Relationship between potency of blocking type thyrotropin-binding inhibitor immunoglobulin in three women with primary myxedema and thyroid function of their neonates

Three neonates born to three mothers with primary myxedema who have thyrotropin-binding inhibitor immunoglobulin (TBII) were continually examined after birth. One neonate showed a high TSH level in mass-screening for congenital hypothyroidism and developed transient hypothyroidism. Her TBII disappeared at 114 days of age, and she remained euthyroid after discontinuation of thyroxin replacement at 146 days of age. The other two neonates were euthyroid, though they had positive TBII. In three mothers, the doses of IgGs that inhibited 125I-TSH binding to the level of 50% were compared. The potency of IgG from the mother whose neonate developed hypothyroidism was stronger than that of IgG from the other two mothers. And the elevation of cAMP induced by bovine TSH in suspension culture with porcine thyroid follicles was significantly reduced in the presence of IgG from the three mothers when compared with normal IgG. The thyroid-stimulation blocking activity was more potent in the mother whose neonate developed hypothyroidism than in the other two mothers. This study suggests that the thyroid function of neonates born to primary myxedema with blocking type TBII is influenced by the potency of TSH-binding inhibitor and thyroid-stimulation blocking activity of the mother.     

Transient hypothyroidism in infants born to mothers with chronic thyroiditis--a nationwide study of twenty-three cases. The Transient Hypothyroidism Study Group

To define the difference in prognosis and the clinical features of transient neonatal hypothyroidism in infants born to mothers with chronic thyroiditis, we conducted a nationwide study of this condition. Sixteen mothers with chronic thyroiditis and twenty-three of their offspring with transient hypothyroidism were registered and reported in this paper. Five (group A) of twenty-two live infants showed physical, mental and/or psychomotor developmental delay (IQ below 80). No significant difference between TSH-binding inhibitor immunoglobulin (TBII) or thyroid-stimulation blocking antibody (TSBAb) activities in groups A and B (normal development) were noted. Moreover, there was no significant difference in thyroid function in the newborn period, ages at the start of thyroid medication or the dose and duration of treatment in the two groups. A striking difference observed between the two groups was the thyroid function of their mothers during pregnancy. In group A, four mothers were hypothyroid during pregnancy, and another mother discontinued thyroid medication in the last trimester and her baby was most delayed at the start thyroid medication. On the other hand, the mothers of only two of seventeen live cases in group B had mild hypothyroidism during pregnancy. There were two sets of siblings whose mother received inadequate treatment during the first pregnancy and adequate treatment during the second pregnancy. The psychomotor, physical and mental developmental delay were observed in their first babies. These findings suggested that maternal thyroid function during pregnancy might be an important factor in the prognosis of infants born to mothers with chronic thyroiditis.     

Transient neonatal hypothyroidism due to transplacental transfer of maternal immunoglobulins that inhibit TSH binding, TSH-induced cAMP increase and cell growth

Transient neonatal hypothyroidism due to transplacental transfer of maternal blocking type TSH receptor antibodies (TRAb) was found in a baby born to a 27-yr-old mother, who had been receiving thyroxine medication for primary myxedema. Maternal IgG inhibited radiolabelled TSH binding to its receptor (TBII), TSH-stimulated thyroid adenylate cyclase (AC) activation (TSII) and TSH-stimulated 3H-thymidine uptake (TGII) in cultured rat thyroid cells (FRTL-5). At birth, the baby's IgG showed similar activities to maternal IgG but all these activities decreased gradually, and disappeared from her serum within 12 weeks of age. In the baby, initially nonvisualized thyroid was clearly visualized on 99 m-Tc thyroid scintigraphy when all these blocking activities disappeared, TSII and TGII being decreased more slowly than TBII, and the baby remained euthyroid after discontinuation of thyroxine. This study suggests that such IgGs induced hypothyroidism and thyroid atrophy in the mother and were responsible for transient neonatal hypothyroidism in the baby.     

