Serum thyroid stimulating hormone level for predicting utility of thyroid uptake and scan.

BACKGROUND: Thyroid uptake and scan (TUS) is a clinical tool used for differentiation of thyrotoxicosis etiologies. Although guidelines recommend ordering a TUS for evaluation of low TSH levels, no specific value is defined. This study aimed to determine a TSH cutoff at which TUSs yield a greater likelihood of successful determination of etiology to avoid unnecessary testing. METHODS: This was a retrospective study on 137 patients seen by an endocrinologist who underwent TUS for evaluation of low TSH (<0.4 µU/mL). A receiver operating curve analysis was performed to determine the TSH cutoff with maximal sensitivity and specificity for prediction of diagnostic utility. RESULTS: Ninety percent of TUSs (n = 123) led to a diagnosis, while 10% (n = 14) were inconclusive or normal. Diagnoses included Graves' diseases (52%), toxic multinodular goiter (19%), thyroiditis (12%), and solitary toxic adenoma (7%). The median TSH value was 0.008 µU/mL (IQR 0.005, 0.011), and the median free T4 value was 1.7 µU/mL (IQR 1.3, 2.8). The ROC analysis produced an area under the curve of 0.86. The optimal TSH cutoff value was 0.02 µU/mL (sensitivity 80%, specificity 93%) for prediction of diagnostic yield. CONCLUSION: This study demonstrates that TSH is a useful predictor of the utility of TUS in yielding an etiology of thyrotoxicosis. Our analysis showed that TUS had a greater likelihood of determining an etiology when TSH was ≤0.02 µU/mL. This information can help clinicians avoid unnecessary cost and patient time burden when TUS is unlikely to aid in determining the etiology of thyrotoxicosis.

Compared with classic Hashimoto's thyroiditis, chronic autoimmune serum-negative thyroiditis requires a lower substitution dose of L-thyroxine to correct hypothyroidism.

PURPOSE: Serum-negative-chronic-autoimmune-thyroiditis (SN-CAT) is considered a milder variant of classic Hashimoto's thyroiditis (CHT). However, its prevalence remains unknown and it is still unclear whether SN-CAT behaves differently in terms of L-thyroxine (LT4) substitution treatment of hypothyroidism. Aims of this study were to estimate the prevalence of SN-CAT in a large series of hypothyroid patients and to compare LT4 requirements in hypothyroid patients with SN-CAT and CHT. METHODS: Five-hundred-eighty-one consecutive patients with primary-autoimmune-hypothyroidism were enrolled in a cross-sectional study. LT4 requirements and thyroid-volume changes were longitudinally evaluated in 49 hypothyroid patients with SN-CAT and in 98 sex and age-matched hypothyroid patients with CHT. RESULTS: In our series the prevalence of SN-CAT was 20.8%. At diagnosis, patients in the CHT and SN-CAT groups had similar male/female ratio, age and BMI, while serum TSH and thyroid-volume were significantly greater in the CHT group. In the longitudinal study, during a follow-up of 8.9 ± 4.6 years, 8 out of 49 (16.3%) SN-CAT patients developed positive tests for of circulating TPO-Ab and/or Tg-Ab. Thyroid-volume significantly decreased in CHT patients, but not in those with SN-CAT. The maximum daily substitution dose of LT4 was smaller in SN-CAT patients as compared with the CHT ones. Multivariate analysis showed that age, BMI, basal TSH and thyroid antibody status independently and significantly predicted the maximum daily substitution dose of LT4. CONCLUSIONS: SN-CAT accounts for a significant proportion of patients with autoimmune hypothyroidism. Compared with hypothyroid patients diagnosed with CHT, the SN-CAT ones require smaller doses of LT4 to correct their hypothyroidism.

Comparison of the New, Rapid, and Fully Automated Kryptor TSH receptor Antibodies Assay (B.R.A.H.M.S.) with the Radioimmunological Assay (B.R.A.H.M.S.).

