinoma who had not received any significant external radiation to the ovaries. RESULTS: The incidence of miscarriages was 11% before any treatment for thyroid cancer; this number increased slightly after surgery for thyroid cancer, both before (20%) and after (20%) 131I, but did not vary with the cumulative 131I dose. Miscarriages were more frequent (40%) in the ten women who were treated with 131I [mean dose: 3.8 GBq (108 mCi)] during the year preceding conception. Incidences of stillbirth, preterm birth, low birth weight, congenital malformation and death during the first year of life were not significantly different before or after 131I therapy. The incidence of thyroid disease and nonthyroidal malignancy was similar in children born either before or after their mothers were exposed to 131I. CONCLUSION: With the exception of miscarriages, there is no evidence that exposure to radioiodine affects the outcome of subsequent pregnancies and offspring. The question of whether an increased incidence of miscarriages within 1 yr of 131I administration relates to gonadal irradiation or to insufficient control of hormonal thyroid status remains to be established.

Abnormalities, Radiation-Induced↗
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↗