Similarity and dissimilarity between clinical and laboratory findings, especially anti-thyrotropin receptor antibody in ophthalmic Graves' disease without persistent hyperthyroidism and hyperthyroid Graves' disease

The aim of this study was to investigate thyroid states, significance of anti-TSH receptor antibodies and the clinical courses of patients with euthyroid Graves' ophthalmopathy. The clinical and laboratory finding of 30 patients with euthyroid Graves' ophthalmopathy were briefly as follows: 1) normal sized thyroid or small goiter; 2) negative or weakly positive thyrotropin binding inhibitor immunoglobulin (TBII); 3) normal thyroid [99 m-Tc] pertechnetate uptake; and 4) frequent observations of low serum TSH values. Besides TBII, thyroid stimulating antibody (TSAb) was measured under low salt and isotonic conditions using FRTL-5 rat thyroid cells. Both TBII and TSAb titers were lower in euthyroid Graves' ophthalmopathy than in hyperthyroid Graves' disease. Serum TSH levels frequently became low in patients considered as euthyroid upon the first examination as well as in Graves' patients in remission, reflecting preceding or mild hyperthyroidism. In follow-up studies, these patients with mildly elevated thyroid hormone levels and low TSH levels seldom reached a state of persistent hyperthyroidism, when TBII was negative or only weakly positive.     

Relationship among thyrotropin (TSH), thyroid stimulating immunoglobulins, and results of triiodothyronine (T3) suppression test in patients with Graves' disease

To investigate the relationship between TSH and abnormal thyroid stimulator(s) in patients with hyperthyroid Graves' disease in whom normal thyroid hormone levels in the serum were maintained by antithyroid drug therapy and in patients with euthyroid Graves' disease, determinations were made of the TSH concentration, action of thyroid stimulating immunoglobulins (TSAb and TBII), and T3 suppression. Out of thirty-three patients with hyperthyroid Graves' disease, twelve patients with subnormal TSH levels were all non-suppressible according to the T3 suppression test results and the detectability of TSAb and/or TBII was as high as 75%. In three out of five patients with euthyroid Graves' disease, the serum TSH level was subnormal. All three showed non-suppressibility in the T3 suppression test and positive action of either TSAb or TBII. One of them became clinically thyrotoxic when the TSAb activity was further increased and TBII became positive, and was therefore diagnosed as having hyperthyroid Graves' disease. The present findings suggest that there are still abnormal thyroid stimulator(s) in patients with hyperthyroid Graves' disease who have low TSH, even if their thyroid hormone concentrations remain normal. Moreover, it is likely that some of the patients with euthyroid Graves' disease are actually in a state of subclinical hyperthyroidism because of the presence of abnormal thyroid stimulator(s).     

Transient hypothyroidism associated with increased anti-microsomal antibodies.

An unusual case of transient hypothyroidism during the course of chronic thyroiditis was reported. A 25 years old female noticed the remarkable enlargement of thyroid gland 3 months after paturition and was developed to be hypothyroidism with decreased blood thyroid hormone and increased serum TSH. The patient recovered to be euthyroid spontaneously in association with the decrement of goiter size. Anti-thyroid microsomal antibody increased concomitantly with hypothyroid period and decreased parallel with the recovery of thyroid function. The ratio of TSH potency estimated by bioassay to that by immunoassay changed during the course. Possible etiologic factors of this transient changes were discussed.     

Significant fluctuation of thyroid function in children with chronic lymphocytic thyroiditis

In order to investigate the degree of pituitary reserve of TSH secretion and the fluctuation of thyroid function in children with chronic lymphocytic thyroiditis, TSH response to TRH was examined in 42 patients, and the thyroid function was carefully followed up in two patients retrospectively and in four prospectively. Increased basal TSH levels were revealed in seven patients (16.8%), and an exaggerated response of TSH to TRH loading in 15 (35.8%). We retrospectively observed spontaneous recovery of thyroid function in two cases. In one of them, two episodes of a transient decrease in thyroid function over a period of several years were noted. Prospectively, low normal T4, elevated TSH and normal T3 were detected in two cases at the first visit. Thereafter, TSH levels decreased to the normal range and the exaggerated response of TSH to TRH became normal. In two other cases, typical transient hypothyroidism occurred during the observation period. These fluctuations lasted for only a few months, and concomitant changes in the size of the thyroid gland were observed. No signs or symptoms suggesting viral infection were noted during the study period. Nor were changes in titers of thyroid auto-antibodies detected. These results show that the secretion of TSH is exaggerated and the thyroid function is decreased in adolescents with chronic lymphocytic thyroiditis, but the thyroid function may fluctuate from euthyroid to hypothyroid within a short period. The causes of these changes, especially of the transient hypothyroidism remain to be classified.     