BACKGROUND: Radioimmunoassays, which are often not automated and time-consuming, are gradually being re-placed in medical laboratories by non-radioactive methods that need to be evaluated. The purpose was to compare the measurement of thyroid-stimulating hormone receptor antibodies (TRAb) by the new Brahms' kit using Kryptor TRACE technology and the Brahms' radioimmunoassay. METHODS: We prospectively collected all samples from patients who received thyroid-stimulating hormone receptor antibodies testing in July 2018 at the University Hospital of Brest. The radioimmunoassay used was the Dynotest TRAK human by BRAHMS Diagnostica (Berlin, Germany). The Kryptor method used the BRAHMS TRAK human Kryptor kit performed with the Kryptor Compact Plus system. RESULTS: The inter-assay coefficient variations for the radioimmunological and Kryptor methods were 11.07% and 8.36%, respectively, with the low level quality control and 8.36% and 4.38%, respectively, with the high level quality control. Forty-four patients were included in the study including thirty-two Graves' disease patients in follow-up. The sensitivity of the radioimmunological method for the detection of Graves' disease was 0.94 and the specificity was 0.73. The sensitivity of the Kryptor method was 0.91 and the specificity was 0.91. A non-proportional systematic bias in favor of higher values of TRAb concentrations with the radioimmunological method was observed: slope of 0.93 (0.74 - 1.07, 95% confidence interval) and an intercept of -0.69 IU/L (-1.58 to -0.30, 95% confidence interval). Compared to the Kryptor method, the radioimmunological method tends to overestimate TRAb concentrations by up to 120%. CONCLUSIONS: The fully automated Brahms Kryptor kit using TRACE technology to measure TRAb reduces sampling time and intra- as well as inter-assay variations. The Kryptor kit underestimates the results of TRAb leading to a lower sensitivity and higher specificity compared to the radioimmunoassay. Thus, the new Brahms Kryptor kit has good laboratory performances but the interpretation of the results must still be performed with caution.

Serum autotaxin levels are associated with Graves' disease.

Graves' Disease is a representative autoimmune thyroid disease that presents with hyperthyroidism. Emerging evidence has shown the involvement of lysophosphatidic acid (LPA) and its producing enzyme, autotaxin (ATX), in the pathogenesis of various diseases; among them, the involvement of the ATX/LPA axis in some immunological disturbances has been proposed. In this study, we investigated the association between serum ATX levels and Graves' disease. We measured the levels of serum total ATX and ATX isoforms (classical ATX and novel ATX) in patients with untreated Graves' disease, Graves' disease treated with anti-thyroid drugs, patients with subacute thyroiditis, silent thyroiditis, Plummer's disease, or Hashimoto's thyroiditis, and patients who had undergone a total thyroidectomy, as well as normal subjects. The serum total ATX and ATX isoform levels were higher in the patients with Graves' disease, compared with the levels in the healthy subjects and the patients with subacute thyroiditis. Treatment with anti-thyroid drugs significantly decreased the serum ATX levels. The serum ATX levels and the changes in serum ATX levels during treatment were moderately or strongly correlated with the serum concentrations or the changes in thyroid hormones. However, the administration of T3 or T4 did not increase the expression or serum levels of ATX in 3T3L1 adipocytes or wild-type mice. In conclusion, the serum ATX levels were higher in subjects with Graves' disease, possibly because of a mechanism that does not involve hyperthyroidism. These results suggest the possible involvement of the ATX/LPA axis in the pathogenesis of Graves' disease.

Painless Thyroiditis and Fulminant Type 1 Diabetes Mellitus in a Patient Treated with an Immune Checkpoint Inhibitor, Nivolumab.

The programmed cell death-1 (PD-1) pathway is a novel therapeutic target in immune checkpoint therapy for cancer. Nivolumab, an anti-PD-1 monoclonal antibody, blocks PD-1 and can restore anti-cancer immune responses by disrupting the signal that inhibits T-cell activation. Nivolumab may induce endocrine-related adverse events, including hypophysitis, autoimmune thyroiditis, and type 1 diabetes mellitus. Here we report a 68-year-old female patient with advanced renal cell carcinoma who was treated with nivolumab. She had positive anti-thyroglobulin antibodies and anti-thyroid peroxidase antibodies with slightly elevated thyroid-stimulating hormone (9.048 µU/mL), and was diagnosed as chronic thyroiditis with subclinical hypothyroidism before nivolumab therapy. She developed painless thyroiditis after the first cycle of the therapy (Day 14). At the 7th cycle of nivolumab therapy (Day 98), hyperglycemia (473 mg/dL) was noted, whereas glycated hemoglobin level was 6.9%. Islet-related autoantibodies were all negative. The glucagon tolerance test showed complete depletion of insulin. Human leukocyte antigen typing showed haplotype DRB1*09:01-DQB1*03:03, which was reported to be closely associated with type 1 diabetes mellitus in Japan. Fulminant type 1 diabetes mellitus was diagnosed, and she was immediately treated with multiple daily injections of insulin. Fulminant type 1 diabetes mellitus is characterized by rapid-onset diabetic ketoacidosis, and negative islet-related autoantibodies, and was proposed as a novel subtype of non-autoimmune diabetes. Preceding painless thyroiditis with positive thyroid autoantibodies observed in the present case, however, raises the possibility that autoimmune mechanisms are involved in the pathogenesis of nivolumab-induced fulminant type 1 diabetes mellitus.

Ultrasound scoring in combination with ultrasound elastography for differentiating benign and malignant thyroid nodules.

OBJECTIVE: The aim of this study was to evaluate the value of ultrasound scores obtained by conventional ultrasonography and ultrasound elastography in the differentiation of benign and malignant thyroid nodules in Chinese patients. METHODS: This study included 297 patients who were referred for surgery for compressive symptoms or suspicion of malignancy. Five hundred and twelve thyroid nodules were examined by ultrasonography. The final diagnosis was based on histological findings. A seven-point ultrasound scoring system based on conventional ultrasonography and a five-point scoring system based on ultrasound elastography were applied independently or in combination. The receiver operating characteristic (ROC) curves were graphed, and the areas under the curves (AUCs) were compared using the χ(2) -test. RESULTS: Solid composition, hypo-echoic appearance, an irregular or blurred margin, an aspect ratio ≥1, intranodular blood flow and presence of microcalcifications were significant predictors of malignant thyroid nodules. The AUC (95% CI) was 0·9067 (0·8817-0·9318) for the ultrasound scores based on conventional ultrasonography and 0·9080 (0·8842-0·9317) for the elasticity scores. The combination of these two scoring systems provided good accuracy with an AUC (95% CI) of 0·9415 (0·9223-0·9606), which was significantly higher than that obtained with the conventional ultrasound scores (χ(2)  = 36·03, P < 0·001) or the elasticity scores (χ(2)  = 12·80, P < 0·001) individually. When we set the cut-point to ≥5, the sensitivity and specificity were 85·22% and 87·38%, respectively. CONCLUSIONS: Elastography in combination with conventional ultrasonography is a promising imaging-based approach that can assist in the differential diagnosis of thyroid cancer.

Clinicopathological features of Riedel's thyroiditis associated with IgG4-related disease in Japan.