Transient subclinical hypothyroidism in early pregnancy

In the present study, a new clinical state of transient subclinical hypothyroidism in 12 early pregnant women is documented. The incidence of transient subclinical hypothyroidism was 18 (0.19%) among 9,453 pregnant women examined in this series in Sapporo. The characteristics of transient subclinical early gestational hypothyroidism in our study may be summarized as follows: temporarily increased TSH in the blood (11.7 +/- 6.3 microU/ml; mean +/- S.D.) in early pregnant women at 8.5 +/- 2.4 weeks of gestation, accompanied with or without reduced FT4 which spontaneously return to normal at 17.9 +/- 7.1 weeks; no subjective complaints and no previous history of thyroid disease; small struma; positive titers of antimicrosome antibody and antithyroglobulin antibody; normal serum hCG; negative results for TSH receptor antibody. None of the infants show any physical abnormality such as struma and none of the patients had neck pain or fever suggesting subacute thyroiditis. The presence of autoantibody to the thyroid gland and echographical findings strongly suggest the existence of Hashimoto's thyroiditis in early pregnant women with transient subclinical hypothyroidism, although the cause of transient subclinical early gestational hypothyroidism remains obscure.     

Adipocyte-TSH-receptor-related antibodies in Graves' disease detected by immunoprecipitation

Fat cell TSH receptor-related antibodies were detected by immunoprecipitation of 125I-TSH-receptor complexes and the nature of the antibodies was analyzed. To 125I-TSH prebound to Triton-solubilized receptors from guinea pig fat tissues, 50 micrograms of immunoglobulin G (IgG) was added and precipitation was effected by the addition of antihuman IgG. Immunoprecipitation values in 13 patients with Graves' disease were significantly (p less than 0.05) higher than those in 11 normal subjects. No significant increase in the values was seen in 8 patients with Hashimoto's disease. No correlation was observed between immunoprecipitation values and titers of antimicrosomal and antithyroglobulin antibodies. Neither was there any correlation between the values and TSH-binding inhibitor immunoglobulins (TBII) detected by the radioreceptor assay. The IgG fractions positive for the immunoprecipitation antibody were found to be poor human thyroid stimulators (HTS) relative to their TBII activities. And a highly significant correlation was observed between TBII and HTS activities among IgGs without detectable antibody by immunoprecipitation (r=0.907; p less than 0.005; n=7). These findings 1) demonstrate that immunoprecipitation assay using fat cell TSH receptor may detect TSH receptor-related antibodies different from TBII in patients with Graves' disease and 2) suggest the antibodies may recognize determinants on the receptor or its vicinity that do not participate in the binding of TSH or thyroid stimulating antibody, and may interfere with thyroidal response to these stimulators.     

Does autoantibody-negative Graves' disease exist? A second evaluation of the clinical diagnosis.

Advanced technical methods are essential for accurate diagnosis of Graves' or Basedow's disease (GD). Inadequate methods may lead to a false diagnostic conclusion. We have analyzed the clinical features and methodology aspects of cases diagnosed as GD with negative findings for TSH receptor autoantibodies. The initial diagnosis was based on clinical findings (patient record, hypermetabolic state, goiter palpation) and laboratory testing (fT4 and TSH). From a total of 255 newly registered patients with GD, fifty-one (20%) were negative in a conventional porcine TBII assay. All fifty-one patients were retested with 131I or 99mTc uptake tests, thyroid scintigraphy, and a second-generation TBII assay. Results disclosed twenty-one cases (8.3%) with diagnosis other than GD: ten cases of autonomous hyperthyroidism (Plummer's disease), seven cases of painless thyroiditis and four cases of euthyroid endocrine ophthalmopathy. All twenty-one patients remained negative in the second-generation TBII assay. Measurement by second-generation TBII assay was performed on the remaining thirty patients initially found negative for TBII. As a result of this reevaluation, only 234 of the original 255 patients had GD. Of those, 231 (204 according to porcine plus 27 according to human TRAb assay) had detectable TBII (98.7%). This investigation stresses the problem of correct diagnosis and the methodological limitations in the assessment of laboratory parameter validity in GD. Based on this work, TSH receptor autoantibody-negative GD is extremely rare.     