Riedel's thyroiditis (RT) is a rare chronic fibrosing disorder characterized by a hard, infiltrative lesion in the thyroid gland, which is often associated with multifocal fibrosclerosis. Immunoglobulin G4-related disease (IgG4-RD) is typified by infiltration of IgG4-positive plasma cells into multiple organs, resulting in tissue fibrosis and organ dysfunction. In order to evaluate the clinicopathological features of RT and its relationship with IgG4-RD, we performed a Japanese literature search using the keywords "Riedel" and "Riedel's thyroiditis." We used the electronic databases Medline and Igaku Chuo Zasshi, the latter of which is the largest medical literature database in Japan. The diagnosis of RT was based on the presence of a fibroinflammatory process with extension into surrounding tissues. Only 10 patients in Japan fulfilled RT diagnostic criteria during the 25-year period between 1988 and 2012. Two patients with confirmed IgG4/IgG immunohistochemical findings demonstrated 43 and 13 IgG4-positive plasma cells per high-power field, respectively, and the IgG4-positive/IgG-positive plasma cell ratios of 20% and less than 5%. Of the 10 patients with RT, two received glucocorticoids, one of whom experienced marked shrinkage of the thyroid lesion. One patient had extra-thyroid involvement in the form of retroperitoneal fibrosis. Although the clinicopathological features of RT suggest that IgG4-RD may be the underlying condition in some cases, further investigation is needed to clarify the etiology of RT in relation to IgG4-RD.

The value of postoperative parathyroid hormone levels in predicting the need for long-term vitamin D supplementation after total thyroidectomy.

BACKGROUND: Few studies have examined the need for vitamin D supplementation after total thyroidectomy. This study examines the role of postoperative day (POD) 1 serum calcium and parathyroid hormone (PTH) levels in predicting the need for long-term vitamin D supplementation after total thyroidectomy. METHODS: A retrospective, single institutional study of patients who underwent total thyroidectomy between January 2007 and December 2008 was performed. Data collected included extent of surgery, final pathology, postoperative calcium (mg/dl) and PTH (pg/ml) values, and duration of vitamin D supplementation. Patients were divided into 4 groups based on POD1 PTH values: group 1 (<5.0); group 2 (5.0-10); group 3 (10.1-20); and group 4 (>20). RESULTS: Of the 104 patients, 26 were in group 1, 12 in group 2, 18 in group 3, and 48 in group 4, with median PTH values of <2.5, 8.2, 14.1, and 30 pg/ml, respectively. All 7 (7%) patients who required vitamin D supplementation >1 month were in group 1. The positive predictive value of POD1 PTH <5.0 in predicting supplementation >1 month was 27% (sensitivity 100%, specificity 80%). Seventy-eight patients had a POD1 PTH level ≥5, and none required vitamin D supplementation >1 month (100% negative predictive value). The positive predictive value of various POD1 calcium thresholds (<7.5, <8.0, and <8.5 mg/dl) was 17, 14, and 15%, respectively. CONCLUSIONS: Postoperative PTH levels better predict long-term hypocalcemia requiring vitamin D supplementation than serum calcium levels. A PTH level ≥5.0 may identify patients who can be safely discharged without routine vitamin D supplementation.

Shared and unique metabolic features of the malignant and benign thyroid lesions determined with use of 1H HR MAS NMR spectroscopy.

The purpose of this work was to investigate the distinct and common metabolic features of the malignant and benign thyroid lesions in reference to the non-transformed tissue from the contralateral gland (chronic thyroiditis and colloid goiter). 1H HR MAS NMR spectra of 38 malignant lesions, 32 benign lesions and 112 samples from the non-tumoral tissue (32 from chronic thyroiditis and 80 samples from colloid goiter) were subjected both to multivariate and univariate analysis. The increased succinate, glutamine, glutathione, serine/cysteine, ascorbate, lactate, taurine, threonine, glycine, phosphocholine/glycerophosphocholine and decreased lipids were found in both lesion types in comparison to either colloid goiter or chronic thyroiditis. The elevated glutamate and choline, and reduced citrate and glucose were additionally evident in these lesions in reference to goiter, while the increased myo-inositol-in comparison to thyroiditis. The malignant lesions were characterized by the higher alanine and lysine levels than colloid goiter and thyroiditis, while scyllo-inositol was uniquely increased in the benign lesions (not in cancer) in comparison to both non-tumoral tissue types. Moreover, the benign lesions presented with the unique increase of choline in reference to thyroiditis (not observed in the cancerous tissue). The metabolic heterogeneity of the non-tumoral tissue should be considered in the analysis of metabolic reprogramming in the thyroid lesions.

The diagnostic predictive value of neutrophil-to-lymphocyte ratio in thyroid cancer adjusted for tumor size.

The role of systemic inflammation has not been clearly defined in thyroid cancers. There have been conflicting reports on whether systemic inflammatory markers have predictive value for thyroid cancers. We aimed to evaluate the association between systemic inflammatory markers and clinicopathological factors in thyroid cancers and to assess their predictive value for thyroid cancers in detail. Five hundred thirty-one patients who underwent surgery for thyroid nodules were included. The patient population consisted of 99 individuals (18.6%) with benign thyroid nodules and 432 individuals (81.4%) with thyroid cancers. In 432 patients with thyroid cancers, neutrophil-to-lymphocyte ratio (NLR) was significantly higher in the cases with tumors greater than 2 cm than in those with tumors less than 2 cm. (p = 0.027). NLR and platelet-to-lymphocyte ratio (PLR) were significantly higher in cases with lateral lymph node metastasis (LNM) than in those without LNM (p = 0.007 and 0.090, respectively). The nodule size was significantly higher in benign thyroid nodules than in thyroid cancers (p < 0.001). When the cases were stratified by tumor size, NLR was a significant predictor of thyroid cancers in cases with nodules greater than 2 cm (Exp(B) = 1.85, 95% CI = 1.15-2.97, p = 0.011), but not in those with nodules less than 2 cm. In thyroid cancers, preoperative NLR was associated with pathological prognosticators such as tumor size and lateral lymph node metastasis. When the size difference between thyroid cancers and benign thyroid nodules was adjusted, NLR could be a significant predictor of thyroid cancers.

Immune Checkpoint Inhibitor-Induced Thyroiditis Is Associated with Increased Intrathyroidal T Lymphocyte Subpopulations.

Background: Immune checkpoint inhibitors (ICIs) frequently cause thyroid dysfunction but their underlying mechanism remains unclear. We have previously demonstrated increased circulating natural killer (NK) cells and human leukocyte antigen (HLA)-DR surface expression on inflammatory intermediate CD14+CD16+ monocytes in programmed cell death protein-1 (PD-1) inhibitor-treated patients. This study characterizes intrathyroidal and circulating immune cells and class II HLA in ICI-induced thyroiditis. Methods: This is a single-center prospective cohort study of 10 patients with ICI-induced thyroiditis by flow cytometry of thyroid fine needle aspirates (n = 9) and peripheral blood (n = 7) as compared with healthy thyroid samples (n = 5) and healthy volunteer blood samples (n = 44); HLA class II was tested in n = 9. Results: ICI-induced thyroiditis samples demonstrated overall increased T lymphocytes (61.3% vs. 20.1%, p = 0.00006), CD4-CD8- T lymphocytes (1.9% vs. 0.7%, p = 0.006), and, as a percent of T lymphocytes, increased CD8+T lymphocytes (38.6% vs. 25.7%; p = 0.0259) as compared with healthy thyroid samples. PD-1 inhibitor-induced thyroiditis had increased CD4+PD1+ T lymphocytes (40.4% vs. 0.8%; p = 0.021) and CD8+PD1+ T lymphocytes (28.8% vs. 1.5%; p = 0.038) in the thyroid compared with the blood. Circulating NK cells, certain T lymphocytes (CD4+CD8+, CD4-CD8- T, gamma-delta), and intermediate monocytes were increased in ICI-induced thyroiditis. Six patients typed as HLA-DR4-DR53 and three as HLA-DR15. Conclusions: ICI-induced thyroiditis is a T lymphocyte-mediated process with intra-thyroidal predominance of CD8+ and CD4-CD8- T lymphocytes. The HLA haplotypes may be involved but need further evaluation. These findings expand the limited understanding of ICI-induced thyroiditis, which could be further translated to guide immunomodulatory therapies for advanced thyroid cancer.