A patient with Graves' disease who developed hypothyroidism associated with thyroid stimulation blocking immunoglobulin during anti-thyroid drug therapy

A girl, 12 years of age, developed Graves' disease compounded with rheumatic fever and idiopathic thrombocytopenic purpura. Thrombocytopenia improved under short-term treatment with steroids and her mitral valvular insufficiency, due to the rheumatic fever, disappeared 4 years later. Initially, she had been treated with propylthiouracil (PTU) for 28 months. She suffered a relapse 9 months after stopping PTU and so she was given further PTU therapy. However, hypothyroidism developed 11 months after the initiation of therapy and continued, though further PTU treatment was discontinued. She now receives 1-thyroxine and maintains a euthyroid state. At the onset of the patient's hyperthyroidism, the TSH-binding inhibitor immunoglobulin (TBII) and the thyroid stimulating antibodies (TSAb) were found to be positive. During the remission period, only the thyroid stimulation blocking immunoglobulin (TSBI) was weakly positive. At relapse, only TBII was mildly positive. When hypothyroidism developed, both TBII and TSBI were positive, and TSAb was negative in all testings of her diluted IgGs. The patient's TBII and thyroid dysfunction were unaffected by high-dose intravenous gammaglobulin therapy or by treatment with prednisolone 0.5 mg/kg/day for 2 weeks. In conclusion, the emergence of TSBI during or after anti-thyroid drug therapy might possibly lead to hypothyroidism in patients with Graves' disease.     

Onset of subacute aggravation of chronic thyroiditis followed immediately by transient hypothyroidism during antithyroid drug therapy for Graves' hyperthyroidism.

A 56-year-old man presented with clinical and biochemical hyperthyroidism with high thyroid 99mTc uptake, positive result for antimicrosomal antibody (MCHA; 1:8,100) and markedly high activities of thyrotropin-binding inhibitory immunoglobulin (TBII; 90.0%) and thyroid-stimulating antibody (TSAb; 2,400%). Fifty days after the initiation of antithyroid drug therapy, he developed a painful tender enlarged thyroid and an accelerated erythrocyte sedimentation rate (ESR), which were followed immediately by hypothyroidism with a transient increase in MCHA titer (peak; 1:218,700) despite of maintenance of high TBII and TSAb activities. Two and a half months after the recovery from hypothyroidism, recurrent hyperfunction was observed with further elevation of TSAb activity (4,643%). After about 2 weeks, recurrences of a painful tender enlarged thyroid and an accelerated ESR, which were followed by abrupt progression to hypothyroidism, were found. Specimens obtained when he had still slightly tender goiter after the first and second episodes of neck pain showed microscopically extremely extended interstitial fibrosis with collapsed follicles and moderate lymphocytic infiltration. Thyroid-stimulation-blocking antibody was not detected at either onset of hypothyroidism. Thus, it is possible that Graves' disease, subacute aggravation of chronic thyroiditis and hypothyroidism coexist in the same individual. In such patients, thyroid status may be determined by the degree of each of the stimulating factors (TSH, TSAb and/or unknown factors) and suppressive or destructive factors (humoral and/or cellular) and may be changed in a very short interval.     

A predicted case with neonatal transient hypothyroidism due to blocking type thyrotropin binding inhibitor immunoglobulins (TBII)

A 26-yr-old female with primary hypothyroidism due to potent blocking type thyrotropin binding inhibitor immunoglobulins (TBII) was advised of the high risk of bearing a baby with neonatal transient hypothyroidism. This prediction proved valid and her baby was found to be hypothyroid with a potent TBII. By expressing the baby's TBII as the absolute concentration, we found an almost linear regression of TBII and the half-life was calculated as 18.0 days. The TBII became undetectable by the 6th month and thyroid medication was stopped, however the baby remained euthyroid with subsequent normal physical and mental development.     

Detection of thyroid-stimulating antibody in patients with inflammatory thyrotoxicosis.