Clinical characteristics of frequently recurring painless thyroiditis: contributions of higher thyroid hormone levels, younger onset, male gender, presence of thyroid autoantibody and absence of goiter to repeated recurrence.

Painless thyroiditis is characterized by transient thyrotoxicosis with complete recovery. Some patients, however, have repeated episodes of thyrotoxicosis, for which the mechanism of recurrence is not clear. We therefore studied the clinical characteristics in 8 patients with 4 or more episodes of thyrotoxicosis and 40 control patients. The age at onset was significantly earlier and the male-to-female ratio was significantly higher in the case group than the control group. The highest FT4 and FT3 levels were higher in the recurrent type. Multiple regression analysis showed contributions of higher peak FT4 level, male gender, presence of thyroid autoantibody, earlier onset, and smaller size of thyroid to repeated recurrence. Since the peak FT4 value, gender, autoantibody, age of onset and size of thyroid contribute to only 27.5% of the repeated recurrence cases, other factors such as genetic susceptibility or inflammatory tissue changes in thyroid may also be contributory. Further studies are needed to elucidate the mechanism underlying repeated recurrence.

Comparison of neutrophil-lymphocyte ratio and platelet-lymphocyte ratio in patients with thyroiditis and papillary tumors.

OBJECTIVE: The neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) have recently been introduced as prognostic markers of thyroid cancer and strong inflammatory markers. The study was performed to investigate the association of the PLR and NLR with thyroid inflammation and papillary cancer. METHODS: Patients with thyroiditis and patients with papillary carcinomas were compared with sex-, age-, and body mass index-matched healthy controls. The NLR and PLR were calculated and compared among the three groups. RESULTS: The NLR was significantly higher in patients with thyroiditis and non-significantly higher in patients with papillary cancer than in healthy controls. The PLR was significantly higher in both patients with thyroiditis and papillary cancer than in healthy controls. Like the NLR, the PLR was not different between patients with thyroiditis and papillary cancer. The NLR was significantly and positively associated with the PLR and white blood cell count. CONCLUSION: The PLR and NLR showed similar results in both thyroid inflammation and cancer. It seems difficult to obtain clear results in separating cancer from inflammatory events using these parameters. We suggest using them as supportive parameters of thyroid papillary cancer or inflammation.

Postpartum Heart Failure Complicated With Thyroiditis: A Concealed Aggravator of Peripartum Cardiomyopathy?

The etiology of peripartum cardiomyopathy (PPCM) remains unestablished, but the involvement of abnormal autoimmunity has been suggested. We report a case of PPCM that was triggered by postpartum thyroiditis. Despite the presence of myocardial damage indicated by cardiac magnetic resonance imaging, the patient's cardiac function completely recovered with the addition of bromocriptine to standard therapies. We discuss the role of thyroid hormones in the development of PPCM through aggravation of a prolactin-dependent antiangiogenic effect, and we argue that more attention should be paid to postpartum thyroiditis as a novel risk factor for PPCM.

High levels of the proNGF peptides LIP1 and LIP2 in the serum and synovial fluid of rheumatoid arthritis patients: evidence for two new cytokines.

The proNGF peptides LIP1 and LIP2 display multiple biological and physiological properties several of which share common features with the nerve growth factor (NGF). The objective of this study was firstly to demonstrate the presence of these peptides in the human sera and secondly to provide evidence for their involvement in inflammatory diseases. Their levels measured by specific enzyme-linked immunosorbent assays (ELISA) were found to be more than 10-fold higher in sera of patients with rheumatoid arthritis (RA), as compared to healthy controls. High levels of LIP1 and LIP2 were also detected in the synovial fluid (SF) of RA patients. These results provide first evidence for a cytokine-like role of the LIP1 and LIP2 peptides.

The value of shear wave elastography in diffuse thyroid disease.

PURPOSE: The aim of this study is to discuss the value of ultrasound-based shear wave™ elastography (SWE) in diffuse thyroid disease (DTD). METHOD: Thyroid stiffness in 154 patients with DTD and 30 normal subjects was measured by SWE. The serum indicators of all subjects were detected. RESULTS: The area under the receiver operating characteristic (AUROC) curve for DTD by SWE was 0.852. The AUROCs of SWE for differentiating chronic autoimmune thyroiditis (CAT) from Graves' disease (GD) and subacute thyroiditis (SAT) were 0.549 and 0.989, respectively. The AUROCs for distinguishing GD from SAT by SWE and the fT3/fT4 ratio were 0.975 and 0.713, respectively. CONCLUSION: SWE aids in the diagnosis of DTD, and SWE is superior to the fT3/fT4 ratio for distinguishing GD from SAT. However, SWE was unsuitable for differentiating CAT from GD.

Radioimmunoassay for measurement of thyroglobulin in human serum.

A specific and reproducible double antibody radioimmunoassay for the measurement of thyroglobulin (HTg) in human serum has been developed. Since antithyroglobulin autoantibodies combine with the [(131)I] HTg tracer, antibody-positive sera were rejected for measurement. Specificity is demonstrated in that thyroid analogous such as thyroxine (T(4)), triiodothyronine (T(2)) monoiodotyrosine (MIT) and diiodotyrosine (DIT) did not crossreact. Sera previously reacted with anti-HTg-Sepharose contained no immunoassayable HTg. Finally, sera obtained from patients after total thyroid ablation for thyroid carcinoma did not contain demonstrable HTg. The sensitivity of the assay is 1.6 ng/ml, and HTg was detectable in 74% of 95 normal subjects. The mean concentration was 5.1 ng/ml +/-0.49 SEM (range <1.6-20.7 ng/ml). Day to day variation in HTg levels is large in some euthyroid subjects and nearly absent in others. HTg was detectable in 90% of the sera obtained in 23 pregnant women at delivery in whom a mean concentration of 10.1 ng/ml +/-1.3 SEM was observed. The mean level for the corresponding newborn infants at birth was 29.3 ng/ml +/-4.7 SEM a value significantly higher than the mean maternal HTg concentration (P <0.01). A group of 17 thyrotoxic individuals all had elevated HTg levels; the mean for this group was 344.8 ng/ml +/-90.7 SEM. In the acute phase of subacute thyroiditis HTg was also elevated in all of 12 patients, and the mean for this group was 136.8 ng/ml +/-74.6 SEM.

Plasma triglyceride metabolism in thyroid disease.

Plasma endogenous triglyceride transport kinetics were determined in 16 hyperthyroid and in 12 hypothyroid patients and the results compared with those of euthyroid control subjects. In addition, the removal of exogenous particulate fat (Intralipid; Vitrum, Sweden) from the circulation and the postheparin plasma lipolytic activity (PHLA) were studied in these patients for further characterization of the alterations of plasma triglyceride metabolism in thyroid disease. In thyrotoxicosis the average plasma triglyceride level was slightly but significantly increased above that of control subjects. This change was associated with augmented production of triglycerides whereas the mean fractional removal rate was not different from normal. There was a significant linear correlation between the concentration and turnover rate of plasma triglycerides in both hyperthyroid and euthyroid subjects but the concentration/turnover rate ratio was less in the former group suggesting that the efficiency of removal of triglycerides from the circulation was improved in thyroid hyperfunction. The elimination of intravenously administered particulate fat occurred more rapidly in untreated hyperthyroid patients than in euthyroid control subjects. The mean PHLA was also above normal in thyrotoxicosis. Upon adequate treatment of the hyperthyroid state the fasting plasma triglyceride concentration was further increased. Hypothyroid patients showed another pattern of alteration of triglyceride kinetics. The synthesis of plasma triglycerides was normal but the fractional removal of both endogenous and exogenous triglycerides was markedly reduced and this change seems to account for the hypertriglyceridemia associated with thyroid hypofunction. The plasma PHLA was also clearly decreased in the hypothyroid state. Plasma FFA and glycerol levels were increased in hyperthyroidism and plasma FFA was slightly decreased in hypothyroid patients, but these variables were not significantly correlated with any parameter of triglyceride metabolism. Endogenous triglyceride turnover rate was significantly correlated with serum protein-bound iodine (PBI) and T3 uptake in thyrotoxicosis but not in hypothyroidism. Removal of exogenous fat was not related to postheparin plasma lipolytic activity but the fractional endogenous triglyceride transport showed a highly significant relationship to this lipase activity in a mixed group of hyper- and hypothyroid patients. The results suggest that thyroid hormones control both production and removal of plasma triglycerides. Different mechanisms for these interactions are considered.