The detection of thyrotropin-binding inhibitory immunoglobulins (TBII) and/or thyroid-stimulating antibody (TSAb) has been reported in some patients with painless thyroiditis (PT) or subacute thyroiditis (SAT). However, its mechanism is unknown. TBII and TSAb measured using cultured FRTL-5 thyroid cells were evaluated in 18 patients with PT, 11 patients with SAT and a patient with SAT-like symptoms. In PT, we detected both TBII and TSAb activities in only 1 patient. This case had first come to our attention with subclinical hypothyroidism and had already had weakly positive TSAb activity (205.9%) 1 year before the present onset of PT. This patient had a transient thyrotoxicosis with a low uptake (24 h) of 123I (4.3%) and 821.0% TSAb activity, and subsequently developed a transient subclinical hypothyroidism. Even after 2 years, she still had positive TSAb activity (382.3%). In SAT, TBII and TSAb activities were not detected during the courses of any patients. A patient with transient thyrotoxicosis, who had a high uptake (30 min) of 99mTc (5.6%) and SAT-like symptoms (painful tenderness on right thyroid lobe and markedly accelerated erythrocyte sedimentation rate), showed positive activities of TBII (34.9%) and TSAb activity (1,366.9%). Histological findings by thyroid needle biopsy performed in the thyrotoxic phase showed coexistence of granulomatous inflammatory changes and hyperplasia with papillary folds of some residual follicular cells.(ABSTRACT TRUNCATED AT 250 WORDS)     

Autoimmune thyroid diseases in women with breast cancer and colorectal cancer

The aim of the study was to compare the prevalence of autoimmune thyroid diseases in three groups of women (66 with breast cancer (CaB), 68 with colorectal cancer (CaC) and 49 without oncological diseases as a control group). Serum levels of thyroid-stimulating hormone (TSH), free thyroxin (fT4), antibodies to thyroglobulin (TGB-ab) and thyroperoxidase (TPO-ab) and tumor markers CEA, CA 15-3 and CA 19-9 were investigated in all subjects by using the chemiluminiscence method. In contrast to Graves' disease (no observed case), autoimmune thyroiditis was diagnosed in 24.2 % women with CaB (4.5 % euthyroid and 19.7 % with subclinical or overt hypothyroidism), compared to 16.7 % in women with CaC (2.0 % euthyroid and 14.7 % with subclinical or overt hypothyroidism) and 16.2 % controls (4.0 % euthyroid and 12.2 % with subclinical or overt hypothyroidism). Serum levels of TGB-ab were higher in the group with breast cancer as compared to those with colorectal cancer and the control group (medians: 35.80 vs. 31.75 vs. 27.70, p<0.001). Similarly, the percentage of positive TGB-ab and TPO-ab serum levels was higher in women with breast cancer as compared to those with colorectal cancer and the control group. The results of the study support the controversial theory that there is an increased prevalence of autoimmune thyroiditis in women with breast cancer.     

Disappearance of blocking type thyrotropin binding inhibitor immunoglobulin (TBII) during thyroid and steroid medication in a patient with autoimmune thyroiditis

A 55 year-old female had suffered from 3 consecutive diseases for a year. The diseases were ulcerative colitis, primary hypothyroidism and idiopathic thrombocytopenic purpura, and had been treated with L-thyroxine (50 micrograms daily) and betamethasone (0.5 to 1.5 mg daily). On examination, the thyroid gland was not palpable at all, thyroid 99 mTc pertechnetate uptake was 0%, and an echogram revealed the existence of an atrophic gland. Thyrotropin binding inhibitor immunoglobulin (TBII) in the serum was elevated to 58.0% and her IgG almost completely inhibited the in vitro cAMP increase due to bTSH. After 5 months TBII turned out to be negative and the inhibitory IgG activity was reduced significantly. The thyroid gland also became visible scintigraphically. Thyroid medication was then stopped. Four months after the cessation of thyroxine, she felt quite well and her thyroid functions remained within the normal ranges. Antibody to Yersinia enterocolitica was positive at a low titer (X20) in the early stages, but elevated reciprocally with the fall in TBII and finally reached X320. In conclusion, evidence of the disappearance of blocking type TBII from the serum was demonstrated for the first time. Steroid might have caused some favorable effects, and this clinical report indicates the possibility that remission of hypothyroidism due to blocking type TBII can be expected.     

Possible binding site of thyrotropin binding inhibitor immunoglobulin (TBII) on the thyrotropin (TSH) receptor, which is different from TSH binding site

A synthetic decapeptide, P-194, which has the sequence No. 103 to 111 of hTSH receptor structure with an additional N-terminal tyrosine, did not bind TSH nor affected its receptor binding and thyroid stimulating activity. Preincubation of P-194 with sera from thyroid patients caused a significant decrease in TBII activity in almost all 12 TBII positive sera and an increase of thyroid stimulating activity in 3 of 7 Graves' IgG studied. In addition, [125I] P-194 bound to serum IgG fraction from thyroid patients with a positive correlation with TBII (N = 35, r = 0.509, p less than 0.01). The P-194 portion may be, at least a part of, TBII binding site distinct from the TSH binding site on the TSH receptor.     