Recurrent silent thyroiditis: a report of four patients and review of the literature.

Silent thyroiditis, excluding postpartum thyroiditis and destructive amiodarone thyroiditis, is a relatively uncommon cause of thyrotoxicosis and recurrent cases are even rarer. We present four patients with recurrent silent thyroiditis. The number of episodes ranged from two to nine. All four patients had episodes that were similar in duration (4-6 weeks) as well as in their clinical (no viral prodrome or neck pain), biochemical (high total triiodothyronine [T(3)], free thyroxine [T(4)], and low thyrotropin [TSH] presence of antibodies to thyroid antigens), and scintigraphic (low radioiodine uptake) findings. Individual symptoms and symptom-free duration (from 1 to 4 years) were more variable. No associations were found with regard to medications, pregnancies, or other disease states previously implicated in thyroiditis. One patient was unsuccessfully prescribed thyroid hormone to prevent recurrence. Three were treated with radioablative iodine therapy during the recovery phase of an episode; they became hypothyroid and take replacement l-thyroxine. They have remained symptom free.

Eye signs and serum eye muscle and collagen XIII antibodies in patients with transient and progressive thyroiditis.

BACKGROUND: There have been reports of the development of ophthalmopathy in patients with subacute thyroiditis (SAT) in the absence of Graves' disease and thyroid-stimulating hormone receptor (TSH-r) antibodies. OBJECTIVE: The aim of the study was to determine the prevalences of eye and eyelid signs and positive eye muscle and collagen XIII antibody tests in patients with SAT and silent thyroiditis (ST) and in patients with Hashimoto's thyroiditis (HT) as chronic thyroiditis controls. DESIGN: Ophthalmopathy was classified as Nunery type 1 (orbital inflammation, proptosis, without restrictive myopathy) or Nunery type 2 (with restrictive myopathy). We tested for antibodies against calsequestrin, flavoprotein (Fp), G2s, and collagen XIII in 5 patients with SAT, 6 with ST, and 11 with HT, and in 12 age- and sex-matched healthy subjects, using an optimized and standardized enzyme-linked immunosorbent assay (ELISA). MAIN OUTCOME: At the first visit, eye signs were found in two patients with SAT, one with type 1 ophthalmopathy and one with type 2 ophthalmopathy, and in three patients with ST, two with type 1 ophthalmopathy and one with dominant upper eyelid retraction only. Later in the course of their illness, one other patient with ST developed mild type 1 disease, giving an overall prevalence of any eye signs of 50% in patients with TT. Five patients with HT had mild type 1 ophthalmopathy and dominant upper eyelid retraction. One or more eye muscle antibodies were detected in three patients with SAT, four with ST, and seven with HT, of which calsequestrin and Fp antibodies were the most commonly found. TSH-r antibodies were detected in only one patient with ST, at the time when she developed Graves' hyperthyroidism following an episode of ST. CONCLUSION: The development of mild, but definite, ophthalmopathy or dominant upper eyelid retraction in patients with TT and chronic (Hashimoto's) thyroiditis in the absence of TSH-r antibodies or Graves' hyperthyroidism is an interesting observation that should be further addressed in larger groups of patients, including those with postpartum thyroiditis. These preliminary findings also raise questions about the mechanism for the link between ophthalmopathy and thyroid autoimmunity.