A case of Graves' disease with false hyperthyrotropinemia who developed silent thyroiditis.

We encountered a patient who developed silent thyroiditis during the course of Graves' disease. The diagnosis of silent thyroiditis was made on the basis of a low thyroidal 131I uptake, no response to the thyrotropin releasing hormone (TRH) test, and subsequent hypothyroidism despite the presence of high titers of thyrotropin (TSH) receptor antibody (TRAb) and thyroid stimulating antibody (TSAb). The patient, in addition, had a discrepancy between serum TSH and thyroid hormone values. This was due to the presence of interfering substances that react to mouse IgG in the sera since serum TSH levels were decreased in a dose dependent manner by the addition of increasing amounts of mouse IgG to the sera. It should therefore be noted that silent thyroiditis can develop in patients with Graves' disease. Furthermore, clinicians should be aware that two-site immunoassay kits that use mouse monoclonal antibodies are subject to interference by some substances, possibly antibodies which react to mouse IgG.     

Thyrotropin reference range--should it be changed?

Current thyrotropin (TSH) reference range established by sensitive assays is from 0.2-0.4 mj.m./l to 4.0-4.5 mj.m./l. Serum TSH reference range was performed using specimens from healthy volunteers without history of thyroid disease but the values distribution is not concordant with Gaussian curve and is skewed toward upper values. It is claimed that upper reference limit for TSH should be declined because of possible incorporation of individuals with unrecognized chronic lymphocytic thyroiditis into initial study. American National Academy of Clinical Biochemistry recommends to examine only euthyroid healthy volunteers without personal or family history of thyroid dysfunction, visible or palpable goiter, with no detectable thyroid antibodies measured by sensitive immunoassays and without any medication except estrogen. Many authors observed that even in such rigorously selected population the upper limit of TSH does not decrease significantly. The other possible factors which may influence TSH values are ethnic features, age, iodine intake, time of phlebotomy or assay sensitivity and specificity. Furthermore there are no epidemiological data showing adverse consequences of serum TSH between 3.0 mj.m./l and 5.0 mj.m./l. And because of it current upper limit for TSH should remain unchanged. However one must realize that many people with TSH values between 3.0 mj.m./l and 5.0 mj.m./l have unrecognized chronic lymphocytic thyroiditis and should be followed because of possible future hypothyroidism. The special care is needed for pregnant women or those planning to be pregnant.     

Circulating chemokine (CXC motif) ligand (CXCL)9 is increased in aggressive chronic autoimmune thyroiditis, in association with CXCL10

Chemokine (CXC motif) ligand (CXCL)9 (CXCL9) has been shown to be involved in autoimmune thyroid disorders, however no data are present about CXCL9 circulating levels in chronic autoimmune thyroiditis (AT) vs controls. Serum CXCL9 (and for comparison CXCL10) has been measured in patients with AT vs normal control and nontoxic multinodular goiter, and this parameter has been related to the clinical phenotype. For this study we selected 189 consecutive patients with newly diagnosed AT, 63 euthyroid controls, 30 patients with nontoxic multinodular goiter. The three groups were similar in gender distribution and age; 26% of AT patients had subclinical hypothyroidism. Serum CXCL9 was significantly higher in AT (148±110 pg/mL) than in controls (71±34 pg/mL) or patients with multinodular goiter (87±35 pg/mL) (p<0.0001). Among AT patients, CXCL9 levels were significantly higher in patients older than 50 years, those with a hypoechoic ultrasonographic pattern or with hypothyroidism. Also CXCL10 was confirmed to be associated with AT, overall in presence of hypothyroidism. In a multiple linear regression model of CXCL9 (ln[pg/mL]) vs age, thyroid volume, TSH, AbTg, AbTPO, hypoechoic pattern, the presence of hypervascularity, and CXCL10 (ln[pg/mL]), only TSH and CXCL10 (ln[pg/mL]) were significantly related to serum CXCL9 levels. We show that circulating CXCL9 is increased in patients with aggressive thyroiditis and hypothyroidism. A strong relation between circulating CXCL9 and CXCL10 has been first shown, underlining the importance of a T helper 1 immune attack in the initiation of AT.